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RACE 2003Ramachandra Anaesthesia Continuing Education

February 20 - 23,2003.

Department of Anaesthesiologyand

Critical CareSri Ramachandra Medical College & Research Institute (DU)

Chennai

The R..A..C..E.. is growing

RACE has entered into its 4th successive year. The necessity for the continuing medical education program in the field of Anesthesia, and encouragement and support shown by all of you have made us to continue with the RACE. Our young, still enthusiastic and energetic department has taken up the challenge under the able guidance of Prof. Vijaylakshmi Kamat and we are pleased to be with you this year also.

We constantly made an effort to improve on and make RACE more interesting and more informative. Accordingly we have made some changes in the Scientific Program. We are organizing a hands-on- workshop on the first day and will have three more days of full academic program. We are forced to have limited registration for the workshop, otherwise we cannot make it hands on.

While retaining the Pro & Con Session, PG Symposium and How I Do It?, as demanded by most of the delegates in their feedback, we have included new sessions like “Debate” on few controversial topics and “Group Discussion” which will cover exam going cases and will be handled by the postgraduate examiners from all over India.

To encourage research work, we have included a “Free Paper Session” for the postgraduates in which few selected papers (after peer review) will be allowed to be presented.

Credit for successful publication of this volume goes first to the authors of various articles who in spite of their busy schedule and time constraints made a valuable contribution to the RACE. We gratefully acknowledge their efforts. Efforts have been made to eliminate most of the errors both technical as well as linguistic to the extent possible. We beg the pardon of the readers if there are any. We sincerely apologise to the authors if any errors or distortion have crept into the texts in the editorial process.

We are extremely grateful to our beloved Chancellor Mr.V.R.Venkataachalam and Mrs. Radha Venkataachalam, Chief Executive Director and other members of the management for the encouragement and support extended to us. We are also thankful to Mr.Selvaraj, Proprietor, Archana Group for helping us in providing accommodation.

The team spirit has paid off again. All faculty members have contributed to the successful conduct of RACE. We would like to specially mention the names of few faculty who formed the core group for the RACE like Dr.Arun, Dr.Pradeep, Dr.Aruna and Dr.Pavendhan. Prof.Vijaylakshmi Kamat and Dr.Mahesh Vakamudi played a vital role by providing the guidance and support needed. Ms. Mala has played a good managerial role.

We are extremely thankful to Mr.Arun, who has been man behind the formatting and setting of the articles in this book.

We will be failing in our duty if we do not remember the financial assistance provided by Nicholas Piramal India Limited, in publishing this book. We are also thankful to all the other sponsors who made the RACE 2003 possible.

We look forward to being with you again.

FACULTY OF ANESTHESIA

RACE 2003 Ramachandra Anaesthesia Continuing Education

Lectures

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

Gas Laws and the Anaesthetist

New Drugs in Anaesthesia

Management of Acute Pain

Anaesthetic Management of a Pregnant Patient for Non Obstetric Surgery

What’s New in Paediatric Epidural Anaesthesia

Ventilation Perfusion Distribution

Functions of the Diaphragm and Anaesthesia

Management of a Brain Dead Organ Donor

Anaesthetic Management of a Morbidly Obese Patient

Anaesthetic Management of Patients with Haemoglobinopathies

Low Flow Anaesthesia

How to get the most out of your CVP Catheter

Anitha Shenoy

Pankaj Kundra

M.R.Rajagopal

Gopinath

Lakshmi Vas

1

8

22

27

33

RamkumarVenkateswaran 42

Vijayalakshmi Kamat

Joseph Rajesh

Manimala Rao

Chandrasekhar

M.Ravishankar

Jigi Divatia

Anaesthetic Management of a PatientWith ESRD for Renal Transplantation Gita Nath

Sedation and Analgesia in Children for procedures outside the OR Ramesh

49

59

70

76

83

92

100

111


Post Graduate Symposia

15. Cardiovascular Physiology SRMC&RI 119

16. Central Neuraxial Blockade Kurnool Medical College 144

17. Patient Positioning Trivandrum Medical Collegel70

How I Do It

18. A 20 year old primi with severe MS Bharathi. R 186 requires Labour Analgesia

19. A 25 year old otherwise healthy male Manjunath Prabhu 194 with Ludwig’s angina is posted for abscess drainage.

Pros and Cons

20. Induced Hypotension is contraindicated in Children

21. Induced Hypotension is NOT contraindicated in Children

22. Strict preoperative blood sugar control to an FBS of 200mgs% is mandatory before elective surgery

23. Strict preoperative blood sugar control to an FBS of 200mgs% is NOT mandatory before elective surgery

24. Spinal Anaesthesia is contraindicated for day care surgery

25. Spinal Anaesthesia is NOT contraindicated for day care surgery

Raja Manoharan 198

LakshmiVas 201

NaheedAzhar 208

Kalyan Chakravarthy 215

ElsaVarghese 219

Rathna 224


Debate

26. Invasive Monitoring in ASA III and ASA IV patients will influence theoutcome of surgery

27. Invasive Monitoring in ASA III and ASA IV patients will NOT influence the outcome of surgery

28. Preoperative tranfusion threshold is a Hb of 8gms%

29. Preoperative tranfusion threshold is NOT a Hb of 8gms%

Work Shops

30. Airway

31. Cardiopulmonary Resucitation

32. Mechnical Ventilation

33. Nerve Blocks

Ashok Bahde

Rajamanoharan

Manjunath Prabhu

Anitha Shenoy

SrinivasanChandrasekharManjunath

TV. Ramakrishnan

Vijayalakshmi Kamat Gita Nath

Rajamanoharan Azhar Hussain

234

237

242

248

255

260

275

315


Dr. Anitha Shenoy Associate Professor Department of Anaesthesia Kasturba Medical College Manipal.

Dr. Ashok Badhe ProfessorDepartment of Anaesthesia & Critical CareJIPMERPondicherry.

Dr. Azhar Hussain ProfessorDepartment of Anaesthesia Kilpauk Medical College Chennai.

Dr.Bharathi. R.Assistant Professor Department of Anaesthesia SRMC&RI Chennai.

Dr. Chandrasekhar Professor of Anaesthesia Kurnool Medical College Kurnool.

Dr. ElsaVarghese Professor & Head Department of Anaesthesia Kasturba Medical College Manipal.

Dr. Gita NathConsultant Anaesthesiologist Al Jazeria Hospital Abudhabi, UAE.

Dr. Gopinath. R.Professor of AnaesthesiaNizam’s Institute of Medical SciencesHyderabad.

Dr. Hanumantha Rao. JConsultant AnaesthetistPeoples Trauma & Emergency Hospital,Guntur

Dr. Hemalatha Professor of Anaesthesia Trivandrum Medical College Trivandrum

Dr. Jigi Divatia Additional Professor Department of Anaesthesia Tata Memorial Hospital Mumbai.

Dr. Kalyan Chakravathy Consultant Anaesthesiologist Kakinada.

Dr. Lakshmi Vas Consultant Anaesthesiologist Mumbai.

Dr. Manimala Rao. S.Professor & Head Department of Anaesthesia Nizam’s Institute of Medical Sciences Hyderabad.

Dr. Manjunath Prabhu Associate Professor Department of Anaesthesia Kasturba Medical College Manipal.


Dr. Narasimha Reddy Professor of Anaesthesia Kurnool Medical College Kurnool.

Dr. Naheed Azhar Assistant Professor Department of Anaesthesia Stanley Medical College Chennai.

Dr. Pankaj Kundra ProfessorDepartment of Anaesthesia & Critical CareJIPMERPondicherry.

Dr. Rajagopal. M.R Professor of Anaesthesia Amritha Institute of Medical Sciences Cochin.

Dr. Rajamanoharan ProfessorDepartment of Anaesthesia Madurai Medical College Madurai.

Dr. Rajesh Joseph Consultant Anaesthetist Meenakshi Mission Hospital Madurai.

Dr. Ramakrishnan. T.V.Associate Professor and Course Co-ordinatorDepartment of Accident and EmergencyMedicineSRMC&RIChennai.

Dr. Ramesh.S.Consultant Anaesthesiologist Child Trust Hospital Chennai.

Dr. RamkumarVenkateswaran ProfessorDepartment of Anaesthesia Kasturba Medical College Manipal.

Dr. Rathna Professor and Head Department of Anaesthesia M.S. Ramaiah Medical College Bangalore

Dr. Ravishankar. M.Professor & HeadDepartment of Anaesthesia & Critical CareJIPMERPondicherry.

Dr. Srinivasan. R.ProfessorDepartment of Anaesthesia SRMC&RI,Chennai.

Dr. Suresh Rao Associate Professor Department of Anaesthesia SRMC&RI,Chennai.

Dr. Thanikachalam.S.Vice-Chancellor & HOD Cardiology, SRMC&RI,Chennai.

Dr. Vijaylakshmi Kamat Professor and HeadDepartment of Anaesthesiology & Critical CareSRMC & RlChennai


LECTURES

Gases exert pressure, are readily compressed and expanded, fill the spaces available to them by diffusion, dissolve in liquids, are capable of flow and have viscosity. Anaesthesiologists constantly deal with gases and hence it is imperative that he/she has a good knowledge of the behaviour of gases. Several laws define the relationship between gas pressure, volume, mass and temperature. They predict the behaviour of gases under changing conditions.

I) BOYLE’S LAW (Fig 1)This law states that volume is inversely

proportional to pressure, if the temperature is kept constant.

Applications:1) VOLUME OF OXYGEN IN A CYLINDER:

Consider an oxygen cylinder with an internal capacity of 5 litres. When full it has a pressure of 13800 kPa. How much oxygen will be available at atmospheric pressure?

According to Boyle’s law, P1V1 = P2V2 Where

V1 is the volume of the cylinder,P1 the cylinder pressure,P2 the atmospheric pressure and V2 the volume of gas available at atmospheric pressure

2) BODY PLETHYSMOGRAPHY:The whole body plethysmography

technique applies Boyle’s law and uses volume and pressure changes to determine lung volume. The plethysmograph consists of a sealed chamber in which the patient sits. Pressure transducers (electronic manometers) measure pressure at the airway and in the chamber. An electronically controlled shutter allows the airway to be occluded periodically, thereby measuring airway pressure changes under conditions of no airflow. According to Boyle’s law, (V x P = k), volume changes in the thorax changes volume in the chamber, which in turn are reflected by pressure changes in the chamber.

II) CHARLES’ LAW (Fig 2)This law states that volume is directly

proportional to temperature, if pressure is kept constant.


Gas laws and the Anaesthetist 1 Anitha Shenoy


V00 T if, P is constant

Where V = Volume, T = Temperature And P = Pressure

VfT is constant, if P is constant.Beware; do not use Celsius of Fahrenheit! Use Kelvin only.

Fig 2: Charles’ Law

Applications:1) DETERMINATION OF THE AMOUNT OF HALOTHANE VAPOUR AT ROOM TEMPERATURE

and the patient’s body temperature, pressure and saturated (BTPS). To make this adjustment, multiply the volume measured by ATPS to BTPS correction factor. There can be a 5% to 10% difference between volumes measured at ATPSand BTPS conditions. The difference can be large enough to invalidate the test results, unless the correction is made.

Ill) GAY LUSSAC’S LAW;At constant volume, pressure is directly

proportional to its temperature.

P oc T if volume is constant

Applications:Consider an oxygen cylinder filled to an

absolute pressure of 13,800 kPa at an ambient temperature of 293° K. A doubling of the absolute temperature doubles the pressure. Thus the cylinder is likely to explode even if the weakening of the cylinder is ignored.

V) AVOGADRO’S LAWAvogadro’s law states that equal volumes

of gases under the same conditions must contain the same number of molecules. Thus, one mole of a gas, at a constant temperature and pressure, should occupy the same volume as one mole of any other gas. This ideal volume is called the molar volume. At STP, the ideal molar volume of any gas is 22.4 L.

Applications:

1) VOLUME OF NITROUS OXIDE IN A CYLINDER

Consider a nitrous oxide cylinder which when full weighs 4.4 kg. How much nitrous oxide does it contain?

According to Avogadro’s law, one gm.mole of any substance occupies 22.4 L.

Thus, 44 g of nitrous oxide would occupy 22.4 L at STP.So, 4.4 kg will occupy

4400x2Z4 = 224Q L gt STp 44


The volume of a gas measured by a spirometer is usually measured at a lower temperature than the body temperature. According to Charles’ law, if pressure remains constant, a volume of gas is directly related to temperature. Volumes measured by a spirometer are at ambient temperature, pressure, and saturated (ATPS) conditions, and must be adjusted for the temperature difference between the spirometer


V) UNIVERSAL GAS CONSTANT:The concept of gas laws can be combined

with that of Avogadro’s hypothesis and the mole as follows:

PV = K1 V/T = K2 P/T = K3

(Boyle’s law) (Charles’ law)(Gay Lussac’s law)

So, PV/T is constant for a given quantity of any gas. For I mole of any gas PV/T equals a unique constant known as the Universal Gas constant.

So, PV = nRT, where n is the number of

moles of the gas. This is equivalent to 1.987 Joules per degree per mole in SI units

Applications:Consider an oxygen cylinder with a fixed

internal volume V. Therefore V in the equation PV = nRT is a constant. R is a constant value 1.987, and if the cylinder is at a fixed temperature, T is also a constant. Thus, from the formula, P is directly proportional to ‘n’, the number of moles, which is the amount of gas in a cylinder. The pressure gauge then acts as a contents gauge, provided the cylinder contains a gas.

VI) VARIATIONS FROM IDEAL GAS BEHAVIOUR: EXPANSION, COOLING AND ADIABATIC COMPRESSION

Boyle’s law describes the gas behaviour under constant temperature, or isothermal conditions. During isothermal conditions, the temperature of an ideal gas should not change with either expansion or contraction. For example, if an ideal gas were to escape from a high- pressure cylinder into the atmosphere, its temperature should not change. In fact, the rapid expansion of real gases causes substantial cooling. This phenomenon is known as the Joule Thompson effect.

A rapidly expanding gas cools because as it expands, the intermolecular forces are broken down. The energy required for this comes from the gas itself and the temperature must decrease. This drop in temperature can be enough to liquefy the gas. This is the primary method used to liquefy air for the production of oxygen.

Whereas isothermal processes keep gas temperature constant, adiabatic compression and expansion have no such restrictions. During an adiabatic process, the heat energy of the gas is allowed to rise or fall as it undergoes changes in pressure and volume. Adiabatic compression of a gas can cause rapid increases in temperature. This can occur in gas delivery systems where rapid compressions can occur in affixed container. The rise in temperature caused by rapid compression can ignite any combustible material in the system. Hence, care must be taken to clear any combustible material from high-pressure gas delivery systems before pressurization.



VII) CRITICAL TEMPERATURE AND PRESSURE

For every liquid there is a temperature above which the kinetic activity of its molecules is so great that the attractive forces cannot keep them in a liquid state. This temperature is known as the critical temperature. The critical temperature is the highest temperature at which a substance can exist as a liquid. The pressure needed to maintain equilibrium between the liquid and gas phases of a substance at this critical temperature is the critical pressure. Together, the critical temperature and pressure represent the critical point of a substance.

Applications:According to these principles, it is

possible to liquefy any gas with a critical temperature above the ambient, simply by applying pressure. Both C02 and N20 have critical temperatures above ambient. Hence, they can be liquefied by simple compression and stored as liquids at room temperature without cooling. But, liquid oxygen has to be maintained below its boiling point (-183° C) at atmospheric pressure. If higher temperatures are required, higher pressures must be used. If any time, the liquid oxygen exceeds its critical temperature of -118.3° C, it will convert immediately to gas.

VIII) DALTON’S LAW OF PARTIAL PRESSURE(Fig 3)

This law states that the contribution which each constituent gas makes to the overall pressure, is in proportion to the number of molecules of the constituent. If each gas existed separately in containers of the same size and shape, then the sum of the pressures in the individual containers would equal the combined pressure of all the gases put together in just one of the containers. The pressure exerted by one of the constituent gas is known as the partial pressure of that gas.

Thus, Dalton’s law describes the relationship between the partial pressure and the total pressure in a gas mixture. According to this law, the total pressure of a mixture of gases must equal the sum of the partial pressures of all the component gases. It also states that the partial pressure of a component gas must be proportional

to its percentage in the gas mixture.Partial pressure = Fractional concentration x total pressure

Applications:1) PARTIAL PRESSURE OF GASES AT THE ALVEOLAR LEVEL:

The partial pressure of oxygen at room air is 760 x 0.21 = 159 mmHg. (dry air)

At 25,000 feet (high altitudes), the FI02 is still 0.21 but total atmospheric pressure is only 282 mmHg. The PI02 there would be equal to

282x0.21 =59 mmHg

At a depth of 66 feet under the sea, at about 3 atmospheres, the PI02 will be

3 x 760 x 0.21 = 479 mmHg.

2) ALVEOLAR GASAlveolar gas which is at atmospheric

pressure of 100kPa, is composed of a mixture of gases. Their partial pressures when added will equal the total pressure of one atmosphere.

P02 = 13.3 kPa PC02 = 5.3 kPa PH20 = 6.26 kPa PN2 = 75.2 kPa Total = 100 kPa

Fig 3: Dalton’s law of partial pressure3) FILLING GAS CYLINDERS WITH GAS MIXTURES.

A cylinder is initially filled to 1380 kPa and thereafter 02 is added to make up to a pressure of 13,800 kPa to produce 10% C02in



IX) HENRY’S LAWThis law predicts how much of a given

gas dissolves in a liquid. According to this principle, the volume of gas that dissolves in a liquid is equal to its solubility coefficient times its partial pressure,

V= OC x Pgas

Where

V = volume of the gas dissolved, oc s the solubility coefficient of the gas in the given liquid and Pgas is the partial pressure above the liquid.

Applications:1) THE AMOUNT OF GAS CARRIED IN SOLUTION

The amount of gas carried in solution in blood is governed by Henry’s law. The solubility coefficient of oxygen is 0.003 ml.dL'1. Thus, at 100 mmHg of oxygen tension and in 100 ml, the oxygen that can dissolve in blood would be 0.3 ml.

2) DEEP SEA DIVING:When divers breathe gases under

pressure, nitrogen and other gases pass into solution in the tissues. If they return to atmospheric pressure, the nitrogen comes out of solution as small bubbles in the joints and elsewhere giving rise to decompression sickness or the Caisson’s disease.

X) POISEUILLE’S LAWDuring laminar flow, a fluid moves in

discrete cylindrical layers or streamlines. The difference in pressure required to produce a given flow, under conditions of laminar flow through a smooth tube of fixed size, is defined by Poiseuille’s law.

where A P is the pressure gradient, Ix is the viscosity of the fluid, I is the tube length,

V is the fluid flow, r is the tube radius and n and 8 are constants.

According to this formula, the driving pressure will increase whenever the fluid viscosity, tube length or flow increases. A greater pressure will be required to maintain a given flow if the radius decreases. If the radius reduces by half, the pressure gradient required to maintain the same flow will go up 16 times!

Applications1) INTRAVENOUS INFUSIONS:

The flow rate obtained is governed by the Poiseuille’s law.

Hence, the flow rate obtained is higher when the cannula is large, and short and the pressure head is higher. Doubling the size of the cannula effectively increases the flow 16 times!

2)AIRFLOWTOTHE LUNGS:For air to flow into the lungs, a pressure

gradient must be developed. This depends on the calibre of the airway, rate and pattern of airflow. Laminar flow occurs when the gas passes down parallel-sided tubes at less than a critical velocity. The airflow rate is determined by the Poiseuille’s law.


Variations in the diameter of the smaller bronchi and bronchioles are particularly critical. A decrease in the diameter of the bronchus increases the pressure gradient 16 times and hence an increase in airway pressure is observed. Endotracheal intubation with a smaller tube also has a similar effect.

XI) THE BERNOULLI EFFECT (Fig 4)When a fluid flows through a tube of

uniform diameter, pressure decreases progressively over its entire length. However, when the fluid passes through a constriction, the pressure drops even further. As the fluid passes into the constricted portion of a tube, its velocity must increase. According to Bernoulli principle, as the velocity increases, the lateral pressure


exerted by the fluid decreases.

Fluid EntrainmentWhen a flowing fluid encounters a very

narrow passage, its velocity can greatly increase. In some cases, the rise in velocity can be so high as to cause the fluid’s lateral pressure to fall below that exerted by the atmosphere, i.e., negative. If an open tube is placed distal to such a constriction, this negative pressure can actually pull another fluid into the primary flow stream. This effect is called fluid entrainment.

Applications1) AIR INJECTOR (Fig 5):

The most common application of fluid entrainment is the air injector. An air injector is used to increase the total gas flow in a gas stream. In this case, a pressurised gas, usually oxygen, serves as the primary flow source. This pressurised gas passes through a nozzle or jet, beyond which is an air entrainment port. The negative lateral pressure created at the jet orifice entrains air into the primary gas stream, thereby increasing the total outflow of the system. The amount of gas entrained can be increased either by increasing the entrainment port or by having a smaller jet.

from a chamber around the jet and thus carries the drugs directly into the trachea.

Fig 7: A small volume jet nebuliser

Fig 5: Air injectors

2) HUMIDIFIERS (Fig 6):A jet of gas entrains water droplets from a

capillary of water into the breathing system.

3) NEBULISERS (Fig 7):These are devices that use the Bernoulli

principle to nebulise drugs. They consist of a central jet of oxygen that entrains the droplets

4) PEEP valves: Some PEEP valves are also built on this principle.

XII) VENTURI PRINCIPLE (Fig 8)A Venturi tube is a modified entrainment

device. A Venturi tube widens just after its jet or nozzle. As long as the angle of dilatation is less than 15 degrees, this widening helps to restore fluid pressure nearly back to prejet levels. The Venturi tube as compared to a simple air injector provides greater entrainment.

Fig 8: Venturi Principle



ApplicationsVENTURI MASKS:

These have a series of tubes with fixed jet orifice and entrainment. The entrainment of air results in a high total flow to ensure that a fixed FI02can be given.

XIII) COANDA EFFECT (Fig 9)This phenomenon also called the wall

attachment is the principle underlying most fluidic circuitry. This effect is seen when fluid flows through a small orifice with properly contoured downstream surfaces. According to Bernoulli principle, the negative pressure created at a jet or nozzle will entrain any surrounding fluid such as air into the primary flow stream. If a carefully curved wall is added to one side of the jet, the

pressure near the wall becomes negative relative to atmospheric. Thus, the atmospheric pressure on the other side of the gas stream pushes it against the wall, where it remains locked until interrupted from some other counter force.

Applications:1) FLUIDIC DEVICES:

A variety of fluidic devices are made based on this principle. They are extensively used to make ventilators work.

2) INFUSION SETS:It is often noticed that the intravenous fluid

sticks to the sidewall of the drip chamber. This is due to Coanda effect and can be avoided by proper designing of the infusion set.

REFERENCES:

1. Scanlan LC, Wilkins RL, Stoller JK. Egan’s Fundamentals of Respiratory Care. 7th ed., London: Mosby, 1999

2. Parbrook GB, Davis PD, Kenny GNC. Basic physics and measurement in Anaesthesia. 4th ed., Oxford: Butterworth Heinemann, 1995

3. Scurr C, Feldman S. Scientific Foundations of Anaesthesia. 2nd ed., London: William Heinemann Medical Books, 1974


Newer Anaesthetic Agents 8 Pankaj Kundra

JIPMER, Pankaj KundraPondicherry.

Promising new anaesthetic agents in the past decadeLocal Anaesthetic Agents: Ropivacaine,LevobupivacaineNarcotics: RemifentanilInhalational Agents: Sevoflurane, DesfluraneIntravenous Induction Agents: PropofolMuscle Relaxants: Rocuronium

Indian Scenario Narcotics: Fentanyl Inhalational: Sevoflurane Intravenous: Propofol, Midazolam Muscle Relaxants: Rocuronium

INTRAVENOUS AGENTS

PROPOFOL

Alkylphenol derivative.(2,6-di-isopropofol)

Physicochemical Properties- pH: 7

Composition10% soyabean Oil

• 2.25% glycerol1.25% purified egg phosphatide

Stable at room temperature

Metabolism1

Liver by conjugation to glucuronide and sulfateMetabolites inactiveClearance of propofol exceeds hepatic blood flow. Thus it is thought to have extrahepatic and extrarenal elimination. Extrahepatic metabolism is confirmed in anhepatic phase of patients receiving liver transplant.

Pharmacokinetics1,2

2 and 3 compartment model Following a single bolus injection, whole blood propofol levels decrease very rapidly as a result of both redistribution and elimination (Figure 1)2 compartment model• Initial distribution half life: 2-8

min• Elimination half life: 1-3 hours3 compartment model• Slow distribution half lives: 1 - 8 min and 30 - 70 min

• Elimination half life: 4 - 23.5 hours Owing to very rapid clearance of propofol from

central compartment, the slow return of propofol from deep compartment contributes little to the initial rapid decrease in propofol concentrations

Context Sensitivity2: Defined, as the time required achieving a 50% decrease in drug concentration after termination of a continuous infusidn targeted to maintain a constant concentration. Context sensitivity half time for infusions up to 8 hours is less than 40 min2. As the required decrease in concentration for awakening following anaesthesia or sedation is less than 50%, recovery from propofol will remain rapid even



WholeBloodconc.(fxg/ml)

Time (min)Fig 1. Time course of whole blood levels after induction dose of propofol 2mg/ per kg

Fig 2. Contact sensitivity of induction agents

after prolonged infusions (Figure 2).

Volume of Distribution1

Volume of distribution in central compartment: 20 - 40 L

Volume of distribution at steady state: 150 - 700 L

Clearance1: Extremely high (1.5- 2.2 L/min)

Pharmacokinetics of propofol can be altered by Age

Elderly have decreased clearance rates butsmaller central volume compartment. Children



have larger central volume compartment (50%) and rapid clearance (25%)

WeightSexWomen have higher volume of distribution and higher clearance rates. Elimination half- life however is similar in both genders. Pre-existing disease• Liver Disease: Results in large steady states and central compartment volumes. Clearance is unchanged but the elimination is slightly prolonged.

Renal Disease: Propofol kinetics unaltered

Concomitant drugs• Fentanyl: Controversial effects

■ No effect following a single dose administration

■ Fentanyl reduces both intercompartmental and total body clearance rates as well as volumes of distribution.

• Sufentanil and Alfentanil: In vitro studies on human hepatocytes suggests that propofol inhibits enzymatic degradation of both these drugs in a dose dependent manner

Pharmacodynamics1. EFFECT ON CENTRAL NERVOUS SYSTEM

Hypnosis: By enhancing the function of GABA-activated chloride channel.i. Onset of hypnosis (2.5 mg/kg): One

brain arm circulation time3

ii. ED50 is 1 - 1.5 mg/kg following a bolus3

iii. Duration of hypnosis:1. Dose dependent: 5 - 1 0 min following 2 - 2.5 mg/kg3

2. Age: Age markedly effects ED95 induction dose being highest at ages less than 2 years (ED95 2.88 mg/kg) and decreasing with increasing age4

Amnesia & Sedation: At subhypnotic doses.Produces a general state of well being5 Direct anticonvulsant effect:i. Recent reports on variety of models

indicate it has a dose dependent anticonvulsive effect.

ii. Grandmal seizures: A rare side effect (1 in 50,000). Therefore used for cortical mapping for epileptogenic foci6.

Electroconvulsive Therapy: Shorter duration of motor and EEG seizure activity when compared to methohexital7. Intracranial Pressure (ICP)8: Decreases ICP in patients with normal or elevated ICP• Normal ICPDecrease in ICP (±30 %) with minimal fall in cerebral perfusion pressure (±10%) Normal cerebral reactivity to C02 and autoregulation are maintained• Elevated ICPEFFECT ON RESPIRATORY SYSTEM10 Apnoea occurs after initial dose of propofol but incidence of apnoea is dependent uponi. Doseii. Speed of injectioniii. Concomitant premedication BronchodilationMaintenance dose of 100mg/kg/min (6 mg/ kg/hour):i. 40% decrease in tidal volume and 20%

increase in respiratory frequency.ii. 58% reduction in the slope of the C02 r

esponse curve: Similar to 1 MAC halothane or a brief infusion of thiopentone (3mg/kg/ min)

Doubling the dose to 200 mg/kg/min produces only a small decrease in tidal volume and a minimal decrease in C02 response curve. This is in contrast to the inhalational agents where doubling of FA will halve the C02 response curve11.

Effect on Cardiovascular System12-13 Induction dose of propofol ( 2 - 2 . 5 mg/kg) results in

• Decrease of 25 - 40% in both systolic and diastolic pressures, but the heart rate remains stable. The stability in heart rate suggests that propofol resets the baroreceptor reflex.

• The above decrease is associated with decrease in Cl, LVSWI, SVR, Mean PAP and PAOP.• Effect is maximum at 2 min after

induction and is due to■ Direct myocardial depression■ Decreased peripheral resistance and preload

• The hypotensive effect of propofol ispotentiated by■ Large doses of propofol■ Pre-existing cardiovascular disease



■ Hypovolemia or CVS decompensation■ Advanced age■ Premedication with opioids■ Concomitant use of nitrous oxide

• Both coronary blood flow and myocardial MR02 are reduced, implying the global myocardial supply-demand is maintained.

4. Other EffectsPain on injection, especially in small veinsDuring prolonged infusions consideration must be kept for the effect of volume as well as the energy provided by intralipid (3 mg/ kg/hour provides 555 kcals/24 hours).This is equivalent to 25% of calorie requirements and 50% of lipid requirements per day Preliminary studies indicate it does not

trigger malignant hyperthermia14 It is safe to be used in porphyria.

DOSE REGIMESThe Bristol Model (1988) SirHumphry Davy Dept of Anaesthesia. UK

It is a widely known and quoted model of propofol pharmacokinetics. The study used a computer algorithm based on a 3-compartment model to design a simple infusion scheme for the manual infusion of propofol to achieve a desired target plasma concentration (3 mg/ml) within 2 min and to maintain this level for the duration of surgery.

The study design was as follows:ASA 1 & 2 patients presenting for superficial body surgery

Premedication with temazepam 20 - 30 mg/

Fig. 3. Metabolism of remifentanil



kg, 90 min before surgery.Fentanyl 3 mg/kg 2 min before the injection of propofol.Propofol 1 mg/kg over 20 sec Propofol 10 mg/kg/hr for 10 min Propofol 8 mg/kg/hr for 10 min Propofol 6 mg/kg/kg/hr thereafter. Vecuronium 0.1 mg/kg and tracheal intubationVentilation with 67% nitrous oxide in oxygen. Results in practice showed an overall mean

blood propofol concentration of 3.67 mg/ml, which is maintained over the subsequent 80 - 90 min. It is important to note the figures for the induction dose of propofol used, and that opioid, nitrous oxide and vecuronium provided balanced anaesthesia. If a loading dose of 2 mg/kg of propofol is used, as in common practice, then additional 1 mg/kg is equal to the amount of drug given above a maintenance rate of 6 mg/kg/hr by the higher infusion rates of the first 20 min. If a loading dose 2 mg/kg of propofol is followed by a 10-8-6 regime, the propofol concentration is likely to be higher than predicted, with the attendant cardiovascular effects.

TARGET CONTROL INFUSION (TCI)TCI is an infusion system, which allows the

anaesthesiologist to select the target blood concentration required for a particular effect, considering the patient’s and operation’s needs, then to control depth of anaesthesia by adjusting the requested target concentration during surgery. The pharmacokinetic program of a TCI-device, however, continuously calculates the distribution and elimination of the intravenous anaesthetic agent, and successively adjusts the infusion rate to maintain a predicted blood or plasma drug concentration. One of the main benefits of TCI over manually controlled infusion systems is, therefore, its greater and better control over the drug concentration and the depth of anaesthesia obtained.

OPIOIDS

REMIFENTANIL15

Physicochemical PropertiesUltra-short acting ^-receptor opioid agonist Chemically designated as 3-[4- methoxycarbony l-4-( 1 -

oxopropyl)phenylamino]-1 - poperidine propanoic acid methyl ester.Molecular wt. 413 Structurally similar to fentanyl, sufentanil and alfentanil.Incorporation of methyl ester group onto the N-acyl side chain of the piperidine ring renders remifentanil susceptible to rapid esterhydrolysis.

PharmacokineticsDose dependent pharmacokinetic profile (shape of the blood concentration-time curve is independent of dose).Distribution: 2 or 3 compartment pharmacokinetic model with limited distribution into the 3rd compartment. Clearance: 2.9 L/min. Exceeds normal hepatic blood flow rates. Consistent with widespread extrahepatic metabolism Mean steady state volume of distribution of 31.8 L.Metabolism: Rapid hydrolysis by blood and tissue esterases (Figure 3).Accumulation of GI90291 is demonstrated after prolonged (12 hour) infusions in patients with renal failure. However, there were no obvious effects on minute ventilation in controls and in patients with renal failure as the metabolite is inactive.Hydrolysis of remifentanil is independent of plasma cholinesterase activity. Thus dosage does not require adjustments in pseudocholinestrase deficiency. Remifentanil metabolism is independent of hepatic function. Remifentanil clearance is unchanged during anhepatic phase of liver transplantation.Pharmacokinetics can be influenced by:

Increasing age: Central clearance and distribution volume decreases, whereas potency increases

Obesity: Pharmacokinetics best correlate with lean body weight.

Context sensitive half time: Unique among fentanyl congeners in that its context sensitive half time is short (only 3-4 min) and independent of the duration of infusion. In contrast, context sensitive half time of fentanyl, sufentanil, alfentanil are all dependent on infusion duration and are longer than that of remifentanil (Figure 4).

Figure 5 compares the 50% and 80%



INFUSION DURATION (min)

Fig 4. Pharmacokinetics of fentanyl, alfentanil, sufentanil, remifentanil



decrement times of remifentanil and alfentanil. The short context-sensitive half-time of remifentanil results in rapid dissipation of opioid effect after the termination of a continuous infusion

PharmacodynamicsThe potency of Remifentanil is similar to that of fentanyl.A 50% isoflurane MAC reduction is produced by 1.37 ng/ml of remifentanil whole blood concentration, compared with plasma concentrations of fentanyl of 1.67 ng/ml. Remifentanil is 20 - 30 times more potent than Alfentanil.Remifentanil’s t1/2keo, a parameter used to describe the delay between peak drug blood level and peak pharmacodynamic effect, is similar to that of alfentanil which is 1.6 min. Central Nervous System

EEG effects are characteristic of• opioids.

It is associated with a dose dependent decrease in mean arterial pressure and cerebral perfusion pressure.

C eiebralvascuirieactkTiy to C 0 is maintained with remifentanil/N20 anaesthesia.

Respiratory SystemDose dependent ventilatory depression. Remifentanil and alfentanil both exhibit a rapid onset of ventilatory depression but the depression caused by remifentanil is much shorter lived. When given by infusion for monitored anaesthesia care, remifentanil was associated with higher ETC02 and lower02 saturation values than propofol.

Cardiovascular SystemMild bradycardia and 15 - 20% decrease in arterial blood pressure may be seenPatients older than 70 years are more susceptible to the haemodynamic effects of remifentanil.Like all opioids, remifentanil can cause significant hypotension when combined with other anaesthetic agents.

INFUSION DURATION (min)

Fig 5. Comparision of alfentanil and remifentanil



Clinical Uses• MONITORED ANAESTHESIA CARE1. Single Intravenous DoseRemifentanil 0.5 -1.0 mg/kg/over 30 - 60 secs Perform local anaesthetic block 90 secs later Combine with either propofol 0.5 -1.0 mg/kg or midazolam 1 - 2 mg to optimize sedation and decrease side effects.

2. Continuous Intravenous Infusion Remifentanil 0.05-0.1 mg/kg/minPerform local anaesthetic block 5-7 min later Following block titrate remifentanil 0.025 - 0.2 mg/kg/min

When given as continuous infusion, remifentanil may be combined with either midazolam 1 - 2 mg or propofol 10-40 fig/kg/ min to optimize sedation and decrease side effects.

• GENERAL ANAESTHESIA1. Continuous Intravenous Infusion Remifentanil 0.5 - 1.0 mg/kg/min for 2 - 3 min Remifentanil 0.125 - 0.25 mg/kg/min maintenance (range 0.05 - 2.0 mg/kg/min) Remifentanil bolus 0.5 -1.0 mg/kg/min every 3 - 5 min

2. Induction of AnaesthesiaAdminister reduced dose of hypnotic

agent (e.g., propofol 0.75 - 1.0 mg/kg, Thiopentone 1.0 - 1.5 mg/kg) 1 - 2 min after starting remifentanil infusion.Administer neuromuscular blocker following loss of consciousness, as per usual practice.

3. Maintenance of AnaesthesiaIsoflurane 0.4 - 0.8% alone or 0.2 - 0.4% with 66% N20Sevoflurane 0.7 -1.4% alone or 0.4 - 0.8% with 66% N20Desflurane 1.5 - 3.0% alone or 0.75 -1.5% with 66% N20Propofol 75 - 200 mg/kg/min alone or 50-150 mg/kg/min with 66% N20

• SPINAL ADMINISTRATIONPresent formulation contains the

inhibitory neurotransmitter glycine as a vehicle, so continuous intrathecal administration of this formulation produces reversible, naloxone- insensitive motor dysfunction. Hence its

administration is not recommended.

• POSTOPERATIVE ANALGESIABecause of the rapid offset of

opioid effect of remifentanil, it is imperative to address postoperative analgesic needs before the conclusion of surgery. Remifentanil (0.025 - 0.2 mg/kg/min) may be continued into the immediate postoperative period until a longer acting opioid (e.g. morphine) is administered.

INHALATIONAL AGENTS SEVOFLURANE AND DESFLURANE15

Desflurane (CF2H-0-CFH-CF3) and Sevoflurane [CFH2-0-CH-(CF3)2] are

Halogenated ether structures1. Halogenation serves to eliminate

flammability and these drugs are halogenated entirely by fluorine

■ Fluorine significantly changes the solubility of these agents. Solubility is reflected in the blood-gas partition coefficients of 0.45 for desflurane and 0.65 for sevoflurane. The decrease in solubility lends itself to an agent that will provide a faster induction of and emergence from anaesthesia when administered in an equivalent MAC.

■ Fluorine also serves to decrease the MAC of desflurane and sevoflurane.

2. Ether linkage is associated with the drugs’ likelihood to sensitize the myocardium to arrhythmias.

3. Vapour Pressure at 20 degree C■ Desflurane: 669 mm Hg■ Sevoflurane: 170 mm Hg

This pressure allows for the administration of sevoflurane through conventional vaporizers. Desflurane, however, has vapour pressure approaching atmospheric pressure and therefore must be administered through a newly developed vaporizer system.

■ This vaporizer produces a controllable and predictable concentration of desflurane in oxygen regardless of changes in ambient temperature (between 18 - 30°C) and gas flow (between 0.2-10 L/min).

■ The vaporizer works by heating desflurane within an enclosure that is at 1500 mm Hg. The gaseous desflurane then passes from the enclosure through variable resistance transducers as controlled by the set delivery concentration and then mixes with the diluents gas.



DesfluraneCENTRAL NERVOUS SYSTEM(CNS)

May potentially alter cerebral blood flow (CBF),cerebral metabolic rate for oxygen comsumption (CMR02), CNS activity and cognitive function. Higher MAC concentrations are required for arterial blood pressure support with phenylephrine infusions. A dose dependent decrease in cerebrovascular resistance regardless of arterial blood pressure support. This suggests Desflurane is a cerebral arteriolar dilator.

Dose related depression of EEG activity up to and including burst suppression. No epileptiform activity has been demonstrated.Awakening Time: In ASA I and II patients is about 5.25 min. after discontinuation of 1 MAC during application of dressing.

RESPIRATORY SYSTEMRapid inhalational induction agent (low solubility)High incidence of breath holding, apnoea and coughing.Potential for laryngospasm is high, and these effects. Maintenance of inspired concentration at less than 6% (1 MAC) minimizes the likelihood of airway irritation. Dose dependent decrease in tidal volume and an increase in respiratory rate.Minute ventilation decreases at 1.66 MAC Depresses ventilatory response to C02, which is indistinguishable from the depression reported for isoflurane and enflurane and slightly greater than that reported for halothane.

CARDIOVASCULAR SYSTEMDose dependent increase in right heart filling pressures and a decrease in systemic vascular resistance and mean systemic arterial pressure.Unlike isoflurane, desflurane doesn’t decrease the cardiac index or left ventricular ejection fraction even at deep levels of anaesthesia.Heart Rate: Increase in rate is demonstrated by > 30 beats/min at 1 - 1.5 MAC Unchanged cardiac output in the presence of increased right sided heart filling

pressures, decreased systemic vascular resistance and increased heart rate suggests that desflurane decreases myocardial contractility.Does not sensitize myocardium to catecholamines.Haemodynamic responses get attenuated at 1.66 MAC

PHARMACOKINETICSSingle halogen substitution of a fluorine atom for chlorine in isoflurane makes desflurane a more stable compound. Stability in presence of soda lime maintained at 40°, 60° and 80°C has been compared as the anaesthetic degradation increases as temperature increases:• At 80°C the rate of degradation per hour:

■ Sevoflurane: 92.2 ± 5%■ Halothane: 16 ± 1.6%■ Isoflurane: 13.1 ± 3.7%■ Desflurane: 0.44 ± 0.26%

• This suggests that desflurane strongly resists biodegradation.

Metabolites:• Fluoride ion: Post anaesthesia urinary

excretion of fluoride ion and organic fluoride in volunteers was comparable with pre anaesthesia excretion rates.

• Trifluroacetic acid (TFAA): Increases significantly in both serum and urine of volunteers after desflurane exposure. TFAA increases are 10 fold less than levels seen after isoflurane exposure.

• No evidence towards hepatotoxicity after exposure to 7.35 ± 0.81 MAC hours of desflurane anaesthesia.

• Desflurane does not cause acute renal toxicity.

• Desflurane has the capacity to trigger malignant hyperthermia in susceptible individuals.

SevofluraneCENTRAL NERVOUS SYSTEM

Effects of sevoflurane similar to other halogenated anaesthetics.At 1 MAC both sevoflurane and isoflurane cause• Significant reduction in CMR02 to 50%.• No change in cerebral blood flow occurs

with either of the agent.



• Significant increase in ICP occurs with both.

• EEG: No evidence of spike or seizure activity.

RESPIRATORY SYSTEMInhalational induction is rapid and pleasant without causing breath holding or coughing. Respiratory depressant Decrease in tidal volume with increasing depth of anaesthesia although respiratory rate is increased.BronchodilationInhibits hypoxic pulmonary vasoconstriction response in a dose dependent manner

CARDIOVASCULAR SYSTEMHalogenated anaesthetic: cardiovascular depressant

• Myocardial depression: More with sevoflurane than isoflurane but less than that with halothane anaesthesia.

• Systemic Vascular Resistance: Decreases SVR but to a lesser degree than isoflurane

• Mean Arterial Pressure: Effect similar to isoflurane.

• Heart Rate: Lesser rise in heart rate as compared to isoflurane

• Does not sensitize myocardial to the arrhythmogenic effects of catecholamines.

METABOLISM AND TOXICITYLacks the stability of halothane or isofluraneRate of degradation at22°C is 6.5% per hour for each degree rise in temperature. Renal effects of prolonged exposure to sevoflurane.• Serum inorganic fluoride levels: 22.1 (± 6.1) mmol/L after 1 hour exposure.• The inorganic fluoride levels associated

with prolonged sevoflurane exposure declined rapidly to less than half the maximal level by 48 hours after cessation of anaesthesia. This is related to a low blood gas partition coefficient, which allows rapid elimination of sevoflurane via the lungs, leaving a little drug to be metabolized after cessation of anaesthesia delivery.

LOCAL ANAESTHETICS Ropivacaine

Ropivacaine was developed in response to the reports of cardiovascular toxicity after accidental intravascular injection of bupivacaine. The main differences from bupivacaine lie in its

• Pure enantiomeric formulation• Improved toxic profile• Lower lipid solubility

ENANTIOMERIC FORMULATIONSubstitution of propyl for the butyl group in the piperidine ring’s tertiary nitrogen atom. Ropivacaine consists of a single enantiomer, the S-stereoisomer• This renders ropivacaine less intrinsically

cardiotoxic.• It is cleared more rapidly from circulation

if injected intravenously which however cannot be substantiated as S- enantiomers are metabolized by the liver more slowly than the corresponding R- enantiomers17.

TOXIC PROFILE CardiotoxicityCardiovascular toxicity of local anaesthetics has effects directly on the myocardium, vascular smooth muscle, and central innervations of the heart.• In both neuronal and cardiac Na+

channels, the S-isomers of the piperidine containing local anaesthetics are less potent than R-isomers. The stereo potency of cardiovascular effects mediated through the vascular tissue and the CNS is unknown18.

• The smaller propyl substitution in (S-) ropivacaine makes it slightly less potent than S-bupivacaine in its effect on single Na+ channels and isolated nerve action potentials19.



• Very slow reversal of Na+ channel blockade after cardiac action potential is a hallmark of bupivacaine. This reversal is considerably faster with ropivacaine20.

• A greater therapeutic index for ropivacaine than bupivacaine, particularly with regard to cardiotoxicity.

CNS Toxicity• Convulsing doses of ropivacaine are

larger than those of bupivacaine but less than those of lignocaine.

LIPID SOLUBILITY21

• Ropivacaine’s low lipid solubility may result in reduced penetration of the large myelinated A<x motor fibres, so that initially these fibres are relatively spared. However during continuous infusions they get blocked. Therefore, motor block produced with ropivacaine has

• A slower onset with ropivacaine• Less dense• Shorter duration when compared to

bupivacaine.

KINETICSRopivacaine is metabolized in liver by

aromatic hydroxylation, mainly to 3-hydroxy- ropivacaine, but also to 4-hydroxy-ropivacaine, both of which have some local anaesthetic activity21.

LevobupivacaineCLINICAL POTENTIAL:

The S(-)enantiomer of bupivacaine, with less cardiovascular and central nervous toxicity, a slightly longer duration of sensory block, but otherwise similar to its parent.

PHARMACODYNAMICS:Compared to bupivacaine it is as

potent, with a trend towards longer sensory block; with epidural usage it produces less prolonged motor block; Differentiation not seen with peripheral placement; lethal dose 1.3 to 1.6 times higher; less cardiac effect including less depression of contractility and fewer arrhythmias; higher convulsive doses. Has not been compared at equipotent anaesthetic doses with ropivacaine.

PHARMACOKINETICS:

_Elimination t1/21.3 hours VD 67L in adult volunteers Protein binding > 97%Metabolism by CYP1A2 and 3A4 Crosses placenta No racemisation in vivo.

DOSAGE:Minimum effective concentration

0.085%; Recommended maximum dosage 150mg for single dose epidural; 12.5mg/hr (10mls/ hr of 0.125% solution) for labour epidural infusion; 18.75mg/hr (15mls/hr of 0.125% solution) for epidural infusion; and 25mg every 15 or more minutes for epidural bolus doses.

15mg for intrathecal placement. 2.5mg/kg for nerve blocks in paediatric patient.

ADVERSE EFFECTS:Potential for hypotension and

cardiac arrest: observe precautions as for all local anaesthetics. Cardiotoxicity and CNS toxicity as noted.

DRUG INTERACTION: Unknown.Of Note:(1) Don’t use 0.75% in obstetrics;(2) Not for paracervical or Bier’s block;(3) Avoid if hypersensitivity to amides (rare).

EMLA (Eutectic mixture of local anaesthetic)21When two compounds are mixed

to produce a substance that behaves with a single set of physical characteristics, it is said to be eutectic. EMLA (5%) contains mixture of crystalline bases of 2.5% lignocaine and 2.5% prilocaine in a white oil: water emulsion. The mixture has a lower melting point, being oil at room temperature, while the individual components would be crystalline solids.

PRESENTATION AND USESEMLA is presented as an

emulsion in tubes containing 5 or 30 gm. It is used to anaesthetize skin before vascular cannulation or harvesting for skin grafts. It should be applied to intact skin under an occlusive dressing for at least 60 min. to ensure adequate anaesthesia.

CAUTIONSMethaemoglobinaemia is caused

by o-toludine, a metabolite of prilocaine______RACE 2003 Ramachandra Anaesthesia Continuing Education


• Congenital or idiopathic methaemoglobinaemia• Infants less than 12 months receiving treatment with methaemoglobin-inducing drugs• Patients on drugs associated with methaemoglobinaemia (sulfonamides, phenytoin)• Do not use on mucous membranes due to rapid systemic absorption• Patients receiving Class I antiarrhythmic drugs (Tocainide, Mexilitine)

NON DEPOLARIZING MUSCLE RELAXANTS

to limit the duration of the block23.□ Avid liver uptake and elimination into bile

due to increase in the lipophillic nature of the molecule with regard tovecuronium24. At appropriate dose, enables tracheal intubation in 60 - 90 sec and may prove a substitute for succinylcholine in rapid tracheal intubation, other aspects of clinical pharmacology of rocuronium seemssimilar to properties of vecuronium25.

PHARMACODYNAMICS

Table 1: Dosage and duration of action of rocuronium


Newer Anaesthetic Agents Pankaj Kundra

received an additional dose of reversal agent. The median (range) dose of neostigmine was 0.04 (0.01 to 0.09) mg/kg and the median (range) dose of edrophonium was 0.5 (0.3 to 1.0) mg/kg. In geriatric patients (n=51) reversed with neostigmine, the median TA/T: increased from 40 to 88% in 5 min.

METABOLISM & ELIMINATIONNo metabolism of rocuronium has yet been reported. Like vecuronium dual hepatic and renal pathways of elimination exist. Unchanged drug

has been recovered from bile and urine24.

REFERENCES1. Simons PG, Cockshott ID, Douglas EJ. Blood concentrations, metabolism and elimination after subanaesthetic intravenous dose of 14C-propofol to male volunteers. Postgrad Med J 61: 64; 1985.2. Hughes MA, Jacob JR, Glass PSA. Context sensitive half time in multicompartment pharmacokinetic models for intravenous anesthesia. Anesthesiology 76: 334; 1992.3. Major E, Verniquet AJW, Waddell TK et al. A study of 3 doses of ICI 35 868 for induction and maintenance of anaesthesia. Br J Anaesth 53: 267; 1981.4. Aun CST, Short SM, Leung DHY, Oh TE. Induction dose response in unpremedicated children. Br J Anaesth 68: 64; 1992.5. McDonald NJ, Mannion D, Lee P et al. Mood evaluation and out patient anaesthesia. A comparison between propofol and thiopentone. Anaesthesia 43: 68; 1988.6. Anonymus. Convulsions after propofol. Pharm J 249: 745; 1992.7. Dwyer R, McCaughey W, Lavery J et al. Comparison of propofol and methohexitone as anesthetic agents for electroconvulsive therapy. Anaesthesia 43: 459; 1988.8. Stephan H, Sonntag H, Schenk HD, Kohlhausen S.

Effects of disoprivan on cerebral blood flow, cerebral oxygen consumption and cerebral vascular reactivity. Anaesthesiologist 36: 60; 1987.9. Mirakhur RK, Shepherd WFI, Darrah WC. Propofol or thiopentone: effects on intraocular pressure associated with induction of anaesthesia and tracheal intubation (facilitated with suxamethonium) Br J Anaesth 59: 431; 198710. Taylor MB, Grounds RM, Dulrooney PD, Morgan M. Ventilatory effects of propofol during induction of anaesthesia. Comparison with thiopentone. Anaesthesia 41: 816; 1986.11. Goodman NW, Black AMS, Carter JA. Some ventilatory effects of propofol as a sole anaesthetic agent. Br J Anaesth 59: 1497; 1987.12. Coates DP, Monk CR, Prys-Roberts C, Turtle M. Hemodynamic effects of the infusions of the emulsion formulation of propofol during nitrous oxide anesthesia in humans. Anesth Analg 66: 64; 1987.13. Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth 60: 3; 1983.14. Hopkinson KC, Denborough M. Propofol and malignant hyperpyrexia (letter). Lancet 1: 191; 1988.15. Johnson SE. Remifentanil: A unique, short acting opioid. Advances in Anesthesia vol. 16, Chapter 4, Mosby Inc. 1999.16. Navarro JR. New Inhalational Anesthetics. Advances in Anesthesia vol. 12, Chapter 4, Mosby - Year Book Inc. 1995.17. Rutten AJ, Mather LE, Mclean CF. Cardiovascular effects and regional clearances of intravenous bupivacaine in sheep: Enantiomeric analysis. Br J Anaesth 67: 247; 1991.18. Lee-Son S, Wang GK, Concus A, et al. Seterioselective inhibition of neuronal sodium channels by local anesthetics. Anesthesiology 77: 324; 1992.19. Wang GK. Binding affinity and stereioselectivity in single batrachotoxin activated Na* channels. J Gen Physiol 96: 1105; 1990.20. Arlock P. Actions of three local anaesthetics: lignocaine, bupivacaine and ropivacaine on guinea pig papillary muscle sodium channels (Vmax). Pharmacol Toxicol 63: 1; 1988.21. Peck TE, Williams MA. Pharmacology for Anaesthesia and intensive care. 1st edition. Chapter 10. Ashford Colour Press, Great Britain.22. Wierda JMKH, Di Wit APM, Kuizenga K et al. Clinical observations of the neuromuscular blocking action of ORG 9426 a new steroidal non-depolarizing agent. Br J Anaesth 64: 521; 1990.23. Min JC, Becavak I, Glavinovic Ml et al. lontophoretic study of speed of action of various muscle relaxants. Anesthesiology 77: 351; 1992.24. Khuenl-Brady K, Castagnoli KP, Canfell PC et al. The neuromuscular blocking effets and pharmacokinetics of ORG 9426 and ORG 9616 in the cat. Anesthesiology 72: 669; 1990.25. Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine and vecuronium for rapid sequence induction of anesthesia in young adults. Anesthesiology 79: 913; 1993.*26. Muir AW, Houston J, Green KL et al. Effects of new neuromuscular blocking agents (ORG 9426) in



anesthetized cats and pigs and in isolated nerve muscle preparation. Br J Anaesth 63: 400; 1989.27. Servin FS, Lavaut E, Desmonts JM. Clinical evaluation of ORG 9426 in cirrhotic and control patients.

Anesthesiology 77: A357; 1993.Shanks CA, Fragen RJ, Ling D. Continuous intravenous infusion of rocuronium in patients receiving balanced, enflurane or isoflurane anaesthesia. Anesthesiology 78: 649; 1993.


Management of Acute Pain 22 M R. Rajagopal

INTRODUCTIONIn June 2002, a Californian jury found a

doctor “liable for reckless neglect in under-treating a man’s pain” and ordered him to pay 1.5 million US dollars to the dead man’s children1.

It has started. We cannot get away with it any more. We have always known that a doctor’s duty is to “cure sometimes, relieve often and to comfort always” but we have seldom taken it seriously. But people have started demanding pain relief now, and we better learn to satisfy them.

Unrelieved pain can cause several adverse physiological changes.1. It causes reflex skeletal muscle spasm that,

specially in upper abdominal surgery or chest surgery, can result in regional hypoventilation and result in postoperative chest complications.

2. Pain causes reflex vasoconstriction. It can possibly impair wound healing in any case, but particularly in people with compromised blood flow, this can be very damaging.

3. Pain causes stress response, with adverse circulatory consequences. This can be very detrimental in people with compromised circulation.

4. Pain prevents early mobilization with attendant complications. Pain relief during recovery from acute injury improves survival and speeds rehabilitation by promoting volitional activity2.

For all these reasons, and also because it is simply our duty to relieve suffering, acute pain has to be treated. Lack of resources is certainly not an excuse. Most pain relief

measures are relatively inexpensive. Pain relief is not necessarily something to be done with expensive electronic gadgetry. There are other options.

We will attempt to briefly review the pathophysiology of pain, and use that understanding to describe various means of pain relief. Then wc shall give attention to what could be done even with limited resources.

PATHOPHYSIOLOGY OF PAINLet us start by making some key points

pertaining to pain mechanisms.

Pain is what the patient says hurts.The International Association for Study

of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”3. It is important to remember that people are different, their emotional states could be different and that it would be necessary to take that into consideration while planning treatment.

A simpler definition is, “Pain is what the patient says, hurts”4. The emphasis is on the patient’s experience. He and no one else can assess his pain properly. Once we accept the definition, we shall escape the pit-fall of being judgemental about someone who is 'too sensitive’ or 'too fussy’ and complains 'too much’ about his or her pain.

Hence, the patient is the most appropriate person to assess the severity of his pain. The message is, “Believe the patient about


Management of Acute Pain 23 M.R. Rajagopal

his pain.”

Pain causes more pain.Unrelieved pain results in steady

worsening of pain. The following description of pathophysiology will make this easier to understand.

Peripheral mechanisms of pain:Any injury causes stimulation of pain

sensing nerve endings, which are called nociceptors. The impulse is transmitted via the C and A-delta sensory nerve fibres to the dorsal horn of the spinai cord. There from, the impulse is transmitted to the thalamus and the sensory cortex.

The initial injury is followed by liberation of chemicals - the nociceptive substances -, which continue to stimulate the nociceptors and perpetuate pain. Of the many such substances (kinins, leukotrienes, substance P, histamine, serotonin, hydrogen and potassium ions and so on), prostaglandins deserve special mention. Prostaglandins sensitize the nociceptor to the other pain producing substances.

It has also been found that silent or sleepy nociceptors are recruited in the face of sustained stimulation. This means that for a particular stimulus, there will be progressively increasing response.

CENTRAL PAIN MECHANISMS AT THE LEVEL OF THE DORSAL HORN

There is some form of sensitization and recruitment at the level the of dorsal horn too. The phenomenon is called “wind-up” - analogous to a wound-up spring. With sustained stimulation from the periphery, the dorsal horn cells seem to get wound up so that with time, there is progressively increasing response to the peripheral stimulus. NMDA receptors are said to play a major role in the development of “windup”.

There is also a process of recruitment at the central level. With time, there is recruitment of adjacent spinal segments so that pain increases not only in intensity, but in extent as well.

In fact with prolonged, unrelieved, acute pain, there can be permanent anatomical changes in the nervous system, so that the pain gets centrally established and becomes chronic pain. It is believed that this is the mechanism of most scar pains.

This entire gamut of changes mean that the earlier pain is treated, the easier it is It also means that in elective trauma (surgery-), pain had better be prevented rather than treated. This is the concept of pre-emptive analgesia.

MANAGEMENT OF ACUTE PAIN:Let us start with some general principles

of pain management.1. All pains are not opioid-sensitive. Roughly

two thirds of acute pain can be treated successfully by opioids. This means that a multi-modal approach works best.

2. Analgesics must be administered round the clock. This may mean the use of continuous infusions or the use of drugs by the clock depending on its duration of action. For example, morphine can be administered either as a continuous subcutaneous or epidural infusion or as 4-hourly bolus doses.

Major pain relief modalities:The following three form the major

modalities of pain relief:1. Prevention of peripheral sensitization by the

use of NSAIDs.2. Application of local anaesthetics, peripherally

or centrally.3. Use of opioids, centrally or peripherally.

By judicious combinations of these, it is possible to achieve adequate analgesia without serious adverse effects. In individual cases, however, there may be other forms of treatment that can be added on. We shall come to them briefly later.

NSAIDs:By preventing sensitisation of

nociceptors and indirectly central sensitisation, NSAIDs contribute to pain relief. However, there are concerns about their safety. The major concerns are:



1. Bleeding tendency because of inhibition of platelet adhesion. There is some controversy; but there does seem to be some evidence at least that it can be a real concern. One study found them to double the bleeding during hip arthroplasty5. But the coxibs appear to be safe. If anything, there seems to be a doubt that coxibs may even have a prothrombotic tendency.

2. Renal dysfunction in those who are predisposed to it. In the surgical context, this can also be a concern in the hypovolaemic. The associated water retention has the potential to worsen hypertension and cardiac failure. It seems doubtful if the chance of this complication is any less with coxibs.

3. Gastritis. But the coxibs appear to be safer than the older generation drugs in this matter.

In spite of these disadvantages, the addition of NSAIDs does seem to improve the quality of analgesia. The combination decreases opioid requirement and decreases the chance of ileus. They are hence recommended particularly in procedures like dental extraction where chance of significant bleeding is negligible.

There is one situation where NSAIDs must be used. In people with chronic arthralgia like in osteoarthritis, rheumatoid arthritis etc, preoperative cessation of NSAIDs causes a flare up of pain (algesic flare). In such cases, it is recommended that coxibs be started and continued through the peri-operative period.

NEWER NSAIDS.Valdecoxib is said to have no effect at

all on platelet function.

Parecoxib is the only Cox-2 selective drug that is recommended for parenteral use.

Etoricoxib is the most potent second generation NSAID yet, three times more selective than rofecoxib.

LOCAL ANAESTHETICSAs used in pain relief, they have a

predominant local effect and some systemic effect (membrane stabilization). The latter,

nevertheless, may be significant when there is a neuropathic component to the pain. Conventionally, they are used most often as epidural injections. Given preoperatively, it can contribute to surgical anaesthesia and confer post-operative analgesia too. Where facilities exist, they had best be given as continuous epidural infusions. An infusion of 0.125- 0.25% bupivacaine would provide adequate analgesia, while permitting ambulation; a dose of 4-8 ml/ hour may be a good starting point. When the pain stimulus is severe, (as in ischaemic pain for example), sometimes it may be necessary to give an anaesthetic concentration of the drug (0.5%) and compromise on mobility. A syringe pump would be the standard equipment for the infusion; a Patient Controlled Analgesia (PCA) device may permit fine-tuning of analgesia.

When a syringe pump is not available, one has to resort to intermittent injections. Too frequent injections are impractical; but on the other hand, at least four hourly injections will be needed if pain relief has to be adequate. And even in that case, the sizeable dose requirement predisposes to hypotension following every bolus injection. Particularly in the context of the unstable circulatory status in many major surgical procedures, this can be quite relevant. Obviously, smaller and more frequent bolus doses are desirable.

Bupivacaine is the local anaesthetic agent used most often. Shorter acting agents like lignocaine have the disadvantage of tachyphylaxis. Ropivacaine seems to have nearly the same duration of action as bupivacaine. It may have an edge over bupivacaine in that it seems to have better selective sensory blockade. With ropivacaine, it is easier to achieve analgesia without motor blockade than with bupivacaine.

Epidural catheters function best for an average of three days. As days go by, blockage, infection, pain on injection and leaks can be problems limiting long term use6.

When epidural infusions of local anaesthetics are not feasible or practical for lack of facilities, even single dose local anaesthetic



blocks can be valuable. By avoiding the maximal pain in the immediate post-operative period, it serves to decrease the sensitization. A single dose epidural block, an interpleural or intercostal block, or a regional block as for herniorrhaphy, can all be very useful, despite the short duration of a single block.

OPIOIDSOpioids can act both centrally and

peripherally. The importance of peripheral opioid receptors is being more and more understood now. Their practical relevance is that the same dose of opioid infiltrated around the incision would be much more effective than a subcutaneous injection elsewhere, because in the former case, we can have the drug acting both on the peripheral receptors as well as systemically.

Addition of opioids to the local anaesthetic agent given epidurally, improves the quality of analgesia. The basic principle is that we are able to achieve rather high neuraxial concentrations compared to systemic drug levels, resulting in excellent analgesia with minimal side effects. Some side effects are possible however, like nausea and vomiting, delayed respiratory depression, urinary hesitancy or retention and itching.

Preservative-free morphine is the agent used most often for this purpose as it has the most opioid-sparing effect compared to IV injection. The dose required is only about one- tenth of the systemic dose. It is about one-third for fentanyl and two-third for buprenorphine. Herein lies the main advantage of morphine over the other opioids for epidural administration - small dose, thus fewer side effects. However, as a practical point, there is the problem of poor availability of preservative-free morphine. (The manufacturers should be able to provide us with this on request.)

However, buprenorphine does have an advantage. It does not have to be given at the required segmental level.

COMBINATION 0!^ DRUGSIn general, we can make the following

recommendations for post-operative analgesia.• NSAIDs, particularly the coxibs would help to

improve the quality of analgesia, but need to be used after weighing the risks and benefits.

• Combination of a local anaesthetic with an opioid would be particularly useful - simple infiltration of these drugs over the site of incision itself may go a long way towards post operative pain relief.

• Preservative free morphine is the best drug for epidural administration, if it can be applied over the segment to be blocked. If the site of administration were distant, buprenorphine would be a better choice.

ANCILLARY MEASURESSeveral other possibilities exist for relief

from acute pain.1. Though not freely available in this country,

Entonox (the compressed mixture of oxygen and nitrous oxide in 50:50 combination) is a good choice for analgesia in the emergency room.

2. It appears that pre-treatment with tricyclic antidepressants decrease opioid requirements presumably by inhibiting reuptake of serotonin and norepinephrine at the inhibitory synapses. While this may have little application as a technique for pain relief in routine practice, this strengthens the case for continuing tricyclics in the peri-operative period in those patients already on it.

3. Sub-cutaneous infusion of lignocaine may supplement analgesia in relatively opioid resistant pains, particularly in patients who have already been in pain for some time, and especially if there is a neuropathic component to the pain (like some patients with burns).

4. Subcutaneous infusion of a sub-anaesthetic dose of ketamine (for example, 5 mg per hour) may help in difficult pains by its action on the NMDA receptors in the dorsal horn of the spina! cord.

5. Transcutaneous electrical nerve stimulation (TENS) is a particularly safe form of pain relief, though it has limited application. The device itself is inexpensive, but they should be used only if sterile conducting pads are available.

RACE 2003 Kamachandra Anaesthesia Continuing Education


Organization of an acute pain serviceMore and more is talked now about the

concept of a pain-free hospital. There is a move favouring institutional commitment to pain relief- making pain the 4th vital sign in the patient’s daily hospital record of parameters. Measurement of pain of course mandates adequate control too.

Most acute pain services are anaesthesiologist-led. But it is important to remember that pain service demands teamwork. It would be impossible to achieve assessment and management of pain in a whole hospital, without adequate personnel. Most pain services depend a lot on nurses. It would be essential to have at least one nurse with special training round the clock in the hospital, who will help the staff nurses with evaluation and pain control. Needless to say, this nurse will need expertise in assessment of pain as well as in the mechanical aspects including the use of devices like infusion pumps and PCA devices. Theanaesthesiologist, then, is able to do the consultant’s job. In fact the presence of such a team is much more important than the high tech devices like PCAs. Last but not least, the importance of explanations to the patient and family cannot be overemphasized. If they know what to expect,

anxiety will be less, and that will lessen the pain experience.

REFERENCES

1. Okie.S. Californian jury finds doctor negligent in managing pain. National news', 15 June 2001, Washington.

2. Tuman KJ, Me Carthy RJ, DeLaria GA, Patel RV, Ivankovich AD. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesthesia and Analgesia 1991; 73:696-704.

3. I ASP Sub-committee on Taxonomy. Pain terms: a list with definitions and notes on usage. Pain 1980; 8:249-52.

4. Black RG. The Chronic Pain Syndrome. Surgical Clinics of North America. 1975; 55:999-1011.

5. Robinson CM, Christie J, Malcolm-Smith N. Non-steroidal anti-inflammatory drugs, perioperative blood loss and transfusion requirements in elective hip arthroplasty. J Arthroplasty 1993; 8:607-610.

6. McQuay HJ. Epidural analgesics. In: Wall PD; Melzack R, Eds. Textbook of Pain 3rd ed. Churchill Livingstone, Philadelphia. 1994: 1025-1034.


Anaesthetic Management of aPregnant Patient for Non-Qbstetric surgery 27 R. Gopinath

INTRODUCTIONEach year for about 80,000 anaesthetics

administered there are 2 % of parturients who undergo surgery. This is largely due to the increase in the endoscopic procedures undertaken to treat conditions common in the childbearing age group like trauma, ovarian masses, appendicitis, gall bladder disease, breast surgery etc. Major surgical procedures like cardiac surgical, neuro-surgical and liver transplants have been performed during pregnancy with good outcomes for both the foetus and the mother. The known problems of foetal development and drug administration to the mother during pregnancy and the risk of abortions make both the physician and the patient wary of an anaesthetic. To assess the risk one has to understand the physiological changes involved during pregnancy and that two lives are involved during the conduct of anaesthesia raising several unique concerns.

ALTERATIONS IN MATERNAL PHYSIOLOGY.All systems are involved in change but

those important to the anaesthetic management are:Respiratory:

Increased oxygen consumption, reduced functional residual capacity, hypocapnia due to increased minute ventilation, likelihood of difficult intubation and trauma to the airway due to increased vascularity of the mucosa.

Cardiovascular:Increase in both the cardiac output and

the blood volume, dilutional anaemia, decreased vascular responsiveness, increased baroreceptor responsiveness, aortocaval compression in the supine position.

Gastrointestinal:The lower oesophageal sphincter tone is usually reduced though gastric pH, volume and emptying are not much altered.

Central nervous system:Inhalational agent MAC and local

anaesthetic requirements are reduced.

Teratogenicity of anaesthetics is probably minimal and has never been conclusively demonstrated. The use of agents like nitrous oxide, which in animal studies may cause vasoconstriction of the uterine vessels and reduce uterine blood flow are of concern but this, has not been demonstrated in human beings. Benzodiazepines were associated with oro-facial abnormalities but again have not been proven in prospective studies. The inhalational agents, narcotics, intravenous agents and local anaesthetics have long been used safely during pregnancy.

There is a slight increase in miscarriages for OR personnel found during a meta-analysis of anaesthetic exposure in the workplace.

DRUGS AND PREGNANCYDrugs offered for use in pregnancy aregrouped into one of five categories:A. Controlled studies show no riskB. No risk in animal studies or no risk supported

by controlled human studiesC. Animal studies indicate a risk but no human

studies availableD. Evidence of foetal risk but benefits outweigh

risk.X Evidence of high risk to foetus, which

outweighs benefitsNA. Not applicable


Anaesthet/c Management of aPregnant Patient for Non-Obstetric surgery 28 R. Gopinath

Types of drugs taken during pregnancy• Drugs of abuse: Opioids & opiates, marijuana,

cocaine, alcohol and nicotine• Sedatives: Benzodiazepines (class D orX)• Oral contraceptives (low risk, evidence

uncertain), cardiac glycosides (safe)• Antibiotics (most class B, although

aminoglycosides can have foetal toxicity and tetracyclines may give congenital defects)

• Antiparasitics (class C, except quinine, class X)

• Anti-asthmatic drugs (GCs may have latent effects and reduce birth weight, anti-histamines may result in blindness)

• Relaxants/sympathomimetics etc (class C)• Diuretics (most class D)• Anticoagulants (not recommended)• Anti-viral drugs (most category C)

Maternal Pharmacokinetic VariablesDuring pregnancy, a number of

physiological changes occur that affect drug absorption, uptake and metabolism.These changes include:• Changes in body fluid volume• Changes in cardiovascular parameters• Changes in pulmonary function• Alterations in gastric activity• Changes in serum binding protein

concentrations and occupancy• Alterations in kidney function

These maternal variables determine the maternal and foetal therapeutic/toxic responses to drugs! Specifically:• Pregnancy is associated with increased

cardiac output (-30%) and plasma volume (-50%) = increased Vd

• Maternal aqueous and fatty tissue spaces increase dramatically in pregnancy (10-30 weeks mainly); total body water increases by -8 L (mostly extracellular water; 40% maternal, 60% foetal/placental)

• Reduction in motility of stomach and gut - increased intestinal transit time (-30-50%) (P4 effect?) and increased mucus formation = raised gut pH

• Nausea and vomiting may also affect gut

transit time and pH.• Decreased serum albumin concentrations

(-25%), but unchanged alpharacid glycoprotein. Binding sites also taken up by steroid and peptide hormones (= more free drug)

• Glomerular filtration rate increases (-50%) with renal blood flow (-50%), resulting in increased renal excretion & creatinine clearance. Rates of hepatic enzyme activity may also be increased (i.e. phenytoin metabolism) or decreased (theophylline/ caffeine) ?steroid effects

• Hyperventilation and increased pulmonary blood flow = increased alveolar uptake of inhaled drugs (i.e. anaesthetics)

Drug disposition in the maternal-foetal unitDrugs that reach the foetus are (almost)

always administered to the mother!Drug -> Mother-> Placenta -> Foetus -> Placenta-> Mother -> Excretion

Foetal Pharmacokinetic Variables• Blood flow through the placenta (maternal

side) increases during gestation (50 ml/min @ 10 weeks of pregnancy - 600 ml/min @ 38 weeks).

• Foetal plasma binding proteins differ from maternal concentrations: albumin 15% > than maternal, but alpharacid glycoprotein -37% lower (so free fractions of basic drugs such as propranalol and lidocaine are elevated)

• Foetal plasma proteins also appear to bind some drugs with lower affinity than in adults (i.e. ampicillin, benzylpenicillin)

• Ion trapping: Foetal plasma pH > maternal: base drugs (i.e. salicylate) are more ionized on the foetal side, hence lesser drug crosses the placenta back to the maternal plasma = apparent accumulation in foetal plasma. Principle also applies to metabolites (more polar, less mobile)

• Fcetal liver expresses metabolizing enzymes (i.e. CYPs), but metabolizing capacity is less than that of mother (some enzymes are foetal- specific)

• Drugs transferred across the placenta undergo first pass through the foetal liver before reaching systemic circulation (modulated by


Anaesthetic Management of aPregnant Patient for Non-Obstetric surgery 29 R. Gopinath

ductus venosus shunt, 30-70% by pass)• Foetal kidney immature: GFR is reduced,

increasing with gestational age but only 2-4 ml/min at term (3% of cardiac output vs 25% in adult). Anion (i.e. penicillin) secretion very low, cation (i.e. cimetidine) secretion is efficient.

• Foetal urine enters the amniotic fluid which may be swallowed by the foetus (however, foetal renal blood flow is only 5% of the blood flow)

Placental PharmacokineticsCritical factors that affect drug transfer

across the placenta:• Physicochemical properties i.e. lipid solubility,

ionization, size, protein binding characteristics.

• Transfer of flow-limited drugs affected by placental flow.

• Compounds that alter blood flow alter maternal drug disposition and placental transfer.

• Placental metabolism (dealkylation, hydroxylatior, demethylation) affects drug transfer across the placenta (usually relatively minor effect compared to foetal or maternal liver).

• Foetal metabolism may also be significant, but may change during pregnancy.

Adverse Effects of Drugs on the Foetus DuringPregnancyMECHANISM:1. Effects on maternal tissues primarily, with

only indirect (secondary) effects on the foetus2. Direct effects on developing foetal tissues3. Indirect effects via interference with the

function of the placenta, i.e., placental transferor placental metabolism

TYPE OF EFFECTS:• Teratogenicity (i.e. thalidomide) - readily

detected at, or shortly aftet, birth• Long term latency (i.e. diethylstilbestrol -

increased risk of vaginal adenocarcinoma after puberty, or abnormalities in testicular function and semen production)

• Impaired intellectual or social development (i.e. exposure to phenobarbitone- alters

programming of the brain)• Predisposition to metabolic diseases (i.e.

Barker hypothesis - low birth weight associated with increased risk of diabetes, hypertension, heart disease in adulthood)

DRUGS KNOWN TO EXERT SIGNIFICANT EFFECTS ON THE FOETUS:

Aminopterin, aminoglycosides, barbiturates, chloramphenicol, chlorpropamide, cortisone, diazepam, diethylstilbestrol, ethanol, heroin, iodide, isotretinoin, methadone, methyltestosterone, methylthiouracil, metronidazole, norethindrone, phenytoin, tetracycline, thalidomide, trimethadione, valproic acid, warfarin

Maintenance of uterine perfusion and maternal oxygenation determine and preserve foetal oxygenation. These are of concern and vital for any anaesthetic during pregnancy. Avoid maternal hypoxia and hypotension at all costs and one should be aware of the effects of all agents used on the maternal cardiovascular system and oxygen delivery.

The most difficult perioperative problem is preterm delivery, which is the leading cause of foetal death due to preterm labour. Prevention and management of the same is very important. The anaesthetic management per se is not related as much as the disease process for the surgical intervention and surgery itself.

ANAESTHETIC MANAGEMENTPerioperative management starts with

assessment preoperatively and should include establishment of pregnancy if in doubt, counseling the patient on the risks of anaesthesia (for the foetus on continuation of pregnancy and so considering delaying surgery till the second trimester with explanation of teratogenicity) and the chances of spontaneous miscarriage, the symptoms of preterm labour and the need for uterine displacement to the left if needed. Documentation of the date of the LMP should be recorded.

Preoperative medications to allay anxiety or pain should be given as appropriate and not withheld, since elevated endogenous maternal



catecholamines will reduce uterine blood flow. Prophylaxis against aspiration should be considered and a combination of an antacid (nonparticulate), H2 -receptor blocker or metoclopramide administered. The obstetrician should be involved and perioperative tocolysis discussed. Indomethacin (oral or suppository) and magnesium sulfate as an infusion are commonly used. Indomethacin has few anaesthetic implications but magnesium use should be viewed with caution due to its interactions with neuromuscular blocking agents and the risk and management of hypotension during potential blood loss and volume replacement.

Intraoperative management is not influenced by the anaesthetic technique as long as maternal oxygenation and perfusion is maintained. A review of 49,000 consecutive pregnancies found that 0.14% required surgery during pregnancy. There was no correlation between the type of surgery, type of anaesthetic, trimester in which surgery occurred, length of surgery, estimated surgical blood loss, or the length of anaesthesia and the outcome of the pregnancy.

Monitoring should include blood pressure, oxygenation, ventilation and temperature. Blood glucose should be checked if the procedure is prolonged. If the surgical field is not a hindrance, continuous or intermittent foetal monitoring should be performed after 20-24 wks gestation to ensure the intrauterine environment is optimized. Loss of beat-to-beat variability is normal after anaesthetics are administered, but decelerations are not. They may indicate the need to increase maternal oxygenation, maintain or increase maternal blood pressure, further uterine displacement, reduce surgical retraction, or begin tocolytic drugs. Foetal monitoring can help assess the adequacy of uteroplacental circulation and foetal perfusion during cardiopulmonary bypass, induced hypotension or procedures with major blood loss and volume shifts.

General anaesthesia should include full preoxygenation and denitrogenation, rapid sequence induction with cricoid pressure, high FI02, slow reversal of relaxants to prevent acute rise in acetylcholine that might induce uterine contractions. Inhalational agents should be kept

below 2.0 MAC to prevent cardiovascular compromise. During the first trimester ketamine at doses of > 2.0 mg/kg may cause uterine hypertonus. Nitrous oxide and propofol may be used. Propofol has recently been shown to reduce oxytocin-induced contractions of the uterine smooth muscle. Early pregnancy does not decrease the concentration of propofol required for loss of consciousness. The increase in \nucosal vascularity and potential for difficult airway must be kept in mind during laryngoscopy.

Regional anaesthesia is advantageous in reducing drug administration and reducing the concerns of teratogenicity during the first trimester and minimizing changes in foetal heart rate variability later in gestation. Prevention of hypotension with adequate preload and uterine displacement and aggressive treatment with ephedrine if needed, is mandatory. The dose of local anaesthetic for central neuraxial blocks can be reduced by one-third from that for the nonpregnant patient due to the increased vascularity in the spinal canal with epidural vein engorgement. Regional anaesthesia provides excellent postoperative pain control while reducing maternal sedation needs and maintaining FHR variability.

Postoperatively, monitoring of the foetal heart rate and uterine activity should be continued. Preterm labour must be treated aggressively and at the earliest sign. The patient should be kept in a location like the labour or delivery suite and provision of nursing expertise in the surgical recovery area should be made available. Systemic pain medications will reduce the foetal heart rate variability and this should be borne in mind during monitoring. Regional techniques are thus best suited and should be used wherever feasible. The risk of thromboembolism is very high in these patients and hence they should be mobilized early, which also entails good pain relief postoperatively. In the recovery period also, good maternal oxygenation and left uterine displacement should be maintained. The help of a paediatrician should be enlisted in the management of the patients when the foetus is of a viable gestational age so that preterm labour and delivery can be managed as well as counseling for the parents.



SPECIAL SITUATIONSThere are specific anaesthetic

considerations for unusual situations like trauma, neurosurgery, foetal surgery and laparoscopic surgeries.

Emergency surgeryAppendicectomy and adnexal masses

are the most frequent conditions needing surgical treatment. In one study, parturients undergoing appendicectomy had an incidence of 18% of postoperative pulmonary oedema or ARDS. Factors of risk for the same were gestational age> 20 weeks, preoperative respiratory rate of more than 24 breaths/ min, preoperative temperature> 100.4 degrees F, a fluid load ( I/O) greater than 4 liters in the first 48 hrs, and concomitant use of tocolytic agents. Anaesthetists should be conservative in fluid management and have central venous pressure monitoring should there be a fluid overload.

TraumaTrauma is the highest cause of maternal

death. Foetal loss in these situations is due to maternal death or placental abruption. An early ultrasound should be done in the emergency room itself to determine viability of the foetus. The mother should receive all needed diagnostic tests to optimize her management, with lead shielding for the foetus when possible. Exposure to less than 5 rad does not increase the risk to the foetus. Ultrasound or MRI is safer.

There are a few indications for emergency caesarean delivery and would include:1. A stable mother with a viable foetus in distress2. Traumatic uterine rupture.3. Gravid uterus interfering with intra-abdominal

repairs in the mother.4. A mother who is unsalvageable with a viable

foetus.

If the foetus is pre-viable or dead, optimizing the mothers’ condition takes precedence. Vaginal delivery at a later date is better than an emergency caesarean section or a laparotomy.

NeurosurgeryNeurosurgical procedures such as an

aneurysm or AVM repair may be required in this age group. All the usual anaesthetics can be used safely and foetal monitoring will be helpful especially when certain techniques are planned.

Induced hypotension reduces uterine perfusion although most agents like SNP, NTG, hydralazine, esmolol, and inhalational agents have been used safely. Foetal monitoring will determine if uterine perfusion is impaired. The anaesthetist should still provide all necessary care for optimal outcome of the mother while informing the surgeon of any concerns. Hyperventilation reduces maternal cardiac output and shifts the ODC to the left thus decreasing release of oxygen to the foetus. High doses of mannitol have been shown to cause foetal dehydration in animals but should not cause concern in the clinical situation. Endovascular management of acute conditions like ruptured intracranial aneurysms has been successfully undertaken during pregnancy. Foetal shielding should be used at all times.

Foetal SurgeryFoetal surgery is performed in very few

centers and for limited indications. The major problem is postoperative preterm labour. Patients often receive preoperative indomethacin and perioperative magnesium sulfate for tocolysis. A high dose of inhalation agents are used for maternal and foetal anaesthesia and for uterine relaxation during surgery and the possibility of reduced uterine perfusion is to be kept in mind.

Laparoscopic surgeryLaparoscopic procedures have been

employed to avoid laparotomy when abdominal pain presents a diagnostic challenge during pregnancy, as well as for some surgical procedures amenable for such surgery like cholecystectomy. Animal studies have shown that pneumoperitoneum with C02 does not cause significant foetal haemodynamic changes, but does induce foetal respiratory acidosis. Normalizing maternal ETC02 produces late and incomplete correction in the foetus. It is important to maintain intra-abdominal pressure as low as possible and limit operative time to the minimum.



Arterial sampling for blood gas analysis is necessary to normalize maternal PC02 if the procedure is'prolonged or difficult. Other technical alterations during pregnancy should include foetal shielding during cholangiograms, pneumatic stockings, left lateral table tilt and an open technique for trocar insertion.

Cardiothoracic surgeryCardiothoracic surgery requiring bypass

has also been successfully performed during pregnancy. The increase in blood volume and cardiac output is maximal at 28-30 weeks and this is the time of high risk for decompensation in patients with cardiac lesions as also immediately post partum. After delivery, the release of aortocaval compression and autotransfusion of uteroplacental blood increases the cardiac output maximally. Those who have severe symptoms and are not responsive to medical management, benefit from surgical interventions, and this should, where possible, be performed in the second trimester when the major risk of teratrogenecity due to drugs, radiation and low flow states of bypass is past and pre term labour is less likely. Combined Caesarean section and bypass too have been successfully performed. Surgery should not be withheld if indicated since mortality is comparable in the mother with non-pregnant states.

After 24 weeks gestation, the foetal status should be monitored and uterine displacement maintained to optimize uterine perfusion. Optimal pressures and flow on bypass are controversial and foetal monitoring is a sensitive measure of perfusion and should be used to optimize flows on bypass. Foetal bradycardia commonly occurs during onset of bypass and slowly returns to baseline with little or no beat-to-beat variability. Hypothermia can oe used although some authors advocate warm

heart surgery. It is essential to avoid high dose vasopressors if possible, to prevent its effect on uterine blood flow, however, optimizing the mothers’ condition is the best way to ensure a good outcome for the foetus.

SUMMARYSurgery during pregnancy may be

necessary and anaesthetists should reassure the mother that anaesthetic agents and techniques do not put the foetus or the pregnancy at risk. Prevention of preterm labour is the greatest concern and may require perioperative use of tocolytics. Good postoperative pain management without sedation will aid in early diagnosis and management of preterm labour and mobilization to prevent thromboembolic complications.

REFERENCES

1. Loebstein, R, Lalkin A, Koren G. Pharmacokinetic changes during pregnancy and their clinical relevance. Clin Pharmacokinet 1997 33(5):328-343

2. organ DJ. Drug disposition in mother and fetus. Clin Exp Pharmacol Physiol 1997 24:869-873.

3. Bailey B, Shinya I. Breast-feeding and maternal drug use. Ped Clin North America 1997 44:41-54.

4. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. New Eng J Med 1998: 338(16): 1128-1137.

5. Garland M. Pharmacology of drug transfer across the placenta. Obstet Gynecol Clin Nth Am. 1998 25(1) 21-42.

6. Boiven JF. Risk of spontaneous abortion in women occupationally exposed to anaesthetic gases: a metaanalysis. Occup Environ Med 1997; 54: 541-8.

7. Friedman JM. Teratogen update: anaesthetic agents, Teratology 1988; 37: 69-77.

8. Hunter JG. Carbon dioxide pneumoperitoneum induces foetal acidosis in a pregnant ewe model. Surg Endosc 1995; 9: 272-9.

9. Rosen MA. Management of anaesthesia for the pregnant surgical patient. Anesthesiology 1999; 91: 1159-63.

10. Weiss BM. Outcome of cardiovascular surgery and pregnancy: a systemic review of the period 1984- 1996. Am J Obstet Gynecol 1998; 179: 1643-53.


What’s New in Paediatric Epidural Anaesthesia 33 Lakshmi Vas

The single most significant major change in the practice of paediatric anaesthesia in the last two decades has been the introduction of regional anaesthetic techniques. Acceptance of the concept that infants and children feel pain and suffer from its consequences has revolutionized the practice of paediatric anaesthesia in that regional anaesthesia and analgesia have become an integral part of paediatric anaesthesia. In children, light general anaesthesia is required to institute regional blocks. The advantages of this technique are minimal general anaesthesia, preemptive analgesia and attenuation of the stress response to surgery.

Lumbar epidural anaesthesia is very useful in children as an epidural catheter can be positioned and the local anaesthetic drug deposited close to the segment of the cord supplying the dermatomes around the proposed surgical incision. The safety is of a lower volume and dose of local anaesthetic, which by a rough formula is 0.1-0.2 ml/kg/segment to be blocked. The catheter passes quite easily in babies even to levels of the cervical cord. The exact placement can be determined by measuring the distance to be traveled, on the catheter. Recently, connecting a nerve stimulator with a metal needle to the saline filled epidural catheter and passing a current will stimulate the segments of the cord at the tip of the catheter and thus confirms the position of the catheter tip. This produces twitches in the muscles supplied by those segments. Position and spread can also be confirmed by omnipaque (iohexol) injection.

In children, the skin-epidural distance varies with age and weight. A rough guide is 1,5mm/ kg till 1 yr and 1 mm/kg thereafter. Since this is a very short distance, care has to \ be taken not to overshoot this distance and puncture

the dura. The exact technique for introducing an epidural needle in children is different from that of adults. In adults, either a hanging drop or a loss of resistance with incremental advancement of the needle identifies the epidural space. In children, hanging drop technique and incremental advancement of needle is not practicable due to the short skin-epidural distance. The needle is continuously and steadily advanced with a continuous checking for loss of resistance to saline. There is a distinct increase in resistance to the advancement of needle tip and also on the plunger of the syringe, when the needle tip enters the ligamentum flavum. The loss of resistance when the needle leaves this ligament and enters the epidural space is also unequivocally distinct.I prefer saline to elicit this, as it is very easy, obvious and avoids the risks of air embolism, which could be catastrophic considering their size and the volumes of air normally injected.

Many drugs have been used for postoperative analgesia. Various authors have used morphine, fentanyl, pethidine, buprenorphine, pentazocine, tramadol, ketamine clonidine, neostigmine and midazolam. Use of the opioid drugs in neonates and infants has to be done in an ICU setting where an anaesthesiologist is constantly available. This is a luxury many of us do not have. So in this age group we rely solely on bupivacaine in a concentration of 0.05 - 0.1- % solution. In older children, we have used ketamine 0.25-0.5 mg/kg and buprenorphine1-2 microgram/kg. Ketamine has the advantage that there is no fear of any possible respiratory depression, but the problem of unpredictability of duration of action and the possibility of hallucinations remain. Buprenorphine, with its extreme lipophilicity, is very predictable in action, lasts about 24-30 hours, and in the dose mentioned has not given any respiratory depression in any of our patients


What’s New in Paediatric Epidural Anaesthesia 34 LakshmiVas

who number about 1500. However, older children do complain of severe nausea, which requires prophylactic ondansetron and metoclopramide. We have also used midazolam in a dose of 25 mcg/kg along with the initial dose of local anaesthetic to prolong the analgesia.

Admittedly, the lumbar epidural puncture requires an extreme degree of expertise and delicacy than caudal or lumbar epidural anaesthesia in adults. It can be attempted only after sufficient expertise has been obtained in adults and older children. More importantly, a thorough understanding of the technique is very essential to its scientific practice.

There are many aspects of epidural anaesthesia that are different and sometimes unique to paediatrics. As these differences are being investigated, new and fascinating facts emerge about the epidural space, and the technique itself. Of particular interest is the difficulty in passing the catheter in a small neonate, the calculation of volume, its spread, the back leak of injected solutions and pressure changes in response to epidural injections. The calculation of the volume of injection has been arbitrary, based more on a permissible limit of local anaesthetic dose than as a specific volume to cover a specific number of dermatomes.

The negative epidural pressure described by Janzen in 1926 becomes positive on injection of local anaesthetic solutions as seen by the tracking back of injected solutions around the epidural catheter in children. We undertook studies to investigate the change in epidural pressures in response to local anaesthetic injections at two different rates of injection, as well as the spread of two specific volumes of radio opaque dye injected into the epidural space in a controlled manner in 10 infants. The results of these two studies were published in the journal ‘Paediatric anaesthesia’. The abstracts of these two papers are given below.

Study of epidural pressuresThe pressure changes in the epidural

space of 20 infants due to injection of local anaesthetic solutions were studied. The pressures developed during the passage of the epidural needle through the ligaments of the spine

and in the epidural space, during the injection of 1 ml of the local anaesthetic, at two rates of injection, over 1 and 2 minutes and the residual pressure at 1 and 2 minutes after each injection were studied. The mean pressure while the needle was being advanced through the ligamentum flavum was 69.14+ 36.95 mm of Hg. The epidural pressure, after the needle had just penetrated the ligament, without eliciting the loss of resistance, was 1+.9.759 mms of Hg. A distinct pulsatile waveform identical to the pulse waveform was observed as soon as the epidural space was entered. The pressure rise varied according to the rate of injection. The pressures were 27.79mm of Hg when the rate of injection was 1 ml/1 min, with a residual pressure after 1 minute being 12 + 5.53 mm Hg and it was 10.14+5.53 mm Hg after 2 minutes of injection. When the rate of injection was 1ml/ 2min, the pressures were 15.66+ 9.48 with a residual pressure after 1 minute being 14.79+ 5.15mm Hg and 12.93 + 5.46mm Hg after 2 minutes of injection. The residual pressures seem to vary more with the volume injected than the rate of injection or the pressures developed during the injection. The relationship between the rate of injection and pressures is significant when compared with the adults where the pressures have been measured after an injection rate of 1ml/ sec and 1ml/5secs. This is a very fast rate compared to our rates of injection of 1 ml over 1 and 2 minutes. Based on the findings of this study, we recommend a rate of 1ml/ 2minutes in infants. In neonates, a slower rate of injection would be preferable.

DiscussionBack leak of injected anaesthetic is a

common feature of paediatric epidural injections. It is an indicator that a pressure high enough to create a gradient between the epidural space and the atmosphere is being reached. This leak is not normally seen in young adults, in spite of a much faster injection. But this may be seen in old people, where again the pressures may rise, to cause increased spread because of decreased space around the spinal nerves4.

The main determinant of the backleak would be the pressures developed in the epidural space iri response to the injection of local anaesthetic solutions. The faster rates of injection used in adults produce jets of fluid from the 3



holes of the catheter. With our 1 ml/min and 1 ml/ 2min injections, in spite of the pressures 59.09mm of Hg (1 ml/1 min) and 34.93 mm of Hg (1 ml/2min) measured at the proximal end of the 90cm long catheter, the drops formed slowly at the side holes in the distal end.

In an infant, the epidural space is a narrow cylinder, where the pressure on injection can rise to very high levels. The spread inside the annular space will likely be as a surge or a slow rise, depending on the rate of injection. Pressing the dura inwards and compressing the cerebrospinal fluid column around the cord can dissipate this rise in pressure. The CSF is supposed to act as a safety valve2 4 by a cephalad displacement. This is questionable because the area of the CSF column is huge compared to the 1.5 cm area of high pressure around the side holes of the catheter. So, it may act as a buffer to absorb the instantaneous pressure rise, without much disturbance to its own pressure or the intracranial pressures. One study8 has shown a sustained rise in the intracranial pressure in response to the epidural injections. Another stud/ of resin injections in the cadaver9 has shown an intracisternal pressure rise with concomitent lumbar epidural space injection. A concomitant measurement of the fontanelle pressures in infants would probably reflect the rise if any in the CSF pressures, due to a cephalad displacement. Another factor limiting the pressure rise, is the leakage of the local anaesthetic through the intervertebral foramina or through the path of least resistance, the cylindrical tract around the catheter made by the larger epidural needle. A sensation of pain, dizziness and nausea on injection has been reported on injection in adults. An increase in the respiratory and pulse rate in anaesthetized children is also known. The infants in this study showed no specific discernible response to the postoperative injections.

Probably high pressures similar to the peak and residual pressures on injection may develop, when the infant is crying, coughing, breath holding or straining to urinate or defaecate etc, though these have not been studied. The possible deleterious effects if any of the pressure rises on injection are not known. The possibility that complications attributed to regional

techniques may actually be compromises of blood supply already present in the patient due to a congenital vascular malformation or compromised blood supply due to hypotension, which got exacerbated by these pressures, remains to be explored.

Any injection through an epidural catheter, even to air requires an effort. Any increased pressure required for injection when the catheter is in the epidural space may not be appreciated by the operator and be attributed to the long length of the catheter or its small internal diameter. This study showed us that, what would be considered as a slight increase in pressure by the hand, translates into significantly high pressures if they were to be measured. This could lead to a complacence, as most operators would be unaware when excessive pressures are being exerted. After measuring the pressures we taught ourselves to moderate the pressures exerted on the piston on the injecting syringe. Also, making the injections slowly over two minutes confers a safety by reducing the pressures exerted.

The epidural pressures just on entering the space varied mainly on the positive side. Only in 3 patients, negative values were observed. The mean pressure was 1+10. Whether this was because of the narrow potential epidural space with pulsating vessels, or a result of positive pressure ventilation or the pressure on the abdomen in the lateral position with the spine flexed, is uncertain.

In a pilot study of 20 other patients done prior to the present study, using loss of resistance, it was surprising to find pressures of 250 mm of mercury when the tip of the needle was in the ligamentum flavum and the column of saline was being bounced against it. The magnitude of this pressure is determined by two factors. One component is the blocking of the fluid column in the advancing needle by the ligament. The second component is the pressure on the plunger by the operator. However, with awareness of this fact, the pressures in the subsequent cases were lowered to 60-150mms of Hg by consciously exerting less pressure on the plunger. The importance of this pressure is that this is the pressure at which the initial small volume (0.5 - 1 ml) of saline is injected into the epidural space



to detect loss of resistance. This leads to a sudden rise of pressure, which decreases rapidly as the injection stops, as soon as the loss of resistance is elicited. This pressure leads to fluid leaking back through the needle, which could be mistaken for CSF, and in our initial practice, this was confirmed by a negative test for glucostix7

The ‘feel’ as the needle passes from the interspinous ligament to the ligamentum flavum was very distinct. When the needle tip was in the former, the feel of bouncing on the plunger of the loss of resistance syringe is less and sometimes, it is even possible to inject a small quantity of saline. This could be misinterpreted as a loss of resistance. This is more likely if air is used for loss of resistance. This is confirmed by the epidurogram, where the spread of the dye in the interspinous ligament is seen. However, once the ligamentum flavum is entered, the bouncing of the piston is distinct and it is impossible to inject anything.

One fairly consistent finding was that the ‘give’ on leaving of ligamentum flavum was so pronounced, that we stopped just short of the epidural space. The catheter, on passing, would encounter a flimsy resistance before passing freely into the space. This felt as if a last thin layer of ligamentum was actually pierced by the catheter. Alternately, a part of the bevel might have been still in the ligamentum giving this impression,The pulsatile waveform seen when the epidural needle tip is in the epidural space was a surprise. It was obviously the pulsations transmitted by the epidural arteries or transmitted from the aorta into the epidural space. This was also registered, even through the fluid filled epidural catheter. Does this mean that the epidural pressure varies with the blood pressure in babies? Does this explain the mildly positive pressure that we found in the epidural space? If there is a pulsatile waveform of pressure in the epidural space, is the loss of resistance elicited a relative one from the high pressures in the ligamentum flavum to that of the lower pressure of the epidural space? We did find subatmospheric pressure in3 cases but in the rest, it was positive. This pulsatile waveform is found so consistently in this study that in other infants it became a test for confirming the epidural placement of needle, especially when a small volume was injected to

transmit these pulsations. Only one study in adults refers to these pulsations. This may be because these pulsations are not very obvious in the capacious adult epidural space but are prominent in the narrow space of infants.

The rates of injection in adults were very fast, with 1 ml/sec or 0.5 ml/sec whereas the recommended rate of injection in children of the whole dose is a few ml over 90-120 seconds11 or 1ml /min 15 Our 1ml over 60 and 120 sec is a very slow rate of injection indeed. However, even at these rates, there was a backleak in many of the babies and epidural pressures were higher than that in adults, 27.79 mm of Hg (37.79 cm of water) against 29 cms of water after 1 ml/minute and 15.09 mms of Hg or 20.52 cm of water after1 ml over 2 minutes. These values were obtained after injection through a 17-gauge needle. In contrast, our pressures were obtained after injection through a 20G catheter, with the solution leaking back along the needle track acting as a relief valve mechanism. This probably reflects the small volume epidural space, which is practically a potential space that gets expanded by the injection of even small volumes of local anaesthetic at very slow rates. We did not record the pressure at which backleak occurs, as it was highly variable. Backleak is important, as it prevents an excessive rise in pressure. However, it causes a loss of effective volume of local anaesthetic remaining in the space to exert an effect. The volume of backleak that correlated with the spread requires to be studied. Interestingly, backleak is not seen commonly when the catheter is introduced from the caudal route, though the injection rate is similar with 1ml/2 min. Probably, the fluid tracking back along the catheter pools in the more capacious caudal epidural space, without steep rises in pressure. Could this mean that there is anaesthesia of the sacral segments in addition to the segmental anaesthesia at the tip of the epidural catheter? Could this also explain the retention of urine associated with central neuraxial blocks instituted from the caudal route? This difference in backleak and its causative pressures with the introduction of catheter between lumbar and caudal routes needs to be studied.

In conclusion, there are many unknown effects associated with epidural injection of local



anaesthetic solutions. The resting epidural pressure in infants may not always be negative. It is preferable to make static measurements of pressure, as the pressure drop factor would be eliminated. Measurement of dynamic pressures with steady injections from infusion pumps would eliminate the variations due to the manual injections. The pressure rise in response to lumbar epidural injection in infants is considerably higher than that of adults even with very slow rates of injection. It is safer to use a slow rate of injection like 1ml/2min in infants and may be, even slower rates in neonates. Further studies are required to assess the degree of spread vis- a-vis speed of injection, the effect of residual pressure on the spread and the resultant block height, the effect of backleak on the spread, and the correlation of epidural pressures to fontanelle pressures and the difference in attained pressures with lumbar and caudal routes of introduction of catheters.

STUDY OF THE SPREAD OF RADIOOPAQUE DYE: ABSTRACT AND DISCUSSION.Aim

Prospective study to assess whether the extent of spread of the dye in the epidural space would vary in direct proportion to the volume, by injecting two volumes of the dye.

Patients and methods10 infants aged 2 - 3 6 days, (mean +

SD,13.30+13.68) and weighing 1.8 kg-4.5kg (mean + SD,2.60 + 0.97) undergoing major thoracoabdominal surgery under epidural and general anaesthesia were selected. At the end of surgery, two volumes of radioopaque dye (omnipaque) 0.5ml/kg and 1 ml/kg were injected into the epidural space at a rate of 1 ml/2minutes. The spread of the dye was studied by taking X rays after both injections in the left lateral position.

ResultsThere were ten different patterns of spread

in the 10 cases. Uniformly circumferential and cylindrical spread was seen only in one infant. In others, there were segregated patches of anterior and posterior spread with or without interspersed patches of circumferential spread. There was variation in the extent, location and

the density of spread, filling defects and skipped segments with both volumes. Back leak of dye along the needle track was seen in 3 cases. Statistically Segments were 9.30 + 3.68 for 0.5ml, for 1 ml/kg 11.50 + 3.03, 3.03, S, P=0.014. Circumferential spread for 0.5ml/kg 2.70 + 2.16, for 1 ml/kg 5.90 + 3.14 3.59, S, P=0.006 . Anterior spread for 0.5ml/kg 3.60 + 1.58 and for 1 ml/kg 7.90 + 2.33 5.88, S, P=0.001. Posterior spread for 0.5ml/kg 8.20 + 3.71 and for 1 ml/kg 9.80 + 3.68 3.54, S, P=0.006. Doubling of spread with doubling of the volume occurred in only 1 patient. There was a variable increase in the extent or in the density of spread with reduction of skip segments with 1 ml/kg dose than with 0.5 ml/kg. The probable reasons for this variable spread and the mechanism of epidural anaesthesia in the presence of such spread is discussed.

ConclusionThere is a difference in quantitative as

well as qualitative spread in different patients and in the same patient with different volumes. There were statistically significant increases in the number of segments, circumferential, anterior and posterior locations of the 1.0ml group than the 0.5ml group. Both the extent and the density of spread improve with a higher volume but not in direct proportion to the volume. 1 ml/kg has a better quantitative as well as qualitative spread than 0.5ml and has a better chance of producing adequate anaesthesia.

DiscussionThe extent of spread of the local

anaesthetic solutions injected into the pediatric epidural space depends on many factors like the volume of injection 1'3, speed of injection 4‘5, the backleak of the solution in the needle track around the catheter35' leaks through intervertebral foramina7A the pressures achieved in the epidural space36-8 and the inherent divisions of the epidural space10-17. This study was carried out with the purpose of assessing the extent of spread with two different volumes, but as the study progressed, it became apparent that the quality of spread was as varied as the extent. Logically, the spread of a dose of 1 ml/Kg, should be double that of 0.5 ml/Kg in an ideal predictable situation. However, neither the blind procedure of epidural placement of drugs nor the nature of



epidural space seemed to be predictable in this study. There were 10 different patterns of spread in the 10 cases with segregation into anterior and posterior patches instead of a uniform circumferential and cylindrical spread. In the same patient, for the two volumes of injection there were differences in the pattern, the density of spread and the leak (more with the higher volume). There were filling defects and skipped segments in both spreads

Doubling of the number of segments covered by the spread with the doubling of the dose occurred in only one patient, but with a large skip of segments in between. In the other patients, though the spread did not double, the density of the spread was better.

The spread of injections in the closed epidural space determines the number of blocked segments, the upper and lower limits of block and the extent of anaesthesia. The quality of anaesthesia and its patchiness if any, are determined by uneven spread. The factors determining the actual spread of the local anaesthetic solution in the epidural space are as follows.

1) The physical divisions within the epidural space10'17

2) The neuraxial spread versus the physical spread of a solution in the epidural space. It has been suggested that there is a subtle distinction between the physical spread of a solution in the epidural space and its neuraxial spread 16 with the former extending beyond the latter.

3) The pressure rise in the closed epidural space in response to injection of space occupying volumes of local anaesthetic solutions, which determines the pressure head, which in turn will determine the spread. The residual pressure after completion of injection in particular, seems to be important in the extent of spread 1'3 6'7

4) The determinants of this pressure, include speed of injection, volume of the injectate, uniformity of injection pressures, the residual pressure after completion of injection, possible transmission and dissipation of pressure to the body of CSF enclosed within the dura mater3'1819'20

leaks along the nerves, along the needle track around the epidural catheter.

5) Leaks that may mean loss of effective volume of local anaesthetic.

Saitoh et al(8) and Burn et al 16 found from radiographic observations in the elderly that there was no correlation between leak through intervertebral foramina and longitudinal spread.

Backleak around a catheter along the needle track is a unique feature of epidural injections in infants and children, probably due to their small capacity epidural spaces. Whether this adds another dimension to the spread of epidurally injected fluids remains to be explored. In this study, backleak was seen in patients 3,7 and 9, especially with a larger dose. But there was more than doubling in the spread with volume in case 9. Apparently the backleak in this baby did not affect the spread.

In the present study, the variables like speed of injection, volume, age and weight were within a uniform range. However, whether the length, breadth and volume of the epidural space, correlate with the body weight is questionable. Since all the injections were performed by the same person (first author) at the same rate (2ml/ min), the pressures were presumed be in a similar range for all the 10 patients. The only unpredictable variable factors were divisions within the epidural space and other determinants of pressure like leaks, pressure on CSF etc.

The most likely reason for the compartmentalization of the injected fluid , the intriguing skipping of segments could be the physical divisions within the epidural space as described in the previous reports of the anatomy of the epidural space.912

Resin injection studies of Harrison et al9 in autopsies of 20 cadavers found that flow of the resin formed a large posterior bulge with thin antero lateral projections on either side. The anterior spread was seen only in 8 out of 20 cases as very thin and incomplete.

Based on cryomicrotone studies of



undisturbed anatomy in a fresh cadaver, Hogan 12 considers the epidural space to have metameric segmentations in the longitudinal axis due to the contact of dura with the ligamentum flavum. These segments start from the middle of the upper lamina to the cephalad edge of the lower lamina. Within each segment also, there is a distinct lateral, anterior and posterior compartments. The posterior compartment has a homogenous pad of fat. In the anterior compartment, the posterior longitudinal ligament (PLL) is closely applied to the dura and blends into the annular ligament at the level of a disc as seen in axial sections. Only caudal to the L4-5, do the dura and PLL part, creating a capacious anterior epidural space.

Savolaine et al described a central midline structure called plica mediana dorsalis 10 with the dorsolateral ligaments issuing from the it 916 of which 4 patterns have been described. Many cases of unilateral spread have been attributed to this 16 21

The findings of Hogan are in contrast to those of Savolair.e and Blomberg.

He proposes that injection of the dye by Savolaine et al and air in the epiduroscopy studies of Blomberg distend the epidural fat pad itself with its lateral attenuations and stretch and suspend it in a posterior epidural compartment to give the artifact called plica and lateral membranes.. Based on pictures in the physiologic state in magnetic resonance imaging22, Savolaine also concedes that plica mediana dorsalis is an artifact due to unnatural transmural dural pressures during distension of epidural space by air or fluid .

The present understanding of epidural space based on these studies is thus :

The homogenous fat in the posterior compartment has no fibrous sections and freely separates from the dura and the ligamenta flava. It is attached by a pedicle to the point where the two left and right portions of the ligamenta flava abut with a vessel entering at this point12. This is the space where the epidural needle and catheter are positioned and the local anaesthetic solution is deposited where it spreads to the other two compartments. This freely separable plane provides a route for the injected fluid or air. The

lateral compartment of the epidural space contains nerve roots, vessels and fat. The fat is lobulated by septae with a plane of septation extending from the exiting nerve root to the PLL. This space is important because this is the area where local anaesthetics come in contact with the nerve roots in their dural cuff. The septae in the lateral and anterior compartments can partially obstruct the flow to cause a pressure rise in response to injections, the decay of the pressure and the residual pressures 36 are independent of the volumes injected123

In our study, the divisions within the epidural space could have confined the dye to the posterior and posterolateral epidural space with less consistent spread to the anterior compartment. Since the volume could not spread in a circumferential manner, it might have spread in a linear manner covering a large number of segments. With the doubling of volume, the pressure head for spread would have been higher, facilitating a denser spread, as well as spread into the less compliant anterior compartment. It is also possible that 0.5ml/kg was an inadequate volume to fill the epidural segments and as a result the higher 1 ml/kg improved the quality rather than the extent of spread . To assess the real effect of volume, the lower dose should probably be 1 ml to study the effects on extent of spread and then double this volume to see if the spread doubles

The spread in patient 1, is interesting in that the lower part spread from T11 to L2 had a helical appearance with alternating anterior and posterior densities. The filling defects in the anterior spread are at the intervertebral discs where the dura is described to merge into the PLL. (12) Thus opposite the bodies, there is a spread with the filling defects opposite the discs. Similarly in the posterior spread, it seems as if there is spread in a metameric segment (12) extending from the upper lamina to the cephalad border of the lower lamina. It was as if the dye flowed from posterior distensible interlaminar areas to the next area that was distensible, the anterior space opposite the vertebral body leaving the non compliant areas in between as filling defects.

Perusal of our epidurograms with their



predominantly posterior and posterolateral spread raises the question, how exactly does epidural anaesthesia act?24 Is it by blocking of the spinal nerves at the intervertebral foramina as they course through the posterolateral epidural space or by diffusion along the dural sleeves towards the cord or through the dura and CSF towards the spinal cord? Is a lack of spread to the anterior aspect of epidural space likely to matter for the quality of anaesthesia?. Do the vagaries of spread explain the reported failure rate of 4- 50 % of cases with epidural anaesthesia?25 27 In the cord itself, is it the posterior aspect with the sensory tracts that require to be blocked, with the anterior tracts of the cord remaining totally or quasi functional? In which case, could this explain the retention of muscle tone and variable levels of motor activity with epidural anaesthesia which contrasts with the total motor paralysis seen with spinal subarachnoid anaesthesia? In the latter, the quantum of local anaesthetic drug with access to the sensory and motor tracts is such that, dense anesthesia of both sensory and motor tracts ensues with resultant analgesia and motor paralysis.

With epidural anaesthesia, the local anaesthetic drug has comparatively easy access to the spinal nerves, particularly the posterior nerve root encased in the dural arachnoid and pia mater. Only the quantity that diffuses into the cerebrospinal fluid through the dural sleeve has access to the spinal cord. Even here, the physical proximity to the posterior sensory tracts would be more than the anterior motor tracts which are geographically more distal. Whether this explains the difference in the quality of motor block between spinal and epidural remains to be explored. 2428 Do the physical barrier of 3 meningeal layers which have to be crossed by the local anaesthetic drug reduce the efficacy of epidurally deposited drug vis-avis density and totality of blockade? These questions could be addressed probably by injection studies of local anaesthetic coloured with a dye into cadavers and then studying the pattern of spread in both epidural and spinal injections. In our patients there was obvious analgesia as evidenced by absence of tachycardia and a stable blood pressure in response to incision. It is probable that the

posterior spread was enough to provide analgesia. Alternatively, the neuraxial spread of local anaesthetic might have been adequate. Burn et al16 found analgesia of the perineum in patients where the spread had not extended below L3 level, highlighting the disparity between physical and neuraxial spread.

In conclusion, there appears to be considerable individual variations in the extent, quality and uniformity of spread. Doubling of the dose does not necessarily double the extent of spread but improves its density and the extent. As a result, use of 1 ml/kg volume is more likely to ensure a better extent and quality of anaesthesia in this age group. However, epidural anaesthesia remains a blind technique where many aspects of the spread of the local anaesthetic agent and the resultant action are yet to be comprehensively elucidated.

References:

1. R. P. Husemeyer and D. C. White. Lumbar Extradural Injection pressures In Pregnant Women, fir. J. Anaesth 1980; 52: 55-592. D.l. Paul, J.A.W. Wildsmith. Extradural pressures following the injection of two volumes of bupivacaine. fir J. Anaesth 1989; 62: 368-3723.Usubiaga JE, Wikinski JA Usubiaga LE. Epidure pressure and its relation to spread of anesthetic solution in the epidural space. Anesth Analg 1967; 46440-446.4. Y.Hirabayashi, R. Shimizu, I. Matsuda and S. Inoue. Effect of extradural compliance and resistance on spread of extradural analgesia, fir. J. Anaesth 1990; 65: 508-513.5. Cardoso MM, Carvalho JC. Epidural pressure and spread of 2% lidocaine in the epidural space: influence of volume and speed of injection of the local anesthetic solution. Reg Anesth Pain Med 1998 ;23:14-9.6. Janzen E. Der negative Vorschlag bei lumbal Punktion. Dtsch. Z. Nervenheilkd 1926;94: 280.7. Lakshmi Vas Phalguni Naregal Savita Sanzgiri, Anupama Negi, Some vagaries of neonatal lumbar anaesthesia. Paediatric Anaesthesia 1999; 9: 217-2238. Hilt H, Gramm H-J, Link J. Changes intracranial pressure associated withanaesthesia, fir. J. Anaesth 1986; 58: 676-680.9. Harrison GR, Parkin IG, Shah JL. Resin injection studies of the lumbar extra dural space. Br J Anaesth 1985; 57: 333-336.10. Edward Savolaine, Jyoti Pandya, Samuel Greenblattet al. Anatomy of the human lumbar epidural space: new insights using CT epidurography. Anesthesiology; 1088; 68: 217-220.11. Bernard Dalens. Lumbar epidural anaesthesia in Regional anaesthesia in infants, children and adolescents. Edited by Bernard Dalens 1sred. Williams and Wilkins. Baltimore, Maryland. 1993, 207-248,12. Bernard Dalens. Regional anesthesia in children. Anesth



Analg. 1989;68: 654-7213. Hogan OH. Lumbar epidural anatomy. A new look by cryomicrotome section. Anesthesiology 1991; 75: 765-775.14.Blanco D, Mazo V, Ortiz M, Fernandez - Llamazares J.Vidai F. Spread of local anaesthetic into the epidural caudal space for two rates of injection in children. Reg Anesth 1996 ; 21: 442-515. Claude Ecoffey, Anne-Marie Dubousset, Kamran Samii. Lumbar and Thoracic Epidural Anesthesia for Urologic and upper Abdominal Surgery in infants and Children. Anesthesiology 1986; 65:87-90.

References for study of spread of radioopaque dye:

1. D.l. Paul, J.A.W. Wildsmith. Extradural pressures following the injection of two volumes of bupivacaine. Br. J. Anaesth 1989; 62: 368-3722. Cardoso MM, Carvalho JC. Epidural pressure and spread of 2% lidocaine in the epidural space: influence of volume and speed of injection of the local anesthetic solution. Reg Anesth Pain Med 1998 ;23:14-9.3. Vas L , Raghavendran S, Hosalkar H, et al. A study of epidural pressures in infants Paediatric anaesthesia, in press.4. Blanco D, Mazo V, Ortiz M, et al . Spread of local anaesthetic into the epidural caudal space for two rates of injection in children. Reg Anesth 1996 ; 21: 442-55. Vas L, Naregal N, Sanzgiri S, et al. Some vagaries of neonatal lumbar anaesthesia. Paediatric Anaesthesia 1999; 9: 217-2236. Usubiaga JE, Wikinski JA Usubiaga LE. Epidure pressure and its relation to spread of anesthetic solution the epidural space. Anesth Analg 1967; 46440-446.7. Y.Hirabayashi, R. Shimizu, I. Matsuda and S. Inoue. Effect of extradural compliance and resistance on spread of extradural analgsia. Br. J. Anaesth 1990; 65: 508-513.8. Saitoh K, Hirabayashi Y, Shimuzu R etal. Extensive spread in the elderly may not relate to decresed leakage through intervertebral foramina. BJA 1995, 75: 688-691.9. Harrison GR, Parkin IG, Shah JL. Resin injection studies of the lumbar extra dural space. Br J Anaesth 1985; 57: 333-336.10. Edward Savolaine, Jyoti pandya, Samuel Greenblatt et al. Anatomy of the human lumbar epidural space : new insights using CT epidurography. Anesthesiology; 1088; 68: 217-220.11. Bernard Dalens. Regional anesthesia in children. Anesth Analg. 1989;68: 654-7212. Hogan OH. Lumbar epidural anatomy. A new look by cryomicrotome section. Anesthesiology 1991; 75: 765-775.13. BlombergRG. The lumbar subdural extraarachnoid

space of humans: An anatomical study using spinaloscopy in autopsy cases Anesth Analg 1987 : 66: 177-8014. Blomberg RG.. The dorsomedian connective tissue band in the lumbar epidural space of humans An anatomical study using epiduroscopy in autopsy cases Anesth Analg 1986 : 65: 747-5215. Bromage P.R.Burfoot M.F, Crowell D.E. etal. Quality of epidural blockade: influence of physical factors. Br .J. Anaesth 1964; 36:342-352.16. Burn J.M,GuyerP.B,Langdon L, The spread of solutions injected into the epidural spaceA study using epidurograms in patients with lumbosciatic syndrome. Br.J.Anaesth-1973: 45: 338-34517. Slappendel R, Gielen M.J.M, Hasenbos MAWM. Etal. Spread of radioopaque dye in the thoracic epidural space. Anesthesia 1988; 43: 939-942.18. Van Niekerk J Bax-Vermierre B.M.J, Geurts J.W.M etal . Epidurography in premature infants. Anaesthesia 1990, 45: 722-72519. .StienstraR, DahanA.AIhadi etal. Mechanism of action of an epidural Topup in combined spinal epidural anesthesia Anesth Analg 1996;83:382-6.20. Blumgart C,H. Ryall D, Dennison B. Mechanism of extension of spinal anaesthesia by extradural injections of local anaesthetic. Br. J.Anaesth. 1992;69:457-46021. BoezartA P, Computerized axial tomoepidurographic documentation of unilateral epidural analgesia. Can J anaesth 1989; 36 697-70022. SavolaineER: Reply to a letter. Anesthesiology 69:798, 1988.23. Rocco AG, Scott DA, Boas RA etal The epidural space behaves as a Starling resistor and inflow resistance is elevated in diseased epidural space Reg anesth 1990; 15(suppl):3924. Bromage P.R. Mechanism of action of extradural analgesia Br. J.Anaesth. 1975;47:199-212.25. Curatolo M, Orlando A, Zbinden A.M. et al. A multifactorial analysis to explain inadequate surgical analgesia after extradural block..Br J Anaesth 1995; 75:274-281.26. .Tanaka K .WatanabeR, Harada T etal. Extensive application of epidural anaesthesia and analgesia in a university hospital: Incidence of complications related to technique. Regional anaesthesia 1993; 18 :34-3827. Seeberger M.D Lang M.L.Drewe J et al Comparison of spinal and epidural anesthesia for patients younger than 50 years of age.Anesth Analg1994;78667-73..Huang JS, lYY.TungCC etal Comparison between the effects of epidural and spinal anesthesia for elective cesarian section; Chung Hua Hsueh Tsa Chih (Chin Med J) 1993;51: 40-7


Ventilation-Perfusion Distribution 42 Ramkumar Venkateswaran

INTRODUCTIONThe primary function of the lung is to

exchange oxygen and carbon dioxide between the atmosphere and blood. For this exchange to be efficient, the air and blood have to be brought in close proximity with each other. The alveolocapillary membrane, with air on one side and blood on the other, provides the ideal thin interface to bring about this exchange of gases. The air on the alveolar aspect of this membrane is constantly being replaced by alveolar ventilation while the blood on the capillary side is being continuously circulated by the pulmonary blood flow. As blood passes along the pulmonary capillary, it takes up oxygen and gives off carbon dioxide. Thus it is evident that both ventilation and blood flow are equally important for effective gas exchange to occur.

The functional lung unit as depicted in Figure 1 shows the alveolo-capillary membrane separating the alveolar gas on one side and the pulmonary capillary blood on the other. For purposes of understanding, one can take this figure to represent the whole lung (though as we go along, we will realise that this generalisation is not exactly true).

Let us first take a look at the gas side of the alveolocapillary membrane. The normal tidal volume in a 70-kg adult is 500 mL. Of this, around 150 mL occupies the conducting airways and does not take part in gas exchange (“wasted ventilation”) while the remaining 350 mL enters the alveoli, alveolar ducts and terminal respiratory bronchioles (termed “alveolar ventilation”) where gas exchange occurs. The minute ventilation of a 70-kg adult breathing at a rate of 15 breaths per minute is 7500 mL (tidal volume x respiratory rate). Of this, around 5250 mL (alveolar ventilation x respiratory rate) actually takes part in gas exchange while the remaining 2250 mL accounts for wasted ventilation. Turning our attention to the blood side of the alveolocapillary membrane, we know that the amount of blood that flows through the pulmonary circulation every minute is equal to the cardiac output which in a 70-kg adult is around 5000 mL. This brings us to the important observation that the total volume of fresh gas (alveolar ventilation) and total volume of fresh blood brought to the alveolocapillary membrane each minute for gas exchange to occur are numerically almost the same. This would give a ventilation-perfusion ratio of 1 which should result in optimal gas exchange as ventilation and blood flow are equally distributed.

Though this may be true in an ideal situation, the same may not be the case in real life. Let us consider an extreme example where the entire ventilation is distributed to one lung and the entire perfusion to the other. If one were to take the overall picture, this would reflect as a ventilation-perfusion ratio of 1 which appears ideal. However, the real situation is far from ideal as in this example, no gas exchange can possibly take place! Thus, for efficient gas exchange to take place not only should the ventilation and perfusion be matched but they should also be equally distributed. The “normal’



lungs, like many other “normal” organs in the body, has its own imperfections even in health. These imperfections are produced by an uneven distribution of ventilation and blood flow.

We shall first consider the causes and consequences of uneven distribution of perfusion (as these are easier to grasp) before going on to study the more complex causes and consequences of uneven distribution of ventilation. We shall then consider the distribution of ventilation and perfusion in relation to each other and clinical implications of alteration in ventilation- perfusion ratio in health and in disease.

DISTRIBUTION OF BLOOD FLOWWhile the total amount of blood flowing

through the lungs depends on the cardiac output, its distribution depends on the hydrostatic pressure in the pulmonary circulation. The pulmonary circulation, unlike the systemic circulation, is a low pressure circuit and blood is rarely distributed evenly to all parts of the lung. Distribution of blood flow in the lungs is gravity dependent. Thus, in an upright individual, more blood flows to the lung bases as compared to the apices of the lung. If the lungs were to be divided into several slices as shown in Figure 2,

slices indicating the range of the lung volume (expressed as a percentage of the whole), alveolar ventilation, blood flow, ventilation-perfusion ratio, and partial pressures of oxygen, carbondioxide and nitrogen.

measurement of blood flow to the individual lung slices would progressively increase as one moves down the lung. Blood flow to the uppermost lung slice which constitutes about 7% of the total lung volume would be 0.07 L/min. The comparative values for the lowermost slice would be 13% and 1.29 L/min respectively. This would result in a blood flow per unit lung volume that is about ten times more at the bottom than it is at the top.

This normal distribution of pulmonary blood flow is affected by changes of posture and exercise. When a subject lies supine, blood flow to the apical zone increases while that to the basal areas remains virtually unchanged resulting in a more uniform distribution of perfusion from apex to base. However, blood flow in the supine position is more in the posterior lung zones when compared to the anterior. In the same way, the dependent lung receives more blood flow in the lateral position. The distribution of blood flow is mainly influenced by gravity, which is related in some way to the hydrostatic pressure within the pulmonary circulation. Exercise brings about an increase in the cardiac output and makes the distribution of blood flow to the apical and basal regions of the lung more uniform.

Causes of differences in distribution of blood flow

Distribution of blood flow in the lungs is gravity-dependent. If one were to imagine the pulmonary circulation to consist of a simple system of tubes, it is easy to understand how hydrostatic pressure within the system will increase as one moves from the apex to the base of the lung. This hydrostatic pressure effect partly explains why blood flow to the base of the lung is more than that to the apex. Pulmonary circulation also differs from other regional circulations in that blood flowing through lung parenchyma is in close proximity to air filled alveoli. Thus, alveolar pressure also has its influence on the distribution of blood flow within the lung. Interaction between the pulmonary arterial pressure (Pa), pulmonary venous pressure (Pv) and alveolar pressure (PA) affects the distribution of blood flow within the lungs. This has been elegantly described by the three zone model of West (Figure 3) which divides the lung into zones on the basis of the above three pressures. In zone 1, alveolar pressure is higher than the pulmonary arterial as well as pulmonary venous pressures (PA>Pa>Pv)- The



higher pressure within the alveoli compresses the thin-walled pulmonary vasculature resulting in an area where there is no blood flow. Though this is a theoretical possibility, pulmonary arterial pressure in healthy individuals is sufficient to raise the blood to the apex of the lung so that under normal circumstances, zone 1 is virtually absent.

Fig 3. West’s three zone model showing distribution of blood flow in the upright lung based on the relative magnitude of alveolar (PJ, pulmonary arterial (PJ and pulmonary venous (Pv) pressures.

In zone 2, pulmonary arterial pressure exceeds alveolar pressure, which in turn exceeds the pulmonary venous pressure (Pa

>PA>Pv)- Blood

flow through this region is governed not by the arteriovenous pressure difference but by the difference between pulmonary arterial pressure and alveolar pressure. Unlike the alveolar pressure that remains constant throughout the lung, the pulmonary arterial pressure progressively increases as one moves from the apex of the lung towards the bases. This explains the increase in pulmonary blood flow observed as one moves down zone 2.

In zone 3, pulmonary venous pressure exceeds alveolar pressure. The pressure gradient between pulmonary arterial and pulmonary venous pressures now determines pulmonary blood flow (P >P >PJ, which is similar to whatx a v A7 1

happens in other vascular beds. If this were true, the pulmonary blood flow should remain constant with increasing distance down the lung. However, as depicted in Figure 3, blood flow increases with increasing distance down the lung even within zone 3. The reason for this is not obvious at first sight. While the pressure within the pulmonary vessels increases as one moves down zone 3, the pressure surrounding these vessels remains

constant (alveolar pressure). Pressure across the vessel wall, the transmural pressure, increases resulting in distension of the pulmonary vasculature and reduction in pulmonary vascular resistance towards the lung bases. Increasing transmural pressure with increasing distance down the lung also causes additional capillaries to open up (a phenomenon called “recruitment”) which further explains the increase in blood flow observed as one moves down the lung through zones 2 and 3.

The three zone model of West explains why pulmonary blood flow increases from the apex to the base of the lung. Hughes et al described another zone at the base of the lung which they termed zone 4 where blood flow actually decreases due to compression of the larger vessels by increase in interstitial pressure (P >P >P >PJ. This effect becomes more' a lor V A7

important as lung volume is reduced from total lung capacity towards residual volume (Figure 4).

Fig 4. Effect of lung volume on distribution of blood flow (TLC= total lung capacity; FRC= functional residual capacity; RV- residual volume).

While at total lung capacity (TLC) blood flow increases down most of the lung, at functional residual capacity (FRC), there is an area of reduced blood flow near the base. At residual volume (RV), blood flow is actually more near the apex than it is at the base. These changes can be explained by the contribution made by larger blood vessels to vascular resistance at low lung volumes. At high lung volumes, extra-alveolar blood vessels are pulled open and their vascular resistance decreases. As these vessels are compressed extraluminally at low lung volumes, they contribute a high



resistance. The lung parenchyma at the lung bases is poorly expanded at FRC resulting in a high resistance in the extra-alveolar vessels and a reduced blood flow. As the vascular resistance is lowest at TLC, blood flow is maximum. At RV, the vascular resistance is very high as the lung parenchyma is least expanded. This results in a compression of the pulmonary vasculature at the lung bases and a redistribution of the blood flow preferentially towards the apex of the lung.

DISTRIBUTION OF VENTILATIONThe right lung receives a slightly larger

portion of the total ventilation as compared to the left (55% versus 45%) in both the upright as well as supine positions. In the lateral position, the dependent lung gets better ventilated regardless of the side on which the subject is lying. This occurs because the cephalad displacement of the diaphragm on the dependent side results in stretching of the muscle fibres of this hemidiaphragm. The resultant greater initial fibre length causes it to contract more effectively during inspiration resulting in better ventilation of the dependent lung. For the same reason, the posterior and basal regions of the lungs get better ventilated in the supine position.

West studied the distribution of ventilation to different lung slices almost 4 decades ago. The uppermost slice, which constitutes 7% of the total lung volume, receives an alveolar ventilation of 0.24 L/min (Figure 2). Corresponding figures for the lowermost slice of the lung are 13% and 0.82 L/min respectively. Thus, while blood flow per unit lung volume increases markedly from the apex to the base of the lung, change in ventilation is not quite so marked and is only a third of that seen with blood flow.

When small amounts of gas are inspired beginning from residual volume, the gas distributes primarily to the upper zones of the lung and the lower zones do not ventilate at all. With progressive filling of the lungs, the lower zones also begin to fill and by the time the lung volume reaches about 20% of its vital capacity, both upper and lower zones are filling at about the same rate. As inspiration continues above this volume, the lower zones fill more rapidly than the upper, which is similar to the pattern of distribution of ventilation seen during normal tidal

breathing.

Causes of distribution of ventilationGravity influences distribution of

ventilation to a much lesser extent than it does the distribution of perfusion. The lung is supported partly by the chest wall and the diaphragm. Because the lung tends to fall away from the chest wall, it creates a negative pressure within the pleural cavity. In the upright position, the lung behaves like a fluid-filled bag with a tendency to sag down towards the base. This results in a more negative intrapleural pressure at the apex of the lung as compared to the lung bases.

The influence of differences in intrapleural pressure on the distribution of ventilation is shown in Figure 5. If the height of the lung is 30 cm and the intrapleural pressure changes by 0.25 cmH20

Fig 5. Effect of intrapleural pressure on distribution of ventilation. Alveoli at the apex and base fall at different portions of the pressure volume curve depending on whether the lung is at (a) functional residual capacity [FRC] or (b) residual volume [RV]. The distribution of ventilation is alterend accordingly

for every centimetre distance down the lung, one can expect a difference in intrapleural pressure of around 7.5 cmH20 between the apex and base of the lung. This in fact is the case as shown in Figure 5 (a) where at FRC, the intrapleural pressure is - 10 cmH20 at the apex and - 2.5 cmH20 at the base of the lung. Because of the lower transpulmonary pressure gradient, alveoli at the bases of the lung are smaller in size as compared to those at the apex. Besides, as can be appreciated in Figure 5(a), the apical and basal parts of the lung are operating at different portions of the pressure-volume curve. Therefore at FRC, alveoli at the base of the lung are not only smaller but are also situated on the more compliant portion of the pressure-volume curve. This means that as inspiration begins from FRC, the smaller alveoli



near the base expand much more than their larger counterparts at the apex.

Figure 5(b) shows that at residual volume (RV) also, there is a difference in intrapleural pressure of 7.5 cmH20 between the apex and base of the lung. Intrapleural pressure at the apex is - 4 cmH20 while that at the base is + 3.5 cmH20. As intrapleural pressure at the base of the lung exceeds airway pressure, alveoli in this region are collapsed and are hence not ventilated. Under these conditions, alveoli at the apex that are located at the vertical compliant portion of the pressure-volume curve undergo preferential expansion with inspiration. Alveoli at the base are situated at the lower horizontal portion of the pressure-volume curve where a large pressure change is needed to open them up (critical opening pressure) before they start receiving part of the ventilation. This explains why when inspiration begins from RV, ventilation is initially distributed preferentially to the apex with the base receiving ventilation only during the latter part of inspiration.

We have until now seen how differences in intrapleural pressure in the upright lung at different starting lung volumes (FRC versus RV) bring about differences in distribution of ventilation. Consider the functional lung unit to consist of an elastic chamber (the alveolus) connected to the atmosphere by a tube (bronchiole). The amount of ventilation of such a unit will depend on the distensibility of the chamber (compliance) and the resistance to flow of gas offered by the tube (airway resistance). Regional compliance and airway resistance vary even within the normal lung. These variations are even more marked in the diseased lung. Thus, one needs to understand how these regional variations in pulmonary mechanics bring about changes in the regional distribution of ventilation between the two lungs, and also between adjacent units within the same lung.

The three lung units shown in Figure 6 illustrate the effect of changes in regional compliance and airway resistance on the distribution of ventilation. Lung unit A has a normal compliance and normal airway resistance. The rate at which its volume changes during inspiration is shown and it can be seen that the

Fig 6. Effect of changes in compliance and airway resistance on regional distribution of ventilation.Unit “A” has normal compliance and airway resistance, Unit “B" has decreased compliance and normal airway resistance while Unit “C" has normal compliance and increased airway resistance

volume change is large and rapid so that it is complete before the expiration for the whole lung begins. By contrast, unit B has a low compliance and normal airway resistance. The change in volume of unit B, though small, is brought about rapidly. Such units are therefore called “fast” alveoli as they consistently achieve their maximum volume fairly rapidly. Finally unit C with its high airway resistance fills so slowly that it does not reach its final volume even when the rest of the lung has begun its exhalation. Such an alveolar unit is called a “slow” alveolus and given adequate time for inspiration; such slow alveolar units will also reach their maximum volume. Because slow and fast alveoli are seen even in the normal lungs (and because they constitute a larger proportion of lung units in the diseased lung), the regional distribution of ventilation will be affected. The time available for lung units to fill to their maximum volume depends on the frequency of breathing. The higher the frequency of breathing, the lesser is the time available for volume exchange to occur. Thus, it is obvious that as frequency of breathing increases, the slow alveolar units will not get adequate time to fill to their maximum extent. This in turn will be reflected as a regional inequality of the distribution of ventilation.

DISTRIBUTION OF VENTILATION-PERFUSION RATIO

We have seen how both ventilation and perfusion increase as we move from the apex to the base of the lung, with the perfusion increasing



to a greater extent than the ventilation. Assuming a total blood flow of 6 litres per minute and a total ventilation of 5.1 litres per minute, we can calculate the blood flow and ventilation in terms of litres per minute per unit lung volume. As ventilation and perfusion are now expressed in the same units, it is a simple matter to divide one by the other to derive the ventilation-perfusion ratio.

The distribution of ventilation, perfusion and ventilation-perfusion ratio in the normal upright lung is shown in Figure 7. It is obvious from the figure that the VA/Q ratio is low at the base of the lung (about 0.6) and increases as we go up the lung towards the apex where it is more than 3. What this means is that alveoli at the base of the lung are slightly overperfused in relation to their ventilation whereas alveoli at the apex are grossly underperfused in relation to their ventilation. The degree by which ventilation is less than or in excess of perfusion is conveniently expressed in terms of the ventilation-perfusion ratio (VA/Q ratio). Va/Q ratio determines how gas exchange occurs in any lung unit or region of the lung.

Fig 7. Distribution of ventilation, blood flow and ventilation-perfusion ratio in the normal upright lung. Ventilation and perfusion increase at different rates as one moves down the lung resulting in a decrease in ventilation-perfusion ratio from apex to base.

To understand how changes in ventilation-perfusion ratio bring about alterations in gas exchange, one needs to go back to the schematic diagram of a functional lung unit that consists of an alveolocapillary membrane separating the alveolar gas on one side from the mixed venous blood on the other. The ideal alveolus depicted in Figure 8(a) has a ventilation- perfusion ratio of 1. The inspired gas entering this


alveolus has a P02 of 150 mmHg and a PC02 of 0 mmHg; the mixed venous blood perfusing this unit has a P02 of 40 mmHg and a PC02 of 45 mmHg. The normal balance between the rates at which oxygen and carbon dioxide are exchanged across the alveolocapillary membrane results in an alveolar P02 of 100 mmHg and an alveolar PC02 of 40 mmHg. Pulmonary capillary blood draining such an ideal alveolar unit will essentially have the same oxygen and carbon dioxide tension as the partial pressure of these gases in the alveolar gas.

Obstructing the conducting airway leading to the alveolus brings about reduction of alveolar ventilation. If the blood flow were held constant, this would result in a lowering of the ventilation-perfusion ratio. The alveolar P02 in a unit with a low VA/Q ratio will fall because less oxygen is being added and the alveolar PC02 will rise because less carbon dioxide is being removed. An extreme situation can be visualised where ventilation is completely obstructed but perfusion continues uninterrupted (Figure 8b). This

Fig 8. Spectrum of ventilation - perfusion (V/Q) ratios showing unit “A” with normal V/Q ratio in the middle, unit “B” representing a "shunt unit" at the left end of the spectrum, and unit “C” representing a “dead space unit" at the right end of the spectrum. Numbers indicate partial pressures of oxygen and carbondioxide in the inspired gas and alveolar gas on the alveolar side of the alveolocapilarry membrane, and blood gas tensions on the capilarry side of the alveolocapilarry membrane.

will result in a ventilation-perfusion ratio that is zero. In respiratory physiology, such a unit is called “shunt”. In a shunt unit, alveolar P02 and PC02 approach the tension of oxygen and carbon dioxide in mixed venous blood; namely, 40 and 45 mmHg respectively. If one were to imagine a lung unit somewhere between the extreme situation depicted in figure 8b and the ideal situation depicted in figure 8a, the alveolar P02


would be in between 40 and 100 mmHg (while the alveolar PC02 would lie in between 45 to 40 mmHg). Alveoli at the base of the lung have a VA/ Q ratio of less than 1 and would therefore fall along the spectrum of VA/Q ratios to the left of the normal alveolus as shown at the bottom of figure 8.

What would happen if on the other hand, one gradually obstructs perfusion leaving ventilation undisturbed, thus increasing the VA/Q ratio? The alveolar P02 would rise because less oxygen is being removed, and the alveolar PC02 would fall because less carbon dioxide is being excreted. An extreme situation results when perfusion to a lung unit is completely obstructed with ventilation continuing uninterrupted. This will lead to a VA/Q ratio of infinity. In respiratory physiology, such a unit where ventilation is wasted constitutes “dead space”. In an extreme situation as described above, the composition of the alveolar gas becomes identical with that of inspired gas with a P02 of 150 mmHg and a PC02 of 0 mmHg. Alveoli at the apex of the lung have Va/Q ratios that are typically more than 3. The alveolar P02 and PC02 in alveolar units nearer the apex of the lung will therefore lie somewhere between the ideal alveolar unit shown in figure 8a and the dead space unit shown in figure 8c (with alveolar P02 being between 100 and 150 mmHg and alveolar PC02 being between 40 and 0 mmHg). Apical alveoli will lie along a spectrum of Va/Q ratios to the right of the normal alveolus as shown at the bottom of figure 8.

A reference to figure 2 shows that alveolar units at the apex of the lung with higher VA/Q

ratios have a P02 of 132 mmHg and PC02 of 28 mmHg while those at the base of the lung with lower Va/Q ratios have P02 and PC02 values of 89 mmHg and 42 mmHg respectively.

SUMMARYWe have until now seen how even in the

healthy lung, ventilation and perfusion are not uniformly distributed throughout the lung. We know that though both ventilation and perfusion increase progressively as we move from the apex to the base of the lung, the increase is more significant and rapid with perfusion. The ventilation-perfusion ratio therefore decreases as we move from the apex to the base of the lung. For alveolar units to exchange oxygen and carbon dioxide in a perfect manner, they should have their ventilation and perfusion also perfectly matched. Such an ideal situation does not exist even in the normal lung. Despite variations in ventilation- perfusion ratio, healthy lungs still bring about effective and nearly perfect gas exchange. The situation is different when one considers a diseased lung where gross VA/Q inequalities occur. These VA/Q inequalities have adverse effects on gas exchange that manifest as hypoxaemia and hypercarbia. An understanding of the effects of altered distribution of ventilation and perfusion on gas exchange helps one to appreciate and treat pathological lung conditions. It is hoped that this review has provided the reader with such an insight.

References1. West JB. Ventilation/blood flow and gas exchange. 3rd Edition. Oxford : Blackwell Scientific Publications, 1977.2. Lumb AB. Nunn’s Applied Respiratory Physiology. 5th Edition. Oxford : Butterworth Heinemann, 2000.


Functions of the Diaphragm and Anesthesia 49 Vijaylakshmi Kamat

The diaphragm is a dome-shaped muscle that separates the thoracic cavity from the abdomen. It is the main muscle of respiration, with a crural portion attached to the upper three lumbar vertebrae, a sternocostal portion attached to the sternum and the lower six ribs, and a central tendon. The crural part acts to stabilize the central tendon and generate downward movement of the diaphragm. The sternocostal portion acts to lift and expand the lower rib cage. The central tendon into which both muscular parts are inserted has a complex bi-domed shape and a central narrow portion so that the two halves can act independently.

ACTIONSContraction of both the costal and crural

fibres causes the diaphragm to descend, decreasing pleural pressure and raising abdominal pressure. Diaphragmatic contraction and pressure against the abdominal contents increase intraabdominal pressure which acts as a distending force on the lower rib cage.

Due to the apposition of the diaphragm to the lower rib cage, the increase in pressure

below the contracting diaphragm directly acts to expand the lower rib cage and contributes to inspiration. This is more marked in the standing position, when the abdomen is noncompliant, and diaphragmatic force is translated into outer rib cage movement.

In the supine position, the central tendon is unable to descend, and its deeply domed shape allows the costal fibres to pull the costal origins, and thus the margins of the rib cage, cephalad. Contraction of the costal fibres and elevation of the lower ribs leads to an increase in the anteroposterior and the transverse diameters of the chest wall. As the dome descends to expand the chest wall and thorax, the abdominal contents are displaced caudally, and intraabdominal pressure rises with outward protrusion of the abdominal wall.

Contraction of the diaphragm, descent of the dome and simultaneous outward movement of the ribs widening the thorax is responsible for 2/3 of quiet resting ventilation. Excursion of the diaphragm during resting ventilation is 1,5cm. In the absence of intercostal muscle contraction, the upper rib cage is drawn in, while the lower rib cage expands.

The effectiveness of diaphragmatic contraction depends on the length of the diaphragm, its shape, and the velocity of shortening. The tension developed by the diaphragm increases with its length up to 125% of its resting length, and can continue to function with as little as 40% of its resting length. It is therefore able to generate tension over a wide range of lung volumes, except if hyperinflation is so severe and the diaphragm is extremely



flattened and shortened that it cannot generate adequate tension and the transdiaphragmatic pressure falls.

At very large lung volumes as in emphysema, the “zone of apposition” decreases, and contraction of the flattened diaphragm during inspiration causes an inward (expiratory) movement of the lower rib cage.

DXAPHRA3M

In infants, the outward movement of the ribs with diaphragmatic contraction alone may be deficient because of the extremely compliant chest wall and the horizontal positioning of the ribs.

To test the extent to which diaphragmatic contraction moves the rib cage in seven awake supine infants during quiet breathing, Pascucci et al1 studied chest wall motion in prematurely born infants before and during spinal anesthesia for inguinal hernia repair.

Infants were studied at or around term (postconceptional age 43 +/- 8 wks). Spinal anesthesia produced a sensory block at the T2- T4 level, with concomitant motor block at a slightly lower level. This resulted in the loss of most intercostal muscle activity, whereas diaphragmatic function was preserved. Rib cage and abdominal displacements were measured with respiratory inductance plethysmography before and during spinal anesthesia.

During the anesthetic, outward inspiratory rib cage motion decreased in six infants; four of these developed paradoxical inward movement of the rib cage during inspiration. One

infant, the most immature in the group, had inward movement of the rib cage both before and during the anesthetic. Abdominal displacements increased during spinal anesthesia in most infants, suggesting an increase in diaphragmatic motion. Thus, in the group of infants studied, outward rib cage movement during awake tidal breathing requires active, coordinated intercostal muscle activity that is suppressed by spinal anesthesia.

In normal subjects, the diaphragm is approximately a hemispherical dome at the end of expiration, but as the central tendon descends and the zone of apposition decreases, it resembles a flattened sheet. In scoliosis, with thoracic asymmetry, the shape and mechanical efficiency of the right and left hemidiaphragms may differ considerably.

Fig 3. Movement of the Diaphragm with exhalation and inhalation

FUNCTIONSThe diaphragm is arguably the most

important skeletal muscle in the body, with complex functions. It has long been recognized as the most important inspiratory muscle, particularly in the supine position. It is responsible for 60-75% of the tidal volume during quiet breathing, and a much smaller percentage with



higher tidal volumes. If the intercostal muscles do not act during inspiration, the fall in intrapleural pressure with diaphragmatic contraction leads to paradoxical inward movement of the rib cage and a fall in tidal volume. This is seen in quadriplegics with spinal cord lesions below C5, and in high neuraxial blocks.

The adult diaphragm is composed of three types of skeletal muscle fibres:a) Type I fibres (slow oxidative, “red” resistant to fatigue). These contain high concentrations of mitochondria and oxidative enzymes, with numerous capillaries and a high myoglobin content, which gives the muscle a dark red colour. They are endurance fibres, resistant to fatigue, and are deficient in infants.b) Type lla (fastoxidative)c) Type lib (fast glycolytic “white” fibres). These have few mitochondria and a high concentration of glycolytic enzymes and large stores of glycogen. They are white due to fewer blood vessels and little myoglobin. They are larger, can generate more force, but fatigue easily.

The proportion of type I fibres in the diaphragm is greater in smaller mammals which have a high metabolic rate and respiratory frequency. In man 55% of the fibres are type I, 20% type lla, and 25% type lib. The resistance to fatigue of the diaphragm is due to the high proportion of fatigue-resistant type I fibres, as well as the ability of the blood flow to the diaphragm to increase in step with ventilation

DIAPHRAGMATIC FUNCTION AND COPDThe dome shape of the resting diaphragm

with the small radius of curvature makes it uniquely efficient in contraction. Thus the longer the resting fibre length and the higher the dome, the greater the excursion during inspiration and the larger the lung expansion.

It has been postulated that COPD and general anesthesia interfere with gas exchange probably due to alterations in the structure and configuration of the chest wall and diaphragm. COPD and hyperinflation of the lungs leads to “flattening” of the diaphragm. Anesthesia and paralysis also change the configuration of the diaphragm.

Like all skeletal muscles, the force generated by the diaphragm is dependant on its initial length. By decreasing diaphragm muscle length, hyperinflation can reduce the pressure- generating capacity of the diaphragm. Dynamic hyperinflation (or auto-PEEP) which occurs at rapid ventilatory rates, as during exercise, can worsen the situation.

The rationale for lung-volume reduction surgery (LVRS) in severe emphysema is to increase the resting length of the diaphragm and restore its normal dome shape, to make it more efficient.2 Several reports, including a randomized control trial3 have consistently shown both subjective improvement in symptoms and a decrease in residual volume following LVRS. The flattened diaphragm in COPD would generate a lower transdiaphragmatic pressure4, be less efficient and expend more energy than the normal diaphragm.

Hence it is reasonable to assume that dyspnea and respiratory failure could be due to fatigue of the diaphragm. Indeed, the diaphragm does exhibit fatigue in the muscle cell in normal subjects under certain circumstances.

IS FATIGUE OF THE DIAPHRAGM A PROBLEM IN PATIENTS WITH COPD?

Counterintuitively, the diaphragm in patients with COPD may be resistant to fatigue, as shown by Polkey et al5 when patients with COPD were exercised on a treadmill to “exhaustion”.

Levine S et al6 obtaining biopsy specimens from patients with COPD, and staining for various isoforms of light and heavy myosin chains, troponin and tropomyosin, found a higher proportion of slow myosin heavy chains. Diaphragms of patients with severe COPD had a higher proportion of type I (slow-twitch) fibers and a lower proportion of type II (fast-twitch) fibers than the normal diaphragm.

As a compensatory mechanism, in severe COPD the proportion of slow-twitch fibers in the diaphragm increases, whereas the proportion of fast-twitch fibers decreases. These data are consistent with the hypothesis that severe



COPD transforms fast-twitch fibers to slow- twitch fibers in the diaphragm. These adaptations may render the diaphragm more resistant to fatigue.

However, only the diaphragms of patients with severe COPD show the switch from fast- twitch fibers to slow-twitch fibers. The functioning of the diaphragms of the patients with less severe COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm. This casts doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragmatic function. Thus the need for LVRS is questioned by many investigators6

EFFECTS OF ANESTHESIAThe supine position and induction of

anesthesia have been associated with basal atelectasis and reductions in FRC7. The etiology of impaired gas exchange under anesthesia could be due to the effects on the diaphragmatic shape and movement. This was studied by Froese and Bryan in 19748. They found that in awake subjects lying supine or in the lateral decubitus position, the dependant part of the diaphragm moved more in a cephalocaudad direction than the nondependant parts. This led them to postulate that the dependant portion, due to the smaller radius of curvature, (Laplace law) and greater length of fibres (length-tension relationship) was able to generate a larger pressure and contracted with a larger displacement than the nondependent portion.

With anesthesia-paralysis, the effect was reversed. The resting level of the diaphragm was more cephalad, and the nondependent portion had the greater excursion. With large tidal volumes, diaphragmatic excursion was more uniform and piston-like. Their data suggest that the redistribution of ventilation (from dependant to nondependent areas of the lung with the change from spontaneous ventilation to paralysis and controlled ventilation) is a result of the effects on the diaphragm.

FLUOROSCOPIC FINDINGS DURING SPONTANEOUS BREATHING:

Excursion of the diaphragm was greatest in dependant portions (which were most cephalad).

FLUOROSCOPIC FINDINGS WITH ANESTHESIA, PARALYSIS AND IPPV:

With small tidal volumes, there was greatest excursion in non-dependant regions; with large tidal volumes, the excursions were pistonlike, equal in all zones.

In the spontaneously breathing awake patient, the predominant movement of the diaphragm was in the dependant portion of the diaphragm (this, in the supine individual would be the crural fibres). Anesthesia induced a cephalad shift in the end-expiratory (FRC) position of the diaphragm and, in the case of spontaneous ventilation, the maximum excursion was still in the dependant portion. Paralysis, followed by positive pressure ventilation, however, caused the greatest excursion in the nondependent portion of the diaphragm. Thus diaphragmatic excursions vary with active or passive movements.

This was explained on the basis of the hydrostatic abdominal pressure gradient, i.e. the abdominal contents, like a water-filled plastic bag, would sink to the bottom and exert the greatest pressure on the most dependant part of the diaphragm, pushing it cephalad.

With anesthesia and paralysis, the cephalad shift of the end-expiratory position of the diaphragm was explained by reduction in normal end-expiratory muscle tone. This shift would reduce FRC and promote atelectasis, which may persist well into the postoperative period7.

It is important to realize that in Froese’s study, only the dependant portion of the diaphragm moved in a cephalad direction; the non-dependant portion moved caudad.

Anaesthesia increases the curvature of the spine, which provides an anchor for all other chest wall structures and may affect diaphragm



and rib cage configuration as well, independent of other factors. This may explain the change in diaphragm shape during anesthesia and paralysis. Other studies continued this line of thought.

Heber et al9 studied 18 consecutive patients undergoing surgery under general anesthesia. Group 1 patients had no neuromuscular paralysis, and Group 2 patients were paralysed with pancuronium. Spiral computerised tomography was performed awake and during anesthesia at end-expiratory level and, additionally, in four patients at end-inspiration for subsequent analysis. There was a significant cephalad displacement of the most cephalad point of the diaphragm dome at functional residual capacity, particularly in its dependent portion, in the pancuronium group.

During anesthesia with no persisting muscle paralysis, there was only a minor and insignificant cephalad shift of the diaphragm dome. However, regional analysis showed that the most dorsal part of the diaphragm was significantly displaced cephalad. Compared with conscious, spontaneous breathing, mechanical ventilation decreased the inspiratory displacement of the dependent part of the muscle. They concluded that this minor movement of the diaphragm may play an additional role in atelectasis formation.

However, not all investigators came up with similar results. Drummond et al10 studied the changes in diaphragm position with induction of anesthesia. Images of a sagittal section of the right hemidiaphragm were obtained using an ultrasound sector scanner in 20 patients in the supine position immediately before, and after, the induction of anesthesia (with thiopentone).

In the awake patient, the mean excursion of the part of the diaphragm that showed the greatest tidal movement was 1.56 +/- 0.52 (SD) cm. The end-expiratory position of this part of the diaphragm was noted before and after induction. Cephalad movement of this position was seen in 10 patients. In a further eight, the end-expiratory position did not change, and in two patients it moved caudally. The mean

movement was 0.36 +/- 0.52 cm in a cranial direction, which was statistically significant but was only 23% of the movement associated with quiet breathing. Their findings did not support the hypothesis that the reduction of lung volume on induction of anaesthesia is caused solely by the movement of the diaphragm. The movement of the diaphragm has been extensively studied under spontaneous and controlled ventilation systems. The general pattern of diaphragmatic displacement was unchanged by increased depth of anesthesia. Controlled ventilation altered the pattern of diaphragmatic displacement. Diaphragmatic displacement and regional volume changes were a function of active contraction or passive movement.

Krayer et al11 found that the motion of the diaphragm was different in the prone vs supine position. In the supine position, movement was greatest in the dependant portion (crural) similar to Froese’s study, while in the prone position, movement was greatest in the costal portion which was now dependant. Hence they concluded that the abdomen does not behave like a fluid-filled container or water column with a hydrostatic gradient, and there must be other factors besides an abdominal hydrostatic gradient to account for regional differences in diaphragmatic movement in the supine position.

Krayer also showed that during anesthesia-paralysis and IPPV, the movement of the diaphragm was variable in different patients, and often piston-like, i.e. the displacement is equal at all levels, not only at large tidal volumes.

COPD, ANESTHESIA AND THE DIAPHRAGMDoes COPD protect against this

cephalad shift? It has been found that the dorsal atelectasis found during induction of anesthesia may not be present in patients with COPD. Is this due to the flattened diaphragm not being able to move cephalad in the supine position?

Patients with COPD have profound chest wall and diaphragmatic abnormalities; does this difference lead to altered motion of the diaphragm under anesthesia and paralysis compared to patients with normal lungs?



Posterior

Fig 4. Diagrammatic representation of scheme used to quantify changes in the pattern of chest wall motion. A mid- sagittal section of the thorax is shown, with end-expiratory (solid lines) and end-inspiratory (dashed lines) positions of the chest wall depicted. Stippled areas indicate edge views of planes used to quantify changes in transverse rib cage area and average diaphragm motion. The arrow indicates the cephalad extent of the area of apposition at end expiration.

Fig. 5. Diaphragmatic excursion from control patient. End-inspiratory video frame has been digitally pasted on video frame of diaphragm at functional residual capacity (FRC) position. Diaphragmatic borders are graphically enhanced.Stippled outline represents end inspiration; thick black line is diaphragm at FRC position. Area between stippled

outline and thick black line represents diaphragmatic displacement. A, Spontaneous breathing, baseline tidal volume. B, Spontaneous breathing, large tidal volume. C, Positive pressure ventilation, baseline tidal volume. D, Positive pressure ventilation, large tidal volume. Note greater excursion in nondependent segments as contrasted with spontaneous breaths; A versus C. These findings are similar to Froese and Bryan

Fig. 6. Diaphragmatic excursion from chronic obstructive pulmonary disease (COPD) patient. Sequence the same as in figure 1. Note similar pattern of diaphragmatic excursion to control subjects, particularly comparing A versus C. Profound respiratory muscle mechanical changes occur in the patient with COPD, especially anatomical flattening of the diaphragm. This should put the patient at a mechanical disadvantage, but surprisingly, contractile function is well preserved. This could be due to length adaptation, where if a muscle is shortened its contraction is diminished, but after a while, adaptation occurs, and it is able to generate the same force at shorter lengths



Kleinman et al12 have shown the remarkable similarity in the shape of the diaphragm in normal and COPD patients under anesthesia.

It was once believed that the greater displacement of the dependant part of the diaphragm under spontaneous ventilation was due to the more curved and stretched portion developing greater force under Laplace law (the smaller the radius of curvature, the greater the contraction and the displacement).

This is an oversimplification as the diaphragm is not one muscle but has crural and costal segments that have different force-length relationships. Crural and costal segments do not exhibit the same relationship to resting fibre length at FRC, nor the same shape of the length- tension curves, nor the same compliances. The diaphragm is not a uniform muscle and we cannot ignore anatomical differences within the diaphragm. We can no longer think of the diaphragm as a single sheet of muscle that contracts and relaxes as a unit, but rather as two distinct muscles with differential function.In fact the diaphragm is like a geodesic dome, with multiple fractions. Domes have been around for centuries. What makes geodesic domes different?

Efficiency. A sphere is already efficient: it encloses the most volume with the least surface. Thus, any dome that is a portion of a sphere has the least surface.

Fig 7. A geodesic dome

A geodesic dome uses a pattern of selfbracing triangles in a pattern that gives maximum structural advantage, thus theoretically using the least material possible. (A “geodesic” line on a sphere is the shortest distance between any two points.) One of the benefits of a geodesic dome is that it is made of triangles. Triangular structures can not deform without deforming the edges, unlike parallelepipeds or other structures based on polygons with more than 3 edges. For example, a triangle can not be squashed, but a rectangle can be squashed into a parallelogram just by changes in angles at the vertices. The idea behind geodesics is to exploit geometry to obtain greater structural integrity.

The crural and costal segments may in fact function as two distinct muscles, that may have different orientations to the chest wall. The muscle bundles of the diaphragm lie along curved lines, and the curvature of the muscle bundles is orthogonal to the tangent plane of the surface at every point along the bundle.

Fig 8. Mathematical construct of the diaphragm

Combination of fibres that lie along lines of principle curvature and geodesics CE crural fibres AC costal fibres

This is the defining property of the geodesic, and by virtue of this curvature, muscle tension is transformed into transdiaphragmatic pressure (Pdi). For a given muscle tension, the Pdi is maximum when the muscle bundles lie along geodesics and lines of maximum curvature. A curved muscle exerts a net force per unit length in the direction of its curvature, and the magnitude of the force is proportional to its curvature. Thus



the contribution of this force to transdiaphragmatic pressure is maximal if the muscle bundle lies along a line of maximum curvature, and the direction of its curvature is normal to the surface. Since the line of muscle bundle is a geodesic, there is no distortion of the surface during 2contraction. This is especially so in the zone of apposition to the ribs, where the Pdi must change the diaphragm shape to conform to the shape of the chest wall.

There is a configurational difference between costal and crural parts of the diaphragm that is independent of the contractile state. The distribution of muscle tension in the diaphragm is a result of its shape, and failure to develop an adequate Pdi could be due to either loss of either tension or curvature.

The muscles of the diaphragm shorten significantly as lung volume increases, and active muscle tension decreases with decreasing length.It would also seem likely that diaphragmatic curvature decreases as the diaphragm descends. In patients with emphysema and hyperexpanded lungs, the diaphragm descends and lateral Xrays show the curvature to be less than normal. The rib cage is also expanded in COPD and this leads to reduced Pdi and reduced range of shortening.

The diaphragm is relaxed at FRC and strectced at low lung volumes. At lung volumes above FRC the shape of the passive diaphragm is determined by the shapes and elastances of the lung, abdominal contents and abdominal wall. Pdi (transdiaphragmatic pressure) is the difference between the pleural pressure and the abdominal pressure, and in practice, between the esophageal pressure (Pes) and the gastric pressure (Pga).

The diaphragm is the only muscle which on contracting simultaneously lowers Pes and increases Pga, and Pdi is the result of diaphragmatic contraction.

DIAPHRAGMATIC PARALYSISThe physiological effects of

diaphragmatic paralysis are influenced by

pulmonary disease, the severity of paralysis and the age of the patient. The most frequently noted abnormality with respiratory muscle weakness, is a reduction in vital capacity, (both inspiratory and expiratory muscle weakness). The most important distinction is whether the paralysis is unilateral or bilateral. Unilateral paralysis is seen after interscalene brachial plexus block, causing a 25% reduction in vital capacity and forced expiratory volume in 1 second. This could be deleterious in patients with poor lung function. Unilateral paralysis could be devastating in infants who would need ventilatory support until the diaphragmatic function is restored or surgical plication is performed.

In patients with isolated or disproportionate bilateral diaphragmatic weakness or paralysis, the vital capacity shows a marked fall in the supine compared to the erect posture because of action of gravitational forces on the abdominal contents. In some patients the postural fall may exceed 50%. In most normal subjects, the VC in the supine position is 5-10% less than in the erect posture, and a fall of 30% or more is associated with severe diaphragmatic weakness. For such patients, phrenic nerve pacing can be performed, as long as there is no obstructive airways disease or decreased lung compliance.

FATIGUEAbnormal patterns of thoracoabdominal

breathing may signify fatigue.a)increased variability in preponderance of thoracic vs abdominal breaths alternating with each other. Some breaths are characterized by clear ribcage preponderance and others with abdominal muscle preponderance. This pattern reflects alternate recruitment of inspiratory rib cage muscles and of the diaphragm.b)frank paradoxical movement of the abdominal muscles..ie inward movement of the abdominal wall during inspiration. Abdominal paradox indicates weak, absent or inefficient contraction of the diaphragm.

These two patterns can be seen in patients showing diaphragmatic fatigue and consequent failure of weaning from mechanical ventilation.



EFFECTS OF EPIDURAL ANESTHESIAHigh spinal and epidural anesthesia may

have effects on the diaphragm which are similar to the patient with spinal injury and quadriparesis.

Diaphragmatic function is not affected in spite of intercostal muscle paralysis, and ventilation and gas exchange are not compromised.

Fig 9. Inspiratory change in the internal transverse cross- sectional area of the thorax as a function of distance from the lung apex in patients during intact breathing and high epidural anesthesia. Arrows denote the cephalad extent of the area of apposition.

DIAPHRAGMATIC DYSFUNCTION AFTER SURGERY

This is common after upper abdominal surgery, especially cholecystectomy, either open or laparoscopic. Hence, the dysfunction is not due to pain or splinting, but due to afferent inhibition of phrenic nerve activity. This reduction in diaphragmatic excursion can be abolished by epidural analgesia which blocks the afferent loop.

Diaphragematic Dysfunction in the ICUProlonged mechanical ventilation results

in depression of the contractile function of the diaphragm, presumably due to intrinsic changes in the muscle fibres. However, there are no human studies to prove this beyond doubt.Patients with rapid shallow breathing are difficult to wean. One of the reasons could be incomplete relaxation of the diaphragm. This is a little explored area, and giving the diaphragm adequate time for complete relaxation is important for two reasons:a) this allows the muscle to return to its original length which would result in optimal contractionb) most of the blood supply to the diaphragm occurs during the relaxation phase.

Hypophosphatemia results in poor contractile function, and difficult to wean patients.Theophylline, on the other hand, given as an infusion for seven days, improves contractile function for 30 days. The clinical implications are unclear.

The functions of the diaphragm are diverse and varied, and are still unraveling. Small wonder then, thet Froese termed it “an elusive muscle”.

REFERENCES1. Pascucci RC et al: Chest wall motion of infants during spinal anesthesia Journal of Applied Physiology 1990; 68:2087-91

2. Danzker DR et al: Surgery to reduce lung volume. NEJM 1996; 334: 1128-9

3. Geddes D et al: Effects of Lung Volume Reduction Surgery in Patients with Severe Emphysema. NEJM 2000; 343:239-45

4. Sinderby C et al: Diaphragm activation during exercise in Chronic Obstructive Lung Disease. American Journal of Respiratory and Critical Care Medicine2001; 163:1637-41.

5. Polkey Ml et al: Exhaustive Treadmill Exercise does not



reduce twitch transdiaphragmatic pressure in patients with COPD. American Journal of Respiratory and Critical Care Medicine 1995; 152:959-64.

6. Fessler HE et al: Lung volume reduction surgery: is less really more? Am J Respir Crit Care Med 1999; 159:1031- 1035.

7. Hedenstierna G et al : Functional Residual Capacity, thoracoabdominal dimensions, and central blood volume during general anesthesia with muscle paralysis and mechanical ventilation. Anesthesiology 1985; 62:247-54

8. Froese AB, Bryan AC: Effects of anesthesia and paralysis on diaphragmatic mechanics in man. Anesthesiology 1974; 41:242-55

9.. Reber A, Nylund U, Hedenstierna G. Position and shape

of the diaphragm: implications for atelectasis formation. Anaesthesia. 1998 Nov;53(11): 1054-61.

10. Drummond GB et al: Changes in diaphragmatic position in association with the induction of anaesthesia. Br J Anaesth. 1986 Nov;58(11):1246-51.

11. Krayeretal: Position and motion of the human diaphragm during anesthesia-paralysis. Anesthesiology 1989;70:891- 98

12. Kleinman BS, Frey K, VanDrunen M, Sheikh T, DiPinto D, Mason R, Smith T.Motion of the diaphragm in patients with chronic obstructive pulmonary disease while spontaneously breathing versus during positive pressure breathing after anesthesia and neuromuscular blockade.Anesthesiology. 2002 Aug;97(2):298-305.


Management of a brain dead organ donor 59 Joseph Rajesh

INTRODUCTIONIn the past few years, much attention

has been focussed on brain death and artificial support of the organs secondary to catastrophic brain injury. Although brainstem death is irreversible, the ability to recover transplantable organs exists only because the technological advances in intensive care can maintain physiologic homeostasis till the inevitable occurs.

Therapy provided for patients with brain injury is mainly directed towards preservation and restoration of neuronal function. When this becomes unsuccessful the patient may go for brainstem death. The critical care physician thus has the responsibility to offer the patient’s family the opportunity to donate organs and the obligation to unknown recipients to provide the best probable organs.

The recovery of viable organs and successful transplantation are dependent on early and appropriate medical management and timely intervention before and after brain death is declared. This is because, even with intensive support, brain dead donors can be maintained only for a short time, before the pathophysiologic changes induced by brain death overwhelm the resuscitative measures.

The issues related with identification of brain dead donors, criteria for brain death, managing these brain dead donors in the ICU and during the operative period would be discussed here.

THE CONCEPT OF BRAIN DEATHBrain death represents the death of the

organism and not the death or necrosis of the brain in the living body. The organism is an

aggregation of living cells, but it can be said that, the organism exists only when this aggregation is put under the control of some modulating or regulating systems such as the central nervous system, endocrine system, immune system etc. Once any of these fail to function, death is inevitable unless some artificial measures are taken. Without these systems, organized functioning of these cells as a part of the whole organism ceases.

The clinical diagnosis of brain death is equivalent to irreversible loss of all cortical and brainstem function, manifesting as loss of consciousness, lack of motor response to deep painful stimuli, and absence of brainstem reflexes.

THE MECHANISMS OF BRAIN DEATHThe aetiology of brain injury may be

secondary to many things like trauma, cerebrovascular accident or generalized hypoxia, but the ultimate mechanism that produces the change is brain oedema. This oedema can be either vasogenic or cytotoxic in nature.

Vasogenic oedema is caused by an increase in vascular permeability after destruction of the blood brain barrier secondary to release of chemical mediators such as histamine, serotonin, angiotensin and bradykinin. This occurs in hypoxia and ischaemia from the altered cellular osmoregulation, which leads to entry of water into the brain parenchyma.

Brain oedema may be focal initially but later spreads throughout the brain. Since the brain is enclosed in a rigid skull, this is associated with increased intracranial pressure. When the ICP exceeds the arterial pressure, the cerebral circulation ceases and brain death ensues.



NEURO PHYSIOLOGIC BASIS OF THE BRAINDEATHRespiration:

Since the primary respiratory centre, consisting of both inspiratory and expiratory neurons, is located in the reticular core of the medulla oblongata, there will not be any spontaneous respiration. The C02 drive of respiration is lost even when the PaC02 reaches 55-60 mmHg.

Cardiovascular functions:The central neurons that control the

circulatory system are distributed in the pontine and medullary reticular core. During brainstem death, the outflow of this system is cut off and results in various haemodynamic alterations in the body.

Regulation of body temperature:The heat sensitive centre in the

hypothalamus regulates the body temperature. In brain death, the neural connection between this temperature regulating centre and the peripheral tissues is lost and the patient becomes poikilothermic.

PATHOPHYSIOLOGICAL CHANGES ASSOCIATED WITH BRAIN-STEM DEATH

The sequence of haemodynamic, metabolic and endocrine changes associated with brain death is well documented. Acute ischaemia due to sudden rise in intracranial pressure or alteration in blood flow commonly initiates a series of physiological responses. The earliest phase involves a period of parasympathetic predominance leading to bradycardia, idioventricular rhythms, or even a short period of asystole. The subsequent phase is associated with marked hyperactivity of the sympathetic system leading to a catecholamine storm. The near maximal sympathetic drive causes tachycardia, severe hypertension, ECG signs of myocardial ischaemia and frequent ectopics. Autotransfusion occurring due to constriction of venous capacitance vessels will increase the cardiac filling pressures, which when combined with the massive degree of arterial hypertension, leads to high left ventricular wall tension and therefore high myocardial oxygen consumption. On the other hand, the surge in catecholamines will cause coronary spasm thus reducing the

supply. This imbalance in oxygen supply demand ratio may be so severe as to cause myocardial ischaemia even in normal hearts. During the peak of the catecholamine surge, the vasoconstriction may be sufficiently severe to cause acute left ventricular failure due to sudden increase in afterload.

Once brain death becomes established, many of the changes are reversed. There will be a rapid fall in the level of circulating catecholamines. As a result, the sympathetic tone and SVR will fall and venous capacitance vessels also dilate. Arterial pressures and cardiac filling pressures will thus fall. Heart rate falls to denervated levels.

A few hours following brain stem death, endocrine changes will occur. They are related mainly to the failure of production of hypothalamic release factors and a decline in the production of anterior and posterior pituitary hormones. Failure of production of ADH will cause diabetes insipidus with inappropriate production of large volumes of dilute urine. Circulating levels of cortisol, triiodothyronine and insulin may all fall as release of ACTH, TRH from the pituitary declines.

Thermoregulation is impaired with a progressive fall in the core temperature. This is due to the effects of increased heat loss as a consequence of vasodilatation and in part due to reduced heat production as a result of loss of thyroid and other metabolic hormones.

IDENTIFICATION OF POTENTIAL ORGAN DONORS

The shortage of suitable organs for transplantation is well known to ICU physicians and transplant surgeons, however organs continue to be lost through failure to identify potential donors and tests for brain death. The majority of organ donors will be patients in the ICU who have suffered a catastrophic brain injury that has progressed to brain death. The major causes of severe coma are trauma, CVA, primary intracraniaI tumours and ischaemic brain injury.

CERTIFICATION OF BRAIN DEATHCertification of brain death is an absolute

requirement prior to retrieval of organs for transplantation. Clinical diagnosis of brain stem



death involves three steps.1. Ascertaining that certain preconditions have

been met.2. Ensuring that reversible cause of nonfunc

tioning brainstem have been excluded.3. Establishing that the comatose patient is

genuinely apnoeic and that the brain stem reflexes are absent.

Preconditions:The patient must be comatose and on a

ventilator. The cause of coma must be firmly established. The duration for subjecting the patient for brain stem death tests vary from case to case as shown in Table 1. §

Exclusions:Certain conditions can mimic brain stem

eath and hence these conditions should be excluded before subjecting the comatose patient for brainstrem fuction testing. Hypothermia (<320). shock, drug intoxication, (anasthetic agents, muscle relaxants, barbiturates, diazepam, high dose bretylium, alcohol amitryptilline), severe metabolic derangements, neurological syndromes like locked - in syndrome, GBS, encephalopathies, of hepatic failure, uraemia, and hyperosmolar coma all can lead on to misdiagnosis of brain death if not tested carefully.

Hypothermia causes loss of brainstem reflexes and pupillary dilation. The response to light is lost at core temperatures of 28-32°C and brainstem reflexes disappear when the temperature drops below 28°C.

When ingested in large quantities, many drugs can cause partial loss of brain stem

reflexes. Clinical diagnosis of brain death should be allowed if drug levels are below the therapeutic range. A reasonable approach is as follows. If the presence of the particular poison is known and the substance cannot be quantified, the patient should be observed for a period of four times the elimination half-life of the substance. If the particular drug is not known, but a high suspicion persists, the patient should be observed for 48 hrs to determine whether change in brain stem reflexes occur, and if no change is observed a confirmatory test should be performed.

Clinical testing:BRAINSTEM REFLEXES:• NO PUPILLARY RESPONSE TO LIGHT:

The pupils are not invariably dilated when the brain stem is dead; this may be because of spinal sympathetic (pupillodilator) centre. The important point is that there should be no pupillary response to really bright light, because this reaction is mediated exclusively by the brainstem. It is advisable to darken the room for this test and use proper medical torches with new batteries.

• NO CORNEAL REFLEXES:When brainstem death is suspected,

much firmer pressure is justified than in conscious patients.

• NO VESTIBULO-OCULAR REFLEXES:The caloric tests require wax free external

auditory canals. The UK code recommends irrigation of 20 ml of ice-cold saline on both sides. The stimulus should elicit no movement

Apnoeic coma caused by Time to testing (Hrs)Major intracranial surgery, Second subarachnoid bleed in a patient with angiographically proven aneurysm 4Spontaneous intracranial haemorrhage (without hypoxic brain damage from respiratory arrest) >6Head injury (Without secondary brain damage from hypoxia, intracranial haematoma or shock) 6-12Brain hypoxia (respiratory obstruction, drowning, cerebral hypoperfusion) 12-24Any of the above (when additional drug intoxication suspected and no screening faciliti as available) 50-100Table 1 Duration for subjecting the patient to tests.



whatsoever in either eye within one minute of completion of the test. In deeply unconscious patients with some residual brainstem function, the eye will be deviated towards the irrigated ear.

• NO MOTOR RESPONSE:No motor response should be present

within the cranial nerve distribution, to adequate stimulation of any somatic area.

There should be no grimacing in response to painful stimuli, applied either to the trigeminal fields (firm supraorbital pressure) or to the limbs (the side of a pencil pressed firmly down against the patient’s fingernail or toenail is the most appropriate stimulus). Pinprick should not be used.

•NO GAG REFLEX, OR REFLEX RESPONSE TO BRONCHIAL STIMULATION BY A SUCTION CATHETER.

• THE OCULOCEPHALIC REFLEXThis is best elicited by fast and vigorous

turning of the head from the middle position to 90°on both sides. Normally, the eye deviates to the opposite side. This movement, along with vertical and horizontal eye movements, must be absent in the brain dead.

• NO RESPONSE TO A TROPINEFailure of heart rate to increase > 5 beats

after 1 -2 mg of atropine IV denotes the absent function of vagus nuclei.

• APNOEAApnoea is confirmed by showing no

respiratory movements during disconnection from the ventilator for long enough to ensure that the arterial C02 tension rises to a level of 60mmHg, capable of driving any respiratory centre neurons that may still be alive.

Method of testingHypoxia is prevented by a combination of

preoxygenation and diffuse oxygenation. If the patient is made to breathe 100% oxygen for 10 mts, very high starting levels of arterial oxygen tension are achieved. It is reinforced with the endotracheal delivery of 02 by a catheter (at 61 /mt.) As a result of endogenous metabolism, PaC02will rise by 2 - 3 mmHg/mt. Provided the

starting PaC02 was 30mmHg; the crucial level of 60mmHg will be achieved within 10 mts. This method is simple and free of complications. If events such as hypotension or cardiac arrhythmias occur, they may be due to failure to provide an adequate source of oxygen or lack of preoxygenation. One should look closely for respiratory movements. When in doubt, a spirometer can be attached to confirm the tidal volumes. Apnoea testing by carbondioxide augmentation is less acceptable and potentially dangerous.

ANCILLARY TESTSSome ancillary tests are adopted when

applying the criteria for brain death and should be used in conjunction with proper clinical judgement. These tests are needed for patients in whom specific components of clinical testing cannot be reliably evaluated as in infants.

• TO EVALUATE THE NEURONAL FUNCTION

• Electroencephalography;A flat EEG may indicate irreversible

dysfunction of the cerebrum. In brain death, the recording of isoelectric EEGs should be carried out over 60 mts, and no electrical activity having an amplitude of more than 2 -3 mv should be recorded. However the criteria for brain death clearly indicates that EEG results are not necessary for the diagnosis of brain death.

• TO EVALUATE THE INTRACRANIAL BLOOD FLOW.

• Cerebral angiographyThis selective four-vessel angiography has

some usefulness in distinguishing certain comatose conditions from brainstem death. This is regularly in practice in Scandinavian countries. Here an iodinated contrast medium is injected under high pressure in both the anterior and the posterior circulations. Intracerebral filling is absent in brain death. Since there are no specific guidelines for interpretation, the results can be conflicting.

Isotope AngiographyRapid intravenous injection of serum albumin

labelled with 99mTc is done with imaging by a gamma camera. There will not be any intracranial activity in the brain dead patient.



Transcranial Doppler Ultrasonography.It is a non-invasive method by which the

velocity of blood flow of intracranial arteries is recorded. Normally blood flows in the same direction during both systole and diastole. After cessation of cerebral blood flow, diastolic flow is initially reversed followed by total loss of perfusion signals. Comparatively, there is huge experience available for this test to other ancillary tests and it can be used in patients who have electroencephalographic activity.

Computed Tomography Simple CT alone does not give any information

regarding the blood flow, but does help in identifying the primary and secondary organic changes. Single photon emission CT, positron emission CT have all been tried with varied success rates in small series of studies.

DECLARATION OF BRAIN DEATHDeclaration of brain death should be done

by a board of medical experts formed by the hospital administration and approved by the government. The UK code now recommends that the tests should be carried out by two medical practitioners who "have expertise in.this field.” One should be the consultant and the other can be either a consultant or a senior resident. When transplantation is planned, neither doctor should be associated with potential recipients. In practice, these doctors can be anaesthetists, neurologists or intensive care physicians.

Practice in various parts of the world differs considerably. Some countries specify the required speciality of the doctors making the diagnosis while others do not.

But all the codes urge that testing should be carried twice. This is to ensure that there has been no error. It ensures that non-functioning of brain stem is not a single finding at one point of time but persisting. The interval period between two testing has been varying in different countries between 3 -6 hrs.

DONOR MAINTENANCEOnce a potential donor is identified and

brain death is certified, medical therapy is directed at maintaining organ function while retrieval is organized. Of primary importance is maintaining adequate tissue oxygenation by the support of

various systems.

Cardiovascular SystemIn brain dead candidates, cardiovascular

instability is inevitable. Hypotension is almost universal and is associated with poor graft function. Other common events encountered are arrhythmias and cardiac arrest, which will become increasingly resistant to therapy with time.

PATHOPHYSIOLOGY:Cause for cardiovascular instability is

multifactorial. It may result from1. The primary (hypoxic) insult leading to brain

death2. Due to the therapy directed at control of

raised ICP3. Physiological changes that result from brain

stem ischaemia and death.4. Direct myocardial contusion resulting in

impaired ventricular function and arrhythmias.

The hypoxic insults severe enough to cause brain death are invariably associated with myocardial damage. The treatment of severe brain injury may include fluid restriction and diuretic therapy, and with the onset of diabetes insipidus, the brain dead patients will become hypovolemic. This will further exacerbate cardiovascular instability. Physiological changes secondary to raised ICP, like hypertension, can cause further structural damage to the heart.

CARDIOVASCULAR SUPPORT:Cardiovascular support is directed at

maintaining tissue perfusion; this requires an adequate cardiac output and tissue perfusion pressure. Immediate therapy is aimed at correcting intravascular fluid depletion with aggressive fluid resuscitation.

Invasive monitoring of arterial and central venous pressure should be instituted if not already in use. In unstable patients, use of a pulmonary artery catheter to monitor cardiac output, PAOP, and SVR is justified. Mean arterial pressure should be maintained at 60 mmHg or greater; CVP up to 15mmHg may be required to achieve this. The choice of resuscitation fluid may be influenced by



measurement of haemoglobin, albumin, electrolyte concentrations, coagulation studies and nature of any ongoing blood or fluid losses. Blood, blood products, colloid and crystalloid solution may all be necessary. In the absence of ongoing blood loss, colloid solution may be necessary, as infusion of large volumes of crystalloid solution in patients with increased capillary permeability, may precipitate pulmonary oedema. If Dl is contributing to fluid depletion, an anti diuretic hormone analogue may be used. In many patients, fluid resuscitation may alone restore the cardiovascular instability; but in some, use of vasopressors may be indicated.

As impaired myocardial contractility is associated with vasodilatation, agents with both inotropic and vasopressor properties may be required. Dopamine is the agent most commonly used. At low doses (2-5 ^g/kg/mt), it may preferentially improve the perfusion of transplantable abdominal organs. At higher doses (5 -20ng/kg/mt), (3 and a adrenergic effects will predominate, p stimulation may be necessary if impaired myocardial function is present, but excessive a stimulation may compromise organ perfusion. If hypotension persists despite adequate fluid resuscitation and low dose dopamine, another vasopressor such as dobutamine may be tried. Obviously the lowest dose of least injurious agent is the preferred approach but may not be possible always. In a few cases, prolonged use of vasopressors may be necessary and in these cases, use of a PA catheter may be indicated to monitor cardiac output and SVR and to titrate the use of vasopressor. The ultimate goal is to achieve a normotensive, euvolemic state. The use of hormonal therapy (triiodothyronine, cortisol and insulin) has been advocated and is still in experimental use.

Arrhythmias are common and found to be occurring in 27 - 56% cases in any form. Common precipitating causes include myocardial damage and electrolyte abnormalities. Diuretic use, inadequately treated Dl and presence of acidosis may further worsen this. Inotropic agents may initiate or worsen this and dose reduction may be necessary. Once these correctable coexisting conditions are treated, arrhythmias can be managed along the conventional lines.

Respiratory systemRespiratory care has aims of ensuring

adequate gas exchange and maintaining the lungs in a suitable condition for transplantation. The lungs of the potential organ donors may be damaged by a variety of processes namely, bronchopneumonia, pulmonary oedema, pulmonary contusion, atelectasis, pneumothoraces, aspiration pneumonitis etc. Trauma may be accompanied by pulmonary contusion and haemopneumothoraces. In a few, this may progress to ARDS. The sympathetic storm accompanying the coning may damage the pulmonary vasculature. As a result, pulmonary interstitial haemorrhages and increased pulmonary capillary permeability may result. All potential organ donors will be apnoeic and mechanically ventilated; they are therefore at risk of barotrauma, atelectasis and infection. Prolonged intubation will result in colonization of pathogenic bacteria.

RESPIRATORY SUPPORTAny delay in optimising the ventilatory

support should be avoided. In those with injured lungs, use of high-inspired oxygen concentration should be avoided. A Pa02 of 80mmHg and above is necessary. The use of PEEP may allow a reduction in FI02, but PEEP of greater than 15 should be avoided. If hyperventilation is employed to control ICP, it should be discontinued once brain death is confirmed and PaC02 should be maintained in the normal range. If this is not possible, moderate hypercarbia can be allowed.

Endocrine issues:Brain death is accompanied by a

number of endocrine abnormalities. Loss of central sympathetic tone results in subnormal levels of circulating catecholamines. The hypothalamus and pituitary are frequently damaged, resulting in reduced or absent secretion of pituitary hormones.

The most frequent manifestation is the development of diabetes insipidus, which is related to inadequate antidiuretic hormone production by the posterior pituitary gland. Urine output may exceed 15 ml/kg/hr; if not adequately treated, it will contribute to hypovolemia, hypotension, and end organ damage. Treatment is either by replacing the



excess urine output with an equal volume of electrolyte solution or administration of antidiuretic hormones.

Treatment with fluid replacement may result in the infusion of large volumes of fluid with rapid swings in serum osmolarity and electrolyte concentrations. This may further cause organ damage and predispose to cardiac arrhythmias. Treatment with an antidiuretic hormone analogue is relatively simple and will result in a reduced incidence of hypotension and better function of transplantable organs. Two antidiuretic hormone analogues are available. Vasopressin has a short duration of action and may be given by intravenous infusion at an initial rate of 1 unit /hr, titrated to maintain urine output at 1-2 ml/kg/hr. A potential adverse effect is splanchnic vasoconstriction, which is undesirable in potential liver and kidney donors.

Desmopressin, an analogue, has a long duration of action and causes minimal vasoconstriction. It may be given by subcutaneous, intravascular and intravenous injections or via the endotracheal tube. Intravenous injection of 0.5 to 1 U/hr, is required to control urine output and gives the most predictable response. However, in excess doses it can produce ATN.

Reduction in hepatic blood flow, and increased sensitivity to catecholamines occur and catecholamine doses should be titrated when DDAVP is used. Hyperglycemia is a common complication of Dl and is treated with insulin infusion.

Serum levels of tri-iodothyronine, insulin and cortisol are low in animal models and triiodothyronine administration improves the haemodynamic stability by maintaining myocardial stores of energy and glycogen; however, the beneficial role of this is still unclear in clinical settings.

CoagulopathyDIC may be seen in up to 28% of the

brain dead patients and 80% of head injury donors. This is probably due to the release of thrombolysins from the necrotic or ischaemic tissues. Aggressive treatment with appropriate blood products may stabilize the condition.

HypothermiaHypothermia occurs in up to 54% of the

patients. This is due to the reduction in heat production and increased heat loss due to vasodilatation. Prior hypothermia must be corrected to allow certification of death. It can be treated by warming the intravenous fluids, gases and by using blankets. Correction of hypothermia will also improve the stability of the cardiovascular system.

Infection:Infection is another common problem

encountered in the management of brain dead patients. Common sources of infections are invasive lines and airway instruments. Delay in the certification and organ retrieval will increase the bacterial colonization and cause active infection. Avoiding such delay and following scrupulous aseptic techniques are required to prevent infection that could result in poor graft function.

TREATMENT IMPLICATIONS1. Minimize crystalloid administration except

where mandatory for the administration of drugs (unless serum osmolality exceeds 350 mOsm/Kg).

2. Treat Dl with DDAVP rather than fluid replacement.

3. Maintain circulating volume with colloid solutions as available. A target CVP of 5 - 10 cmH20 is appropriate for most cases.

4. Transfusion of blood may be required to maintain haemoglobin concentration between 9-11 g/dl.

5. Vasoactive drugs should be chosen carefully and used judicially to avoid vasoconstriction and possible ischaemic damage to donor organs.

6. Inotropic support, if already instituted, may be slowly reduced if mean arterial pressures are above 60 -70 mmHg.

7. Lung ventilation should be aimed at maintaining a normal PaC02 and Pa02. PEEP values up to 5 -10 cmH20 can be applied, provided that haemodynamic disturbances are not severe.

8. A FI02of 0.6 is ideal.9. Physiotherapy of the chest including

bronchial toileting should be done aggressively.

10. Complete aseotic techniques should be



followed for airway and vascular procedures.11. Chest radiography and blood gas and

biochemical status should be monitored along the lines of any other ventilated patients

12. Antibiotic therapy should be continued if clinical evidence of infection exists

13. All efforts should be made to maintain the core temperature within normal limits like infusing warmed fluids, using HMV filters, blankets etc.

14. Near normal acid base status and electrolytes especially serum potassium and glucose should be maintained within normal limits.

ORGAN SPECIFIC CONSIDERATIONS: • Kidney:

Using Hydroxyethyl starch as a volume expander during resuscitation produces nephrosis like osmosis in the renal tubules, which is associated with greater dialysis requirements in the recipient.

Mean dopamine infusion >7.5 jig/kg/mt seems to be associated with delayed graft functioning.

Low levels of vasopressin are associated with oliguria in the recipient. In some centres, routine vasopressin estimation and prophylactic vasopressin administration is performed.

Donor pre-treatment with IV lignocaine prior to kidney procurement leads to decreased incidence of dialysis and earlier return of kidney function. This is probably secondary to vasodilatory, platelet disaggregating, and Ca channel blocking properties of the drug.

• Liver:A multivariate analysis shows poor initial

graft function seen in donors with1. High levels of alanine transaminase2. ICU stay > 3 days.3. High glucose levels.

PancreasGraft survival rate is inversely

proportionate to the duration of brain death prior to organ procurement.

Pancreas islet cell yield is higher if the donor blood glucose level is at least 120 mg%

without hypotension.

CONTRAINDICATION TO DONOR ACCEPTANCE:

Extracerebral malignancy (except localskin neoplasm, Ca. Cervix in situ)Uncontrolled sepsisActive viral infectionHepatitis A or BCytomegalovirusHerpes simplexAIDS - The presence of HIV antibody is also a contraindication.

When possible hepatitis C - positive donor may be used in a hepatitis C - positive recipient.

CRITERIA FOR INDIVIDUAL ORGANS TO BE ACCEPTABLE FOR TRANSPLANTATION:

Due to the shortage of suitable organs and the increasing success of transplantation, the current trend is to accept the organs that would previously have been considered unsuitable. But the ultimate responsibility for accepting or rejecting a potential donor lies with the transplant surgeon.

Kidneys:• Age<70 years• Adequate renal perfusion• Adequate urine output (Not an

absolute requirement)Liver:

• Age<65 years• Organ size compatible with potential

donor• Haemodynamic stability• No history of alcohol abuse or

hypertensionHeart:

• Age <50 years• Organ size compatible with potential

recipient

• Haemodynamic stability- No prolonged cardiac arrest (not

an absolute requirement)- Cardiac index > 2.5L/m2/mt with- PCWP upto12 cmH20- SVR 500 - 1200 dyne.sec/cm5

- Inotropic support <5mgm/kg/mt.



- <50% discrepancy between left and right heart filling pressures in the face of abnormal PVR

- No ECG evidence of infarctionLungs:

Age < 50 yearsOrgan size compatible withpotential recipientNo history of chronic lungdiseasesNon smoker (not an absolute requirement)Pa02 >250 mmHg with FI02 0.6 PEEP 10cm H20(max)

ANAESTHETIC MANAGEMENT OF A BRAIN DEAD PATIENT FOR MULTIPLE ORGAN HARVESTING In the operating theatre:

Optimal donor management remains important when the donor is taken to the operating room for organ retrieval. The same principles apply to the intraoperative setting also. Maintaining homeostasis with good haemodynamic stability and good diuresis is the key for successful organ recovery.

GOAL:To avoid ischaemic organ damage by

optimising perfusion and maintaining homeostasis.

PRE ANESTHETIC EVALUATION:It includes review of medical and surgical

histories including the cause of the brain death, haemodynamic stability, ventilatory status, acid base and electrolyte values and other organ functions and various investigations.

INTRAOPERATIVE CARE:It is essentially similar to that of other

critically ill patients undergoing major surgery although management of pathophysiologic changes unique to the donor should be clearly understood.

GENERAL PRECAUTIONS:The OR should be kept warm with the

availability of warming blankets and warmed intravenous fluids. A large volume of crystalloids, colloids, blood and blood products should be made available.

MONITORS:The monitors should include ECG,

Invasive arterial pressure monitoring, Central venous pressure monitoring, oxygen saturation, EtC02, temperature and urinary output.

The donor is positioned on the operating table and ventilation continued with a high tidal volume to achieve a PaC02 that is within the normal range. It is necessary that all infusions and monitors be connected before any surgical incision is placed. General anaesthetic agents are required to blunt sympathetic responses during surgery. Mass reflex is caused by neurogenic vasoconstriction and stimulation of adrenal medulla by the spinal reflex arc and will be manifested as tachycardia, perspiration and involuntary movements, which include arm and hand movements, hence at times muscle relaxants may also be necessary.

Isoflurane is the agent of choice because the degree of myocardial depression is less than other agents, halothane is avoided ,in liver donors, and enflurane is better avoided in kidney donors.

POSITIONING OF VASCULAR LINES:The surgical procedure for thoracotomy

in case of retrieving the thoracic organs may involve early ligation of the left innominate vein and the right subclavian artery. A peripheral arterial line must be started on the left arm either in the radial, ulnar, or brachial artery. Placing the arterial lines in the other areas should be avoided since the ability to measure arterial pressure and sample the blood will be lost at critical times of the procedure.

Venous access and Swan - Ganz is provided by multiple cannulation of the right IJV. The ability to monitor CVP or infusing large volume will be lost, once the left innominate vein is ligated. In the majority of the centres, the Swan - Ganz sheath and triple lumen catheter are inserted separately in the IJV. This approach permits the measurement of CVP, infusion of inotropes, administration of hormone replacement, rapid volume replacement and sampling ability.

MANAGEMENT OF VENTILATION:Ventilation is continued with large tidal



volumes, using an FI02 of 0.6, achieved by using either oxygen- air or 02-N20.The use of an FI02 of 0.6 provides the maximum 02 content in the blood, to ensure adequate oxygen saturation, while being unlikely to cause 02 toxicity to the donor lungs. In hypothermic donors, mild respiratory alkalosis is preferred to improve tissue perfusion.

HAEMODYNAMIC MONITORINGHaemodynamic monitoring will include,

monitoring direct arterial pressure through an arterial line, continuous CVP and PA pressures via a Swan - Ganz catheter. Inadvertent wedging should be avoided as it can cause possible lung ischaemia in donors. Baseline values of HR, BP, PAP, CVP, and PCWP are recorded. Baseline acid base status and electrolyte estimations are also done.

MANIPULATION OF CIRCULATING VOLUMEThe goal of the circulatory care is to

preserve perfusion of all organs that are to be procured by maintaining the systolic blood pressure between 100 -120 mmHg, with a CVP of less than 10 cmH20 and minimal inotropic support. Hypotension is associated with increased incidence of ATN and non-functioning of the kidneys as well as poor functioning of the liver. Intravascular volume is adjusted with the guidance of CVP. Colloids or RL can be used to manage the fluid deficit. Hypotonic solutions like 5% dextrose should be used to replace insensible losses. This may decrease the requirement of vasopressin. Excessive urine output (>200 ml/ hr) is replaced by hypotonic solutions with replacement of KCI. If hypotension persists even after volume replacement, inotropic support may be initiated, with dopamine as the first choice. Vasopressors like phenylephrine (Alpha stimulants) should be avoided as they cause reduction in splanchnic and coronary blood flow. Severe cases of tachycardia and hypertension caused by mass reflex may be controlled by general anaesthetics, beta blockers or with calcium channel blockers. Arrhythmias (ventricular and supraventricular) are treated with conventional antiarrhythmic agents. If bradycardia is persisting, it should be treated with isoproterenol or epinephrine, because these patients will not show any response to atropine.

In case of cardiac transplantation,

approximately 10% of the blood volume (500ml) is taken under gravity through Swan Ganz into a blood collection bag. This is subsequently used as the major component of the pulmonary preservation solution and this also reduces the left ventricular filling pressure. It is subsequently replaced by 20% albumin to maintain the colloid oncotic pressure of the plasma. Other crystalloid solutions are inappropriate for volume expansion in these situations. Target values for PCWP are between 5and 8 cmH20 and slightly higher values may be used if lung transplantation is not being considered.

Management During SurgeryASSESSMENT OF THE HEART AND LUNGS:

After median sternotomy, macroscopic examination of thoracic organs is done. In particular, evidence of established coronary artery disease in the donor is sought. The visual impression of ventricular wall motion is also noted. The presence of obvious congenital anomalies of the heart is also excluded.

After the heart is examined, both the pleural cavities are widely opened and examination of the lungs is performed. Areas of lobar collapse may be reinflated using controlled manual ventilation under vision and counter compression of normal lung tissue by the surgeon may allow the reexpansion of such collapsed areas and significantly improve the gas exchange. The application of PEEP of 5 - 10 cm of H20 is essential to maintain the FRC and the haemodynamic consequences will be small as the pleura is opened.

HAEMODYNAMIC MANIPULATION:During the abdominal dissection, adrenal

manipulation, both hypertension with periods of hypotension can occur due to catecholamine excess and impaired venous return respectively. During these events, colloid loading, inotropic support and or vasodilatation are adjusted to maintain homeostasis. Although hypertension is best controlled by vasodilators, the resulting tachycardia carries the risk of inducing ischaemia, which will have a deleterious effect on the heart, if transplantation is planned. Although best avoided, the b adrenergic blockers can be used with caution.


of a brain dead organ donor 69 Joseph Rajesh

HYPOTHERMIAHypothermia is seen among 86% of the

brain dead donors due to the loss of hypothalamic function. As the temperature goes below 32 °C, ECG changes like prolonged PR, QT interval and wide QRS complexes are seen. T wave inversion, ST segment depression and decreased threshold for ventricular fibrillation are seen below 28°C. Hypothermia also produces a left shift of the ODC, increase in blood viscosity, a decrease in splanchnic blood flow and glomerular filtration, hyperglycemia, and metabolic and respiratory acidosis. Hence body temperature must be kept within the normal range by keeping the OR warm, by infusing warmed fluids, and by using blankets, warmer etc.

ANTICOAGULATION:Before cannulating any major vessels,

full anticoagulation doses of heparin are administered .The consequences of unrecognised inadequate anticoagulation and thrombosis within the organs during transport would be disastrous.

PHARMACOLOGICAL INTERVENTIONS:Adequate diuresis is important, because

urine output is c prognostic indicator of graft function. Though low dose dopamine may be effective in maintaining adequate renal perfusion and diuresis, high dose may lead to tubular necrosis and non-functioning of the graft. For persistent oliguria, mannitol (0.25 - 0.5 g/kg) and furosemide 40 mg may be used to induce diuresis before division of the renal pedicle and prevent ischaemia induced ATN.

Alpha-adrenergic receptor blockers such as phenoxybenzamine may be useful to produce renal vasodilatation but have a doubtful effect in multiple organ procurement because of their effects on other organs.Some centres recommend broad-spectrum. antibiotics.

ACID BASE & ELECTROLYTE STATUS:Complete haemodynamic profiles,

including arterial and mixed venous acid-base and02 status are made at regular intervals. Estimations of serum electrolytes, especially potassium and glucose are done and supplemented appropriately. Metabolic acidosis caused by inadequate tissue perfusion can

potentially depress the myocardium and is corrected with sodium bicarbonate or THAM.

Electrolyte imbalances (hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia and hypomagnesemia) due to marked fluid shifts in Dl may cause arrhythmias and myocardial dysfunction, and they are treated along the general guidelines.

Once cardioplegia is induced, no further supportive care is needed. After cross clamping of the aorta, mechanical ventilation and monitoring are disconnected and all cannulas are removed.

The sequence of removal of organs is, heart, lungs, liver, pancreas, intestine and kidneys.

SUMMARY:The ICU and its staff play a major role in

solid organ transplantation. The medical care of the donor may be complex and challenging. Delay in certifying brain death and organizing the organ retrieval will make preservation of organ function more difficult and should be avoided at all costs. Much therapy remains empirical and continued research is required to further define optimum management of the donor.

References:1. David.J. Powner, et al Brain Death

definition, Determination and Physiological effects of donor organs, The Text Book of Critical Care, 1894-1899.

2. Eelco F.M. Wijdicks, The Diagnosis of Brain Death: The New England Journal of Medicine, April 2001, Volume 344: 1215 -1221.

3. Finfer. S. R. Support of the Potential Organ Donor; Principles and Practice of Critical Care; 484 - 493.

4. Johnston. K.R. et al, Optimization of Multiorgan Donors and Selection of Thoracic Organs for Transplantation, Principles and Practice of Critical Care; 431-444.

5. Pallis.C, Brain Stem Death: The evolution of a concept. Text book of transplantation (75-100)

6. Ron Shapiro et al, Management of Potential Cadaveric Donor; up to date 10.1 July 2001.

7. Tarek Razek et al, Issues In Potential Organ Donor Management; Surgical Clinics of North America, June 2000 : Volume 80. No.3.

8. William shoemaker, Ake grenvik : Multiple organ Procurement ; Text book of critical care (fourth edition -1910-1923)


Anaesthetic Management of a Morbidly Obese Patient 70 S. Manimala Rao

Obesity means excessive body fat and the term obese is derived from a Latin word that means fattened by eating. The amount of fat tissue is increased to such an extent that mental and physical health is affected and life expectancy is reduced.

Body mass index (BMI) or Quetelet’s index is calculated from subjects’ height and weight. It is used to indicate obesity. Obesity is indicated by BMI > 30.0 (M), > 28.6 (F). Many clinical parameters depict women as pear shaped, accumulating fat at the bottom and this is regarded as safe, fat being stored between the skin and the body wall. In men, we find the classic beer belly look compared to the rounded apple, here the fat is stored in the internal organs. Morbid obesity is when BMI is more than 40 kg/m2.

PREVALENCE AND EPIDEMIOLOGYThere is a slow but steady increase in

obesity. In UK the statistics showed an increase; in 1980 - 6% males and 8% females and in 1987 - 8% males and 12% females were regarded as obese. Obesity in children is also on the rise. Prevalence varies with the socioeconomic status. In developed countries, poverty is associated with a greater prevalence whereas in developing countries, there is a higher prevalence amongst the affluent. Obesity is complex, wherein the net energy intake exceeds the net energy expenditure over a prolonged period of time.

PATHOPHYSIOLOGYThe brain controls the appetite by means

of signals triggered by dietary breakdown products and also by autonomic signals produced by disturbance of the stomach and intestines.

The multiple signals generated are processed by complex interactions between neuronal networks and neuro transmitters. Most important of them are cholecystokines 8 (CCK 8), which act at the gut and the brain. It induces satiation, is released at the beginning of a meal and promotes pancreatic secretion of insulin, which lowers the sugar and increases the appetite. Insulin crosses the blood brain barrier and triggers the hypothalamus, which juggles many other signals. Therefore, the complexity of weight maintenance is evident. 25-30% of human variations in BMI are genetic and the rest is due to environmental factors. It is a complex picture as to how normal weight is maintained. The pathways regulating weight form a series of redundant regulatory loops. If one is weakened or attenuated, the other can take over. It is this redundancy that regulates calorie storage, but the same redundancy makes it hard to get a handle on how to prevent and treat obesity. It is an imbalance between food intake and energy expenditure. The balancing act involves neural signaling and endocrinal processes. These can be both central and peripheral. Problems can occur any where in this complex system.

GENETIC PREDISPOSITIONObesity tends to be familial. Children of

two obese parents have a 70% chance to become obese. The genetic issues account for 30% and are linked to at least 6 genes. 70% is dependent on environmental factors. Genetic susceptibility may predispose to environmental issues.

ETHNIC INFLUENCESIn USA, the African Americans and

Mexicans have a higher rate of obesity than the Whites. Asian migrates have a more central



distribution of fat associated with increased risk of diabetes and coronary artery disease.

MEDICAL DISEASESCushing’s disease, hypothyroidism,

medications like steroids, antidepressants and antihistamines may also lead to obesity.

RISK FACTORSMale gender, middle age, night sedation,

evening alcohol can all compound the problem. Other features which can help identify are BMI > 30 kg/m2, hypertension, observed episodes of apneoea during sleep, hypoxemia, hypercapnia, changes in ECG and ECHO. Definite diagnosis is made by polysomnography in the sleep laboratory. The obese pose great challenges to surgery, anaesthesia, obstetrics, trauma and in the ICU.

Diabetes, hypertension, hyperlipidemia, heart diseases, increased rates of colon and breast cancer, asthma are all linked to rising levels of obesity. A BMI>29 kg/m2 increases the prevalence of pulmonary embolism. The risk of coronary artery disease is doubled if BMI is > 25kg/m2. A BMI of 35kg/m2 leads to a 40-fold increase in developing diabetes, respiratory diseases, sleep apnoea and osteoarthritis. The risk of death increases with body weight. Mortality rises exponentially with increasing body weight.

CHANGES IN VARIOUS SYSTEMS OBESITY AND RESPIRATORY SYSTEM

5% of morbidly obese will have Obstructive Sleep Apnoea (OSA), frequent episodes of apnoea or hypercapnia, snoring and daytime sleepiness. Recurrent apnoea leads to hypoxia, hypercapnia, pulmonary and systemic vascular hypertension, which in turn leads to right ventricle failure. Loss of pharyngeal muscle tone and significant narrowing of airway increases airflow turbulence.

Acid base disturbances of Obstructive Sleep Apnoea (OSA)

Respiratory acidosis is limited to sleep, in the beginning. The longer the problem, alterations occur in breathing patterns with desensitization of the respiratory center to hypercapnia leading to type II respiratory failure.

This leads to increased dependence on the hypoxic drive for ventilation - Pickwickian syndrome, which is characterized by obesity, hypersomnolence, hypoxia, hypercapnia, right ventricular failure and polycythemia.

AirwayPerfect airway, particularly upper is

essential before any anaesthetic management. In obese patients, difficulties are encountered for mask ventilation; tracheal intubations may be difficult. The percentage of difficult intubation is quoted to be 13%. Excessive fat at the upper airway, short neck, high anteriorly placed larynx and restricted cervical spine movements are a few problems.

Obesity and gas exchangeIncreased mass of abdominal and

thoracic contents alters the lung volumes. Decrease in functional residual capacity (FRC) is seen exponentially with increasing BMI. Expiratory reserve volume and total lung capacity are decreased.

FRC may be reduced in the upright position to the extent that it falls within the range of the closing capacity with subsequent small airway closure, ventilation perfusion mismatch, right to left shunting and arterial hypoxemia. The reduction of FRC impairs the capacity of obese patients to tolerate apnoea. They desaturate rapidly after induction of anaesthesia despite preoxygenation due to the smaller 02 reservoir and increased oxygen consumption. Residual volume remains normal or slightly increased due to the increased gas trapping and coexisting obstructive airway disease.

02consumption and C02productionBoth are increased in obese patients as

a result of the metabolic activity of excess fat and increased workload on supportive tissues. With exercise, Oz consumption rises more sharply in the obese than in the non-obese.

Gas exchangeOnly a modest defect in gas exchange

is noted in the obese patients with a reduction in Pa02, increase in Aa02gradient and increase in shunt fraction. This is increased markedly with



induction of anaesthesia. PEEP improves the condition, but at the expense of cardiac output and 02 delivery.

Compliance and ResistanceIncreased BMI exponentially decreases

the compliance. As the fat content increases, compliance decreases, but it is also due to a decrease in lung compliance. This is due to the increase in pulmonary blood volume, increased total respiratory resistance and shallow rapid breathing which can limit maximum ventilatory capacity. These are all more marked in the supine position.

Work of breathingThere is a 30% increase observed in the

work of breathing. If hypoventilation occurs in daytime, the work of breathing may approach four times that predicted.

CARDIOVASCULAR SYSTEMA higher incidence of cardiovascular

morbidity is associated with obesity. Mild to moderate hypertension is found in 60-70%, severe in 5-10%. It is the commonest problem followed by ischaemic heart disease. An expansion of extracellular volume resulting in increased blood volume and cardiac output is characteristic of obesity-induced hypertension. The exact mechanism is not known, but an interplay of genetic, hormonal, renal and haemodynamic factors are implicated. Hyperinsulinaemia, activating the sympathetic nervous system and causing sodium retention, increases the pressor norepinephrine and angiotensin II activity. Concentric hypertrophy of the left ventricle leads to cardiac failure. Obesity is an independent risk factor for Ischaemic Heart Disease (IHD) and this is more common in individuals with central obesity. Blood volume is increased, most extra volume being distributed to the fat organ. Splanchnic blood flow is increased by 20%, while renal and cerebral blood flow are normal. A 3- 4mmHg increase in systolic and 2mmHg increase in diastolic pressure is noted for every 10kg increase of weight.

Cardiac arrhythmias can be precipitated in the obese by any number of factors, viz. hypoxia, hypercapnia, electrolyte imbalance,

diuretic therapy or fatty infiltration of the conducting tissue.

Cardiac functionObese patients are at risk of a specific

form of obesity induced cardiac dysfunction. Left ventricular systolic and diastolic functions are affected. Obesity induced cardiomyopathy is well documented. Blood volume is increased and cardiac output increases by 20-30ml/kg of excess body fat. The obese tolerate exercise poorly. Any increase in the cardiac output is by an increase in the heart rate.

OBESITY AND DIABETESType II Diabetes mellitus is an

independent risk factor. The incidence of abnormal glucose tolerance in patients undergoing bariatric surgery is more than 10%.

THROMBOEMBOLIC DISEASEDeep vein thrombosis appears twice as

common in obese patients. It is the commonest complication of bariatric surgery with an incidence of 2.4% - 4.5%. It is due to prolonged immobilization that leads to venous stasis and polycythemia, and increased abdominal pressure with increased pressure on the deep veins. Decreased fibrinolytic activity with increased fibrinogen concentration could also be responsible.

OBESITY AND Gl DISORDERSThe obese have an increased integral

abdominal pressure, a high volume and low pH of gastric contents, delayed gastric emptying and an increased incidence of gastro esophageal reflex. They also have a high risk for aspiration of gastric contents followed by pneumonia. Gastric volume is 75% higher than in normal individuals.

DRUGS, PHARMCODYNAMICS AND KINETICSObesity leads to an alteration in the

distribution, binding and elimination of many drugs. For drugs with narrow therapeutic indices like aminoglycosides and digoxin, toxic reactions can occur if the patients are dosed according to actual body weight. Drug dose should be reduced keeping the lean body mass in view. Absorption of drugs orally remains unchanged in the obese patient.



Volume Of Distribution (VD)The apparent volume of distribution of a

drug in the obese patient is influenced by a number of factors which include, the size of the fat organ, the increase in lean body mass, the increase in blood volume and cardiac output, reduced total body water, alterations in plasma protein binding and lipophilicity of the drug. Highly lipophilic drugs have an increased volume of distribution (Thiopentone). Increase in the volume of distribution will reduce the elimination half-life unless the clearance is increased. Thiopentone, Benzodiazepines, and potent inhalation agents, may persist for a longer time after discontinuation. Regarding protein binding, alterations may occur due to the high levels of cholesterol, inhibiting protein binding; therefore more free drug is available. In contrast, increased concentrations of a acid glycoprotein may increase the degree of protein binding of other drugs (e.g. local anaesthetics), thus reducing the free plasma fraction.

EliminationClearance is mostly reduced in obese

patients. Cardiac failure and decrease in liver blood flow may slow elimination of midazolam and lignocaine. Renal clearance is increased in obesity because of the increased renal blood flow and GFR. If renal impairment is present, elimination takes a longer time.

Hepatic metabolism is altered in obese patients for volatile agents. Reductive metabolism of halothane is more in obese patients. This may be an important factor in liver injury. Nephrotoxicity can occur due to high fluoride concentrations with halothane and enflurane. Sevoflurane has high hepatic metabolism but does not show adverse effects. Isoflurane does not increase fluoride concentration, and remains the agent of choice in the obese.

ANAESTHETIC IMPLICATIONS Preoperative:

Thorough clinical examination is mandatory with excellent and relevant history taking, checking BP with an appropriate sized cuff to identify hypertension and looking for signs of cardiac failure, viz. increase in jugular pulse, added heart sounds, pulmonary crackles, hepato

jugular reflex and peripheral edema. These signs may be difficult to elicit in the morbidly obese. A thorough assessment of the respiratory system for OSA is very essential.

InvestigationsBesides routine investigations, ECG is

mandatory as tachyarrhythmias are common. Echo may be difficult but will provide valuable information regarding eccentric left ventricular hypertrophy. TEE may provide more insight. Cardiological evaluation is beneficial for further investigation. Optimization of blood pressure, treatment of cardiac failure, or if necessary, coronary angioplasty may be suggested. X-ray chest, lung function tests and baseline arterial blood gases may be useful in the morbidly obese. A thorough history regarding respiratory function and sleep apnoea are a must. Signs of right ventricular failure must be looked for.

Airway assessmentIt is mandatory to plan the type of airway

management. A thorough examination can prevent catastrophes, as it will enable us to select the best technique for the patient. Preoperative evaluation of the airway must include:

1. Assessment of the head and neck; flexion, extension and lateral rotation.

2. Assessment of jaw mobility and mouth opening.

3. Inspection of the oropharynx.4. Checking the patency of the nostrils5. Inspection of previous anaesthetic

charts.

If potential airway obstruction is suspected at direct or indirect laryngoscopy, CT scan of soft tissues would be helpful.

Assessment of veins for placing infusion must be done in the preoperative visit. Examination of the feet and back for any ulcer or sore is mandatory. Examination of the calf muscles for any redness or tenderness gives a fairly good idea regarding deep vein thrombosis.

Preoperative medicationAvoid narcotics and sedatives. Avoid

intramuscular and subcutaneous injections. If fibre optic intubation is planned, include an



antisialogogue. All morbidly obese must have acid aspiration prophylaxis. A combination of the H2 blocker, ranitidine 150mg and prokinetic metaclopramide 10mg orally given 12 hrs and 2hrs before surgery will reduce the risk of aspiration. Some anaesthetists prefer to give 30ml of 0.3 M sodium citrate before induction. Continue the normal medications on the day of surgery. Stop ACE inhibitors the day before surgery. Dextrose- Insulin regimen should follow in all diabetics, unless it is a very short surgical procedure. Insulin requirements may increase in the postoperative period. Prophylactic antibiotics are given as per the hospital protocols, after discussion with the surgeon and the microbiologist.

POSITION AND TRANSFERExtra care, special tables and adequate

padding of pressure areas should be provided. Appropriate manpower to shift is mandatory. Compression of inferior vena cava is avoided by lateral tilt or a wedge. Transfer of obese patients is done in their own bed. Special beds are ordered in other countries.

INTRAVENOUS LINESPeripheral lines may be difficult.

Establish central lines in the beginning to avoid calamities. Even these are difficult in the morbidly obese. Doppler or ultrasound guided placements could reduce complications.

MONITORINGIntraarterial blood pressure measurement

is advocated for all but most minor procedures, ECG, Pulse oximetry, Capnography and neuromuscular monitors are essential. Central venous catheters are essential and PA Catheters should be used where indicated.

REGIONAL ANAESTHESIAWhere it is possible and feasible, regional

anaesthesia should be administered. One can reduce the use of opioids, inhalational agents, reduce postoperative complications, and prevent the loss of airway and aspiration. Excellent postoperative analgesia can be given by placing the epidural catheters in the sitting position, using ultrasound for identification of the space. Local anaesthetic requirements are 50-70% reduced in the morbidly obese. Higher blocks are

common. Blocks extending above T5 can cause cardiorespiratory collapse. All resuscitation equipment should be handy.

SYSTEMIC OPIOIDSThese are hazardous in obese patients;

intramuscular route is not recommended. If intravenous route is preferred, patient controlled analgesia should be the best option. Oral analgesics like paracetamol and cox2 inhibitors may be appropriate. Postoperative analgesia with local anaesthetics and opioids via the epidural catheter will provide ideal pain relief with minimal complications.

OBSTETRICS AND MORBIDLY OBESEAll attending complications are

compounded. Regional anaesthesia is a better choice; avoid general anaesthesia as far as possible. Putting an epidural catheter during labor is a better option. Local anaesthetic requirement may be reduced by up to 25% in the obese pregnant state.

OBESE PATIENTS AND TRAUMAThe out come in obese patients with

trauma is poor. The obese patients have more blunt trauma and chest trauma is more compared to head injury. Investigations are more difficult to handle and interpret. They may require earlier respiratory support and higher oxygen concentration.

OBESE PATIENT IN THE ICUIt is held that the outcome is poor for

these patients. Postoperative pulmonary events are more in obese patients. Morbidly obese may present in the emergency room and intensive care with formidable challenges. A better understanding of the pathophysiology and complications may improve the outcome. Anaesthesiologist has a major role to play as the perioperative physician at every level.

BARIATRIC SURGERY The indications for bariatric surgery are as follows:

BMI >40kg/m2

BMI >35kg/m2 with co morbiditiesShould show that dietary attempts have beenineffective



Bariatric surgery (weight reductive surgery) addresses both perioperative care and long-term management. The patients must have a clear understanding of the risks, benefits and complications, and may require life long management strategies.

Types of Bariatric surgeryBariatric surgery comprises two types

namely restrictive and malabsorptive. The common operations include Roux-en-Y grade bypass, vertical banded gastroplasty, bitropancreatic diversion and its variations, various gastric banding procedures, gastric bypass procedures and laparoscopic procedures of the above-mentioned operations.

The preoperative evaluation consists of obesity evaluation, behavioural evaluation, medical evaluation, surgical evaluation, which includes education & potential risk, and anaesthetic evaluation. A team is usually available in other countries for patients with morbid obesity undergoing bariatric surgery.

OBESITY ASSOCIATED -MEDICAL CONDITIONS

The various medical conditions associated with obesity are:

• CAD• Cardiomyopathy• Cerebrovascular disease• Diabetes mellitus and other endocrine

diseases• Infertility

• Hepatobilary disease and gall stones• Malignancies, depression• Degenerative joint disease, chronic back

pain• Respiratory abnormalities• GE reflux• Sudden death

COMPLICATIONSThe complications associated with

bariatric surgery are as follows:• Nutritional deficiencies• Cardiovascular disease and sudden

death

• Pulmonary embolism, which is a leading cause of death

• Bleeding and splenic injury• Gastrointestinal leaks - shown by

tachypnea and tachycardia• Wound infections 1-3%, wound

dehiscence, vomiting and diarrhea• Sternal dilation

The morbidity and mortality has come down for these procedures to <19%.

As we enter the new millennium, severe obesity remains an incurable disease. The consequences and cost to society are significant. Though etiology is becoming more clear, non- surgical treatments are still inadequate for achieving sustained and significant weight loss. Surgical procedures have evolved into safe and effective options. Newer technologies such as laparoscopy should further advance the field. For appropriately selected patients, surgery can achieve the weight loss necessary to prevent the development of significant medical conditions and improve the quality of life. Unfortunately, dietary indiscrimination and malabsorptive eating behaviour can result in weight loss failure despite an excellent surgical result. Therefore, preoperative evaluation and education is a corner stone for long-term success.

CONCLUSIONSMorbidly obese patients can be

encountered more commonly in the West. But with changing lifestyles, a high incidence is now seen in the younger individuals. One may encounter them in the practice of anaesthesia for different types of surgical procedures, bariatric surgeries, trauma and in the ICU setup. They do pose tremendous challenges. Understanding the pathophysiology, anticipating the problem and preventing calamities by a systematic approach will certainly bring down the rate of complications.

REFERENCES

1. J.P.Adams and P.G.Murphy. Obesity in anaesthesia and intensive care. BJA 2000; 85 (1 ):91 -108.

2. Anthony P.Adams, Jereney N Cashnar. Recent Advances in Anaesthesia and Analgesia. Churchill Livingston 2000; Chapter II, Vol 21.


Anaesthetic Management of Patients with Haemoglobinopathies 76 Chandrasekhar

The pathophysiology and points of interest regarding the anaesthetic management including blood transfusion for haemoglobinopathies will be discussed below. These include:

• Thalassemias• Hereditary Spherocytosis• Sickle Cell Anaemias

The most important clinical manifestations of haemoglobinopathies are based on oxygen carrying capacity and adequacy of tissue oxygen delivery owing to either abnormal concentrations as in anaemia, polycythemia or abnormal structures as in sickle cell disease, hereditary spherocytosis and in thalassemia.

management of these disorders both in terms of medical and anaesthetic management.

CALCULATION OF ARTERIAL OXYGEN CONTENT:Ca02 = (Hb x 1.39) Sa02 + Pa02(0.003)

where Ca02 = arterial oxygen content (ml/dl), Hb = haemoglobin (g/dl), 1.39 = oxygen bound to haemoglobin (ml/g), Sa02 = Saturation of haemoglobin with oxygen, Pa02 = arterial partial pressure of oxygen (mm Hg), 0.003 = dissolved oxygen (ml/mm Hg/dl)

Fig. 2 Oxyhaemoglobin dissociation Curve and various factors that shift the curve either way, of importance to

Haemoglobinopathies:

Certain physiological parameters need to be known which are of importance in the

GENERAL GUIDE LINES FOR BLOOD TRANSFUSIONS AND MANAGEMENT OF BLOOD LOSS DURING THE PERIOPERATIVE PERIOD:Haemoglobin Transfusions rarelyconcentration >10 G/dl indicated



Haemoglobin T ransfusions almostConcentrations <6G/dl always indicated,

especially when the anaemia is acute

Haemoglobin Decision to transfuseconcentration 6-1 OG/dl is determined by

patient’s risk for complication from decreased tissue oxygenation (patients with ischaemic heart disease)

Transfusion trigger is not recommended for application in all patients as it ignores physiologic and surgical factors unique to individual patients.

It is advocated to use preoperative autologous donation in selected patients, intraoperative blood salvage and acute normovolemic haemodilution when appropriate.

(3-Thalassemia major (Cooley’s Anaemia):This is more prevalent in Greek and

Italian children. It is an inability to form [3 -Globin chains of haemoglobin. So the result being, the adult haemoglobin A is not formed and anaemia develops during the first year of life, as foetal haemoglobin with two alpha chains and two gamma chains disappears.

BASIS FOR DECISION TO ADMINISTER TRANSFUSIONS PREOPERATIVELY:• Cause of anaemia• Degree of anaemia• Duration of anaemia• intravascular fluid volume• Urgency of surgery• Likelihood of intraoperative blood loss• Age of the patient• Co-existing diseases

Ischaemic heart disease Cerebrovascular disease Peripheral Vascular disease Lung disease

THALASSEMIASA number of inherited disorders

characterized by decreased rates of synthesis or failure to synthesize structurally normal haemoglobin. Severe thalassemia (Thalassemia major) is rare, whereas mild forms of this type of anaemia (Thalassemia minor) are common. Blood transfusion is the only treatment available for thalassemias at the moment.



Fig 4. Pathogenesis of B-Thalassemias.

PRESENTATION PROFILE:Jaundice, hepatosplenomegaly,

susceptibility to infection, cardiac haemochromatosis leading to death, Supra Ventricular cardiac dysrhythmias and congestive heart failure (sensitivity to digitalis).

ANAESTHETIC POINTS OF INTEREST:Overgrowth of maxillae can make

visualization of glottis difficult during laryngoscopy for tracheal intubation

Haemothorax, Spinal cord compression secondary to extramedullary haematopoiesis and destruction of vertebral bodies.

TREATMENT:Hydroxyurea is helpful in some patients

with sickle cell (3-Thalassemia, Bone marrow transplantation may be recommended and splenectomy may be necessary if hypersplenism leads to pancytopenia.

(J-Thalssemia minor:It is a heterozygote state (trait) that

typically results in mild anaemia. Relatively normal RBC count differentiates anaemia from Iron deficiency anaemia. This is more frequently encountered than before. Fig 5. Clinical Photograph of child with B-Thalassemia, Skull

X-ray (hair on end appearance in the outer table, also called crew cut appearance) and compression fracture of the vertebra due to extramedullary haematopoiesis. (from above downwards respectively).

a - Thalassemia:This is due to lack of production of A

chains of adult haemoglobin. Homozygous form is incompatible with life. Heterozygous forms suffer from mild hypochromic and microcytic anaemia. Occasionally they may present for splenectomy to control haemolysis or for blood transfusions to treat anaemia.



SICKLE CELL ANAEMIASickle cell disease is an inherited

disorder that ranges from the usually benign sickle cell trait to the debilitating, often fatal sickle cell anaemia. HbS shifts the oxy haemoglobin dissociation curve to the right, so the oxygen delivery is enhanced with this and a P50 of 31 mm Hg reflects this. Anaemia is relatively well tolerated in these patients but the complications that follow because of sickling are life threatening. Confirmation of the presence of HbS depends on Hb electrophoretic studies.

Pathophysiology:Valine is substituted for glutamic acid

on the p-globin chain resulting in HbS.

When deoxygenated, the HbS has unique property of forming insoluble globin polymers. Sickle cell trait is benign because the cellular concentration of HbS is too low for polymerisation to occur under most conditions, and it is the HbS polymers that cause the cellular injury characteristic of sickle cell disease.

A Pa02 of less than 40 mm Hg can initiate sickling of RBCs in patients who are homozygous for HbS, whereas a Pa02as low as 20 mm Hg is known to produce sickling in patients with sickle cell trait.

Formation of sickling is more extensive in veins than in arteries emphasizing the importance of acidosis.

Increased viscosity, acidosis irrespective of Pa02, decrease in body temperature or exposure to a cold ambient environment favours the sickling by virtue of vasoconstriction. (Fig. 6)

Clinical Presentations.The clinical presentations are due to

haemolysis and blockage of microvasculature with sickle cells. Sometimes the abdominal pain and musculoskeletal pain, which could be excruciating, can mimic surgical emergencies. Aplastic and sequestration crises can make the clinical picture much worse. Infarctive crisis can

be triggered by trauma and infection such as that associated with increased body temperature. Patients experiencing sequestration crises with RBCs landing in the liver and the spleen may become hypovolemic.

Vasoocclusive complications leading to painful episodes can warrant the services of the anaesthetist for pain relief include; stroke, renal insufficiency, liver disease, splenic sequestration, proliferative retinopathy, priapism, spontaneous abortion, leg ulcers, osteonecrosis. Complications related to haemolysis can be anaemia, cholelithiasis, and acute aplastic episodes. Infectious complications secondary to Streptococcus pneumoniae, Escheriae Coli and osteomyelitis, can also occur.

VASO OCCLUSION:This is the single most important

pathophysiologic process that results in most of the acute complications of sickle cell disease. Hb polymerisation is the initial step and follows the ordeal as shown in Fig 6. Once microvascular occlusion ensues, resultant hypoxia causes further sickling and the start of a vicious cycle that results in tissue infarction, release of inflammatory mediators, and pain. Multiple organ system dysfunction produced by infarctive events is the major reason and prolonged survival is unlikely. Cerebral infarction can occur in children and intracranial haemorrhage in adults. Cardiomegaly may be due to CHF secondary to repeated pulmonary emboli. Increased alveolar to arterial differences for oxygen most likely reflect pulmonary infarctive events. Infarctive events in kidneys can lead to papillary necrosis with haematuria, impaired ability to concentrate urine and ensuing renal failure. Chronic cholelithiasis is due to increased loads of bilirubin secondary to haemolysis. Functional hyposplenism due to auto infarction of the spleen occurs as shown in Fig 7. Acute pain crises often accompanied by fever and leukocytosis in the absence of sepsis suggests that acute pain crises initiate an acute inflammatory syndrome.

ACUTE CHEST SYNDROME:The pathogenesis is not well understood,

makes things difficult with a mortality of 10% and



is a medical emergency. The patient presents with lower chest wall pain, fever, cough, pleuritic chest pain, arterial hypoxemia, pulmonary hypertension, and radiologic evidence of lung infiltrates more so in the lower lung fields. Some patients develop rib infarcts. Recurrent episodes of this condition can lead to progressive pulmonary fibrosis and chronic respiratory insufficiency.

Treatment includes supplemental oxygen, CPAP is some and mechanical ventilation in others guided by blood gas analysis. Early intervention with exchange transfusion to achieve HbS concentrations of less than 30% usually reverses respiratory failure. Inhaled nitric oxide may be beneficial in these patients decreasing the right ventricular after load, and redistributing pulmonary blood flow to better ventilated areas of the patient’s lungs.

Blood Transfusions in Sickle cell Anaemia:• Goal of transfusion is to decrease

haemoglobin S concentrations to less than 30%.

• Urgent: When blood is sequestered in an enlarged spleen, sudden and severe anaemia

Fig 7. Auto splenectomy in Sickle Cell Anaemia

occurs in children• Arterial Hypoxemia: In Acute Chest

Syndrome, RBC transfusions and supplemental oxygen therapy are helpful.

• Renal Failure and Symptomatic anaemia: Transfusion therapy may benefit these patients as also administration of erythropoietin.

Anaesthetic points of interest:This disease carries a special risk for

anaesthesia and surgery. It requires admission to the hospital 12-24 hours before surgery for



optimal hydration with IV fluids. Patients requiring emergency surgery are often at greatest risk for postoperative sickle cell disease related complications (consult haematologist always). Patients with sickle cell trait do not require blood transfusions preoperatively except before open- heart surgery or extensive thoracic surgery. The aim of transfusion is to increase the haematocrit to 30% (only for major surgeries).

Preoperatively, ventilation should not be depressed by aggressive premedication.

Perioperatively, the goal is to maintain near normal arterial oxygenation, hydration, body temperature, proper position, avoiding acidosis that can follow hypoventilation and replacement of blood loss as and when necessary.

Administration of supplemental oxygen is necessary in patients in whom regional techniques are selected.

Avoid overzealous transfusion of RBCs to prevent circulatory stasis. There may be a theoretical hazard in the use of extremity tourniquets as they predispose to localized circulatory stasis, acidosis and hypoxia with subsequent sickling.

There is no evidence that specific anaesthetic drugs are optimal for administration. Regional techniques are preferred over general anaesthesia. In fact there is evidence to show that circulating sickle cells have been reduced during and following general anaesthesia. Epidural and spinal anaesthesia produce compensatory vasoconstriction and decreased Pa02 in the nonblocked areas, making these areas theoretically vulnerable to infarction.

Patients with sickle cell trait tolerate cardiopulmonary bypass with no increased risk whereas attendant low peripheral blood flow, hypothermia and acidosis pose extra risk to patients with sickle cell disease.

The postoperative period is very critical for these patients. Incisional pain, use of analgesics, a high incidence of pulmonary infections and expected decreases in arterial

oxygenation predispose to sickling. So it is necessary to maintain near normal arterial oxygenation, give adequate IVfluids for hydration, consider incentive spirometry for improvement of lung function and oxygenation. The patient should be observed in the hospital overnight as acute chest syndrome may occur as a complication with peak incidence after 48 hours of surgery. PCA or neuraxial opioids are better choices for postoperative analgesia.

Pain Relief in the management of painful episodes.

There is no standard method for pain relief, resulting in institution of all possible measures like:• Fluid Replacement (3-4 litres/day in adults)• Analgesics - Opioids (morphine) in regular

doses and for breakthrough pain as well, PCA with morphine and adjunctive drugs like NSAIDS taking into consideration the standard contraindications forthese drugs. Response is followed up with pain scales and the pain therapy is optimally tailored to the individual patient. Extradural analgesia has been used

Fig 8. Dactylitis in Sickle Cell Anaemia.

in the pain management of sickle cell crises wherever possible.

HEREDITARY SPHEROCYTOSISOwing to the abnormalities in the RBC

cell membrane, water enters the RBCs along with sodium at an increased rate resulting in swollen



or spherocytic cells. These abnormal structures cannot be compressed unlike biconcave RBCs, so are vulnerable to rupture and produce haemolysis as they pass through the spleen. Deficiency of one of the skeletal proteins, Spectrin seems to be the most common biochemical abnormality in patients with all forms of Hereditary spherocytosis.

Clinical Presentation:This includes mild jaundice, anaemia,

and reticulocytosis. Cholelithiasis secondary to chronic haemolysis and increases in the plasma bilirubin concentrations are common.

Anaesthetic points of interest:Infection or folic acid deficiency may

trigger a haemolytic crisis, resulting in anaemia of profound nature, vomiting and abdominal pain mimicking a surgical emergency.

These patients commonly present for splenectomy, which can reduce haemolysis phenomenally but can increase the propensity for infection with bacteria (more commonly with pneumococci) in these patients. Splenectomy can lead to 80% survival of the RBCs.

Fig. 9 Effects of alterations in the cytoskeletal proteins in the red cell membrane on the shape of red cells. Spherocytic cells are less deformable than normal and are therefore trapped in the splenic cords, where they are phagocytosed by macrophages.


Low Flow Anaesthesia 83 M. Ravishankar

INTRODUCTION:The technique of reusing the expired gas

for alveolar ventilation after absorption of carbon dioxide can be traced to the very beginning of Anaesthesia when Dr. John Snow used caustic potash to absorb C02 from the expired gas. This concept was considerably simplified by the introduction of the “To and Fro” system by Waters and the circle system by Brian Sword, which utilised sodalime for absorption ofC02. It reigned supreme in the early half of this century when expensive and explosive agents like cyclopropane were utilised. The introduction of non-explosive agents like halothane and plenum vaporisers which performed optimally only in the presence of higher flows resulted in low flow anaesthesia becoming less popular. With the added knowledge of the disadvantages of using high percentages of 02 for prolonged periods and the necessity to use a second gas to control the percentage of oxygen, coupled with the complexities involved in the calculation of uptake of anaesthetic agents during the closed circuit anaesthesia made this technique even less popular. However, the awareness of the dangers of theatre pollution with trace amounts of the anaesthetic agents and the prohibitively high cost of the new inhalational agents, have helped in the rediscovery of low flow anaesthesia.

DEFINITIONLow flow anaesthesia has various

definitions. Any technique that utilises a fresh gas flow (FGF) that is less than the alveolar ventilation can be classified as ‘Low flow anaesthesia’. Baum et al1 had defined it as a technique wherein at least 50% of the expired gases had been returned to the lungs after carbon dioxide absorption. This would be satisfied when

the FGF was less than about two litres per minute.

Baker2 in his editorial had classified the FGF used in anaesthetic practice into the following categories:

For most practical considerations, utilisation of a fresh gas flow less than 2 litres/ min may be considered as low flow anaesthesia.

The need for low flow anaesthesia.Completely closed circuit anaesthesia is

based upon the reasoning that anaesthesia can safely be maintained if the gases, which are taken up by the body alone, are replaced into the circuit taking care to remove the expired carbon dioxide with sodalime. No gas escapes out of the circuit and this would provide for maximal efficiency for the utilisation of the fresh gas flow. The very nature of this system requires that the exact amount of anaesthetic agent taken up by the body be known, since that exact amount has to be added into the circuit. Any error in this could lead to a potentially dangerous level of anaesthetic agent being present in the inspired mixture with its attended complications. Hence, there exists a need for a system that provided the advantages of the completely closed circuit and at the same time, reduced the dangers associated with it. Low flow anaesthesia fulfilled these requirements.

Low flow anaesthesia involves utilising a fresh gas flow, which is higher than the metabolic



flows, but which is considerably lesser than the conventional flows. The larger than metabolic flows provides for a considerably greater margin of safety and allows variations in the fresh gas flow composition and strict compliance to the uptake is not necessary. Hence, the conduct of anaesthesia is greatly simplified, at the same time providing for the economy of the fresh gas flows.

EquipmentThe minimum requirement for conduct

of low flow anaesthesia is absorption of C02 from the expired gas, so that it can be reutilised for alveolar ventilation. Two systems were commonly used in the past, i.e., the “To and Fro” system introduced by Waters and the circle system introduced by Brian Sword. The To and Fro’ system, because of its bulkiness near the patient and other disadvantages, has gone out of vogue. The circle system using large sodalime canisters is in common use. The circle system should have the basic configuration with two unidirectional valves on either side of the sodalime canister, fresh gas entry, reservoir bag, pop off valve, and corrugated tubes and ‘Y’ piece to connect to the patient. The relative position of fresh gas entry, pop off valve, and reservoir bag are immaterial as long as they are positioned between the

expiratory and the inspiratory unidirectional valves that function properly and C02 absorption is efficient at all times.

MonitoringInspired 02 concentration should be

monitored at all times if N20 is used as one of the adjuvant gas. If monitoring of end tidal anaesthetic concentration is available, the administration of low flow anaesthesia becomes very easy. In the absence of that, a few calculations have to be carried out for deciding on the amount of anaesthetic agent to be added to the system.

THE PRACTICE OF LOW FLOW ANAESTHESIA:

The practice of low flow anaesthesia can be dealt with under the following three categories:

• Initiation of Low flow anaesthesia• Maintenance of Low flow anaesthesia• Termination of Low flow anaesthesia.

INITIATION OF LOW FLOW ANAESTHESIA.The primary aim at the start of low flow

anaesthesia is to achieve an alveolar concentration of the anaesthetic agent that is adequate for producing surgical anaesthesia

Fig 1 : Factors affecting the build up of alveolar tension



(approximately 1.3 MAC). The factors that can influence the build up of alveolar concentration should all be considered while trying to reach the desired alveolar concentration. These factors can broadly be classified into three groups (fig. 1); 1) Factors governing the inhaled tension of the anaesthetic, 2) Factors responsible for the rise in alveolar tension, 3) Factors responsible for uptake from the lungs thus reducing the alveolar tension.

Factors governing the inhaled tension of the anaesthetic:1 The circle system is often bulky and has a

volume roughly equal to 6-7 litres. Besides this, the FRC of the patient, which is roughly3 litres, together constitutes a reserve volume of 10 litres to which the anaesthetic gases and vapours have to be added. With the addition of FGF, the rate of change of composition of the reserve volume is exponential. The time required for the changes to occur is governed by the time constant, which is equal to this reserve volume divided by the fresh gas flow. This represents the time required for 67% change to occur in the gas concentration. Three time constants are needed for a 95% change in the gas concentration to occur. Hence, if a FGF of 1L/min is used, then 30 minutes will be required for the circuit concentration to reflect the gas concentration of the FGF. If the FGF is still lower, then a correspondingly longer time will be required.

2. The functional residual capacity of the lung and the body as a whole contain nitrogen, which will try to equilibrate with the circuit volume and alter the gas concentration if satisfactory denitrogenation is not achieved at the start of anaesthesia. Hence, as a prelude to the initiation of closed or low flow anaesthesia, thorough denitrogenation must be achieved with either a non-rebreathing circuit or the closed circuit with a large flow of oxygen and a tight fitting facemask.

3. The anaesthetic agent could be lost from the breathing system due to solubility of the agent in rubber, and permeability through the corrugated tubes. Though the amount of loss

will be minimal, it should be considered atthe start if the aimed anaestheticconcentration is low.

Factors responsible for rise in alveolar tension of the anaesthetic agent:1. CONCENTRATION EFFECT:

The concentration effect helps in raising the alveolar tension towards the inspired tension, but hinders it, if an insoluble gas is present in the mixture. The rate of rise of alveolar partial pressure of the anaesthetic agent must bear a direct relationship to the inspired concentration. The higher the inspired concentration, the more rapid is the rise in alveolar concentration. At a low inspired concentration, the alveolar concentration results from a balance between the ventilatory input and the circulatory uptake. If the latter removes half the anaesthetic introduced by ventilation, then the alveolar concentration is half that inspired. The concentration effect modifies this influence of uptake. When appreciable volumes are taken up rapidly, the lungs do not collapse; instead the subatmospheric pressure created in the lung by the anaesthetic uptake causes passive inspiration of an additional volume of gas to replace that lost by uptake, thus increasing the alveolar concentration and offsetting the mathematical calculations. Similarly, if an insoluble gas (e.g., nitrogen) is present in the inspired mixture, as the blood takes up the anaesthetic gas, the concentration of the insoluble gas will go up in the alveoli, reducing the concentration of the anaesthetic agent.

2. ALVEOLAR VENTILATION:The second factor governing the delivery of

anaesthetic agent to the lung is the level of alveolar ventilation. The greater the alveolar ventilation, the more rapid is the rise of alveolar concentration towards the inspired concentration. This effect is limited only by the lung volume; the larger the functional residual capacity, the slower the wash in of the new anaesthetic gas.

Factors responsible for uptake from the lungs thus reducing the alveolar tension:

Uptake from the lung is the product of three factors: solubility of the agent in the blood, the cardiac output and the alveolar to venous partial pressure gradient.



1. BLOOD GAS SOLUBILITY:“Solubility” is the term used to describe

how a gas or vapour is distributed between two media. At equilibrium, that is when the partial pressure of the anaesthetic in the two phases is equal, the concentration of the anaesthetic in the two phases might differ. This is calculated as a coefficient. When it is between blood and gas it is called blood gas solubility coefficient. If other things are equal, the greater the blood/ gas solubility coefficient, the greater the uptake of the anaesthetic, and slower the rate of rise of alveolar concentration.

2. CARDIAC OUTPUT:Because blood carries anaesthetic away

from the lungs, the greater the cardiac output, the greater the uptake, and consequently the slower the rate of rise of alveolar tension. The magnitude of this effect is related to the solubility: the most soluble agents are affected more than the least soluble agents.

3. ALVEOLAR TO VENOUS PARTIAL PRESSURE GRADIENT:

During induction the tissues remove all the anaesthetic brought to them by the blood. This lowers the venous anaesthetic partial pressure far below that of the arterial blood. The result is a large alveolar to venous anaesthetic partial pressure difference, which causes maximum anaesthetic uptake and hence lowers the alveolar partial pressure.

Considering the above mentioned factors at the start of anaesthesia, two facts become apparent:1. Induction if performed using low flows

would take an unacceptably long time.

2. If induction is done with an intravenous agent, unless special precautions are taken, it may take a very long time to achieve the desired alveolar concentration. Once the desired concentration is achieved, it will be difficult to change it. Hence, termination of action would take a long time after the discontinuation of the agents.

Methods to achieve desired gas and agent concentrationUSE OF HIGH FLOWS FOR A SHORT TIME:

This is by and far the commonest and the most effective technique of initiating closed circuit. By using high flows for a short time, the time constant is reduced thereby bringing the circuit concentration to the desired concentration rapidly. Often, a fresh gas flow of 10L of the desired gas concentration and 2 MAC agent concentration is used so that by the end of three minutes (three time constants) the circuit would be brought to the desired concentration. The large flows and high agent concentration also compensate for the large uptake seen at the start of the anaesthesia. Mapleson3 using a spreadsheet model of a circle breathing system has calculated that, by using a FGF equal to minute ventilation and setting the anaesthetic agent partial pressure to 3 MAC, the end expired partial pressure of halothane will reach 1 MAC in4 minutes and that of isoflurane in 1.5 minutes. The major advantages of this method are the rapidity with which the desired concentration is achieved, the ability to prevent unexpected rise in the agent concentration and the ability to use the commonly available plenum vaporisers to achieve the desired concentration. This also has the added advantage of achieving better denitrogenation, so vital to the conduct of low flow anaesthesia. The chief disadvantage would be the high flows required which would compromise on the economy of the gas utilisation and the need for scavenging systems to prevent theatre pollution. This period of using high flows for a short period at initiation goes by the name of “loading”.

PREFILLED CIRCUIT.The second method is utilising a different

circuit like Magills for preoxygenation. Simultaneously, the circle is fitted with a test lung and the entire circuit is filled with the gas mixture of the desired concentration. Following intubation, the patient is connected to the circuit thereby ensuring rapid achievement of the desired concentration in the circuit. But all the factors discussed above will be effective in preventing fast build up of the alveolar concentration to attain surgical anaesthesia.



USE OF LARGE DOSES OF ANAESTHETIC AGENTS.

The third method consists of adding large amounts of anaesthetic agent into the circuit so that the circuit volume + FRC rapidly achieves the desired concentration as well as compensates for the initial large anaesthetic gas uptake. To execute this, the patient is connected to the circuit, which is filled with oxygen (used for preoxygenation), after intubation. Fresh gas flow is started with metabolic flows of oxygen and a large amount of nitrous oxide, often in the range of 3-5 litres per minute. Oxygen concentration in the circuit, which gradually falls, is continuously monitored and the nitrous oxide flow is reduced once the desired oxygen concentration is achieved (33 - 40%). The obvious disadvantage of this method is the potential for errors and hypoxia if the oxygen monitor were to malfunction. Hence this method is seldom used. The method discussed above is often used to build up the agent concentration in the circuit. The commonly used agents are halothane and isoflurane. This involves setting the VOC to deliver a large amount of the agent while using low to moderate flows uo that the required amount of vapour is added into the circuit. The usual requirement of anaesthetic agent is approximately 400 - 500 ml of vapour in the first 10 minutes, which implies an average need of 40 - 50 ml of

vapour per minute during the first 10 minutes. Most of the vaporisers allow a maximal concentration of 5% to be delivered. At a setting of 5% in the vaporiser, with a FGF of one litre/ minute, the required mass of 500 ml of vapour could be added to the circuit so that the alveolar concentration could be built up. The setting in the vaporiser can be brought down to 0.5 - 0.8 % after 10 minutes and titrated according to the surgical needs.

Injection techniques.An alternative method for administering

the large amounts of the agents is by directly injecting the agent into the circuit, a form of VIC4'5'6'7'8 This is an old, time-tested method and is extremely reliable. Each ml of the liquid halothane, on vaporisation yields 226 ml of vapour and each ml of liquid isoflurane yields 196 ml of vapour at 20°C. Hence, the requirement of about 2ml of the agent is injected in small increments into the circuit. The high volatility coupled with the high temperature in the circle results in instantaneous vaporisation of the agent. The injection is made through a self sealing rubber diaphragm covering one limb of a metal T piece or a sampling port, inserted into either the inspiratory or the expiratory limb (fig. 2).

The injection is made using a small bore needle and a glass syringe. Placing a gauze piece

Fig 2. Closed circuit configuration for injection technique



or a wire mesh inside the T piece often helps in the vaporisation of the liquid. The intermittent injections are often made in 0.2-0.5 ml aliquots manually. Doses should never exceed 1 ml at a time. Doses exceeding 2 ml bolus invite disaster. Intermittent injections can often be easily substituted with a continuous infusion with the added advantage of doing away with the peaks and troughs associated with intermittent injections.

The exact dose to be used is calculatedthus:Priming dose (ml vapour) = Desired concentration

x{( FRC + Circuit volume) +(Cardiac output x BG Coeff.)}

The Cardiac output and the FRC can be estimated for the patient based on standard nomograms, minutes of the closed circuit anaesthesia. Besides this, an amount of agent necessary to compensate for the uptake of the body must also be added and this is calculated depending on the uptake model being used (vide infra).

THE MAINTENANCE OF LOW FLOW ANAESTHESIA

This is the most important phase as this is stretched over a period of time and financial savings result directly from this. This phase is characterised by1 Need for a steady state anaesthesia often

meaning a steady alveolar concentration of respiratory gases.

2 Minimal uptake of the anaesthetic agents by the body.

3 Need to prevent hypoxic gas mixtures.

Since the uptake of the anaesthetic agent is small in this phase, the low flow anaesthesia is eminently practical. Adding small amounts of the anaesthetic gases to match the uptake and providing oxygen for the basal metabolism should suffice. If CCA is used, this would be directly equal to the uptake and hence provides for the monitoring of the oxygen consumption and the agent uptake. If low flow anaesthesia is used, then besides the uptake, the amount of gas, which is vented, is also added to the circuit to maintain steady state anaesthesia.

Management of the oxygen and nitrous oxide flow during the maintenance phase:

The need to discuss the flow rates of N20 and 02 arises specifically because of the possible danger of administration of a hypoxic mixture. Let us analyse the following example. 33% oxygen is set using a flow of 500 ml of 02 and 1000 ml of N20. Oxygen is taken up from the lungs at a constant rate of about 4 ml/kg/min. N20 is a relatively insoluble gas and after the initial equilibration with the FRC and vessel rich group of tissues, the uptake is considerably reduced. In this situation, there is a constant removal of02 at a rate of 200 - 250 ml/min, where as the insoluble gas N20 uptake is minimal. Hence the gas returning to the circuit will have more N20 and less of 02. Over a period of time, due to concentration effect, the percentage of N20 will go up and that of 02 will fall, sometimes dangerously to produce hypoxic mixtures.

Various short cuts are available to make low flow anaesthesia easy of which the most popular technique is the ‘Gothenburg technique’9. Most of the other techniques approximate this and hence it deserves a special mention.

THE GOTHENBURG TECHNIQUE:Initially high flows, oxygen at 1.5 l/min

and nitrous oxide at 3.5 l/min had to be used for a period of six minutes after the induction of anaesthesia and this constitutes the loading phase. This is followed by the maintenance phase in which the oxygen flow is reduced to about 4ml/kg and nitrous oxide flow adjusted to maintain a constant oxygen concentration in the circuit. The usual desired oxygen concentration is about 40%. The use of an oxygen analyser is very important since the nitrous oxide added is directly based on its readings and hence any errors would be dangerous.

Other authors have made similar recommendations10'11,12'13'14. Most of the authors opine that the oxygen consumption under anaesthesia is about 200 - 250 ml. However, there is a wide disparity in the amount of nitrous oxide to be added into the circuit. This controversy is consistent with the basic controversy surrounding the uptake of the anaesthetic agents and is dealt with in detail in a later stage. For most practical



purposes, in the absence of an oxygen analyser, the following technique is safe to use. A high flow of 10 lit/min at the start, for a period of 3 minutes, is followed by a flow of 400 ml of 02 and 600 ml of N20 for the initial 20 minutes and a flow of 500 ml of 02 and 500 ml of N20 thereafter. This has been shown to maintain the oxygen concentration between 33 and 40 % at all times.

Management of the potent anaesthetic agents during maintenance phase.

This is easily accomplished by dialling in the calculated concentration on the plenum vaporiser for the flow being used. For example, suppose the anaesthetic uptake for a desired concentration of 0.5% halothane is 7.5ml/min (vide infra). If a FGF of 500ml/min is being used, then the dial setting should be 1.5%, for at this setting and for the used flow, the total vapour output would be 7.5ml/min. If a flow of 1000ml/min is being used, then the dial setting should be 0.8%. In practice the actual dial setting often over estimates the actual output since the plenum vaporiser under delivers the agent at low flows. Hence, the dial setting is fine-tuned depending on the endpoints being achieved.

During completely closed circuit anaesthesia, the most popular method of adding agents into the circuit is by the injection technique. This is often used to initiate the closed circuit anaesthesia as described earlier. Later, the same setup is used to continue the anaesthesia by adding either small boluses or by constant infusion into the circuit. The dose to be added depends on the uptake model being used for the conduct of the closed circuit. The endpoint for adding the agent can be the achievement of the desired end tidal agent concentration, measured using an agent analyser. This would be the most accurate method. The end point may also be based on the haemodynamic stability15.

Simple rule of the thumb techniques1617 for adding the anaesthetic agents into the circuit both during the loading phase and the maintenance phase has been suggested.

Weir and Kennedy4 recommend infusion of halothane (in liquid ml/hr) at the following rates for a 50 kg adult at different time intervals.

0-5 min 27 ml/hr5-30 min 5.71 ml/hr30-60 min 3.33 ml/hr60-120 min 2.36 ml/hr

These infusion rates had been derived from the Lowe’s theory of the uptake of anaesthetic agent (vide infra). They had approximated isoflurane infusion (in liquid ml/hr) based on the Lowe’s formula as follows:

0-5 min. 5 - 3 0 min. 30-60 min. 60-120 min.

14 + 0.4X wt. ml/hr.0 2 X initial rate. 0.12Xinitial rate.0.08X initial rate.

For halothane infusion, they had suggested that the above said rates be multiplied by 0.8 and for enflurane, multiplied by 1.6. These rates had been suggested to produce 1.3 MAC without the use of nitrous oxide. The infusion rates had to be halved if nitrous oxide is used.

The other salient points to be considered during the maintenance phase are the following: a) Leaks must be meticulously sought for and prevented since they would decrease the efficacy of the system. Flows must be adjusted to compensate for the gas lost in the leaks, b) Most of the gas monitors sample gases at the rate of 200 ml/min, which may be sometimes as high as half the FGF. Hence, care must be taken to return the sample back to the circuit to maximise the economy of FGF utilisation. Some gas analysers like Ohmeda Rascal add air to the sample exhaust. This if returned to the circuit would result in dilution of the anaesthetic mixture and accumulation of nitrogen within the circuit and hence should be vented. This mandates utilisation of a flow adequate to compensate for this loss. Recent studies18 have shown that venting of the gas from the analyser does not alter the dynamics to any large extent and can safely be done.

CONTROVERSIES IN THE UPTAKE MODELS OF ANAESTHETIC AGENTS EXPONENTIAL OR LINEAR?

Knowledge of uptake of anaesthetic agent is very important in the practice of closed



and low flow anaesthesia since, the very technique calls for the addition of an amount of anaesthetic agent, which is taken up by the body. In fact, mutually contradicting models exist on the uptake of anaesthetic agents. The Lowe’s theory*3'*4, which has wider acceptance, ascribes the anaesthetic uptake to an exponential model. It states that the uptake of agent is inversely proportional to the square root of the time, implying that the uptake decreases exponentially with time. It necessitates calculation of unit dose (Appendix 1). This unit dose is the amount of anaesthetic agent to be added to the closed circuit during the time intervals of 0-1 min, 1-4 min, 4-9 min, 9-16 min, and so on. Besides that, the circuit and the FRC and the circulating blood of the patient had to be brought to the desired concentration with a prime dose.Prime dose = {(circuit volume + FRC) +

(Q xk)} x desired Concentration.

This prime dose had to be added into the circuit during the first 9 minutes of closed circuit anaesthesia.

The practical implication of this is that to maintain closed circuit, one must calculate the agent and gases to be added into the circuit using hair-splitting exponential equations, often frightening the anaesthetist. It has been one of the main causes for the reluctance in the widespread usage of the closed circuit anaesthesia.

In total contrast to this exponential theory is the linear model proposed by CY Lin 1214 He states that the uptake of anaesthetic agents is a near constant over the clinically important concentrations. Hence, he advocated adding the anaesthetic agent as a constant rate infusion into the circuit throughout the anaesthetic procedure. Lin had contended that the FRC constituted an extension of the breathing circuit and the washin into it could not be considered as uptake by the body. He had suggested a simple method of conducting the closed circuit anaesthesia: It had consisted of using a high flow of nitrous oxide and oxygen (6 L/min and 4 L/min respectively) for 3 minutes (three time constants). At the end of 3 minutes, the flows had been reduced to metabolic flows and closed circuit started. Potent agents had

been added either through a VOC (like a copper kettle) or by direct injection into the circuit. The anaesthetic agent required to washin the circuit volume and the FRC of the patient had constituted the prime dose and it should be added to the circuit during the first ten minutes, besides the dose required to compensate for the uptake of the agent. The formula to calculate the amount of agent to be added into the circuit to equal the uptake had been:

Uptake of anaesthetic agent = desired concentration x alveolar ventilation x fractional uptake ( ml of vapour).

The fractional uptake (= 1 - FA/ F,) for halothane had been calculated as 0.5 and that for enflurane, as 0.4. He had concluded that anaesthesia thus conducted produced a nearly constant inspired and expired concentration implying that the uptake of the anaesthetic agents had been a near constant.

Unfortunately very little literature exists on the efficacy of either of these models. The study conducted to compare these two models in our Institute, revealed that predictive performance of both the models were statistically similar, and linear uptake model had scope for improvement where as the exponential model had no such scope. Lin’s linear model however has a distinct superiority in the form of simplicity.

TERMINATION OF LOW FLOW ANAESTHESIA

Unlike the initiation or the maintenance of the closed circuit, termination is less controversial. There are only two recognised methods of termination of the closed circuit. They are as follows:

Towards the end of the anaesthesia, the circuit is opened and a high flow of gas is used to flush out the anaesthetic agents, which accelerates the washout of the anaesthetic agents. This has the obvious advantage of simplicity but would result in wastage of gases.

The second method is the use of activated charcoal8 Activated charcoal when heated to 220°C adsorbs the potent vapours almost completely. Hence, a charcoal-containing



canister with a bypass is placed in the circuit. Towards the end of the anaesthesia, the gas is directed through the activated charcoal canister. This results in the activated charcoal adsorbing the anaesthetic agent resulting in rapid recovery and at the same time, reducing theatre pollution. Nitrous oxide, due to its low solubility is washed off towards the end by using 100% oxygen.

To conclude, the low flow closed circuit anaesthesia has many advantages to offer. To list a few,1 Enormous financial savings due to use of low

fresh gas flows as well as the agent.2 High humidity in the system leads to fewer

post anaesthetic complications.3 Maintenance of body temperature during

prolonged procedures due to conservation of heat.

4 Reduction in the theatre pollution.

The perceived disadvantages are not real:1 The need to accurately adjust the flows of

gases. The system is inherently stable once a steady state is reached and small errors in the dosage of the agents or the gases would be of no concern.

2 Accumulation of trace gases20. It has, however, been often overestimated21.

3 Need for monitoring equipment. Oxygen monitor is the only one that is necessary and since it is part of the basic monitoring it cannot be considered as a disadvantage.

With a proper understanding of the concepts of practice, the low flow anaesthesia technique can safely be used in all surgical procedures lasting more than an hour.

REFERENCES1 Baum JA, Aithkenhead: Low flow

Anaesthesia. Anaesthesia. 50 (suppl).: 37-44, 1995

2 Baker AB: Editorial. Low flow and Closed Circuits. Anaesthesia and Intensive Care. 22: 341-342, 1994

3 Mapleson W: The theoretical ideal fresh gasflow sequence at the start of low flow anaesthesia Anaesthesia 53(3):264-72, 1998

4 Weir HM, Kennedy RR: Infusing liquid anaesthetic agents into the closed circle anaesthesia. Anaesthesia and Intensive Care. 22: 376-379, 1994

5 Wolfson B: Closed Circuit Anaesthesia by Intermittent Injections of Halothane. British Journal of Anaesthesia. 34: 733 - 737., 1962

6 Thorpe CM, Kennedy RR: Vaporisation of Isoflurane by Liquid Infusion. Anaesthesia and Intensive Care. 22: 380-82, 1994

7 Hampton JL, Flickinger H: Closed Circuit Anesthesia utilising known increments of Halothane.Anesthesiology 22: 413-418, 1961

8 Philip JH: ‘Closed Circuit Anaesthesia’ in ‘Anesthesia Equipment: Principles and Applications’. Edited by Ehrenwerth J, Eisenkraft JB, Mosby Year Book Inc., 1993, Chap 30.

9 Dale O, Stenqvist O: Low flow Anaesthesia : Available today - A routine tomorrow. Survey of Anesthesiology. 36: 334-336, 1992

10 Cullen SC: Who is watching the patient? Anesthesiology 37: 361-362, 1972

11 Baker AB: Back to Basics - A Simplified Non - Mathematical Approach to Low Flow Techniques in Anaesthesia. Anaesthesia and Intensive Care. 22: 394-395., 1994

12 Lin CY, Benson JW, Mostert DW: Closed Circle Systems - A new direction in the practice of Anaesthesia. Acta Anaesthesiologica Scandinavica. 24: 354-361., 1980

13 Lowe HJ: ‘The Anesthetic Continuum’ in the book, ‘Low flow and closed circuit anesthesia’. Edited by Aldrete JA, Lowe HJ, Virtue RW, Grune & Stratton, 1979, pp 11-38

14 Lowe H: ‘Closed- circuit anesthesia’, in the book ‘Clinical Anesthesiology’ Edited byMorgan GE, Mikhail MS, Appleton and Lange, 1992, pp 112 -115.

15 Da Silva CJM, Mapleson WW, Vickers MD: Quantitative study of Lowe’s square root of time method of closed system anaesthesia. British Journal of Anaesthesia. 79: 103-112., 1997

16 El - Attar AM: Guided Isoflurane injection in a totally closed circuit. Anaesthesia. 46.: 1059-1063., 1991.

17 Eger II E: “Uptake and Distribution”, in the book “Anesthesia”, Edited by Miller RD, Ed4, Churchill Livingstone,1994, p118.

18 Bengtson J, Bengtsson J, Bengtsson A, Stenqvist O: Sampled gas need not be returned during low-f!ow anaesthesia. Journal of Clinical Monitoring 9(5): 330-4, 1993

19 Lin CY: Uptake of Anaesthetic Gases and Vapours. Anaesthesia and Intensive Care. 22: 363-373, 1994

20 Morita S, Latta W, Hambro K, Snider MT: Accumilation of methane, acetone and nitrogen in the inspired gas during closed circuit anesthesia. Anesthesia and analgesia. 64: 343-347, 1985

21 Baumgarten R: Much ado about nothing: Trace gaseous metabolites in closed circuit.Anesthesia and Analgesia. 64: 1029-1030, 1985


How to get more from your Central Venous Cather 92 Jigi Divatia

In recent years, central venous cannulation is practised increasingly in anaesthesia and intensive care for a variety of indications (Table 1). Broadly, these indications are monitoring of central venous pressure (CVP) and access for intravenous infusions. Recently, it has become possible to measure cardiac output via a central venous catheter and a peripheral arterial catheter equipped with a sensor for the indicator. The central venous oxygen saturation (Scv02) has also been used to guide hemodynamic therapy in severe sepsis. This review will focus on measurement and monitoring of CVP, especially the physiological basis for interpreting the CVP, as well as outline the newer uses of the CVP in hemodynamic monitoring and therapy.

Measurement of the CVP gives important haemodynamic information regarding the status of the cardiovascular system and response to therapy. Clinically, measurement of the CVP is used for two purposes:(1) to gain information about cardiac function, and (2) to gain information about the adequacy of vascular volume. It performs this dual function because physiologically the right atrial pressure is the interface between the two major determinants of cardiac output: cardiac contractility and venous return. Because CVP influences and is influenced by, both of these physiologic functions, it is an extremely useful measure of cardiovascular function. However, the process of haemodynamic measurements makes several assumptions regarding the cardiovascular

Measurement of CVP Intravenous access Therapeutic procedures

Major surgery Rapid administration of fluids and blood

Insertion of transvenous pacemaker

Anticipated major blood loss Anticipated major fluid shifts

Total parenteral alimentation Insertion of catheters for haemodialysis and plasmapheresis

Significant cardiac disease Administration of Vasoactive agents and concentrated potassium infusions

Aspiration of air emboli

Significant pulmonary disease Administration of Chemotherapeutic and other irritant drugs

Pulmonary hypertension Frequent blood sampling Insertion of a pulmonary artery catheter

Table 1. Indications for central venous cannulation.



system. Hence, the CVP can be confusing and difficult to interpret. In the following sections, we will try to review some essential concepts as they relate to interpreting central venous pressures.

CARDIOVASCULAR PHYSIOLOGY Preload and Cardiac Output

The major determinants of cardiac function are heart rate and stroke volume. The stroke volume itself is dependent on preload, afterload, and myocardial contractility. The relationship between preload and cardiac output is expressed in the Frank-Starling cardiac function curve. Essentially, the force of contraction is proportional to the initial end-diastolic fibre length. In clinical terms the end-diastolic fibre length is expressed as the end-diastolic volume of the ventricle. This in turn is more conveniently expressed as the end-diastolic pressure, with the assumption that the ventricular compliance is normal. Provided the atrioventricular valves are normal and open at the end of diastole, the mean end-diastolic pressure of the ventricle is equal to the atrial pressure. Thus the mean atrial pressure is the filling pressure of the

corresponding ventricle, and the atrial pressure can be approximated as the preload of the ventricle. While there are important differences between the right and left ventricles (the left ventricle is less compliant, more contractile, has a greater afterload and has a slightly higher filling pressure than the right ventricle), under normal circumstances, the right side of the heart and lungs can be viewed as passive conduits for the passage of blood. It is then possible to discern a relationship between the right sided filling pressure (right atrial pressure or CVP) and the left ventricular cardiac output, and it is possible to use the CVP as a measure of the left ventricular preload. Various assumptions made in approximating the CVP as a measure of the left ventricular preload are summarised in Table 2. The relationship between right atrial pressure and cardiac output can be used to plot the classical Frank-Starling cardiac function curve, where right atrial pressure is a measure of preload. Any factor that increases heart rate or contractility or decreases afterload will cause a greater cardiac output for the same preload.

Statement Assumption Fallacy

LVEDV a LVEDP (preload)

Left ventricular compliance is normal, pressure and volume are linearly related

Compliance may change with pathology e.g., LVH, myocardial ischaemia or infarction.P-V relationship is not linear.

LAP = LVEDP RAP = RVEDP

Mitral and tricuspid valves are normal, and fully open in diastole

Does not hold if valves are stenotic or regurgitant, or when A-V valves are closed in diastole (nodal rhythm,A-V dissociation)

RAP a LAP Equivalent function of right and left ventricle

Relationship between right and left sides of the heart is affected by several factors

Table 2. Assumptions inherent in using CVP.


How to get more from your Central Venous Cather 94If it is accepted that the CVP is a

Jigi Divatia

measure of preload, the factors that will affect it are blood volume, venous tone, ventricular compliance, myocardial contractility and afterload. If all the other factors are kept constant, the CVP will give some indication of the contractility, i.e., a failing ventricle is associated with a high CVP. The preload is also affected by changes in afterload. An acute change in the right ventricular afterload by pulmonary embolism causes a rise in CVP, while administration of a peripheral vasoconstrictor like phenylephrine will increase the left ventricular afterload and the CVP. When the acute load is relieved, the CVP will fall. However the commonest causes of variations in CVP during anaesthesia are alterations in blood volume or venous tone, both of wtych are accentuated by posture. For example, during spinal anaesthesia in the supine position, venous tone and venous return are reduced, resulting in a low CVP. Following infusion of fluids, the CVP will return towards normal. However, postoperatively as the anaesthetic-induced vasodilatation recedes, and is replaced by vasoconstriction due to pain, cold, shivering and acidosis, the relative blood volume may be too high, and the CVP will rise.

Ventricular ComplianceThe cardiac function curve uses the right

atrial pressure to represent preload. More accurately, preload is the resting myocardial fiber length or, in the intact heart, end-diastolic ventricular end-diastolic volume. Unfortunately, the relationship between pressure and volume is not linear. The ventricles are able to expand to accept a change in pressure. Cardiac output will increase with little change in the right atrial pressure, until the limits of ventricular expansion are reached. At that point, cardiac output no longer improves but right atrial pressure increases rapidly. Disease states and different physiologic states can change the position & shape of the curve. Consequently, a single measurement of right atrial pressure cannot accurately predict end-diastolic volume. However, determining the compliance (i.e., the change in pressure for a given change in volume) will add valuable information about the system.

Vascular ComplianceJust as the heart demonstrates variable

compliance, the vascular system is able to adjust to changes in volume with minimal changes in

pressure. A rapid increase in vascular volume results in a rapid increase in venous return as well as right atrial & mean systemic pressures. Within seconds, circulatory reflexes begin to adjust these pressures & venous return toward normal. In addition, stress relaxation of the vasculature (not dependent on autonomic reflexes) allows further compensation over the ensuing minutes. Similar compensation occurs for decreases in vascular volume. Consequently, a single measurement of right atrial pressure cannot accurately predict vascular volume. However, determining the compliance of the system can provide valuable clues to the status of the vascular volume.

CLINICAL UTILIZATION OF CVP MEASUREMENT

The most common reasons for CVP measurement are to help determine the state of volume. As can be seen in Table 3, a single measurement of the CVP helps somewhat in defining circulatory status but leaves considerable overlap in possible interpretations.

USING COMPLIANCE TO IMPROVE INTERPRETATION

Rapid changes in vascular volume can help further define the cardiovascular status if the time course of compliance changes is remembered. This is the principle of the “fluid challenge”. A rapid infusion of 300 to 500ml of fluid in a normovolemic adult with good cardiac function will result in a moderate increase in CVP (2 to 4mm Hg) with a return nearly to baseline within 10 to 15 min. A minimal initial rise in CVP implies a reduced vascular volume. A large initial rise in CVP implies a heart that is noncompliant or an elevated vascular volume or both. If the CVP returns to baseline rapidly (within 5min), it implies a reduced vascular volume, which can accommodate additional volume by rapid changes in vasomotor tone. A slower return toward baseline indicates that stress relaxation is occurring & the vascular volume is elevated for the current cardiac status. Table 4 indicates how a fluid challenge can improve the interpretation made on the basis of the CVP alone.

The addition of information about cardiac output can further improve diagnostic accuracy. Actual measurement of cardiac output is best



CVP Cardiac Status Vascular Volume

Low Reduced Reduced(<6mmHg) Normal Reduced

Hyperdynamic Normal

Normal Depressed Reduced(6-12mmHg) Normal Normal, reduced or elevated

Hyperdynamic Elevated or normal

Increased Normal Elevated(>12mmHg) Depressed Normal, elevated or reduced

Hyperdynamic Elevated

Table 3 . Possible interpretations of a single CVP reading.

CVP Initial Return to Cardiac Vascular Cardiacincrease baseline status volume outout

Below normal + Rapid Normal Reduced LowHyperdynamic Reduced Low to normal

+ to ++ Moderate Depressed Reduced Very lowHyperdynamic Normal High

Normal + to++ Rapid Normal Reduced Low to Normal++ Moderate Normal Normal Normal

Hyperdynamic Normal High++ Slow Normal Elevated High

Hyperdynamic Elevated Very High

+++ Rapid Depressed Reduced Very Low+++ Moderate Depressed Normal Low+++ Slow Depressed Elevated Low to Normal

Above Normal ++ Moderate Normal Elevated HighHyperdynamic Elevated Very High

+++ Moderate Depressed Reduced Very Low+++ Slow Depressed Normal Low

Depressed Elevated Low to Normal

Table 4. Possible interpretations of CVP measurement with volume challenges



but frequently indirect assessment using clinical signs may be enough to provide the additional data needed (but see section below on the CVP and hemodynamic therapy). For example, the patient with a low CVP who has a moderate return toward baseline could have either a depressed cardiac status with a reduced vascular volume or a hyperdynamic heart with a relatively normal vascular volume. Determining which situation exists in a given patient should not be difficult using clinical signs.

CALIBRATED TRANSDUCER vs WATER MANOMETER

Originally, central venous pressures were measured using a column of water in a marked manometer. The CVP is the height of the column in cm of H20 when the zero point of the column is at the level of the right atrium & the fluid reaches equilibrium when allowed to flow freely into or out of the central venous catheter. More recently, CVP measurement utilizing a calibrated transducer has become common. In this case, a transducer properly calibrated in mmHg is connected to the central venous catheter, placed at the level of the right atrium & the pressure waveform displayed on an oscilloscope or paper. The difference in units of measurement between these two methods should not be forgotten when switching from one technique to another. The relative density (specific gravity) of mercury to water is 13.6. Thus, a 1- mm column of mercury would have the same weight as a 1.36cm column of water. At low pressures, these differences are not very great but at higher pressures they can become significant (Table 5)

cm H20 MmHg

1.36 13 2.25 3.710 7.415 1120 14.6

Table 5. Equivalent pressures with water manometer & calibrated transducer

The main advantage of water manometer measurement is simplicity. The CVP can be measured easily & quickly by connecting widely available disposable plastic tubes to the central venous catheter. The major disadvantages of this system are the inability to analyze the CVP waveform & the relatively slow response of the water column to changes in intrathoracic pressure. The latter can lead to an overestimation of the central venous pressure during mechanical ventilation & occasionally, an underestimation during spontaneous ventilation. With the widespread use of electronic pressure monitoring for arterial & pulmonary artery pressures, calibrated transducer measurement of CVP has become more common. Because it is generally more accurate & allows observation of the waveform, transducer measurement is preferred when it is available.

THE CENTRAL VENOUS WAVEFORMA typical central venous waveform is

shown in Fig 1. It consists of three positive deflections labeled the a-,c-, & v-waves as well as two major depressions labeled the x & y- descents. The a-wave represents the increase in right atrial pressure that occurs during atrial contraction. The c-wave is caused by a slight elevation of the tricuspid valve into the right atrium during early ventricular contraction. The x-descends corresponds to the period of ventricular ejection & reflects the emptying of blood from the heart. The v-wave is the increase in atrial pressure that occurs as venous return continues while the tricuspid valve is closed. The y-descent is the drop in atrial pressure that occurs when the tricuspid valve opens & blood flows into the right ventricle. Figures 1 and 2 relate the waves of the CVP to the cardiac cycle and heart sounds.

In cardiac tamponade & constrictive pericarditis, the right atrial, right ventricular diastolic, pulmonary artery occlusion & left ventricular diastolic pressures are elevated & nearly equal to each other.The a-wave will be absent in atrial fibrillation, and characteristic changes in the typical waveform pattern occur in many pathologic conditions (Fig 3). A cannon



FIGURE 3. Schematic representation of heart structures, blood flow, and jugular venous pulse waveforms under normal (A) and abnormal conditions (B and C). (B) A giant a wave caused by tricuspid stenosis. (C) A large v wave caused by tricuspid regurgitation. IVC = inferior vena cava; RA = right atrium, RV = right ventricle; SVC = superior vena cava.

CVP MEASUREMENT AND INTRATMORACIC PRESSURE

Since the central veins are located inside the thorax, CVP measurements are influenced by changes in intrathoracic pressure. Consequently, the CVP fluctuates with he thorax, CVP measurements are influenced by changes in intrathoracic pressure. Consequently, the CVP fluctuates with respiration, decreasing with a spontaneous inspiration & increasing with a positive pressure respiration. In order to minimize the effects of respiration, the CVP measurement should be taken at end exhalation, when the muscles of respiration are at rest & intrathoracic pressure is stable at its resting level.

Positive end expiratory pressure (PEEP) applied to the airway at the end of exhalation, may be partially transmitted to the intrathoracic structures. Therefore, a CVP measured while patient is receiving PEEP may be higher than



under the same cardiovascular circumstances if he was not receiving PEER A more accurate measure of right heart filling pressure is the transmural right atrial pressure, that is intravascular right atrial pressure minus intrathoracic pressure. Under most circumstances, measuring CVP referenced to atmosphere is adequate because intrathoracic pressure remains constant. However, when PEEP is applied, pleural pressure increases more than right atrial pressure, so that transmural right atrial pressure(true filling pressure)decreases. This effect is rarely significant if the PEEP is less than 7.5cm H20. The cardiovascular effects of such an increase in CVP are twofold: a decrease in venous return and a decrease in cardiac output. This may be erroneously interpreted as a deterioration in cardiac function. An obvious solution to this problem is to measure the CVP only when the PEEP has been removed. However, the beneficial effect of PEEP on gas exchange is lost very quickly when it is removed and may take a prolonged period to recover when PEEP is reapplied. This subjects the patients to the dangers of hypoxemia. The only accurate method of compensating for the effects of PEEP on central pressure measurements is to measure the transmural pressures. Unfortunately, simple accurate measurement of intrathoracic pressure in the clinical setting is difficult. From a practical standpoint, PEEP does not usually cause a large change in the CVP, especially in patients with stiff lungs. It is best not to remove PEEP for measurements, recognizing that the numbers obtained may be slightly higher than would be found without PEEP, and to assess the change in CVP in response to fluid challenge as a guide to therpy.

Central Venous Catheterisation and Hemodynamic therapy

The pulmonary artery catheter has been considered the gold standard to guide hemodynamic therapy in shock and cardiac failure. The PCWP is considered the most suitable measure of preload (subject to the assumptions outlined in Table 2), and the cardiac output is measured by thermodilution. Modern pulmonary artery catheters allow continuous cardiac output minitoring, continuous mixed venous oxygen saturation (Sv02) monitoring, as well as measurement of right ventricular end-

diastolic volume as the preload, albeit of the right heart. Pulmonary artery catheterization is an invasive procedure, and recent articles have cast doubt on its utility, and there is increasing interest in non-invasive or less invasive methods of measuring cardiac output. The central venous catheter remains central to these measurements in a number of these new technologies.

Use of the Central Venous oxygen saturation (Scv02)

Rivers and colleagues2 studied early goal- directed therapy designed to optimize cardiac preload, afterload, and contractility. Theyrandomly assigned patients to this therapy or to standard (control) therapy at the time of presentation, before admission to the intensive care unit. After arterial and central venous cannulation, the standard- therapy group underwent treatment that included critical care consultation and were transferred to the intensive care unit as soon as possible (on average, after 6.3 hours). The group randomly assigned to early goal-directed therapy was treated in the emergency department for at least 6 hours (average, 8.0 hours) before admission. These patients received, in a sequential fashion, fluid resuscitation, vasopressor or dilator agents, red-cell transfusions, and inotropic medications to achieve target levels of central venous pressure (8 to 12 mm Hg), mean arterial pressure (65 to 90 mm Hg), urine output (at least 0.5 ml per kilogram of body weight per hour), and central venous oxygen saturation (at least 70 percent). Patients who did not have a response to these approaches underwent sedation and mechanical ventilation. In-hospital mortality differed significantly between the two groups: 30.5 percent in the group assigned to early goal-directed therapy and 46.5 percent in the group assigned to standard therapy. During the period from 7 to 72 hours, the patients assigned to early goal-directed therapy had significantly higher mean central venous oxygen saturations and arterial pH values and lower lactate levels, base deficit values, and organ-dysfunotion scores than those assigned to standard therapy.

Thus a hemodynamic therapy based on CVP monitoring and Scv02 measurement, without a pulmonary artery catheter in early sepsis produced dramatic beneficial results. CVCs incorporating a fibreoptic sensor to continuously monitor Scv02 will soon become



available. This approach represents a major advance and a simplified method of hemodynamic therapy.

Cardiac OutputThe PiCCO Technology is based on a

hemodynamic monitoring method, which is a combination of transpulmonary thermodilution and arterial pulse contour analysis. The cold bolus traverses the lungs after being injected through a CVP line, and that the thermodilution curve is being measured in a systemic artery. The method provides the user with the following parameters:- Intrathoracic Blood Volume (ITBV) which is a volumetric measure of cardiac preload;- ExtraVascular Lung Water (EVLW) which reflects the level of pulmonary edema, if increased.

The measurement of these and several other parameters requires a single bolus injection of cold saline through any central venous line and a modified (thermistor-tipped) arterial catheter, eliminating the need for a Right Heart Catheter (RHC). The transpulmonary measurement of CO is at least as accurate as the conventional bolus thermodilution using the right heart catheter.3 However, transpulmonary (“arterial”) CO is not affected by respiratory variations meaning that the measurement is not dependent on the moment of bolus injection during the ventilation cycle. ITBV can be regarded as the best bedside measure of static cardiac preload, since it represents total cardiac preload volume.4-6 It may be more representative than conventional filling pressures or right ventricular end-diastolic volume. However ITBV is a calculated parameter based on complex equations, and its routine use requires further validation.

Lithium Dilution cardiac outputThe LiDCO System consists of a

proprietary disposable lithium sensitive sensor which is attached to an existing arterial line, a connector which sends a signal from the sensor to a monitor and a monitor which displays a computation of cardiac output. The LiDCO System provides an indicator dilution method of

measuring cardiac output. A small dose of lithium chloride is injected via a central venous catheter; the resulting arterial lithium concentration-time curve is recorded by withdrawing blood past a lithium sensor. Indicator dilution curves recorded in arterial blood consist of primary and secondary curves due to the initial circulation and then recirculation of the indicator. Clinical trials have been completed that demonstrate that the LiDCO System is at least as accurate as thermodilution.

In conclusion, it is vital to interpret the CVP correctly to make accurate haemodynamic diagnoses and to initiate therapy. The trend of the CVP and responses to fluid challenges and other therapeutic measures are more important than a single value. All information should be ultimately interpreted in the clinical context. Despite its limitations, the CVP remains a vital haemodynamic parameter which can be easily and safety monitored. It may be necessary at some stage to obtain further information, eg, by echocardiography, or by pulmonary artery catheterisation.

REFERENCES

Most of the material including Tables are based on :Otto CW, "Central venous pressure monitoring “ in Monitoring in Anaesthesia and Critical Care Medicine, editor Blitt CD, 1st edition, Churchill Livingstone, New York, 1985.Other references:

1. Karnath B, Thornton W, Beach R. Inspection of Neck veins. Hospital physicians, May 2002. 43-47.

2. Rivers E, Nguyen B, Ressler J, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19): 1368-77.

3. Sakka SG, Reinhart K, Meier-Hellmann A: Comparison of pulmonary artery and arterial thermodilution cardiac output in critically ill patients. Intensive Care Med 25: 843-846, 1999

4. Lichtwarck-Aschoff M, Zeravik J, Pfeiffer U: Intrathoracic blood volume accurately reflects circulatory volume status in critically ill patients with mechanical ventilation. Intensive Care Med 18: 142- 147, 1992;

5. Hedenstierna G: What value does therecording of intrathoracic blood volume have in clinical practice? . Intensive Care Med 187137-138

6. Sakka SG, Meier-Hellmann A, Reinhart K: Assessment of intrathoracic blood volume and extravascular lung water by single transpulmonary thermodilution. Intensive Care Med 26: 180-187, 2000


Anaesthetic management of a Patient withESRD for Renal Transplantation 100 Gita Nath

For patients with end-stage renal disease, renal transplantation is the treatment modality which gives the best quality of life and survival.11'21 This patient population includes relatively younger patients with primary renal disease at one end of the spectrum, and older patients with renal failure secondary to diabetes or hypertension, with diffuse atherosclerosis and heart disease at the other end. With improvements in anaesthetic and surgical techniques as well as immunosuppressive drugs, many patients are being accepted for transplantation that would have been considered unsuitable earlier. However, this means we, as anaesthesiologists, have to deal with sicker patients with greater pathophysiological compromise. Hence it is important for us to have a clear understanding of the changes in physiology as well as pharmacology in renal failure.

PATHOPHYSIOLOGIC EFFECTS OF CHRONIC RENAL FAILUREFluid and Electrolyte disturbances

The primary function of the kidneys is to regulate the volume and composition of extracellular fluid. End-stage renal failure is usually associated with hypervolemia due to a greatly reduced glomerular filtration rate and several electrolyte disturbances. 131 Patients presented for renal transplantation are usually well prepared with dialysis and other measures, but even so there is very little margin for error. Overdialysis can lead to hypovolemia and cardiovascular collapse but a positive balance of as little as 500 ml may tip the patient into pulmonary oedema. Most patients produce some urine - 500 to 100 ml/day or even more. But this volume is fixed - it cannot be regulated according to the needs of the body. The few remaining nephrons are, in fact, in a state of maximal osmotic diuresis.

There is a chronic anion gap metabolic acidosis in renal failure due to retention of sulphates and phosphates. Mild acidosis usually persists despite dialysis and is even helpful as it compensates for anaemia. However the decrease is buffer base reduces the margin of safety, and severe acidemia can be caused by relatively mild ventilatory depression. An important point to keep in mind is the relation between H+ and K+. A change in pH of 0.1 results in a 0.5 mEq/L change in serum K+. That is, a decrease in pH from 7.4 to 7.2 may increase the serum K+ from 5.5 to 6.5 mEq/L.

The usual consequence of ESRD on K+ balance is hyperkalemia due to diminished or absent loss through the kidney. The level should be normalized preoperatively by regular dialysis. Hyperkalemia may be worsened or precipitated by conditions such as catabolic stress, acute acidosis - either metabolic or respiratory, and drugs such as ACE inhibitors. Similarly, a patient with borderline low serum K+, maybe due to overzealous dialysis, can be pushed into hypokalemia by hyperventilation. Magnesium is handled by the kidney in a fashion similar to potassium. Hyper-magnesemia is relevant to the anaesthetic assessment, as it causes muscle weakness and potentiates the action of muscle relaxants.

Phosphate elimination depends on the kidneys and hyper-phosphatemia may persist despite dialysis. In addition, renal synthesis of Vitamin D3 (1,25-dihydroxy-chole-calciferol) is deficient in renal failure resulting in reduced calcium absorption from the gut. Both hyperphosphatemia and hypocalcaemia stimulate the parathyroid glands causing parathyroid hyperplasia - this is called secondary hyperparathyroidism. The released parathormone



causes bone resorption leading to renal osteodystrophy. In some patients one or more parathyroid glands become autonomous - the so-called tertiary hyperparathyroidism. These patients present with hypercalcaemia and may show metastatic calcification. They may need parathyroidectomy, retaining either a small part of one parathyroid or a forearm autograft of parathyroid tissue. Hypophosphataemia is less common, may be due to excessive dialysis or antacid therapy, and is deleterious as it causes muscle weakness and ventilatory insufficiency.

AnaemiaThis results from decreased

erythropoetin production from the kidney as well as diminished erythrocyte survival.1341 There are also several compensatory mechanisms for this chronic anaemia. The increased level of 2,3 DPG in the erythrocytes and the acidosis present in renal failure result in a rightward shift of the haemoglobin dissociation curve, thus increasing oxygen delivery to the tissues. There is a compensatory increase in the cardiac output and the lowered viscosity helps in better peripheral perfusion. Evalurtion of the effort tolerance of the patient gives one a better idea of his physiological reserve than the Hb value. In fact it has been shown that many haemodialysis patients with hematocrit levels around 25% tolerate treadmill exercise.151 However, in those patients with reduced cardio-respiratory reserve for other reasons, for example coronary artery disease, haematocrit values of around 30% should be aimed for, using recombinant erythropoietin therapy or pre-operative transfusions if necessary.

CoagulopathyPlatelet dysfunction is seen in uremic

patients. It is thought that activation of glycoprotein llb/llla receptors on the platelet membrane is impaired by a dialyzable uremic factor. This results in reduced platelet binding to von Willebrand-Factor VIII complex and fibrinogen, and impaired thrombus generation. Anaemia is an additional contributor to platelet dysfunction as erythrocytes enhance platelet function by releasing ADP and inactivating vascular prostacyclin (PGI2).

The prothrombin time and activated thromboplastin time are usually normal in uremia

unless there is residual heparin in the body after the previous dialysis. Since the platelets counts are normal as well, uremic coagulopathy can be difficult to detect as platelet function tests are not commonly performed. Alternatively, bleeding time can be measured. This is a sensitive indicator of platelet dysfunction but the results are somewhat operator variable.16 71

Platelet function can be improved by effective dialysis. Other measures to treat bleeding diathesis in uremia are desmopressin, which releases von Willebrand-Factor VIII complex from the endothelium, and conjugated oestrogen, whose mechanism of action has not been elucidated. Erythopoetin is helpful by correcting anaemia as well as increasing the number of glycoprotein llb/llla receptors on the platelets. For refractory patients, cryoprecipitate is effective, as it is rich in von Willebrand’s factor and fibrinogen.

HypertensionThis has an intimate relation with renal

failure, as it can be both the cause as well as effect. Expansion of extracellular fluid volume along with disturbances in vascular autoregulation produces hypertension in these patients. There are several mechanisms involved as recently summarized by Mailloux: (1) inappropriately increased angiotensin II in relation to volume and exchangeable sodium, (2) increased vascular sensitivity to endogenous pressors, (3) increased cardiac output in the presence of an inappropriately high peripheral vascular resistance, and (4) failure to fully suppress vasoconstrictor systems[8].

Some patients become normotensive after the initiation of dialysis but many need multiple drugs to bring the blood pressure under control. The exact management of the antihypertensive therapy during the peri-operative period needs to be carefully thought out. One concern is to prevent excessive hypertension, especially at critical times such as anaesthetic induction and intubation, so as to avoid adverse effects on the heart and cerebral vasculature. However, after revascularizing the kidney, we need to maintain a good perfusion pressure (at least 130-140 mmHg systolic or 90-100 mmHg mean pressure), as this is one of the most important factors influencing the outcome of the



transplantation procedure. Overtreatment of the hypertension can make it difficult to achieve this.

Most antihypertensive drugs should be continued till the day of surgery. Sudden cessation of clonidine or beta blockers can result in rebound hypertension. However ACE inhibitors have been found to be associated with intraoperative hypotension, hence it is better to omit this group of drugs on the day of surgery.19101

Post-operatively, many patients become normotensive. Hence it is better to withhold antihypertensives initially and monitor the blood pressure closely. Drugs can be restarted if the patient becomes hypertensive.

Heart and CRFFirst of all we need to consider the effects

of hypertension on the heart, such as left ventricular concentric hypertrophy, decreased LV compliance, diastolic dysfunction and propensity to myocardial ischaemia. Apart from this, the incidence of cardiomyopathy and coronary artery disease is high in these patients, and is a major cause of morbidity and mortality.

LV dysfunction may be caused by ischaemic heart disease, diabetes, hypoalbuminemia, anaemia etc. In addition, uremia itself causes uremic cardiomyopathy which is seen on echocardiography as LV dilatation and ineffective ventricular hypertrophy. This is reversible following renal transplantation, and ejection fractions of less than 30% have been shown to normalize to 69% six months after transplantation.1111 Thus LV dysfunction per se is not a contraindication to transplantation but the presence of congestive heart failure before the patient goes on dialysis is an independent predictor of mortality.1121

Uremic patients show peripheral insulin resistance and decreased lipoprotein lipase activity and are thus prone to hyperglycemia and hypertriglyceridemia. In addition many of them have pre-existing diabetes. For these reasons, coronary artery disease has a high incidence of 17-34 % in uremic patients. Hence all symptomatic or high risk patients (those with diabetes or hyperlipidemia, smokers,) should be screened before surgery. Dipyridamole-thallium

scanning has been found to have a high false negative rate because the myocardial microcirculation has a reduced response to dipyridamole. Dobutamine stress ECG performs better as a screening test in these patients.1131

Uremic pericarditis may cause pericardial effusion which may be haemorrhagic due to the heparin received during dialysis. Pre-operative echocardiography should detect this condition and if cardiac tamponade is present a sub-xiphoid pericardiostomy should be done under monitored anaesthetic care.'141

Miscellaneous Problems.Due to restricted diets and loss of protein

during dialysis, hypoalbuminemia is common, favoring the formation of interstitial and pulmonary oedema. The poor nutrition and anaemia also predispose the patient to infections. Nosocomial infections are especially common at dialysis access sites. The incidence of hepatitis B and C is high in haemodialysis patients due to frequent exposure to blood and blood products. Many of them become asymptomatic carriers.

PHARMACOLOGIC CHANGES IN CRFThe response of patients to many drugs

is different in renal failure, due to pharmacokinetic as well as pharmacodynamic reasons. Clinically, patients seem more sensitive to sedatives and hypnotics. This is because of increased pharmacodynamic effectiveness of the drug as well as increased availability at the effect site. Thiopentone and diazepam are highly protein bound drugs, and the unbound fraction is increased when there is hypoalbuminemia.

In general, to produce the effect of the drug, a therapeutic concentration has to be produced in the volume of distribution. Therefore the initial dose is similar to normal patients, with two exceptions - if the volume of distribution is reduced, as for morphine, alfentanil and remifentanil1151, and secondly if the drug is highly protein bound, as discussed above.

For maintenance dosing, the behaviour of the drug depends on its mode of elimination and whether there are any significant active metabolites. Drugs which totally or predominantly


Anaesthetic management of a Patient withESRD for Renal Transplantation _________ 103 Gita Nath

depend on renal excretion can be given in normal doses for the initial effect but maintenance doses must be greatly reduced. It may be better to avoid these drugs if alternatives are available.

Some drugs have an alternate route of elimination, such as biliary excretion for

d-tubocurarine and hepatic metabolism for pancuronium and vecuronium. These also should be given in normal doses initially but subsequent doses may be reduced and delayed. Drugs which are not affected by renal failure can be given in the usual doses. (Table-1)

Drug Pharmacokinetics Drug Class Specific Drugs Change in dosing

Highly protein bound Barbiturates

Benzodiazepine

ThiopentoneMethohexitoneDiazepam

Reduce dose by 30-50 %

Reduced VD Narcotics MorphineAlfentanilRemifentanil

Reduce initial dose

Predominantly renal elimination

Muscle relaxants

Antibiotics

CVS

GallamineMetocurinePenicillinsCephalosporinsAminoglycosidesDigoxin

No change in loading dose. Reduce maintenance dose.Avoid ifalternative available

Partially eliminated by kidney

Anticholinergics

Cholinergics

Muscle relaxants

AtropineGlycopyrrolateNeostigminePyridostigmineEdrophoniumTubocurarinePancuroniumVecuroniumRocuroniumDoxacuriumMivacurium

No change in loading dose. Reducemaintenance dose by 30-50 %.

Elimination not affected by renal failure

IV anaesthetics

Narcotics

PropofolKetamine

FentanylSufentanilRemifentanil

Muscle relaxants SuccinylcholineAtracurium

Table 1: Dose Adjustment in Renal Failure



Drug Metabolites Activity Comments

Morphine Morphine 3-glucuronide Antanalgesic

Morphine 6-glucuronide Analgesic Very delayed

Pethidine Nor-pethidine Neuro-excitatory

Diazepam Oxazepam Sedative

Midazolam 1 -hydroxy midazolam Sedative

Pancuronium 3-hydroxy pancuronium Relaxant

Vecuronium Des-acetyl vecuronium Relaxant

Atracurium Laudanosine Neuro-excitatory

Table 2. Drug Metabolites in Renal Failure

Several drugs have active metabolites which are not significant in normal patients. However if repeated or excessive doses are given to patients in renal failure, the metabolites accumulate and can produce prolonged or delayed effects. The effect produced by the metabolite may be similar to the parent drug or may be antagonistic or toxic, as listed in Table 2[16,17,18,19]

Pharmacokinetics of inhalational agents are not affected by renal failure, but some of the agents can affect the kidney. The classic nephrotoxic agent is methoxyflurane, which is metabolized in the body to a large extent (upto 75% of the absorbed amount), and one of the products of its metabolism, the fluoride ion, produces high output renal failure. As much as 24-45 % of the absorbed halothane is metabolized, but it does not form fluoride, hence it does not cause renal toxicity. Only 2-8 % of the absorbed enflurane is metabolized, but it produces fluoride levels approaching the nephrotoxic threshold (40-57 mmol/L). Just 0.2 % of the absorbed isoflurane is absorbed, and it produces fluoride levels in the range of 4 mmol/L, hence there is little fear of renal toxicity. About 1 -5 % of the newer agent sevoflurane is metabolized and fluoride levels of upto 50 mmol/L are seen, but this agent has not been associated with renal toxicity. The newest agent, desflurane is metabolized least of all (0.02 %), so it is least

likely to produce any organ toxicity, but its cost and the need to change vaporizer technology make it unlikely to come into common usage [20'21].

PRE-OPERATIVE ASSESSMENT AND PREPARATION

The patient should be carefully assessed, keeping in mind the various physiological derangements discussed earlier. In the history the following points should be noted:• Cause and course of the disease• Symptoms such as angina, bleeding

diathesis• Duration and type of dialysis, side effects

and complications• Effort tolerance to estimate the

cardiopulmonary reserve• Daily urine output• Previous anaesthetic history• Medications taken by the patient

During physical examination one should assess the following:• State of hydration, anaemia, fever• Blood pressure, in the supine and erect

positions• Cardiovascular system, for LVH, pericardial

effusion, signs of congestive failure• Lungs for pleural effusion, pneumonia• Signs of coagulopathy



The following laboratory investigations should be included:• Haematological - Hematocrit, leucocytes,

platelet count, coagulation studies including Ivy bleeding time

• Biochemical - BUN, creatinine, Na+, K+, HCO'3Ca++, Phosphate, Mg++, Albumin, Glucose

• Serological - Hepatitis B and C, HIV status• ECG - for myocardial ischaemia, LVH,

arrhythmias, electrolyte effects• Chest X-ray - Cardiomegaly, pericardial or

pleural effusions, pneumonia• Echocardiography-Assessment of

myocardial function, ventricular hypertrophy, pericardial effusion

If the patient is on haemodialysis, preoperative dialysis should be performed the day before surgery. The amount of fluid removed and the post-dialysis biochemistry should be noted. The effect of residual heparin wears off by 6 hours, and should not interfere with surgery. CAPD may be continued till the time of surgery.

Antihypertensive therapy should be continued till the day of surgery but ACE inhibitors should be omitted. Premedication, if necessary may include a small dose of oral benzodiazepine. For patients at risk of aspiration, a H2 blocker, metoclopramide and sodium bicitrate may be given.

INTRA-OPERATIVE MANAGEMENTRoutine monitoring should include ECG,

oxygen saturation, capnography, neuromuscular monitor and temperature. Care should be taken to protect the arm which has the dialysis access- neither an IV line nor a blood pressure cuff should be placed on that arm. It is better to avoid invasive blood pressure monitoring in case the radial artery is needed for creation of an AV fistula in the future. For the same reason, it is preferable not to use the cephalic vein at the wrist for IV access.

A central venous line is mandatory in all patients, whether under general or regional anaesthesia, to aid in fluid management. Patients with LV dysfunction may need pulmonary artery catheterization.

A urinary catheter is necessary for monitoring the urine output. In should be noted that the bladder is initially filled with saline by the surgical team, and the catheter is clamped, in order to facilitate surgical access to the bladder for re-implantation. This fluid should be excluded, while monitoring urine output after revascularizing the kidney.

Renal transplantation is usually done in the supine position. Great care should be taken to protect the limb with dialysis access. Due to renal osteodystrophy, the bones are very fragile; hence any change in position should be done gently. Attention should be paid to padding the various pressure points - impairment of skin integrity as well as pre-existing peripheral neuropathy should be kept in mind.

Preventive measures should be taken against hypothermia, which may include adjustment of ambient temperature, warming mattress, insulation of all exposed body parts, heater-humidifierfor the inspired air, forced hot air warmers and fluid warming systems. These measures should be continued during the recovery period.

These patients already have impaired immunity because of the primary condition. In addition, immunosuppressive therapy will be instituted to prevent rejection. Hence great attention should be paid towards aseptic technique. On the other hand, they have a higher incidence of blood borne infections such as Hepatitis B and C and HIV. Hence the medical staff should take measures to protect themselves.

Selection of anaesthetic technique:The goals of anaesthetic management

of renal transplantation are:• To tailor the anaesthetic keeping in mind all

the physiological derangements detailed earlier.

• To take measures to optimise functioning of transplanted kidney

• To ensure that there are no residual effects of the anaesthetic drugs or techniques, in case graft functioning is delayed.



• If post-operative dialysis becomesnecessary, to delay it as much as possible so that the interval between surgery and administration of heparin is longer. In essence, this involves avoiding fluid overload and potassium build-up.

As long as the above principles are kept in mind, the actual anaesthetic technique does not make a difference to the outcome. Renal transplantation has been successfully managed using general as well as regional anaesthetic techniques such as spinal and epidural anaesthesia122'. The concern with regional anaesthesia is the risk of hypotension which, if treated with aggressive fluid administration, may lead to pulmonary oedema when the block wears off. Apart from this, expected length of the operation and poor patient cooperation influence the choice of anaesthetic technique. Coagulopathy, which would contraindicate a regional technique, should also be borne in mind, since this may occur even with normal platelet count, prothrombin time and activated thromboplastin time.

Regarding general anaesthesia, both inhalational as well as intravenous techniques can be equally effective. As far as possible drugs whose pharmacokinetics are not affected by renal failure should be used, but this has to be balanced against the availability of resources and the previous experience of the anaesthetist. As with many issues in anaesthesia, it is more important to choose one’s anaesthetist than the anaesthetic technique.

Induction of anaesthesia:Preoxygenation is advisable in these

anaemic patients to improve the oxygen reserve. The intravascular volume is often somewhat depleted after the last dialysis, and carefully titrated fluid increments may be given to avoid hypotension. The goal is to avoid excessive hypotension, but at the same time, prevent excessive hypertensive response to intubation. A bolus dose of a narcotic (e.g. fentanyl 2-3 mic/ kg) helps towards this end.

Thiopentone, etomidate and propofol are the choices available for induction of anaesthesia. Ketamine is not suitable because of its

hypertensive effect. The dose of thiopentone should be reduced because of the reduced protein binding. The usual recommended induction dose of 2 mg/kg propofol causes hypotension even in normal patients, hence carefully titrated doses should be given, checking the blood pressure between doses. Propofol seems to prevent the intubation response much more effectively than thiopentone.

If the risk of aspiration is present, a single dose of succinylcholine may be given as long as the serum potassium is less that 4.5 mEq/L. Rocuronium is the other choice, since it produces satisfactory intubating conditions in 60 to 90 seconds and can be used to maintain relaxation till the end of the procedure. Rapacurium is another steroidal non-depolarizing relaxant, with slightly faster onset than rocuronium, but it has now been withdrawn because of an unacceptably high incidence of adverse events.

If there is no risk of aspiration, the nondepolarising agent can be given directly. Atracurium and cis-atracurium are the relaxants of choice because of their spontaneous breakdown independently of the kidneys or liver. Vecuronium or rocuronium may also be used but the maintenance doses should be reduced and delayed. Pancuronium should be avoided, now that so many alternatives are available. Neuromuscular monitoring is mandatory in these cases t23]. Mivacurium is another agent which doesn’t depend on the kidneys for elimination, but its action is so short-acting that it has to be given by infusion. The large amount required for such a long operation means that it is not cost- effective [24].

After intubation, the patient is ventilated with an oxygen/nitrous oxide or oxygen/air mixture. Excessive hypocapnia or hypercapnia should be avoided, bearing in mind the possible shifts in potassium with changing blood pH. For maintenance of anaesthesia, either a nitrous oxide-oxygen-inhalational agent combination or an intravenous propofol-narcotic infusion can be used with equally good results125 26 271. Isoflurane is probably the best inhalational agent, from the renal point of view Fentanyl, sufentanil or alfentanil can all be used for maintenance of narcotic effect Remifentanil has the advantage of lack of


Anaesthetic management of a Patient withESRD for Renal Transplantation__________ 107 Gita Nath

cumulationt28]. Morphine and pethidine are better avoided, because of accumulation of their metabolites morphine-6-glucuronide and nor- pethidine, with analgesic and neuro-excitatory effects respectively116171.

After induction, minimal fluids are given as long as the blood pressure is adequate. Extra fluid administered at this time redistributes into the extravascular space and is not available for renal perfusion after anastamosis. It is better to fill up more rapidly closer to the time of clamp release. Hartmann’s solution and Ringer Lactate solution should be avoided as they contain potassium.

OPTIMIZING FUNCTION OF THE TRANSPLANTED KIDNEY:

Three aspects of management critically affect the outcome of renal transplantation - the management of the renal donor, how well the graft is preserved and thirdly, perioperative management of the kidney.

1. Management of the donorLiving donors are involved in about 25%

of all renal allografts in the United States, but contribute to the majority of renal transplants in India. All living kidney donors, related or unrelated, should be in excellent health, without any medical problem which increases the risk of anaesthesia. Also they should not have any condition which makes them prone to renal failure in the future, such as hypertension and diabetes.

The operation is performed in the lateral position with the kidney bridge elevated. The key point in managing these patients is to keep the kidneys well oxygenated and perfused, and take measures to reduce their oxygen consumption. Good hydration is mandatory. Some centres make it a practice to give IV fluids overnight. In any case, 1.5 to 2 litres of crystalloids should be infused during the initial part of the operation, and this is followed by 10-12 gm of mannitol. A small dose of lasix may help by blocking the chloride pump in the thick ascending loop of Henle, thus reducing oxygen consumption in a poorly perfused and vulnerable area of the kidney. The urine output should be monitored and a good diuretic response ensured. Maintenance of a good perfusion pressure is important and the colour

and turgidity of the kidney are good indicators of its perfusion. Direct acting vasopressors should be avoided, so that renal artery spasm is not induced. From the surgical side, the kidney and its hilar structures should be handled gently, since spasm of the renal artery can be very troublesome. Some surgeons request 5000 units of heparin before clamping the artery - this can be reversed with protamine 50 mg after the kidney is harvested.

After removal of the kidney, anaesthesia is continued according to one’s normal routine. It is important to ensure that the donor does not come to any harm as the result of his generous action, hence special care should be taken to avoid any anaesthesia or surgery related complications. If the 11th or 12th rib was resected during surgery, a high index of suspicion should be maintained to detect the occurrence of a pneumothorax. Special attention should be directed towards postoperative analgesia, as donor nephrectomy is a very painful operation. Intermittent injections of morphine or pethidine are not really effective. Other methods such as patient controlled analgesia, epidural local anaesthetic or opiate infusions, wound infusion with bupivacaine and other techniques are more effective.

Cadaveric donors contribute to the majority of renal transplants done in the developed world, and cadaveric transplantation is becoming commoner in India as well. The salient points in managing cadaver donors are:

• A protocol for brain death certification should be in place in each institution. This should be followed meticulously so as to afford no chance for anyone to point a finger.

• Haemodynamic stability and good gas exchange criteria give the best results. Contraindications to organ harvesting are prolonged hypotension and hypothermia, systemic sepsis, malignancy, DIC, hepatitis B or C and HIV seropositivity. Relative contraindications are age (above 70), diabetes, vascular diseases, elevated serum creatinine and high requirement for vasopressors.

• A Pa02 of at least 100 should be



maintained with normocapnia. The arterial pressure should be kept above 100 mmHg, with aggressive fluid treatment. If intravascular volume is adequate but blood pressure is still below 90 mmHg, inotropes can be added, such as dobutamine, low dose dopamine, or low dose adrenaline. High doses of vasopressors, with a vasoconstricting effect such as high dose dopamine, high dose adrenaline and noradrenaline are associated with a worse graft function possibly because of renal vasoconstriction [29], The urine output should be maintained above 100 ml/hr using mannitol, lasix and dopamine, if necessary.

• This treatment is continuedintraoperatively. Muscle relaxants are given to suppress the reflex motor response to surgery. Ventilatory and circulatory support is discontinued after the organs are harvested.

2. Preservation of the harvested organTotal ischaemia time starts when the

donor renal artery is clamped, and ends after the anastamosis when the artery is unclamped in the recipient. Minimizing the ischaemia time is critical in preservation of the kidney. Warm ischaemia is especially deleterious to the kidney as oxygen consumption continues with no oxygen supply. Warm ischaemia starts when the renal artery is clamped and stops when the kidney is cooled by perfusion with a cold solution. Cold ischaemia starts when the core of the kidney becomes cold, as is evidenced by clear perfusion fluid flowing out of the cut end of the renal vein. Cold ischaemia can be maintained for upto 36- 72 hours by storing the kidney at4°C but results are better if the cold ischaemia time is less than 24 hours.

Warm ischaemia time resumes when the kidney is removed from the cold contained and is placed in the recipient and ends when the kidney is perfused again after completion of the vascular anastamosis.

For short ischaemia times, the composition of the perfusate does not matter so much, and perfusion with ice-cold normal saline gives as good results as if a special preservative solution was used. For longer periods of storage, several solutions are available. Euro-Collins solution contains high concentrations of

potassium (110 mM), magnesium sulphate (30 mM), and phosphate (57.5 mM), which mimics intracellular fluid composition; and mannitol which makes the solution hypertonic and prevents cell swelling within the kidney. The UW solution (University of Wisconsin solution) contains lactobionate, raffinose, and hydroxyethyl starch for their osmotic effect, phosphate as a buffer, adenosine for ATP synthesis during reperfusion, glutathione as a free-radical scavenger, allopurinol to inhibit xanthine oxidase and the generation of free radicals, and magnesium and dexamethasone as membrane-stabilizing agents. The UW solution gives better results and can be used for all intra-abdominal organs. Machine perfusion with a cold solution similar to UW solution further extends the cold ischaemia time of the kidney[30).

3. Other measures to optimise graft function• Perfusion Pressure: This is the key factor which influences immediate graft function, and any delay in graft functioning is associated with a worse outcome for the graft in the early posttransplant period as well as long term I31'32). Hence, haemodynamic management is geared towards providing a perfusion pressure of at least 120 mmHg at the time of clamp release. The following measures may be taken towards this goal:• Close haemodynamic monitoring, with frequent checks of blood pressure and CVP• Aggressive intravascular volume expansion. Fluid loading with 1-2 litres of normal saline is done while the vascular anastamosis is being done.• It is important to anticipate and expect hypotension after release of clamps because of reperfusion of the ischaemic vascular bed of the graft and washout of metabolites. Repeated checking of blood pressure is very important. The surgeon’s assessment of the firmness or turgidity of the graft is a useful index of the adequacy of the perfusion pressure.• If verapamil has been added to the renal perfusate, it can cause hypotension on being washed into the circulation when the clamp is released. To cover this, calcium chloride 0.25 gm can be given before and a further 0.25 gm after clamp release.

• Mannitol 10-20 gm before clamp release: This acts by expanding the intravascular volume,



reducing cellular swelling, increasing tubular urine flow and reducing the potential for tubular obstruction, scavenging free radicals and increasing the release of intrarenal prostaglandins.

• Albumin has been found to improve the graft outcome at doses of 0.8 to 1.6 gm/Kg [33-34]. Albumin acts by improving the oncotic pressure and thus expanding the intravascular volume, especially in patients with hypoalbuminemia.

• Loop diuretics such as frusemide block the chloride pump in the thick ascending loop of Henle, and increase resistance against ischaemic injury. Despite several theoretical reasons, it is not clear whether they improve transplant outcomel351.

• Verapamil has been shown to improve graft outcome, either when administered to the recipient [36) or added to the renal perfusate.

• Low dose dopamine is said to enhance renal perfusion by selective renal vasodilatation and also promotes natriuresis. However, several studies have not been able to show an improved outcome during cadaver renal transplantation with dopamine 2-3 mic/Kg/min t37 38 39). Hence routine use of dopamine is not recommended.

• The Kidney Cocktail. Some centres infuse a kidney cocktail just before the anastamosis is completed. This consists of 600 ml 1/4 normal saline with albumin 37.5 gm and mannitol 80 gm. For cadaver transplantation, they add 80 mg frusemide[4].

MONITORING OF KIDNEY FUNCTIONThe initial assessment of urine output is

made soon after renal revascularization, by looking out for urine to spurt from the end of the ureter. Once ureteric implantation begins, urine output cannot really be monitored till the bladder is closed. One should be careful to exclude the volume of saline initially used to distend the bladder from the measured urine output.

TROUBLE-SHOOTINGIf there is a delay in urine formation,

prerenal factors should be evaluated first of all, such as perfusion pressure, the anastamosis,

arterial spasm or thrombosis, venous occlusion or thrombosis etc. The consistency of the kidney and thrill at the site of the anastamosis can help confirm good blood flow. Intraoperative Doppler can also evaluate the anastamotic flow.

Post renal factors are outflow tract obstruction due to kinking, clot, oedema; or leakage of urine from the bladder implantation site. The problem may be as simple as a kinked or blocked urinary catheter, or even an air-lock in the catheter drainage bag.

When all these factors are excluded, a biopsy of the transplanted kidney may be necessary to evaluate for acute tubular necrosis or graft rejection.

RECOVERY FROM ANAESTHESIAPotential problems which should be

anticipated at recovery are delayed emergence, respiratory depression, hypo or hypertension, respiratory depression and pulmonary oedema. Adequate recovery of neuromuscular function must be ensured before extubation. Persistent weakness due to hypermagnesaemia may be antagonized by giving calcium. As far as possible it is better to avoid postoperative mechanical ventilation because of the risk of pulmonary infection.

The patient should be transferred to a dedicated transplant unit for postoperative management. Apart from barrier nursing, cardiorespiratory and renal functions are monitored closely for the next few days. Postoperative pain is usually not a problem. Once the kidney has started working, there is no problem with accumulating metabolites, and morphine can be used safely.

CONCLUSIONTransplant anaesthesia is a specialized

field which requires a good understanding of the physiological trespass in patients with renal failure, familiarity with transplant medicine and expertise in the management of these patients. Good anaesthetic management, in liaison with the transplant surgeon and nephrologist, is of paramount importance in avoiding delayed graft function with all its possible sequelae and complications.


Anaesthetic management of a Patient withESRD for Rena( Transplantation 110 Gita Nath

REFERENCES1. Cameron Jl. Differences in quality of life across renal replacement therapies: a meta-analytic comparison. Am J Kidney Dis 2000; 35(4): 629-372. Rabbat CG. Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada. J Am Soc Nephrol 2000; 11(5): 917-223. Sladen RN Anesthetic considerations for the patient with renal failure.- Anesthesiol Clin North America 2000; 18(4): 863-82, x.4. Sprung J, Kapural L, Bourke DL,O’Hara JF. Anesthesia for kidney transplant surgery. Anesthesiol Clin North America2000; 18(4): 919-51.5. Lundin AP, Stein RA, Brown CD, et al: Fatigue, acid-base, and electrolyte changes with exhaustive treadmill exercise in haemodialysis patients. Nephron 1987; 46:57-62.6. Mahesh K. Preoperative Care of Patients with Kidney Disease. American Family Physician 2002; 66: 8.7. Dember LM. Critical care issues in the patient with chronic renal failure. Critical Care Clinics 2002; 18: 2.8. Mailloux LU: Hypertension in chronic renal failure and ESRD: Prevalence, pathophysiology, and outcomes. Semin Nephrol 2001; 21:146-156.9. Powell CG. Severe hypotension associated with angiotensin-converting enzyme inhibition in anaesthesia. Anaesth Intensive Care 1998; 26(1): 107-9.10. Licker M. Cardiovascular responses to anesthetic induction in patients chronically treated with angiotensin- converting enzyme inhibitors. Can J Anaesth 2000; 47(5): 433-40.11. Cho WH, Kim HT, Park CH, et al: Renal transplantation in advanced cardiac failure patients. Transplant Proc 1997; 29:236-238.12. Harnett JD, Foley RN, KentGM, etal: Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis, and risk factors. Kidney Int 1995; 47:884-890.

13. Herzog CA, Marwick TH, Pheley AM: Dobutamine stress echocardiography for the detection of significant coronary artery disease in renal transplant candidates. Am J Kidney Dis 1999; 33:1090.14. Figueroa W, Alankar S, Pai N, et al: Subxiphoid pericardial window for pericardial effusion in end-stage renal disease. Am J Kidney Dis 1996; 27: 664-7.15. Dahaba AA End-stage renal failure reduces central clearance and prolongs the elimination half life of remifentanil- Can J Anaesth 2002; 49(4): 369-74.16. Angst MS, Buhrer M, L6tsch J: Insidious intoxication after morphine treatment in renal failure: Delayed onset of morphine-6-glucuronide action. Anesthesiology 2000; 92: 1473-6.17. Hasselstrfim J, Berg U, Lofgren A, Sawe J: Long lasting respiratory depression induced by morphine-6- glucuronide? Br J Clin Pharmacol 1989; 27: 515-8.18. Sear J: Effect of renal function and failure. In Park GR, Sladen RN (eds): Sedation and Anesthesia in the Critically III. Oxford, Blackwell Science, 1995, pp 108-2919. Hall LG - Analgesic Agents. Pharmacology and Application in Critical Care Crit Care Clin 2001; 17(4): 899- 923, viii.20. Baden JM, Rice SA. Metabolism and Toxicity of Inhaled Anesthetics. In Miller RD (ed): Anesthesia. 5th ed., Copyright © 2000 Churchill Livingstone, Inc, pp 155-167.

21. Conzen PF, Nuscheler M, Melotte A, et al: Renal function and serum fluoride concentrations in patients with stable renal insufficiency after anesthesia with sevoflurane or enflurane. Anesth Analg 1995; 81:569-75.22. Murakami M, Nomiyama S, Ozawa A, et al: Anaesthetic management of pediatric renal transplantation for chronic renal failure. Masui 1993; 42:263-270.23. Murray MJ - Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 2002; 30(1): 142-56.24. Head-Rapson AG Pharmacokinetics and pharmacodynamics of the three isomers of mivacurium in health, in end-stage renal failure and in patients with impaired renal function. - Br J Anaesth 1995; 75(1): 31-6.25. Ickx B Propofol infusion for induction and maintenance of anaesthesia in patients with end-stage renal disease. - Br J Anaesth 1998; 81(6): 854-60.26. Babacan A Assessment of total intravenous anesthesia in renal transplantation. Transplant Proc 1998; 30(3): 750-3.27. Jirasiritham S Total intravenous anesthesia for general operations in post-renal transplant patients. Transplant Proc 1998; 30(7): 3897-8.28. Hoke JF Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers. Anesthesiology 1997; 87(3): 533-41.29. O’Brien EA, Bour SA, Marshall RL, et al: Effects of use of vasopressors in organ donors on immediate function of renal allografts. Journal of Transplant Coordination 1996; 6:215-216.30. Van der Werf WJ, D’Alessandro AM, Hoffmann RM, Knechtle SJ. Procurement, Preservation, And Transport Of Cadaver Kidneys. Surgical Clinics of North America 1998; 78(1) 41-54.31. Dawidson I, Ar’Rajab A: Perioperative fluid and drug therapy during cadaver kidney transplantation. In Terasaki, Cecka (eds): Clinical Transplants. Los Angeles, 1992, pp 267-27932. Rajamani AR, Kamat VN, Poojara L, Arunkumar AS. Haemodynamic variables affecting kidney allograft function. Intensive Are Medicine 2002; 28: (Suppl 1) S10233. Willms CD, Dawidson IHA, Dickerman R, et al: Intraoperative blood volume expansion induces primary function after renal transplantation: A study of 96 paired cadaver kidneys. Transplant Proc 1991; 23:1338-1339.34. Dawidson IJ Intraoperative albumin administration affects the outcome of cadaver renal transplantation - Transplantation 1992; 53(4): 774-82.35. Shilliday I, Allison ME: Diuretics in acute renal failure. Renal Fail 1994; 16:13-17.36. Dawidson I, Rooth P, Lu C, et al: Verapamil improves the outcome after cadaver renal transplantation. J Am Soc Nephrol 1991; 2:983-990.37. Grundmann R, Kindler J, Meider G, et al: Dopamine treatment of human cadaver kidney graft recipients: A prospectively randomized trial. Klinische Wochenshrift 1982; 60:193-197.38. Kadieva VS, Friedman L, Margoulius LP, et al: The effect of dopamine on graft function in patients undergoing renal transplantation. Anesth Analg 1993; 76:362-365.39. Sandberg J, Tyden G, Groth CG: Low-dose dopamine infusion following cadaveric renal transplantation: No effect on the incidence of ATN. Transplant Proc 1992; 24:357.


Sedation and Analgesia in Children for Procedures outside the OR 111 S. Ramesh

“ 6 year old Master X has been fearful of the repeated lumbar punctures that he must undergo for intrathecal medical administration, as well as his occasional bone marrow aspirations. His previous experiences include being held down while he screamed, with a long period of being silent and withdrawn after each procedure as no sedation or analgesics were given during these procedures. So Master X thereafter refused to come to see any doctor, withdrawn from his friends and needed lot of psychological consults ”

So children who undergo painful medical procedures not only have their physiological function affected, but also face complex psychobiological demands.

Painful diagnostic or therapeutic procedures are often necessary during emergency care of children who have already painful and frightening injuries and illnesses. For example, in a study done by us in 1997, it was found that 90% of lumbar punctures in the paediatric emergency department were performed without sedation or local analgesia. There are many reasons why effective anxiolysis, analgesia and sedation are not in commonplace in the emergency department. The explanations for less use of analgesia or sedation include lack of consensus about optimal safe effective methods, medications, patient monitoring, lack of physician familiarity with local anaesthetic techn^ :?s and dosing, insufficient time to carry outset ■■rd belief that children have only a short tern, of pain.

In India, the past decade has seen what may be considered a revolution in the recognition

and treatment of pain and anxiety in children. Advantages of safe and effective management of pain and anxiety in the emergency department include reduction of psychological trauma and its sequelae, reduction of stress for the paediatricians and parents and a good success for the procedures.

Due to the diversity in population, no ‘cookbook’ is available for the method and medication to be used for a particular procedure. What we must rely on is a broad understanding of the pharmacokinetics and the physiological effects of diverse agents. So this article will review some definitions, pain pathways, various medications available to us, principles of conscious sedation and a few examples of emergency procedures.

NEUROPHYSIOLOGY OF PAIN:‘Pain’

- “ An unpleasant and emotionalexperience associated with actual or potential tissue damage or described in terms of such damage”

_ Pain is ‘suffering’ or ‘distress’_ Pain is what the patient ‘says it is’

The basic mechanism of pain perception has four components, transduction, transmission, perception and modulation. Noxious mechanical, thermal or chemical stimuli excite primary afferent fiores that transmit information about the potential injurious stimuli from the periphery to

dorsal horn of the spinal cord. The pain repulse is transmitted via A delta (large, myelinated) and C (small, unmyelinated) fibres. The tissue injury causes release of inflammatory mediators, (eg.potassium, bradykinin,



Table 1: Stages of Sedation

prostaglandins, cytokines, catecholamines and Substance P) that sensitises the A and C fibres, which recruit other neurons, resulting in hyperalgesia. This nociceptive sensory input reaches the second order neurons in spinothalamic,spinoreticular andspinomesoencephalic tracts and is then widely distributed throughout the brain. As there is no single pain centre, the perception and modulation occurs within a distributive neuromatrix.

PRINCIPLES OF SEDATION AND ANALGESIA IN CHILDREN (Tab 1)Definitions:

Narcotic - A drug that inducesdrowsiness, sleep or stupor with analgesia

Sedative - A drug that calms or soothes without inducing sleep

Analgesic- A drug that relieves pain

Sedation and analgesia is something that many children will need during their stay in the emergency room. Unfortunately, the focus of medical care too often centres entirely on the physiological components of the child’s problem, and the emotional or painful aspects of a child’s treatment are ignored. Several factors amount for the anxiety and fear experienced by their children so unt for the anxiety and fear experienced by children during their stay in the emergency room including invasive procedures and the presence of unfamiliar people and medicines. Because no single agent can be expected to be effective in every patient, paediatricians should be familiar with different agents and be able to switch from one to another, when a particular agent is either ineffective or leads to adverse effects. Sedative

and analgesic drug’s indication and dosages cannot be given like that of antibiotics, but should be titrated to effect.

Stages of Sedation:The American Academy of Paediatrics

defines conscious sedation as a medically controlled state of depressed consciousness that allows protective reflexes to be maintained, maintain a patent airway and obey commands. Deep sedation is defined as the medically controlled state of unconsciousness from which the patient is not easily aroused. Although the term conscious sedation is used frequently, it is a misnomer because it implies some degree of co-operation on the part of the child. When frightened children are sedated to the point that they do not respond to a painful stimulus, it is by definition deep sedation (or even general anaesthesia!). So it is very important to distinguish between consciousness and deep sedation.

“ The phrase (Conscious Sedation) is an oxymoron that should be removed from the medical literature. When caring for children, particularly when they have to remain quite for any length of time, one must induce pharmacological coma; let us be honest and call deep sedation is exactly what it is and take proper care of these deeply sedated patients” - Charlie Cote.M.D.

NPO guidelines for conscious or deep sedation:(Tab 2)

Fasting guidelines are the same as for any anaesthetic regardless of how ‘light’ the sedative technique be and are given in Table 1.

Age Solids & non-clear Liquids (including milk)

clear liquids

Children > 36 months 6—8 hrs 2 — 3 hrsChildren 6 to 36 months 6 hrs 2-3 hrsChildren < 6 months 4- 6 hrs 2 hrs

Table. 2 NPO Guidelines



Is an Intravenous catheter necessary?Needle phobia is universal among

children. Previously healthy children who present for painful procedures will not have pre-existing IV access. It would be difficult to manage a child during a painful procedure without an IV access. Intravenous access is important for any emergency drugs to be administered, for fluid administration if there is any hypotension and for administering sedative or analgesics intravenously. If EMLA (Eutectic Mixture of Local Anaesthetic) is available, it can be applied an hour before the procedure for a painless IV access.

Which are the best sedatives or analgesics for children who undergo painful procedure?

This ‘million dollar’ question is most difficult to answer. There are no definitive techniques for a given procedure. The ultimate choice depends on the paediatrician’s preferences and comfort and the answers to the following questions.1. Is the procedure painful? e.g. Lumbar

puncture, bone marrow aspiration.2. What is the duration of the procedure?3. Does the child need to be motionless (EEG,

CT Scan, MRI)4. Is the child outpatient or inpatient?

Potential Risks of SedationAirway obstructionHypoventilationApnoeaCardiopulmonary impairment

Commonly used drugs:1. Benzodiazepines2. Trichlofos sodium3. Pethidine/Promethazine/Largactil4. Morphine5. Fentanyl

6. Ketamine7. Propofol8. Non-Narcotic analgesics9. Local anaesthetics

BENZODIAZEPINES:The benzodiazepines are sedative,

anxiolytic and anticonvulsant but are not analgesic. The biggest advantage of these drugs is their amnesic property. Of all the drugs midazolam has anterograde and retrograde amnesia. Of the benzodiazepines midazolam is the preferred agent for sedation in the emergency room because it is water soluble, has a shorter duration of action and a quicker onset of action than diazepam and lorazepam. Because of pain during IV injection, erratic absorption during intra muscular injection and long duration of action, diazepam is not a suitable sedative in the emergency department. Midazolam has minimal haemodynamic effects and is metabolised by the liver and excreted by the kidneys. IV Flumazenil can reverse Midazolam sedation at a dose of0.01 mg/kg/dose up to a maximum of 0.04mg/ kg-

In the event a combination of midazolam and narcotic is contemplated, the dosage of both must be individualized and administered by titration rather than by a fixed dosage schedule.

TRICHLOFOS SODIUM:Trichlofos sodium has been used for

rendering children immobile during painless procedures, like ophthalmological examinations, Echocardiogram, EEG, CT Scan and MRI Scan. Despite the safe records and absence of respiratory depression in sedated children, it is advisable to have continuous pulse oximetry monitoring during the procedure. Combination of Trichlofos and paracetamol can be used if a mild analgesic effect also is required. The dose is 50

Midazolam Onset DurationOralPer Rectum Intranasal IM IV

0.5 - 0.7mg/kg 0.25 - 0.5mg/kg 0.2 - 0.5mg/kg 0.05 -OASmgfkg 0.05 - 0.15mg/kg

15 - 20 min 10-30 min 5-15 min 10-20 min 2-3 min

45 - 90 min 60 - 90 min 45 to 60 min 60 -120 min 30 - 60 min

Table. 3 Dose, onset and duration of action of midazolam



to 100 mg/kg and the onset time is in 30 to 40 minutes and the duration of action is 90 to 120 minutes.

PETHIDINE / PROMETHAZINE / CHLORPROMAZINE

The combination of pethidine 2mg/kg, promethazine 1 mg/kg, and chlorpromazine 1mg/ kg called the ‘lytic cocktail’ has been used for many years for sedation in children especially for cardiac catheterisation. Due to availability of better drugs and significant episodes of hypotension, apnoea, prolonged recovery and dystonic reactions, the above combination is no longer recommended.

morphine. Its faster onset of action, short duration and potent analgesic effect makes this drug the narcotic of choice for a wide variety of painful procedures in the emergency room. If fentanyl is given fast, it might cause respiratory depression and apnoea. Fentanyl causes a mild decrease in the heart rate and a peculiar effect of chest wall rigidity, which may impair ventilation. Naloxone will reverse the adverse effects of fentanyl. The combination of Fentanyl and midazolam is very good for severe painful procedures but one should be cautious of respiratory depression or even arrest due to it synergistic effect. The newer drugs, ultra short acting alfentanil and sufentanil have not yet entered the Indian market.

MORPHINE (Tab 4)Morphine is the gold standard narcotic

agent with which other narcotic analgesics are compared. It is a very good analgesic but the main disadvantages are histamine release (not suitable for children with reactive airway disease), is long acting, may cause hypotension especially in hypovolemic children and its metabolite Morphine-6-glucoronide is also a potent narcotic. It causes much more nausea and vomiting than other opiates. Though it is an excellent analgesic agent for postoperative analgesia, it is not an ideal agent for emergency room procedures due to its

longer duration of action.FENTANYL:(Tab 5)

Fentanyl is a potent synthetic opiate agonist and is 100 times more potent than

KETAMINE:(Tab 6)

Ketamine was introduced as an intravenous anaesthetic agent and produces dissociative anaesthesia producing a profound analgesia and sedation while maintaining spontaneous respiratory effort. Though it was introduced as an anaesthetic agent, it is being used widely for relief of pain associated with many procedures by the non-anaesthesiologist, because of its potent analgesic effect and its property of preserving the laryngeal and pharyngeal reflexes. Because of its bronchodilatory effect it is a very good analgesic agent for an asthmatic child. It increases the heart rate and the blood pressure. The unpleasant hallucinations seen often in adults occur less frequently in children. Since Ketamine increases salivation, it is mandatory to administer an antisialogogue (glycopyrrolate or atropine), before injecting ketamine. No reversal agent for ketamine

Morphine Onset DurationSC 0.1 -0.15mg/kg 10 min 4 - 5 hrsJM 0A - 0.15ing/kg lOmin 4-5 hrsIV 0.1 -0.15mg/kg 2-5 min 4 - 5hrs

Table.4 Dose, onset and duration of action of morphine

Fentanyl Onset DurationIV 1-3 microgram/kg 2-3 min 45 - 60 min

Table. 5 Dose, onset and duration of action of fentanyl


Sedation and Analgesia in Children for Procedures outside the OR S. Ramesh

Ketamine onset DurationPO 6-10 mg/kg 10-30 min 1 - 2 hrsIM 3 -5 mg/kg 2 -10 min 60 - 90 minIV 1 -2 mg/kg 30-60 sec 10 - 30 min

Table. 6 Dose, onset and duration of action of ketamine

Propofol onset DurationIV 1 - 4mg/kg 60 secs 10 — 15 min

Table. 7 Dose, onset and duration of action of propofol

exists. Ketamine should never be taken lightly and resuscitation equipment and drugs should be ready when it is administered.

PROPOFOL:(Tab 7)

Propofol, which was used initially as a general anaesthetic, due to its short half-life, is now widely used for short-term sedation. Though long term (>48hrs) sedation with propofol may cause severe metabolic acidosis, it is being recommended for procedures like CT Scan, MRI, Intercostal drainage insertion and Central Venous line placements. Propofol is a lipid emulsion and is very painful during IV injection, which can be alleviated by prior administration of 0.5mg/kg of lignocaine or mixing with the propofol solution itself. If propofol to be given in small doses, it is advisable to dilute it with 5% Dextrose. This agent is associated with some drawbacks like apnoea, hypotension, and airway obstruction and so it is mandatory that the paediatrician using it should be well trained in airway management

NON-NARCOTIC ANALGESICS:The weak analgesics like paracetamol

and non-steroidal anti-inflammatory drugs are the most commonly used drugs in general paediatric practice and sometimes in postoperative analgesia. Though they are very useful in mild pain, they may not be very useful in procedure related pain in the emergency room.

LOCAL ANAESTHETICS:(Tab 8)

Local anaesthetic agents are Sodium Channel blockers preventing depolarisation of the nerve. To act at the Sodium Channel, local anaesthetics must first enter the cell in the nonionised form and then act inside the cell. Local anaesthetics are weak bases, so at a physiological pH, they exist primarily in the ionised state. In certain local conditions like infection and inflammation, a state of relative tissue acidosis exists and the local anaesthetic is not effective. Adding epinephrine to the local anaesthetics causes vasoconstriction, which decreases the rate of absorption and thereby prolongs the duration of the block and reduces the toxicity. Epinephrine containing local anaesthetics should never be used in areas supplied by end arteries such as fingers, toes, penis and the tip of the nose.

The two drugs, which are commonly used, are lignocaine and bupivacaine. Lignocaine has a shorter onset and shorter duration of action while bupivacaine has a longer onset and duration of action. The toxicity includes tinnitus, anaphylaxis, convulsions, cardiac arrhythmias and cardiovascular collapse. The arrhythmias are more common with bupivacaine than lignocaine and are difficult to treat.

Dose Onset DurationLignocaine (plain) 4mg/kg 3 to 6 min 60 -90 minLignocaine (adrenaline) 7mg/kg 5 to 10 min 90 - 120minBupivacaine 2.5 mg/kg 10 -15 min 180-240 min

Table. 8 Dose, onset and duration of action of local anaesthetics



EM LAEMLA is a Eutectic mixture of local

anaesthetic cream, which is a mixture of lignocaine, and prilocaine in a water based cream, which provides analgesia even in intact skin. It should be applied at least 60 minutes before. There are some reports of methhaemoglobinaemia in children less than 6 months due to the presence of prilocaine. Its main usage is for IV placement but it can be used for lumbar puncture and circumcision.

General guidelines for using Local anaesthetic agents:1. Use smallest possible needle (24 or 25 g) to

raise the wheal. First inject subcutaneously and then raise the intradermal wheal to prevent pain

2. All resuscitative equipments and drugs should be ready to manage any over dosage or toxicity.

3. It is always safer to have an IV line in place4. To prevent intravascular injection, always

aspirate before injecting the local anaesthetic.

Infiltration local anaesthesia as an adjunct to sedative drugs is very useful in the following situations:1. Lumbar puncture2. Suturing small lacerated wounds3. Central venous line placement4. Arterial line placement5. Intercostal drainage tube insertion6. Bone marrow aspiration and biopsy7. Liver and kidney biopsy

Digital Nerve Block:Of all the other regional nerve blocks,

the most useful block to be learnt is the digital nerve block.

The paired digital nerves enter the digits medially and laterally. Inject 1 to 2 ml of local anaesthetic in the Web space on either sided of the finger or the toe. The usual approach is to enter from the dorsal surface where it is less painful. Epinephrine containing local anaesthetic should never be used. It is very useful for suturing finger injuries, removal of warts and foreign body removal.

Synergism:If you combine two drugs of different

mechanisms of action, one may potentiate the other and reduce the dose requirement of each of them for optimal usage. But at the same time, it may carry the increased risk of respiratory depression.

2 + 2 = 4 Additive effect2 + 2 = 6 Synergistic effect

Example 1- Midazolam and FentanylCombining a sedative and an analgesic

will be very effective for many procedures like lumbar puncture, wound suturing, closed fracture reduction and immobilization. The main advantage of midazolam is amnesia with mild muscle relaxation. Both the drugs should be diluted and injected slowly and titrated to the desired effect without exceeding the upper dose limit of each drug for that particular child. When these combinations are given, it is mandatory to monitor the patient by pulse oximetry. The paediatrician administering these combinations must be skilled in airway management and resuscitation.

Example2 - Atropine or Glycopyrrolate (0.02mg/ kg), Midazolam (0.05mg/kg), Ketamine (0.5 to1 mg/kg)

It is a good combination for painful procedures like wound suturing and fracture reduction. This cocktail effect is not reversible and airway reflexes may not be maintained.

SOME SUGGESTED GUIDELINES FOR THE PROCEDURES:Lumbar puncture:

NPO guide lines ConsentMidazolam 0.1 to 0.2 mg/kg EMLA or local infiltration with 24 Or 25 gauge needleIf airway expert is available, midazolam and fentanyl combination can be tried.

Wound suturingNPO guidelines ConsentMidazolam + Fentanyl combination Local infiltration



EchocardiographyTrichlofos 50 to 100 mg /kg Intranasal midazolam (0.4mg/kg), onset is in 5 -15 minutes and the duration of action is 25 to 45 minutes.

CT ScanNPO guidelines ConsentTry Midazolam or TrichlofosIf not possible, IV Propofol 2 to 3mg /kgis idealIt is advisable to use IV propofol in the presence of skilled airway personnel.

Haemato- Oncological procedures:NPO guidelines ConsentMidazolam+Fentanyl+Local infiltration Atropine/glycopyrrolate + Midazolam + Ketamine + Local infiltration

RAPID SEQUENCE INTUBATION IN THE EMERGENCY ROOM

The indications and details of the procedure are beyond the purview of this chapter and here, I will be highlighting only the sedatives, induction agents and the muscle relaxants used during the procedure. The main principle here is that the medications are injected fast and theyare preloaded according to the weight of the child.1 Brief history and assessment2. Preperation of equipment and medications3. Preoxygenation4. Premedications5. Sedation and induction of unconsciousness6. Cricoid pressure7. Muscle relaxation8. Intubation9. Verification of ET tube position10. Documentation

Premedication:Atropine or Giycopyrrolate

0.02 mg/kg IV to decrease the secretionsand vagal toneLignocaine 1 mg/kg IV is sometimes is used to provide local airway anaesthesia and blunt ICP response to intubation especially in head trauma.

Sedation and induction of unconsciousness.(Tab 9)

THIOPENTONE:It is an ideal induction agent for this

procedure. It is an ultra short acting barbiturate and has some cerebral protective effect. The major disadvantage is that it causes hypotension. Thiopentone is available in powder form and should be diluted with normal saline and injected as a 2.5% solution and the dose is 4 to 5mg/kg IV.

KETAMINE:There are two clinical situations where

ketamine is considered strongly for induction. One is an asthmatic child because of the bronchodilatory effect and the other is a patient with shock since ketamine is a sympathomimetic agent. The dose is 2mg/kg IV

Midazolam + Fentanyl combination can also be used but higher dosages are needed.

PROPOFOL:Its rapid onset and short duration of

action makes this agent very ideal for rapid induction. Though the manufacturer recommends this agent for children over 3 years, there are many reports of its usage in younger children. It blunts the laryngeal reflexes during intubation. The dose is 2 to 4mg /kg IV.

Muscle relaxants.(Tab 10)

Suxamethonium is the drug of choice for rapid sequence intubation because of its rapid onset and rapid recovery but the disadvantages are bradycardia, fasciculations, and release of potassium.

The alternative to suxamethonium is Rocuronium, which is a non-depolarising muscle relaxant whose onset of action is similar to suxamethonium but the duration of action is longer.

Vecuronium has also been used at a higher dosage of 0.2 to 0.3mg /kg to provide a rapid onset, but the duration is very much prolonged.



Agent Dose (iv) Unset DurationThiopentoneKetaminePropofolMidazolamFentanyl

4 -5mg/kg 1 - 2 mg/kg 2- 4mg/kg

0.05mg — 0.02mg/kg2-4 microgram/kg

10-30 sec 1 —2 min 20 sec 1 -2 min 1 -2 min

10-30 min 15 - 30 min 10 -15 min 30 - 60 min

30 - 60 minTable.9 Dose, onset and duration of action of induction agents

Agent Dose (iv) Onset DurationSuccinylcholineRocuroniumVecuroniumVecuronium

2-mg/kg 1 mg/kg 0.1 mg/kg 0.2 mg /kg

30 - 45 sec 45 - 60 sec 1.5 -2 min 60 - 90 sec

4- 10 min 30-45 min 25 - 40 min 60 - 90 min

Table. 10 Dose, onset and duration of action of muscle relaxants

Only physicians who have a complete knowledge of the medications used and are skilled in airway management should perform the rapid sequence intubation.

General recommendations for sedation and analgesia in the emergency room

Assess the child and beware of ‘FullStomach’ in the emergency situationNPO guidelinesObtain consentEstablish the venous accessCheck airway and resuscitative equipmentincluding suction apparatusMonitor heart rate and Oxygen saturationAll the medications to be diluted and labelledand inject at a very slow rate. Afteradministration of each drug, flush the lineAfter injecting one drug, before injectinganother drug, wait at least for 15 to 20seconds. Watch the respiration.

In the midazolam + fentanyl combination, inject midazolam first Administer Atropine/Glycopyrrolate, then midazolam and finally ketamine Document before and after Sedation

REFERENCES

1. American Academy of Pediatrics Committee on Drugs: guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics 1992:89:1110-1115.

2. Cote CJ: Sedation Protocols: why so many variations? Pediatrics: 1994; 94:281 -283

3. The Pediatric Emergency Medicine Course book (APLS) Third Edition 1998.

4. Paediatric Clinics of North America, June 2000, Acute Pain in Children

5. The Pediatric Clinics of North America, December, 1999: 1215 to 1247. “Ouchless emergency department”

6. American Society of Anesthesiology: Standards, Guidelines and Statements, 1999.


POST GRADUATE SYMPOSIA

Cardiovascular Physiology 119 Latha, Sathya, Rajkumar

INTRODUCTIONUnderstanding cardiovascular physiology

is mandatory for the treatment of cardiovascular disorders and shock states. This article attempts to deal with CVS physiology from a clinical standpoint, to promote physiology-based treatment of common CVS conditions. It does not intend to be a complete treatise on the subject but merely seeks to kindle interest in the fascinating piece of equipment that is the heart. This article is divided into 3 segments: the first deals with cardiac electrophysiology and the cardiac cycle with an overview of cardiovascular reflexes of relevance to the anaesthesiologist. The second deals with the physiological aspects of ventricular function and its relevance to the anaesthetic management of valvular heart disease. The last part deals with the coronary circulation in health and disease.

THE CARDIAC CYCLEEvents that occur from the beginning of

one heart beat to the next constitute one cardiac cycle. It comprises cardiac filling (diastole) followed by contraction (systole) and is initiated by the spontaneous generation of an action potential in the sinoatrial node. At a heart rate of 72 beats/min, the duration of each cycle is 0.8 sec, of which systole is 0.3 sec and diastole is0.5 sec. At higher heart rates, the shortening of diastole is more than that of systole, a phenomenon that is of significance in many disease states.

Electrophysiology of the HeartWith regard to the electrical activity, the

heart consists of 2 types of fibres: quiescent (those that require an external stimulus for

initiation of electrical activity), and automatic (those that generate electrical activity spontaneously, without any external stimulus). Examples of automatic cells are the SA node and secondary pacemaker cells. Examples of quiescent cells are the atrial and ventricular cells. Before we go into the mechanisms of action potential generation, it is worthwhile discussing the subject of transmembrane potentials.

TRANSMEMBRANE POTENTIAL (TMP)The TMP is recorded by inserting

capillary microelectrodes into single cardiac cells. Depending on the state of cell activation, two types of TMPs may be recorded: the TMP during electrical inactivity (resting membrane potential, or RMP; usually -90 mV), and that during electrical activity (action potential). In the resting state, the inside of the cardiac cell is more negative than the outside, hence the cell is said to be polarized. Stimulation leads to the entry of positive ions causing the cell to lose its polarization, a phenomenon termed depolarization. Finally, the net outward movement of positive charges again restores the TMP to its original state of polarization; this is called repolarization.

FACTORS DETERMINING RMPAt rest, the cardiac cell membrane is

permeable only to K+ and not to any of the other ions. Thus the RMP is mainly determined by the K+concentration inside and outside the cell, given by the formula: RMP= -62 log [K(

+] / [Ko+].

Changes in the ratio between extracellular and intracellular K+ produces a change in the RMP; an acute increase in the K + causes a less

O

negative RMP and vice versa.



ACTION POTENTIAL OF A QUIESCENT CARDIAC CELL

The generation of an AP in a quiescent cardiac cell is an all-or-none phenomenon. This means that any stimulus strong enough to increase the TMP (i.e., make it less negative) from the RMP to a so-called “threshold” potential (typically -65 mV) generates the AP; a weaker stimulus will not generate an action potential (AP). The phases of the action potential are (Fig. 1)\

repolarizes toward the RMP.

At the end of a repolarization, electrical charge is restored by the Na+-K + pump; this pumps 3 Na+ ions out of the cell in exchange for only 2 K+ ions into the cell. Thus, there is a loss of 1 positive ion inside the cell, resulting in the negative RMP. The RMP is primarily dependent on K+ flux, as the cardiac cell during phase 4 is permeable to K+ but not to other ions.

• Phase 0= Rapid depolarization or upstroke (the portion above 0 mV is called the overshoot); Ionic basis: Na+ in

• Phase 1= Early rapid repolarization; Ionic basis: Na+ inactivated; K+ out (negligible)

• Phase 2= Plateau; Ionic basis: Ca2+ in• Phase 3= Final rapid repolarization; Ionic basis:

K+ out• Phase 4= RMP (electrical diastole).

REFRACTORINESSThis is a characteristic of cardiac

excitable tissue. During the plateau phase of the AP, the cell cannot be re-excited regardless of the strength of the stimulus (absolute refractory period, ARF). The basis for this is the inactivation of the Na+ channels; they open only at the onset of repolarization.

Between the end of the ARP and full recovery of normal excitation is the relative refractory period (RRP). During the RRP, the required stimulus to depolarize the cell is either larger than normal, or the resultant action potential is smaller or slower to propagate than normal. The refractory period protects the heart from the risk of tachycardia in sympathetic over activity. It also prevents many dangerous ventricular arrhythmias.

Phase 1 is due to the rapid entry of Na+ ions down their electrochemical potential gradient. For the Na+ channel to open fully, a critical portion of the cell membrane must be depolarised to a level of TMP termed the threshold potential (-60 to-70 mV).

Immediately following the phase 0, a small, steady outward flow of K+ current starts, accounting for the TMP becoming more negative (phase 0 • phase 1). However, this is soon followed by a slow inward flow of Ca2+ ions causing the phase 2 plateau of the AP. Similar to the Na+ channel, this also exhibits time- and voltage- dependent conductance. Any change in extracellular Ca2+ is reflected on the plateau of the AP.

Phase 2 is followed by closure of the Ca2+ channels making the outward K+ flux the predominant current. The cell thus well and truly

ACTION POTENTIAL OF AN AUTOMATIC CELL

The pacemaker cardiac cell is unique among excitable tissues in being spontaneously excitable. This autonomy is important in that it makes the heart rate relatively independent of extrinsic stimuli like neural control. As shown in Fig. 2, the automaticity is due to the unstable phase 4 potential (prepotential; pacemaker potential) unlike the stable phase 4 of quiescent



cells. The phase 4 of pacemaker cells exhibits a spontaneous slope making the TMP less negative. Under the right circumstances, pacemaker cells will depolarize to threshold potential to generate an AP The ionic basis for the prepotential appears to be the slow efflux of K+ ions out of the cell.

Relationship of the ECG to cardiac cycle:Depolarization of the atria produces the

P wave. Ventricular depolarization produces the QRS complex. The intervening period is the PR interval produced due to the delay in conduction

Fig. 3. ECG and the Action Potential

INTERVALS DURATION (Sec) EVENTS PR interval 0.12 to 0.20 Atrial depolarization

and conduction through AV node

QRS 0.08 to 0.10 Ventricularcomplex depolarization and

a trial repolarization QT interval 0.90 to 0.43 Ventricular

depolarization andventricularrepolarization

ST segment n and T Ventricular

repolarization

in the AV node.

The part of the ventricular repolarization plateau formed by the plateau of the action potential is represented by the ST segment, while the subsequent part formed by the refractory

period of the AP is represented by the T wave

Applied Electrophysiology: Arrhythmia FormationECTOPIC FOCI OF EXCITATION

All cardiac cells have the ability to generate a spontaneous action potential. However, under normal circumstances, the SA nodal rhythm is active as the frequency of discharge of the SA node is more rapid than that of the other conducting tissues. In abnormal conditions, the latter can discharge spontaneously (abnormal automaticity). If such an irritable ectopic pacemaker discharges once, the result is a beat that occurs before the next expected normal beat, called extrasystole. If this focus discharges repetitively at a rate higher than that of the SA node, it produces rapid, regular tachycardia (atrial/ventricular/nodal as the case may be).

RE-ENTRYThis occurs in the presence of an

aberrant conduction system that allows a wave of excitation to propagate continuously within a closed circuit, the so-called “circus movement”. Many different aberrant pathways have been described of which perhaps the most famous is the bundle of Kent, implicated in the Wolff- Parkinson-White syndrome. This is an abnormal extra bundle of conducting tissue connecting the atria to the ventricles.

A wave of conduction from the SA node has two routes of passage: one, through the normal conducting system from the atria to the AV node; and the other through the aberrant bundle from the atria directly to the ventricles. As the aberrant bundle has a faster velocity of conduction than the more refractory AV node, the impulse is rapidly transmitted to the area of the ventricle where the bypass tract ends. The depolarization occurs earlier than it would have occurred via the AV node, accounting for the short PR interval. However, subsequent transmission of this anomalous impulse is slower than normal as it has to be conducted via the non-specialized ventricular muscle; this accounts for the slurred



upstroke in the R wave. By then, the normal impulse from the AV node depolarizes the specialized conducting tissue and the rest of the ventricle is depolarized quickly; therefore, the duration of the R wave is not prolonged. This is a description of normal conduction in the presence of a Kent bundle.

Under specific circumstances, re-entry occurs causing the supraventricular tachycardia of WPW syndrome. This occurs when the bypass tract is refractory during anterograde conduction of a cardiac impulse, which now gets conducted via the AV node. After depolarizing the ventricle, this same impulse can now travel retrograde via the Kent bundle and depolarize the atrium; this depolarization can again travel down via the AV node establishing a repetitive circus movement, and tachycardia. Obviously, drugs that cause increased AV nodal refractoriness like verapamil and digoxin may worsen the tachycardia by promoting conduction along the bypass tract. Drugs that slow the ventricular response and increase bypass tract refractoriness like class la agents, beta blockers and amiodarone are useful.

PHASES OF CARDIAC CYCLEWiggers (1915) & Lewis (1920) were the

major contributors to the cardiac cycle diagram that shows the interrelationship between atrial events, ventricular events, aortic pressure, JVP, ECG and heart sounds. The durations mentioned here are at physiological heart rates.

There are 2 major phases: diastole and systole. (Fig.4) For simplicity of understanding, we will confine our discussion to the left ventricle (LV) although the events apply equally to the right ventricle (RV).

SystoleISOVOLUMETRIC CONTRACTION (0.06 sec)

At the end of diastolic ventricular filling, as the intraventricular pressure exceeds the atrial pressure, the mitral valve closes, and LV contraction begins. The initial phase is characterized by contraction of the ventricle against a closed outflow valve (aortic valve). Thus, with both the inlet and outflow valves remaining closed, there is an increase in the intraventricular

Fig. 4. The Cardiac Cycle Diagram

tension without a change in the intraventricular volume (hence termed isovolumic). When the ventricular pressure exceeds the pressure in the outflow arteries, the semilunar valves open and the phase of rapid ejection follows.

PHASE OF MAXIMUM EJECTION (0.11 Sec) Following the opening of the aortic valve,

blood is ejected into the aorta with tremendous force giving rise to the stroke volume. The LV pressure continues to rise for a short period into ejection. The aorta undergoes systolic expansion and the flow rate into the aorta exceeds the peripheral run off. The sinuses of valsalva create eddy currents, which prevent the aortic cusps from occluding the coronary ostia during ventricular systole.

PHASE OF REDUCED EJECTION (0.14 sec) With the aortic pressure approaching the

LV pressure, the velocity of ejection begins to


f


decrease. However, there is still flow of blood from the ventricles to the major vessels due to aortic distensibility (windkessel effect). This phase corresponds to the T wave of ECG. Ejection is terminated when the aortic pressure exceeds the LV pressure leading to closure of the aortic valve. Typically, the end-systolic volume of the LV (LVESV) is 50-60 ml. Ejection fraction is that fraction of end-diastolic volume of LV that is ejected.

DiastoleDiastole marks the phase of relaxation

and filling of the ventricles with blood draining from the atria. It comprises:

PROTODIASTOLE (0.03 sec)The ventricles begin to relax and there is

retrograde flow into the major vessels leading to closure of the semilunar valves (S2 sound).

ISOVOLUMETRIC RELAXATION (0.06 sec)There is a sharp drop in the

intraventricular tension as the ventricular muscle relaxes. With both the AV and semilunar valves being closed, there is no change in the LV volume (isovolumic). The electrical event behind this event is the rapid ATP-dependent uptake of Ca++ from the cytosol into the sarcoplasmic reticulum. This mechanism is impaired in myocardial ischaemia, reperfusion and heart failure.

PHASE OF RAPID FILLING (0.11 sec)When the LV pressure drops below that

in the LA, the mitral valve opens and LV filling starts. Filling is rapid at its onset due to the large pressure gradient, but slows down as the LV pressure approaches the LA pressure.

PHASE OF REDUCED FILLING- DIASTASIS (0.2 sec)

This is the longest phase of diastole as both atrial and ventricular pressures equilibrate and the pressure gradient decreases.

ATRIAL SYSTOLE (0.1 sec)Approximately 25% of the LV filling

results from atrial contraction. It is an important determinant of LV preload in disease states characterized by reduced passive filling like in

mitral stenosis, aortic stenosis, poor LV compliance (hypertensive heart disease, ischaemic heart disease, myocardial fibrosis) and cardiac failure. An effective atrial kick requires coordinated atrial contraction that can only occur in sinus rhythm.

Energy Basis of the Cardiac CycleThe energy requirement for the cardiac

cycle is unequally distributed between systole (85% of the total energy) and diastole (15%). Contrary to popular perception, diastole is also an active process. Energy is required for the Ca++ reuptake that initiates diastole. Ischaemic states impair diastolic relaxation earlier than systolic function. The inequity of energy requirements is utilized by the heart in compensating for altered loading conditions in many disease states (explained in the section on valvular heart disease).

CARDIOVASCULAR REFLEXESNo understanding of the circulatory

reactions of the body is possible unless we start first with the fundamental properties of the heart muscle itself, and then find out how these are modified, protected and controlled under the influence of the mechanisms - nervous, chemical and mechanical - which under normal conditions play on the heart and blood vessels.

-EH Starling, 1920

IntroductionCardiovascular reflexes are integrated

pathways regulating cardiovascular function. They depend on and affect the interplay between the vascular system, the heart and the brain. Understanding cardiac reflexes is important to the anaesthesiologist as they are affected by disease states and anaesthetic techniques alike. Each reflex has a receptor that is stimulated by a specific stimulus, an afferent limb, a centre, an efferent limb and an effector organ (Tabje 1).

Baroreceptor reflex (Fig. 5)Also called the carotid sinus reflex, it is

of primary importance in the maintenance of haemodynamic stability. The primary stimulus for the baroreceptor reflex is a change in blood



REFLEX STIMULUS RECEPTOR AFFERENT CENTRE EFFERENT RESPONSE

Baroreceptorreflex

Change In BP carotid sinus aortic arch IX, X

NTSVasomotor

Center

I ML tract Change in contractility and

heart rate

Chemoreceptorreflex

.pH*pCO*.pa

carotid and aortic bodies IX, X

Chemo Sensitive area of

medulla XBradycardia, hypertension,

hyper, ventilation

Bainbridgereflex

Increased filling of right atrium

Stretch receptors in RA wall X

Dorsal motor nucleus of

vagus

Vagal and Sympathetic

fibres

heart rate contractility

Bezold Jarisch reflex

SerotoninVeratridingCapsaicin

pain receptors (C fibre endings^ x

: braycardia

Respiratory and Vasomotor

Center XApnoea

hyperpnoea

hypotension&bradycardia

Valsalvamanoeuvre

forced expriation against closed

glottisBaroreceptor Explained in

text

Cushing reflex 'inlCT VMC ' discharge of RVLM

hypertension and

Oculocardiacreflex

Pressure over globe of eye

Short and long cilliary nerves

Ciliary ganglion Gasserian ganglion Vagus Reflex

bradycardia

Vasovagalreflex

Traction on gall bladder,

mesentery anal dilation

X Vagal nucleus X„ BP

bradycardia apnoea

Table 1. Summary of the cardiovascular reflexes. Key: IX = Glossopharyngeal nerve : X = Vagus.

Fig. 5 The Baroreceptor reflex arc. NTS= nucleus of the tractus solitarius : VMC = vasomotor centre

pressure inducing reflex changes in the heart rate. The baroreceptors are mechanoceptors in the heart and the great vessels. In the heart, they are located in the walls of the right and left atria at the entrance of the superior and inferior vena cavaeand the pulmonary veins (i.e., at the venous inlet in the right and left). In the arterial circulation, stretch receptors are located in the walls of the carotid sinus and the aortic arch. The baroreceptors respond to stretch (distension) of the structures in which they are located and discharge at an increased rate when the pressure within these structures rises. Afferents from the receptors project onto the nucleus of the tractus solitarius (NTS) that is the nucleus of the vagus nerve; other afferents end in an inhibitory pathway to the C1 cells (sympathetic). Thus, baroreceptor stimulation (due to hypertension) leads to vagal stimulation and sympathetic inhibition, the net effect being a drop in the blood pressure and heart rate, vasodilation and decrease in the cardiac output.

The converse occurs during arterial hypotension. There is a decrease in the tonic baroreceptor discharge, leading to the removal of both sympathetic inhibition and parasympathetic stimulation. The result is increased sympathetic output and decreased vagal output, causing hypertension, tachycardia and increased CO.

The theoretical range of mean arterial pressure for baroreceptor stimulation is 30-150 mm Hg; however, a linear relationship between MAP and baroreceptor output exists only at pressures of 70-110 mm Hg.

Resetting of baroreceptors is known to occur in chronic hypertensives in whom they are set for a higher BP. Antihypertensive treatment restores baroreceptor sensitivity to basal levels rapidly, with some studies demonstrating a beneficial effect after just 1 week of treatment.

Bainbridge reflex (Fig. 6)This reflex responds to changes in the

right atrial filling pressure sensed by stretch receptors present in the cavoatrial junction. Whenever there is increase in the right atrial pressure, there is inhibition of parasympathetic activity, leading to tachycardia and increased contractility. Following volume-expansion under anaesthesia, this reflex competes with the



Fig. 6 Bain bridge reflex

baroreceptor-mediated decrease in heart rate. The magnitude of HR response to the Bainbridge reflex depends on the basal HR; it is attenuated when the initial HR is high.

Chemoreceptor reflex (Fig. 7)The receptors are the carotid body and

the aortic body. This reflex responds to changes in pH (acidosis), Pa02 <50 mm Hg and C02 tension (hypoxia and hypercapnia). The afferent nerves are the IX and X, which send the impulses

(Fig. 7) Chemoreceptor reflex

to the chemosensitive area of the medulla. The response is primarily to increase ventilation (hyperventilation) but also increased parasympathetic output, leading to bradycardia and decreased contractility.

Coronary chemoreflex or the Bezold-Jarisch reflex (Fig. 8).

This is a variant of the chemoreceptor reflex. Pain receptors (C-fibre endings) present on the left ventricular wall respond to noxious stimuli such as serotonin, veratridine with the afferent impulses carried by the vagus to the respiratory and vasomotor centre of the medulla. The response is apnoea followed by rapid

(Fig. 8). Bezold-Jarisch reflex

breathing, hypotension and bradycardia. Its clinical significance may lie in the pathogenesis of reperfusion injury seen with the release of noxious substances after myocardial infarction.

The anaesthesiologist must be particularly wary of this reflex as it has been implicated in sudden, unexplained, refractory cardiac arrest seen in spinal anaesthesia. Risk factors for this catastrophe include high level of blockade, hypovolaemia, reverse Trendelenberg tilt etc.

Cushing’s ReflexIncrease in intracranial tension leads to

ischaemia of the vasomotor area. The response

is an increase in BP and CO in order to increase the cerebral perfusion. Increase in BP results in reflex bradycardia.

Oculocardiac reflexPressure or traction on the globe of the

eye (particularly the medial rectus) sends afferent impulses via the ciliary nerves and ophthalmic nerve to the Gasserian ganglion, resulting in profound bradycardia. This is a common reflex in ophthalmic surgery occurring in almost 30-90%



of the cases. It may be attenuated by premedication with atropine orglycopyrrolate.

Fig. 10 Oculocardiac Reflex

Valsalva manoeuvre (Table 2)This test is done to assess the

baroreceptor reflex activity in autonomic neuropathy. It is the forced expiration against

CARDIOVASCULAR PHYSIOLOGY: VENTRICULAR FUNCTION

Understanding ventricular function is the cornerstone of managing patients with heart disease and shock states. This article addresses cardiovascular physiology from a clinical standpoint.

INTRODUCTIONSimply stated, the function of the

ventricle is to pump the blood that it receives into the aorta and the pulmonary artery. This process is divided into 2 distinct phases: systole and diastole, the electromechanical events behind which have been detailed earlier. The mechanical properties of cardiac filling and ejection will be explained now, from the relationship between the single cardiac fibre and the intact heart, to the

Stage Mechanism Effect

1. Onset of straining Increase in intrathoracic pressure added to pressure of blood in aorta

Increase in BP (with mild decrease in HR)

2.Sustained straining Increase in intrathoracic pressure causes decrease in venous return

Decrease in BP, increase in HR

3. Onset of release Decreased venous return causes decrease in BP and decrease in baroreceptor discharge

Decrease in BP and increase in HR

4. Well after release Intrathoracic pressure returns to normal, still peripheral vessels constricted.

Increase in BP and decrease in HR

Table 2 . Stages of the Valsalva Manoeuvre

a closed glottis producing increased intrathoracic pressure, increased CVP and decreased venous return. This is sensed by the baroreceptors to result in sympathetic stimulation. As the glottis opens, and venous return increases, the BP and cardiac output increase leading to baroreceptor reflex.

Apart from the cardiovascular reflexes described above, there are perhaps unknown and unnamed reflexes, as exemplified by the observation of sudden cardiorespiratory arrest that develops during anaesthesia and stress in otherwise autonomically competent individuals. Further research is necessary to understand these events.

pathophysiological basis of anaesthetic management of common cardiac conditions. To make matters simple, the discussion always pertains to the left ventricle, unless otherwise specified.

CARDIAC MUSCLE AS A SPRING: THE CONCEPTS OF PRELOAD AND AFTERLOAD

The sarcomere may be likened to a spring with both its ends attached, one to the ceiling and the other to a load that must be lifted from the ground {Fig. 11).The spring comprises two distinct elements- the contractile element, CE (the muscle) and the series elastic element, SE (elastic fibres). Contraction of the sarcomere to lift the load consists of 2 sequential steps-



Other end of muscle attached to load

Fig. 11 Cardiac muscle as a spring

isometric contraction (contraction without change in length), followed by isotonic contraction (contraction with shortening of the sarcomere).

In isometric contraction, the contractile element (CE) shortens following activation, stretching the elastic element (SE). The elongation of SE compensates for the contraction of the CE thus keeping the total sarcomere length constant (isometric). This initial phase of contraction is isometric up to the point where the force generated equals the total load that has to be lifted. Once the force exceeds the load, the muscle shortens and the load is lifted a certain distance with a velocity (isotonic contraction). The velocity is determined by the state of the CE and the total load. During the period of shortening, the SE remains constant.

PrincipleFrom the analogy of the spring, it is clear

that the force of contraction of the spring (the cardiac muscle) depends on 3 factors:1. the initial length of the spring;2. the load to be lifted; and3. the integrity of the muscle and elastic

tissue.

INITIAL LENGTH OF THE MUSCLE (PRELOAD) The greater the initial length of the

sarcomere, the greater will be the force generated. (A bigger spring will be able to lift a

bigger load!) However, it is also common sense that if the spring were stretched beyond a point, it would get distorted, and become unable to contract at all. This is the concept of preload. Preload for the isolated muscle fibre is defined as the initial length of the muscle fibre. In the intact ventricle, the initial fibre length is determined by the volume of blood inside the chamber; more the volume, longer the length, and greater the force of contraction. However, like in the spring, if the volume is increased beyond a point, the fibre is distorted, and the force of contraction decreases. This is the basis for Starling’s Law of the heart, which states that: The law of the heart is that the mechanical energy set free on the passage from the resting to contracted state depends on the area of chemically active surfaces, i.e., on the length of the muscle fibres. In other words, the stroke volume is directly proportional to the initial length of the muscle, till physiological limits are reached.

THE LOAD THAT IS TO BE LIFTED (AFTERLOAD)

It is obvious that the heavier the load, the slower will be the force of contraction. The tension (force) in the spring required to lift the load will be higher; in the extreme example, if the load is higher than the maximum force that could be generated by the muscle, the load will never be lifted, i.e., the contraction will remain isometric, as the muscle does not shorten. In the intact heart, the afterload is the impedance (resistance) offered by the aorta to ventricular ejection. It could also be explained as the tension (force or stress) generated in the ventricular wall during isotonic contraction.

THE INTEGRITY OF THE MUSCLE AND ELASTIC TISSUE

The generation of an adequate force requires that the muscle as well its series elastic fibres are normal in structure and function. Abnormal muscle function affects systolic shortening. Abnormal elastic function as in fibrosis affects systolic lengthening. Both conditions are detrimental to cardiac contractility. The cellular basis of cardiac contractility is based on this



relationship between the tension (force) and the velocity of shortening.Experimentally, the maximum velocity of shortening has been used in many studies to assess contractility.

CONTRACTILE FUNCTION OF THE INTACT HEART: THE CARDIAC OUTPUT

The cardiac output (CO) is the amount of blood pumped into the peripheral circulation per minute. It is a measurement reflecting the status of the entire circulatory system, not only that of the heart, and is primarily governed by autoregulation in tissues.CO = Stroke Volume (SV) x Heart Rate (HR)

To compare patients with different body sizes, the CO may be corrected in relation to body surface area (BSA). It is then called Cardiac Index (Cl).Cl= CO / BSA Normal 2.5-3.5 L/min/m2.

Stroke VolumeIt is the volume of blood ejected by the

ventricle with each single contraction.SV = End-diastolic volume (EDV) - End-systolic volume(ESV)

DETERMINANTS OF STROKE VOLUME1. Preload2. Afterload3. Contractility4. Heart rate

PRELOADAs explained earlier, preload in the

isolated muscle represents the load imposed on the muscle fibre before contraction, and is the end-diastolic fibre length. In the intact heart, the preload is the ventricular wall stress at end- diastole. However, as the wall-stress is difficult to measure clinically, various approximations have been made substituting for the wall stress. They are:1. Substituting ventricular volume for the wall

stress: LVEDV in an intact heart has been shown to be linearly related to the stroke volume and is thus an excellent estimate of the preload. However, it is difficult to measure clinically. Normal LVEDV = 70- 100 ml /m2.

2. Substituting ventricular pressure for ventricular

volume: These are popular clinical tools owing to their relative simplicity of measurement. However, the relationship between volume and pressure is not linear and may be inaccurate. The various pressures that have been approximated to the LVEDV include:• LVEDP: The most closely related to

LVEDV; difficult to measure, hence clinically not useful. Normal LVEDP = 12 mm Hg.

• Left Atrial Pressure (LAP): Useful in select situations like intra-cardiac surgery, in which a left atrial catheter may be placed by the surgeon.

• Pulmonary artery occlusion pressure (PAOP): Erroneously called the pulmonary capillary wedge pressure (PCWP), this is a less accurate estimate of LVEDV as it is affected by factors such as placement of the pulmonary artery catheter, airway pressure, and positive end-expiratory pressure (PEEP). However, it remains a popular bedside tool due to its simplicity.

• Central venous pressure (CVP): Perhaps the least accurate but the most widely used estimate of preload. In addition to being affected by all the factors affecting PAOP, it is also affected by lung disease, pericardial disease and right ventricular dysfunction. However, despite these limitations, the trend of the CVP and the response to interventions like the fluid challenge may still be used to successfully predict the LV preload.

Determinants of PreloadPreload to the ventricle is determined by:

1. Venous return to the atria, which in turn is determined by:• Total blood volume• Body Position• Venous tone• Pumping action of skeletal muscle

2. Transmural pressure: The pressure gradient for venous filling of the heart is the mean circulatory filling pressure (MCFP) minus the



Response of CVP to IV fluid challenge Inference

No or mild increase returning rapidly to baseline

Hypovolemia

>4 mm Hg increase from baseline and remains the same for >3-5 min

Normovolemia or hypervolemia; further fluid therapy with caution

>4 mm Hg increase from baseline and decrease in BP

LV failure

Table 3. Inference of response of CVP to IV fluid challenge

right atrial pressure (RAP). The RAP may be affected by the intrathoracic pressure and intrapericardial pressure.

Clinical Applications of Preload1. There are many mechanisms by which

anaesthesia affects the preload:• Altering the effective circulating blood volume

due to venodilation, increase in venous capacitance and peripheral venous pooling.

• Positioning• Changes in the intrathoracic and

intrapericardial pressures due to positive pressure ventilation and PEEP.

2. In any situation of decreased cardiac output, the first intervention that must be thought of is a change in preload. As mentioned above, a simple estimation of the CVP trend (or any other approximation of the LVEDV) and response to fluid therapy may be a valuable guide to the volume status of the patient. After measurement of the baseline CVP (or PAOP), a bolus of intravenous fluid is given rapidly within 10-15 minutes, and the change in CVP is noted. The volume of fluid depends on the initial CVP: 200 ml if the initial CVP <6 mm Hg, 100 ml if the CVP is 6-8 mm Hg, and 50 ml if the CVP >8 mm Hg (Table 3).

AFTERLOADAs explained earlier, afterload in the

isolated muscle is the force resisting muscle fibre shortening. In the intact heart, as an analogy to preload that is defined as the ventricular wall- stress at end-diastole, afterload may be defined as the ventricular wall stress at end-systole (or

ejection).

Equation can be applied to afterload asfollows:T = Pr/2h

In clinical practice, it is easier to measure it by the arterial impedance to the ejection of the stroke volume (systemic vascular resistance, SVR), although it does not take into account factors like the LV radius and wall thickness.SVR = MAP - RAP / CO, where MAP = Mean Arterial Pressure RAP = Right Atrial Pressure.

ImplicationThe shift from a low CO- high SVR

condition to a more favourable high CO - low SVR condition can be achieved by the use of vasodilators. The rationale of the treatment of LV or RV failure by after load reduction is based on this principle.

DeterminantsVENTRICULAR VOLUME

If both normal and eccentrically hypertrophied ventricles shorten their internal circumference (270r) or internal diameter by 25%, the SV ejected by the dilated ventricle will be nearly three times as large as that ejected by the normal ventricle. However, assuming the same end-systolic pressure (ESP) and wall thickness for both ventricles, LV systolic wall stress and oxygen consumption will be much higher for the



eccentrically hypertrophied ventricle than for the normal one.

IMPLICATION - Treating cardiac dysfunction with a positive inotrope, such as dobutamine, will decrease the end systolic dimensions of the LV and increase SV, yet leave LV wall stress unchanged or even decreased.

VENTRICULAR WALL THICKNESS (h)Wall thickness is the denominator in the

Laplace formula. Thus when h increases, stress will decrease and vice versa. When comparing concentric with eccentric ventricular hypertrophy, the latter not only has a wider radius (r) but also has a thinner wall (h) compared to the concentrically hypertrophied ventricle. For identical pressures, the systolic ventricular wall stress will be higher in the dilated or “failing" ventricle than in the hypertrophied “hypertensive” left ventricle.

SYSTOLIC INTRAVENTRICULAR PRESSUREIntraventricular pressure is an important

component of afterload, and an inverse relationship exists between SV and LV pressure. When the systolic arterial pressure suddenly increases, as after cross clamping of the thoracic aorta, SV initially decreases, then normalizes through a compensatory increase in LVEDV or heterometric autoregulation. Later, the increase in EDV is followed by an increase in cardiac contractility while LVEDV and LVEDP normalize. This phenomenon is called the Anrep phenomenon and the adaptive mechanism that explains it is called “homeometric autoregulation”. The Anrep phenomenon should be more pronounced under anaesthesia and when cardiac function is already depressed.

CONTRACTILITYAn intrinsic property of cardiac muscle,

it determines the amount of work the heart can perform at a given load. It is primarily determined by the availability of intracellular Ca++. All agents with positive inotropic properties increase intracellular Ca++ while negative inotropes have the opposite effect. In the assessment of ventricular function, the assessment of ventricular contractility is probably the most complex as it is very difficult to devise indices that are

unaffected by loading factors. Some indices that are relatively independent of loading factors are:

Isovolumic indices1. Vmax (maximum velocity of myocardial fibre

shortening)2. Peak pressure development (dp/dt);

Ejection Phase Indices1. Initial ventricular impulse2. Maximum aortic blood acceleration3. Ejection fraction: LVEF is an unreliable index

of LV contractility as it is highly dependent on loading factors. In particular, it is unreliable in patients with VHD.

Pressure Volume LoopAlthough the PV loop allows a more

precise appreciation of LV contractility relatively independent of preload, its technical difficulty makes it unattractive. PV loops are explained in detail in relation to the pathophysiology of valvular heart disease.

Determinants of ContractilityFACTORS INCREASING CONTRACTILITY1. Sympathetic Stimulation: Direct increase of

the force of contraction, as well as indirect increase due to increased heart rate (rate treppe effect or Bowditch phenomenon);• The association between heart rate and

contractility is called the staircase effect. Tachycardia in the range of 60-120 beats/ min leads to a higher availability of Ca++to the contractile proteins and improves contractility (positive staircase effect).

• Further increases in the HR decrease the contractility (negative staircase effect) due to decreased accumulation time for Ca++ in storage sites and diastolic Ca++overload in the cytosol.

2. Administration of positive inotropic drugs.

DECREASING CONTRACTILITY1. Parasympathetic stimulation and bradycardia,2. Sympathetic inhibition via withdrawal of

catecholamines or blockade of adrenergic receptors,

3. Administration of p adrenergic blocking drugs, calcium channel blockers or myocardial



depressants,4. Myocardial ischaemia and infarction,5. Intrinsic myocardial diseases such as

cardiomyopathy, and6. Hypoxia and acidosis.

Heart RateThe HR is a major determinant of the

CO. It is primarily governed by the rate of phase 4 depolarisation of the sinoatrial (SA) node. The natural frequency of the SA node is faster (110 times/min) than the other potential pacemakers of the heart, causing an “overdrive suppression” of the latter. Neural and humoral mechanisms are the extrinsic factors controlling the HR. Sympathetic stimulation increases the HR and parasympathetic stimulation decreases it.

The tachycardia induced by sympathetic stimulation and vagal inhibition (atropine) is qualitatively different. In the former instance, there is a shortening of the action potential, systole and diastole. In atropine-mediated tachycardia however, diastole is reduced but there is a prolongation in the duration of the action potential and systole. This impairs coronary filling and increases the myocardial work, both of which are undesirable in ischemic heart disease.

DIASTOLIC FUNCTIONAt physiological heart rates, diastole

oocup:es appmxin ate^2/Srd of the cardiac cycle. Despite this, the study of diastolic function is frequently relegated to the background owing to technical difficulties and lack of awareness of its importance. However, with the realization that diastolic dysfunction and impairment of diastolic ventricular compliance appear earlier than systolic dysfunction in many cardiac conditions, study of diastole is receiving increasing attention.

Phases of Diastole1. Isovolumic relaxation2. Rapid ventricular filling3. Atrial contraction

DeterminantsISOVOLUMIC RELAXATION

This is the period following ventricular ejection, initiated by the rapid re-uptake of Ca++ ions into the sarcoplasmic reticulum. The

decrease in LV pressure can be described by an exponential function and expressed as a time constant (called Trelax). Determinants of relaxation time include:1. Load: The greater the load, the faster the

relaxation.2. Inactivation: This depends on the active

sequestration of Ca++ from the troponin to the sarcoplasmic reticulum (ATP dependent Ca++ pump). Conditions where cytosolic Ca++ may be abnormally high leading to delayed relaxation are:A. Failure of the Ca++ pumpB. Ca++ leaks out of the sarcoplasmic

reticulumC. Myocytes unable to extrude Ca++

D. Increased affinity of troponin for Ca++

3. Coronary blood flow: Adequate blood flow is essential for the supply of ATP.

4. Homogeneity: Segments with regional wall motion abnormalities due to ischaemia will have a prolonged relaxation time

5. Alterations in inotropy affect relaxation.A. Catecholamines increase Ca++ re-uptake

and improve relaxation in normal myocardium. However, by worsening the asynchrony of contraction in compromised myocardium, they decrease Ca++ reuptake and prolong relaxation in ischaemic myocardium.

B. Beta blockade prolongs relaxation in normal myocardium, but improves relaxation in ischaemic myocardium by reducing the asynchrony of contraction.

6. Effect of halogenated agentsA. Halothane and Enflurane prolong Trelax by

decreasing contractility, decreasing load, and decreasing coronary blood flow

B. Isoflurane has no effect on relaxation. The coronary vasodilation produced by isoflurane nullifies the effects of decreased contractility and load.

7. Effect of drugs: Coronary vasodilators like nitrates, inodilators (dobutamine), calcium channel blockers and myocardial revascularization may improve diastolic function or reverse exercise induced ischaemia.

VENTRICULAR FILLINGWhile isovolumic relaxation is caused by



the dissociation of cross-bridges between actin and myosin, LV filling is due to elongation of sarcomeres that follows the opening of the atrioventricular valves. Factors impairing the efficiency of filling include:1. Increased end-systolic volume2. Myocardial fibrosis3. Valvular heart disease4. Tachycardia (by shortening the duration of

diastole)

MECHANICAL EVENTS IN THE CARDIAC CYCLE-THE PRESSURE-VOLUME LOOP

During a cardiac cycle, for any given ventricular volume, there is a ventricular pressure (wall stress). The pressure-volume (PV) loop is a plot of a series of values of ventricular pressure (wall stress) against ventricular volume fora single cardiac cycle. Cineangiographic techniques enable the measurement and plotting of PV loops.

Shape of the P-V LoopThe PV loop comprises 4 segments,

corresponding to:1. Ventricular filling2. I sovolumic contraction3. Ejection4. Isovolumic relaxation.

The cycle begins as diastole at OMV when the mitral valve opens and ventricle fills (OMV to CMV). Systole begins at the end- diastolic point (CMV) and ends at the end systolic point (CAV). The point OAV represents the opening of the aortic valve; thus the phase of contraction prior to that (CMV to OAV) represents the isovolumic contraction of the ventricle, and that after OAV is the phase of ejection (OAV to CAV), which ends with the closure of the aortic valve. The ventricle encounters its afterload when the aortic valve opens, so that the end systolic point reflects the influence of both contractility and afterload. Following ventricular ejection and isovolumic relaxation, the mitral valve opens to start the next cycle.

Important Points in the PV LoopThe shape of the PV loop is influenced

by many factors including the preload, the afterload, and the contractility. The end-systolic

Fig. 12 OMV= Opening of mitral valve; CMV= C losurc of mitral valve; 0 AV= Opening of aortic valve; CAV= Closure ofaoitie valvePhase 1= Isovolumic phase ofsystole; Phase 2)= Ejection phase ofsystole Phase 3=Isovolumic relaxation phase; Phase 4- Ventricular fillingESPVR 1= End-systolic PV relationship of normal heartESPVR 2= End-systolic PV relationship (ESPVR) after increased contractilityESPVR 3= End-systolic PV relationship (ESPVR) after depressed contractilityEDPVR= End-diastolic PV relationship (EDPVR) of normal heart.

PV relationship (ESPVR) can be marked as a point; its slope is an excellent measure of the cardiac contractility. If the contractility is not altered by medications or other factors, the ESPVR lies on the same slope with varying preloads and afterloads. If the contractility changes (for example, pump failure due to myocardial ischaemia causing reduced contractility), the slope of the ESPVR is shifted to the right.

The PV loop, ESPVR and diastolic PV relationship provide useful models for graphically analysing ventricular performance in the normal heart and for illustrating changes in preload, afterload and myocardial systolic and diastolic function that occurs with valvular dysfunction.

These principles of cardiovascular physiology provide the basis of understanding and managing the alterations in loading conditions and cardiac function found in patients with valvular heart diseases.

RIGHT VENTRICLE FUNCTIONThe right ventricle is affected in many

disease states, particularly in acute and chronic respiratory diseases. The RV is different from the LV in the following respects:1. Thinner wall

• Hence more susceptible to changes in afterload than the LV; if the pulmonary artery pressure (RV afterload) increases suddenly, the RV is less capable of increasing its contractility than the LV



would in a similar situation.• Thus, the treatment of RV failure cannot

be successful without reducing the pulmonary arterial pressure.

2. The thinner wall also confers a greater distensibility to the RV. Thus, when acute or chronic increases in the RV pressure or volume occur, it may dilate and cause the interventricular septum to bulge into the LV. This explains why the PAOP may be high in many patients with ARDS even in the presence of a normal LVEDV.

PATHOPHYSIOLOGY OF VALVULAR HEART DISEASE

Valvular heart disease (VHD) is frequently encountered by the anaesthetist. Understanding the pathophysiology is mandatory to understand anaesthetic goals. VHDs affect cardiac function mainly by causing abnormal loading conditions. Common to all VHDs is an initial period of compensation of the cardiac chambers to maintain cardiac output in the face of abnormal loading conditions. With the progress of the disease however, compensation reaches a maximum, and decompensation and cardiac failure follow. The anaesthetic management depends not only on the pathophysiology of the VHD but also on the compensatory responses. In most cases, the goal is to maintain the compensatory mechanisms intact

Afterload Mismatch and Preload ReserveLet us take the case of a VHD that

produces gradually increasing impedance to ejection (afterload). If left uncompensated, the gradual increase in afterload would produce a gradual decrease in ejection fraction and stroke volume, termed afterload mismatch (loop A ->B). However, the ventricle compensates by increasing the preload (EDV). In accordance with the Frank-Starling mechanism, SV is preserved by augmenting the contractile force at this higher preload (loop B -> C). This compensation by augmenting the preload is termed preload reserve. Later in the disease, the ventricle decompensates when the afterload increases to such an extent that even the maximal limit of preload reserve is inadequate to maintain a normal SV, even with a normal contractility (loop CD). This example demonstrates how a ventricle with a normal contractility may still be unable to maintain a normal SV due to abnormal loading conditions. The appropriate treatment in this case for instance, would not be inotropic support, but a decrease in the afterload.

The compensation by increasing the preload makes sense for the energy balance of the heart. The ventricle does work (expends energy) during the entire cardiac cycle. However, there is a large discrepancy in the consumption of energy in systole and diastole. Work done in the ejection phase is more energy-consumptive when compared to work done for ventricular filling. Thus, in response to increased afterload, although the logical compensatory response is that of more forceful ventricular contraction, the energy balance is better preserved if more preload is recruited. With this background, let us now analyse 4 common VHDs.

Aortic Stenosis (AS)PATHOPHYSIOLOGY

The problem in AS is that of increased impedance to ventricular ejection, i.e., increased afterload. Stroke volume is maintained by recruiting the preload reserve.

The increased pressure to ejection necessitates an increased intraventricular pressure, thereby prolonging the isovolumic contraction phase. This intracavitary systolic pressure generated to overcome this stenosis,



directly increases myocardial valve tension in accordance to Laplace law: Wall tension = Pr / 2h

The ventricular muscle minimizes wall stress by increasing its thickness (in accordance with the Laplace equation, increasing wall thickness “h” reduces LV stress). However, the hypertrophied muscle needs more oxygen, and thus is exquisitely sensitive to myocardial ischaemia. Also, hypertrophy impairs diastolic relaxation and ventricular compliance, and slows

Fig 14. PV loop in AS

passive LV filling, making it more dependent on left atrial contraction and a higher LA pressure.

The analysis of the PV loop illustratesthat:1. The peak pressure generated during systole

is much higher owing to a high transvalvular pressure gradient.

2. The slope of the diastolic limb is steeper reflecting reduced LV diastolic compliance that is associated with the increase in chamber thickness, i.e., a small change in diastolic volume produces relatively larger changes in pressure.

3. The systolic limb of the PV Loop shows preservation of pump function, as evidenced by maintenance SV and EF.

ANAESTHETIC CONSIDERATIONS (CARDIAC GRID)Preload The preload reserve must not be

interfered with by anaesthetic agents. High filling pressures may be required.

Afterload Already elevated by the lesion, but relatively fixed; systemic hypotension to be prevented due to risk of myocardial ischaemia.

Contractility Although not a problem usually, low preinduction blood pressures may be corrected using inotropes.

HeartRate Not too slow (decreased CO);not too fast (myocardial ischaemia).

Rhythm Sinus rhythm at all times.Supraventricular arrhythmias may need to be cardioverted.

Ischaemia Myocardial ischaemia is an everpresent risk. Tachycardia and hypotension are to be avoided.

Aortic Regurgitation (AR)PATHOPHYSIOLOGY

Unlike AS, where the problem is one of chronic increased afterload, AR has a chronic increased preload. The LV has 2 outlets: forward into the aorta, and backward into the LV chamber. The regurgitated blood causes an increased end- systolic, and an increased end-diastolic volume. As explained earlier, the work done for preload (diastolic work) is less than that for contractile work. Thus, the stress on the LV is not as high as in AS. The 2 components determining afterload



act in opposite ways in AR. Increased preload and LV radius increase LV wall stress. However, the impedance to ejection is low. Hence, although there is some LV muscle thickening (LVH), it is

not marked (eccentric hypertophy).The PV loop illustrates the

compensatory mechanisms to AR (1 -> 2 -> 3 illustrate the increasing severity of AR). Initially, the LV compensates for the reduction in forward SV by recruiting the preload reserve with the entire PV loop becoming enlarged and shifted to the right. The LVEDV increases manifold, but the LVEDP usually is normal. There is virtually no isovolumic diastole phase, as ventricle is filling throughout diastole. The isovolumic phase of systole is also brief because of low aortic diastolic pressure. This minimal impedance to forward ejection of a large total SV allows for the performance of maximal myocardial work at a minimal cost in terms of oxygen consumption. In the compensated phase, the LV contractility is normal evidenced by a normal ESPVR. Decompensation shifts it to the right. Causes for decompensation include myocardial ischaemia due to LVH, exhaustion of the preload reserve and impaired diastolic compliance due to excessive LV dilatation.


interfered with by anaesthetic agents. Normal to high preload is needed.

Afterload Reduction by anaesthetic agents or

vasodilators will augment forward flow.

Contractility Not a problem in most cases; if required, inodilators are suitable to augment contractility.

HeartRate Bradycardia to be avoided!Controversy regarding deliberate tachycardia: mild tachycardia may be beneficial by reducing the LV volume, and raising the aortic diastolic pressure.

Rhythm Usually not a problem.Ischaemia Myocardial ischaemia is a risk due

to the low aortic diastolic pressure.

Mitral Regurgitation (MR)MR is similar to AR in its

pathophysiology. The regurgitant mitral valve allows 2 outlets for the LV, forward into the aorta, and backward into the LA. Forward SV is maintained by recruiting the preload reserve, producing a chronic LV volume overload with all its consequences. LV contractility is usually preserved in the presence of eccentric hypertrophy.

The additional feature is the effect on the pulmonary circulation. The increased LA volume raises the LA pressure, pulmonary venous and arterial pressure, and finally causes increased RV afterload. The PV loop illustrates these features. The shaded area is the normal PV loop. Loop A is early (compensated) MR while loop B is late (decompensated MR) with depressed myocardial contractility.

Fig 16 PV loop in MR



This equation highlights the importance of the heart rate in maintaining the transvalvular flow. By shortening the duration of diastole and the diastolic filling time, tachycardia may precipitate acute pulmonary oedema. Similarly, loss of left atrial contraction (most commonly due to atrial fibrillation) also precipitates decompensation. Reducing ventricular afterload cannot increase the stroke volume since concurrent venodilation aggravates diastolic underfilling.

ANAESTHETIC CONSIDERATIONS (CARDIAC GRID)

Fig 17 PV loop in MS

Anaesthetic considerations are similar to those for AR.Mitral Stenosis (MS)

MS causes problems of underfilling of the LV during diastole. Thus, the usual compensatory mechanisms of preload reserve cannot be recruited. Compensatory responses to maintain adequate LV filling involve the creation of an abnormally high pressure gradient across the mitral valve, causing high LA pressures and LA enlargement.

The raised LA pressure is reflected on the valveless pulmonary circulation, raising the pulmonary venous, and later the pulmonary arterial pressures, finally leading to increased RV afterload and RV failure in severe cases. LV contractility and afterload are usually not an issue. Understandably, the LV PV loop (dashed line= Normal; dark line= MS) does not reflect the severity of the disease. The only abnormality may be a reduced end-diastolic volume. All other phases will be normal.

The relationship between LV filling and transvalvular pressure gradient (TPG) is as below:

TPG a (TFR)2 TFR = CO/DFTThus, PG a (CO / DFT)2, where TFR = Transvalvular flow rate; CO = Cardiac output; DFT = Diastolic filling time; TPG = Transvalvular pressure gradient.

Preload

Afterload:

Contractility:

Heart Rate Rhythm

Ischaemia

must be maintained to ensure adequate flow across the stenotic valve.LV afterload must not be lowered. RV afterload must be lowered.LV contractility is usually not a problem; RV contractility is to be maintained.Slow to allow adequate DFT. Atrial fibrillation often; control ventricular response.Usually not a problem.

THE PV LOOP IN CARDIAC FAILURE Systolic Failure

In the PV loop, systolic failure manifests as an increase in left ventricular end-systolic volume and as a reduction in the extent of shortening (stroke volume).

Fig. 18 PV loop in systolic cardiac failure

The LVEDP is increased concomitant with the increase in left ventricular volume. As indicated by the arrow, the diastolic portion of the pressure -volume loop has simply shifted to the right along



the same pressure volume relation. No change in distensibility has occurred.

Diastolic FailureThere is an upward shift of LV diastolic

pressure volume relation that indicates a decreased left ventricular diastolic distensibility such that a higher diastolic pressure is required to achieve the same diastolic volume.

No change in end diastolic volume or systolic shortening has occurred.

CORONARY CIRCULATIONThe heart, which acts as the pumping

organ of blood, has to generate its own perfusion pressure and has to provide flow to the entire body. With the myocardium being almost entirely dependent on aerobic metabolism, the matching of oxygen delivery with oxygen demand is the essential challenge before the coronary circulation.

UNIQUE FEATURES OF CORONARY BLOOD FLOW1. Unlike all the other organs where blood flow

occurs constantly, the left ventricle gets its blood supply only during diastole as the coronary arteries are compressed during myocardial contraction.

2. The absence of anastomoses between the left and right coronary arteries means that critical occlusion of any segment of the coronary vasculature cannot be compensated by the other sided vessels.

3. Perhaps the most significant difference from other vascular beds is that the heart extracts 70% of the arterial oxygen content at rest, resulting in a coronary venous oxygen saturation of about 30%. (This is in contrast to the rest of the body where the oxygen extraction is only 25% of the oxygen delivery).

The implication of this is that there is very little reserve for the heart to increase its oxygen extraction in times of increased oxygen requirement. The only way by which oxygen delivery can be increased is by increasing the blood supply by coronary vasodilation.

ANATOMY OF THE CORONARY CIRCULATIONThere are two main coronary arteries:

right and left, originating at the coronary ostia, which are situated 0.7-1 cm above the roots of the semi lunar cusps. This position ensures that they are never occluded by the opening of the aortic valve during systole. The main trunks of both the coronary arteries pass towards their respective atrioventicular grooves before turning circumferentially around the base of the heart.

The coronary trunks are distributed on the epicardial surface before plunging into the myocardial mass, where they divide sequentially to give rise to a rich network of capillaries. The pattern of the coronary artery consists of:

1. Epicardial or large conductance vessels offering little resistance to blood flow.

2. Intramyocardial or resistance vessels ranging in size from 10-250 pm in diameter. 45-50% of the total coronary vascular resistance resides in vessels larger than 100jim in diameter. During intense pharmacological dilatim, t±iepaxpartimaf the total corcnary vascular resistance cte to large arteries and veins is evoi greater.

3. Subendocardial plexus of vessels.



THE LEFT CORONARY ARTERYThe LCA arises from the left aortic

sinus and divides almost immediately into two branches namely the left anterior descending and left circumflex artery.

Left Anterior Descending (LAD)The LAD divides into the septal

perforators and the diagonals. These give several branches to the anterior septum as it passes

Fig. 21 The left coronary artery

along the anterior interventricular groove towards the apex of the heart.

Left Circumflex Artery (LCX)It courses around the base of the left

ventricle along the coronary sulcus and terminates in the posterior descending branch and the posterolateral branch. The obtuse marginals are 1-4 in number and supply the lateral wall of the ventricle.

Thus the branches of the LCA supply the entire left ventricle (except for the posterior base of the LV free wall), the anterior 2/3rds of the interventricular septum, the anterior left margin of the free wall of the right ventricle, the apex, the lower half of the interatrial septum and the left atrium.

THE RIGHT CORONARY ARTERY (RCA)The RCA originates in the right

coronary sinus and reaches the posterior interventricular groove. The branches of the RCA are the conus artery, sinus node artery, and the

acute marginal artery. The RCA supplies the anterior and posterior (diaphragmatic) walls of the right ventricle (except the apex of the RV, which is supplied by the LAD), the right atrium and the sinus node, the posterior one third of the interventricular septum, the AV node, the upper half of the interatrial septum, and the posterior base of the left ventricle.

The sinus node is supplied by the right atrial artery, which arises in most cases from the RCA. The AV node is supplied by a branch that takes off from the RCA at the crux (the crux is

Fig 22 The Right coronary artery (RCA)

the meeting point of the atrioventicular, the interventricular and the interatrial segments on the posterior surface of the heart).

The conus and septal branches may have great importance in supplying blood flow to vascular beds below obstructions in the main coronary arteries.

CORONARY ANATOMY AND THE ECGKnowing the regional distribution of

coronary supply is important in localizing the site of myocardial damage in ischaemic heart disease (Table 4).

PATTERNS OF CORONARY DISTRIBUTIONThe pattern of distribution is somewhat

variable, particularly in the posterior aspect of the ventricular walls and septum. Schlesinger has



Electrocardiogram leadCoronary artery

responsible for ischemiaArea of myocardium

supplied by coronary artery

II, III, aVF Right coronary artery Right atrium Interatrial septum Right ventricle Sinoatrial node Atrioventricular node Inferior wall of left ventricle

v3-vBLeft anterior descending coronary

arteryAnterior and lateral wall of

left ventricleI, aVL Circumflex coronary artery Lateral wall of left ventricle

Sinoatrial node Atrioventricular node

Table. 4 Coronary Anantomy and the ECG

described three general patterns of coronary distribution based on the artery of origin of the posterior descending artery (PDA). There are 3 recognized patterns:

1. Right Coronary preponderance2. Balanced distribution3. Left Coronary preponderance.

When the RCA supplies the posterior aspect of the LV, the term right coronary dominance is applied. Conversely in left coronary preponderance, the LCA supplies some of the

Fig. 23 Distribution of the coronary arteries to the ventricular walls

contiguous right ventricle.

Data and studies in human hearts show anatomic predominance of the RCA over the LCA in the majority of the cases (up to 48%) and balanced distribution in 34%.

Importance of the pattern of coronary distribution

Although the pattern of coronary distribution may have no functional implication in

the normal heart, this anatomic distribution acquires its significance in the outcome of coronary artery disease.

For example, sudden occlusion of a large right coronary artery could be fatal, whereas occlusion of a small right coronary artery that takes no part in the blood supply of the left ventricle would cause no significant myocardial damage. Patients with left coronary preponderance are more apt to succumb to coronary occlusion. Regardless of this anatomic preponderance, the flow to LCA is always greater than to the right, probably related to the increased bulk of the muscle mass supplied by the left coronary artery.

MYOCARDIAL CAPILLARY CIRCULATIONThe coronary capillary network has an

organization comparable to that of corresponding small vessels in other tissues. The distribution of the capillaries is quite uniform in the human left and right ventricles, reaching 4000 per sq.mm of tissue. The maximum distance necessary for diffusion has been calculated to be 8 fim.

Interestingly enough, this uniformity of distribution is not shared by all parts of the heart. The IVS has lesser capillary density than the ventricles. The AV node has a rather scanty supply of capillaries. As a result of this dispersed capillary network, the diffusion distance within the conducting system is much greater than to the ventricular myocardium, making it more vulnerable to ischaemia.

THE COLLATERAL CIRCULATIONArterial anastomotic connections exist

between portions of the same (homocoronary)



coronary artery and between different (intercoronary) coronary arteries. The collaterals have a diameter varying from 40-200 microns. Both types are found throughout the full thickness of the ventricular walls except the layers just under the epicardium. Even repeated brief (2 minute) episodes of ischaemia can serve as stimuli for collateral vessels to open out. The collateral blood supply can prevent the development of infarction and preserve myocardial viability when the obstruction develops gradually over a period of months.

Rest versus exerciseUnlike normal coronary vessels,

collaterals are maximally vasodilated even at rest. They do not have the capability to dilate further in times of increased oxygen requirement, like exertional states. For instance, a patient with 80- 90% obstruction of a major vessel with well- developed collaterals may not complain of anginal pain under basal resting conditions, but may develop ischaemia or even infarction after exertion. It follows that eliciting information about effort tolerance by history or other means may be the best method to unmask the presence of CAD in a patient.

CORONARY VEINSVenous drainage is distinctly different

in the two ventricles. This drainage system forms3 main veins namely:1. The coronary sinus2. The anterior right ventricular veins3. The Thebesian veins.

The main coronary venous drainage tends to retrace the course of the coronary arteries, passing towards the atrioventricular groove and terminating in the coronary sinus, which empties into the right atrium through its posterior wall.

NEURAL CONTROL OF THE HEARTThe atria are abundantly innervated by

the sympathetic and parasympathetic nervous systems, but the ventricles are supplied principally by the sympathetic nervous system. These nerves affect cardiac output by changing the heart rate and strength of myocardial contraction. Maximal sympathetic nervous

system stimulation can increase cardiac output by about 100% above normal. Conversely, maximal parasympathetic nervous system stimulation decreases ventricular contractile strength and subsequent cardiac output only about 30%, emphasizing that parasympathetic nervous system stimulation of the heart is small compared to the effect of sympathetic nervous system stimulation.

Other homeostatic mechanisms forming the cardiovascular reflexes have been dealt with earlier.

CORONARY BLOOD FLOWResting coronary blood flow is 225-250

ml/minute or 4-5% of the cardiac output. Assuming that the normal adult heart weighs about 280 g, this is equivalent to a blood flow of 75 ml/100g/min. The resting myocardial oxygen consumption (Mv02) is 8-10 ml/100g/min, or about 10% of the total body consumption of oxygen. As explained in the section on ventricular function, LV distension is a major determinant of Mv02. For instance, the oxygen consumption of the arrested, non-distended heart is 1 ml/100g/ min compared to 5 ml/100g/min in the arrested but distended heart.

Determinants Of Coronary Blood Flow (CBF)CBF is mainly determined by 4 factors

including:1. Perfusion pressure (coronary perfusion

pressure or CPP)2. Myocardial extravascular compression3. Myocardial metabolism4. Neurohumoral control.

CORONARY PERFUSION PRESSURE (CPP) The CPP is the pressure head that

drives blood into the coronary arteries. The CBF is proportional to the pressure gradient across

the coronary circulation.

The perfusion pressure for any given organ is the pressure difference between the driving pressure in the arterial side minus the pressure in the venous side. In all the other organs the perfusion occurs throughout the cardiac cycle, hence the driving pressure is the mean arterial pressure (MAP). In the LV however, the resistance



vessels in the left ventricle being effectively compressed in systole, the perfusion occurs mainly in diastole. So the left ventricular perfusion pressure is the difference between the aortic diastolic pressure and LV end-diastolic pressure. On the other hand, since the RV pressure does not exceed the coronary pressure even during systole, it receives its blood supply throughout the cardiac cycle (Fig 15).

the critical closing pressure or zero flow pressure (Pzf). However, many authors have shown that the Pzf is only a theoretical entity and the CBF continues well below the critical closing pressure, so long as the coronary arterial pressure is more than the coronary sinus pressure. The increase in the subendocardial blood flow even in the presence of a greater degree of extravascular compression is brought about by maximal

MYOCARDIAL EXTRAVASCULARCOMPRESSION (MEC)

Under normal conditions, the MEC contributes only a small component to the total coronary vascular resistance. Extravascular compression forces during systole are greater in the subendocardial zones than in the subepicardial zones. Experimentally, it has been shown that flow throughout the coronary circulation stops at pressures far in excess of the pressure in the coronary sinus, termed as

preferential dilatation of subendocardial plexus of vessels. In patients with CAD, since the subendocardial vessels are already in a dilated state, they cannot dilate any further and suffer the most by way of ischaemia.

MYOCARDIAL METABOLISMMyocardial metabolism is a powerful

regulator of CBF. Normally CBF and metabolism are closely related such that coronary sinus oxygen saturation changes little over a wide range of Mv02. Hypotheses of metabolic control propose that vascular tone is linked either to a substrate such as oxygen or ATP, or to the accumulation of metabolites such as C02 and H+. Increases in arterial and coronary sinus PC02 cause increases in coronary blood flow in the absence of changes in the Mv02.

Adenosine is a powerful coronary vasodilator and it is hypothesized that release of adenosine may serve as a feedback signal that induces coronary vasodilatation, augmenting CBF in proportion to myocardial metabolic needs.



NEURAL AND HUMORAL CONTROLThe coronary arteries are richly

innervated by adrenergic and parasympathetic nerves. Both alpha-1 and alpha-2 adrenoceptors are present in coronary arteries and activation by neuronally released or circulating norepinephrine causes coronary vasoconstriction. On the other hand, beta-1 and beta-2 adrenoceptors in the large and small coronary arteries mediate vasodilatation. The endothelial cells present in the myocardium synthesize vasoactive substances such as Endothelial Derived Relaxing Factor (EDRF), prostacyclin and angiotensin converting enzyme (ACE). A wide variety of stimuli like acetylcholine, thrombin, histamine and tissue hypoxia mediate the release of these vasoactive substances to produce coronary vasoconstriction.

Coronary AutoregulationAutoregulation is an intrinsic

mechanism to keep the organ blood flow constant despite changes in the arterial perfusion pressure. For a given Mv02, the CBF will remain relatively constant between MAP of60-140mm Hg. Normal coronary sinus oxygen tension (CS02) is <20 mm Hg. Autoregulation will be effective when CS02 is <25 mm Hg, but is completely lost when CS02 >32 mm Hg. Autoregulation can be intensified by vasoconstriction (increased oxygen extraction) and attenuated by vasodilation (decreased oxygen extraction). The degradation of autoregulation with alpha blockade suggests a benefit of adrenergic coronary vasoconstriction. The exact mechanism of coronary autoregulation is not known although myogenic, tissue pressure and metabolic factors have been hypothesized.

Coronary Reserve and Reactive HyperaemiaMyocardial ischaemia causes intense

coronary vasodilation. Following a 10-30 second coronary occlusion, restoration of perfusion pressure is accompanied by a marked increase in coronary flow. This large increase in flow is called reactive hyperaemia. The difference between resting coronary blood flow and peak flow during reactive hyperaemia represents the Autoregulatory Coronary Flow Reserve. The reserve is greater with higher perfusion pressure and lower MvOz.

CORONARYSTEALCoronary steal is an important

phenomenon that may affect coronary blood flow to ischaemic myocardium. Steal occurs when the perfusion pressure for a vasodilated vascular bed is lowered by vasodilation in a parallel vascular bed, both beds usually being distal to a stenosis. Classically a steal can occur when an inflow- restricted vessel supplies two parallel vascular beds. If one of the vascular beds can dilate but the other is already maximally dilated and when these two vascular beds are exposed to a vasodilatory stimulus, blood flow can increase

Fig 27 Coronary Steal

only in the bed capable of vasodilation.

Let us take an example to illustrate this phenomenon. As discussed already, in areas of myocardium supplied by occluded arteries, blood supply is maintained by collaterals from neighbouring arteries. Even under resting conditions, these collaterals are vasodilated to the maximal extent with no further scope to increase their blood flow. If this collateral bed shares its blood supply with a parallel vascular bed that retains its capability to vasodilate, the blood supply of the collateral bed may suffer if the blood flow to the latter increases (as they share the same source).

In the figure shown (Fig. 18), a normal coronary artery A divides into two branches: B (completely occluded) and C (stenosed, partially occluded). C normally supplies an area of myocardium, but now has to provide collaterals D to sustain the area of myocardium normally



deriving its blood supply from B.

Thus the scenario may be summarized as:2 main branches B and C; normally, B supplies the area of myocardium B’; C supplies the area of myocardium C’.

B completely occluded; C partly occluded. Due to disease of artery B, C gives collaterals (D) to myocardium B’ in addition to normal vessels to myocardium C’.

Myocardium B’ is now dependent for its blood supply on collaterals (D) arising from C.

The functional dynamics of this arrangement under resting conditions are that both the normal artery C and the collateral D are of normal calibre with both areas of myocardium B’ and C’ being perfused well. The patient will have no ischaemic symptoms.

However, the functional dynamics change markedly in conditions of exertion that necessitate vasodilation of the vessels. Whereas the normal artery C can vasodilate, collateral artery D cannot. As the blood flow across the proximal stenosis is fixed, there is no scope for both C and D to get adequate blood supply. In the event, C will “steal” blood from the collateral D rendering the myocardium B’ ischaemic. The patient may have myocardial ischaemia.

Reducing the level of exertion reduces the oxygen requirement, thereby restoring basal functional dynamics, restoring blood supply to myocardium B’.

To quantify the example, (the flow in the ischaemic region is 20 ml/min/100g and is determined by the collateral driving pressure or the difference between distal pressures in the bed supplying collaterals (80 mm Hg) and the ischaemic bed (20 mm Hg). Flow in the distribution of the stenotic vessel is normal at 70ml/min/100g and is evenly distributed between the subendocardium and subepicardium). During vasodilator administration at a constant BP, flow increases in the non-ischaemic bed to 200 ml/ min/100g, but becomes maldistributed between

the subendocardium and the subepicardium. In addition, pressure distal to the stenosis falls to 50 mm Hg causing a reduction in the collateral driving pressure. As a result, flow to the ischaemic region decreases to 10 ml/min/1 OOg.

Usually the distal pressure is low in the occluded arterial bed and there is a small gradient in the mean pressure across the stenosis.

To summarize, the conditions predisposing to the steal phenomenon are:1. An inflow restricted (stenotic) vessel supplies

two parallel vascular beds;2. One of the vascular bed can dilate but the

other is already maximally dilated;3. Both beds are exposed to vasodilatory

stimuli.

Examples of vasodilatory stimuli include exertion, isoflurane and or agents such as dipyridamole, nitroprusside and adenosine.

Another type of steal is the transmural steal occurring in the myocardium, diverting blood from the subendocardial to the subepicardial areas. This is because the lower limit of autoregulating perfusion pressure is greater for the subendocardia! layers than for the subepicardial layer; subendocardial blood flow may be reduced when subepicardial blood flow is preserved.

CONCLUSIONCardiovascular physiology is a

fascinating subject. Application of physiology to the understanding and management of disease states would go a long way towards improving the quality of care. With the advent of technology, CVS physiology is also rapidly evolving into a bedside tool for diagnosis and therapy of many cardiac and non-cardiac diseases. The coming years are bound to be path breaking.

REFERENCES1. International Practice of Anaesthesia. Editors:

Cedric Prys-Roberts, Burnell R. Brown. Butterworth-Heinemann 1996.

2. Cardiac Anesthesia. Editor: Joel A. Kaplan. WB Saunders Company. 4th Edition, 1999.

3. Anesthesia. Editor; Ronald D. Miller Churchill Livinstone. 5th edition, 2000.


Central Neuraxial Blockade 144 D.Anil Kumar, S.K.Arif Pasha & Rani Manjusha

ANATOMY AND PHYSIOLOGY OF THE SUB ARACHNOID AND THE EPIDURAL SPACE

We anaesthesiologists practice central neuraxial blockade routinely. So it becomes imperative on our part to be well versed with the anatomy and physiology of the subarachnoid and epidural space

VERTEBRAL COLUMN:The vertebral column is composed of 33

vertebrae (7cervical + 12 thoracic + 5 lumbar + 5 fused sacral + 4 coccygeal).

It consists of two curves called the :1) Primary curve and2) Secondary curve

At birth there is only the primary curvature i.e. a single concave curve anteriorly.The secondary curves .namely the cervical and the lumbar curves appear as the neonate starts to support his head and starts to sit and stand respectively.

Noting the directions of the spinous process of these vertebrae is of importance to us at the time of introducing the needle to enter these spaces.

Spinous process of the cervical vertebra:The spinous process of the cervical

vertebra is short and bifid (with the exception of C1 and C7) and is directed almost horizontally to the body of the vertebra.

Spinous process of the thoracic vertebra:The spinous process of the thoracic

vertebra is long and is inclined at an angle of 45 to 60 degrees to the body of the vertebra and the skin.So the needle should be directed at an angle

of 45 to 60 degrees cranially, to follow the upper border of the spine to enter the ligamentum flavum. Spinous Process of the Lumbar Vertebra:

The spinous process of the lumbar vertebra is directed horizontally backwards .virtually 90 degrees to the body of the vertebra and the skin. So the needle is to be directed perpendicular to the skin.

ANATOMY OF THE SPINAL CORD:The spinal cord is the continuation of the

central nervous system from the medulla oblongata.The lower extent of the cord varies with age.• Early fetal life upto 3 months of gestation; it occupies the whole length of the vertebral column• 3 months of gestation to birth: it extends to the 2nd coccygeal vertebra• At birth; it lies at the L3 vertebra and the dural sac ends at S3• At one year: it lies at the lower border of L1 and the dural sac ends at S2• Adult: it lies at the lower border of L1 and the dural sac ends at S2.

Cross section of the spinal cord:It is divided into grey and white matter.

The grey matter is divided in to 9 laminae, namely, LAMINA1 TO LAMINA 9. Lamina 2 and 3 are called the SUBSTANTIA GELATINOSA OF ROLANDO. It acts as a processing center for the information from the somatic receptors and relays it to the brain. It contains ‘C FIBRES’. Lamina 1 and 5 contain ‘ A DELTA FIBRES'.

Receptors of the spinal cord:• Opioid receptors: \i2,kappa,delta• NMDA receptors• GABA receptors• Alpha 2 adrenergic receptors



Fig 2. Extent of spinal cord

Blood supply of the cord:Spinal cord is perfused via one anterior

spinal artery and two posterior spinal arteries and reinforced by radicular arteries arising from the segmental arteries namely: ascending cervical,posterior intercostals, lumbar and the lateral sacral arteries. Anterior radicular arteries are small and variable in number. They usually arise from the lower cervical,lower thoracic and the upper lumbar. One of this is considerably large and is called the ARTERIA RADICULARIS MAGNA / ARTERY OF ADAM KIEWICZ. It is usually single ,on the left side, and arises from the lower thoracic or upper lumbar and supplies the lower 2/3rd of the cord. Anterior spinal artery supplies the anterior 2/3rds of the spinal cord, sparing the posterior columns. Posterior spinal artery supplies the posterior 1/3 rd of the spinal cord.

APPLIED ANATOMY OF BLOOD SUPPLY: Anterior spinal artery thrombosis:Predisposing factors for the anterior spinal artery thrombosis are:• Elderly patient• Peripheral artery disease• Hypotension• Addition of vasoconstrictors

Spinal cord veins:They are 6 in number in the piamater.

One each is present in the anterior and posterior median fissure and a pair each along the dorsal and ventral nerve roots and drain into the Superior

Fig 3. Blood supply of the spinal cord



vena cava via the vertebral, azygous and the hemiazygous veins.

APPLIED ANATOMY:They are valveless and accidental

injection of local anaesthetic would produce systemic toxicity.

ANATOMY OF THE EPIDURAL SPACE I PERIDURAL SPACE /EXTRADURAL SPACE.

Epidural space is a potential space between the dura and the spinal canal.

Boundaries:Superiorly: foramen magnum, Inferiorly:

sacral hiatus, Anteriorly: posterior longitudinal ligament, Posteriorly : ligamentum flavum and Laterally: the pedicles and the intervertebra I foramina.

Contents:Nerve roots, fat, loose areolar tissue,

lymphatics and blood vessels which include the Batson’s venous plexus.

Significance of the epidural veins:They are valveless and form a

communication between the pelvic veins below and the intracranial veins above .They drain into the Inferior vena cava via the azygous veins. So any obstruction to the IVC leads to the distension of the epidural veins, thereby decreasing the epidural space and the requirement of the LA dose.

Width of the epidural space:Cervical:1-1.5mm,upper thoracic:2.5-

3mm,lower thoracic 4-5mm,lumbar5-6mm.

Plica mediana dorsalis:It is a septum in the epidural space

which divides the space into ventromedian and two dorsomaedian compartments and the failure of these to communicate freely leads to patchy analgesia.lt extends from the dura to the ligamentum flavum and leads to narrowing of the space and tenting of the dura.

Differences between cervical,thoracic and the lumbar epidural spaces:

The spinal canal in the thoracic space is

narrow and is completely occupied by the spinal cord, leading to the pushing of the dura against the ligamentum flavum.This decreases the margin of safety of the thoracic route as compared to the cervical and the lumbar routes in the midline approach.

Difference in the contents of the epidural space below 6 years of age:

The space has spongy,gelatinous lobules, in contrast to the densely packed fat globules and fibrous strands in adults. This leads to rapid longitudinal spread of the drug in this age group.

Pressure in the epidural space:Thoracic region = -1 cm of H20, Upper lumbar = -1 to -3 cm H20, Lower lumbar= -0.5cm H20.

ANATOMY OF THE SACRAL EPIDURAL SPACE:

Fig 4. The Sacral epidural space

Sacral hiatus:It is an inverted ‘V’ shaped opening

situated 3 to 5 cms from the coccyx or just beneath the superior gluteal cleft. It is formed due to the failure of fusion of the laminae of S4 and S5. It is covered by the sacrococcygeal membrane.



Boundaries of the sacral hiatus:Superiorly: Spine ofS4Inferiorly and Laterally : Sacral cornu, whichrepresents the inferior articular surface of S5.

Boundaries of the sacral canal:Anteriorly: sacral bone, Posteriorly: lamina,and Laterally: the foramina.

Capacity of the canal:30 to 35 ml

Length of the canal:10 to 15cms.

Contents:Fat, loose areolar tissue .venous plexus

formed by the internal vertebral plexus, and the dural sac which ends at the upper border of S2 or the line joining the two posterior superior iliac spines.

ANATOMY OF THE SUBARACHNOID SPACE:It is the space between the arachnoid

and the piamater.

Contents:CSF,nerve roots, blood vessels that

supply the cord,and the incomplete trabecular network. This incomplete trabecular network is formed by the extensions of the piamater namely the ligamentum denticulatum and the posterior sub arachnoid septum.

Fig 5. The Virchow Robin space

Virchow Robin Spaces:The subarachnoid space communicates

with the tissue spaces around the vessels in the piamater and accompanies them as they penetrate the cord. These extensions of the subarachnoid space are termed as the Virchow Robin Spaces. It is thought to be the pathway for the local anaesthetic (LA) injected into the subarachnoid space to permeate the cord.

CSF formation:CSF is an ultra filtrate formed by means

of an active process from the choroid plexus of the lateral ventricles..

Rate of formation: 0.4ml/min (25ml/hror 600ml /day).

The total volume in an adult is estimated to be 120-150 ml. Of this approximately 25 -30 ml occupies the spinal subarachnoid space.

Control of production:Choroid plexus receives nor adrenergic

innervation from the sympathetic chain through the superior cervical ganglion.This secretory innervation , as with salivary and ciliary body secretions,is mediated by beta adrenergic receptors.

Absorption of CSF:Is through cerebral arachnoid villi,which

drain into venous sinuses especially the superior sagittal sinus.

Composition of CSF:pH: 7.4 -7.6, sodium=140 -150 meq/l,

chloride= 120 -130 meq/l, bicarbonate 25 - 30meq/l, proteins 15-45 mg/dl, glucose 50 - 80 mg/dl, non protein nitrogen 20-30 mg/dl.

Characteistics of CSF:Specific gravity=1.003 - 1.009, density

at room temp of 22-24 deg cel is 1.0002 and at body temp of 37 deg cel is 1.0003, with an average pressure of 110mm water.

PHYSIOLOGICAL EFFECTS OF CENTRAL NEURAXIAL BLOCKADE:

Sympathetic denervation forms the comer



stone for the various physiological changes that follow Central Neuraxial Blockade.The extent of physiological changes that follow depend on the height of block attained i.e above T4 (High block), below T4 (low block).

MECHANISM OF BRADYCARDIA IN CENTRAL NEURAXIAL BLOCKADE:

In lowCNB: Bain Bridge Reflex.,In high CNB: due to block of the cardiac

accelerator fibers, which leads to unopposed parasympathetic activity.

02 TRANSPORT AND UTILITISATIONSlowing of blood flow,through the

anaesthetized area .leads to increased 02 extraction and increased A - V 02 difference.

Hypotension and decrease in the mean arterial pressure lead to decreased myocardial oxygen demand.

Effects on the respiratory system:Central neuraxial blockade is featured by

the relaxation of the abdominal and the intercostal muscles .which comprise the major expiratory muscles, this causes a decrease in the expiration and expiratory reserve volume(ERV). This decrease in ERV is of importance in patients with COPD. It is



associated with a decreased clearance of tracheobronchial secretions. ABG, VT, maximum inspiratory volume and negative intra pleural pressures remain unchanged.

CAUSE OF RESPIRATORY ARREST IN CENTRAL NEURAXIAL BLOCKADE:

This is attributed to hypotension induced ischaemia of the medullary center and rarely due to involvement of the phrenic nerve in the case of sensory block upto T1 level.

Effect on GIT and the hollow viscera:T5-L1 preganglonic fibers are inhibitory

to the gut, while innervation from the vagus is stimulant. So Central neuraxial blockade produces sympathetic denervation that results in unopposed vagal action and thereby an increase in contractility of the gut with normal peristalsis and relaxed sphincters, which permit better operative conditions.

Endocrine and metabolic effects:

Central neuraxial blockade blocks both the afferent pathways and the efferent pathways and therefore the metabolic and the endocrine responses to noxious stimuli. Central neuraxial blockade above T6 decreases epinephrine, nor epinephrine and insulin release with little or no change in glucagon levels.Glucose tolerance is also minimally affected. Central neuraxial

blockade upto T8 -T10 causes no decrease in epinephrine and nor epinephrine release.

Fat metabolism:Block upto T6 causes decreased plasma

glycerol and free fatty acids.

Thermo regulation:Sympathetic denervation causes

hypothermia by increased heat loss from peripheral pooling in the anaesthetized areas. Hypothermia could also result from the redistribution of heat from central to peripheral regions.There is compensatory vasoconstriction in the non anaesthetized regions above the block, which leads to shivering.

Effects on regional blood flow:HEPATIC BLOOD FLOW:

Decrease in the hepatic blood flow is directly proportional to the degree of hypotension.This decrease in the blood flow is associated with increased systemic arterial and hepatic venous 02 content. So, there is increased hepatic extraction of oxygen .despite a decreased hepatic blood flow.

RENAL AND CEREBRAL BLOOD FLOW:These are under the influence of their auto

regulatory mechanisms until there is a drop in the mean arterial blood pressure to 55mm Hg, at which their blood flow decreases proportionally.

TECHNIQUES OF CENTRAL NEURAXIAL BLOCKADECentral neuraxial blockade can be achieved by intrathecal and extradural anaesthesia.

A). Intrathecal or sub arachnoid or spinal anaesthesia.- Midline approach- Paramedian approach ( In difficult spinal.) -Taylor approach- Continuous spinal technique

B) Extra dural anaesthesia.- Cervical epidural -Thoracic epidural- Lumbar epidural -Caudal epidural



C) Combined epidural and spinal anaesthesia.

INDICATIONS:1. Intraoperatively:

• Anaesthesia for lower limb surgeries, perineal procedures and Caesarean section

• ,To provide controlled hypotension

2. For providing analgesia:• Post-operative analgesia• Obstetric analgesia• For relief of intractable pain as in

crush injury chest (Relief from pain reduces paradoxical respiration and allows the patient to clear the lower airways by coughing freely) and lumbar disc lesions (for relief of sciatic pain).

CONTRAINDICATIONS:Absolute:1. Patient refusal.2. Localised infection / Generalised infection.3. Raised ICP / Active CNS disease.4. Coagulation disorders5. Sensitivity to local anaesthetic drugs6. Severe blood loss / shock.

Relative:1. Severe headache / backache2. Medicolegal conditions3. Diseases of the spinal column (arthritis,

metastasis, osteoporosis)4. Blood in CSF - failure to clear after 10 to 15ml

of aspiration.5. Inability to achieve placement of needle after

3 attempts6. Neurological diseases or simulators(residual

paralysis, poliomyelitis).

EQUIPMENT:Spinal needlesThe standard spinal needle consists of 3 parts:1. Hub2. Cannula and3. Stylet with sizes varying from 18 to 29 gauge.

The various needles are/1. Quincke - Babcock needle2. Pitkin needle3. Greene needle

4. Whitacre needle5. Tuohy needle6. Sprotte needle

Epidural needles:1. Tuohy needle with huber point2. Crawford point needle3. Husted needle - modified Tuohy needle with a

rounded tip and bevel opening.

The Spinal, epidural or caudal anaesthesia is preceeded by a preanaesthetic checkup of the patients with examination of the spine, airway and othersystems. On the day of surgery, IV access should be secured. Premedication should be given depending on the patient or circumstances. Preloading is done by adequate volume of fluid infusion if necessary. Patient should be positioned .The area of puncture should be cleaned with antiseptic solution and draped. We can now proceed with our anaesthetic technique.

Drugs:Along with local anaesthetics, other

groups of drugs can also be used for central neuraxial blockade.

TECHNIQUE:Spinal anaesthesia:

Dural puncture can be done in the lateral flexed or sitting position at the widest interspinous space or at the desired space, usually through the midline approach. In difficult cases and in old patients, the paramedian approach can be selected. Needle in the subarachnoid space is confirmed by loss of resistance and aspiration of CSF.

Continuous spinal technique:-In earlier days CSA was achieved by

malleable needle insertion into the dural sac, which is called LEMMON technique.

Tuohy technique:Introduction of wide bore spinal needle

into the dural sac and insertion of micro catheter into the subarachnoid space. This procedure is associated with a lot of complications like :1. Breaking of catheter 2. Kinking of catheter etc.,

Epidural anaesthetic technique:



Fig 6. Technique of epidural anaesthesia

As epidural space is a potential space, solutions do not readily flow due to the low compliance: gravitational influences are very minimal.• Lateral position is the widely accepted

position. Sitting position is indicated in obese patients or when perineal anesthesia is desired.

• For upper thoracic / cervical region block, sitting position provides a greater ease of insertion of the needle into the epidural space and the level at C7 and T1 is the recommended space, as the thoracic spines of T1, T2 ,T11 and T12 are horizontal while those of T3, T4, T9 and T10 are some what oblique and the spines of T5 and T8 are almost vertical.

DETECTION OF EPIDURAL SPACE:Negative pressure detection technique,

loss of resistance technique when the ligamentum flavum is pierced.

NEGATIVE PRESSURE TECHNIQUES:-1. Hanging drop sign technique of GUTIEREZ2. Capillary tube method3. Manometer technique

LOSS OF RESISTANCE TECHNIQUE:-1. Syringe technique - using air or normal saline.2. Spring loaded syringe technique3. Balloon technique4. Brook’s device5. Vertical tube of dawkins.

Continuous epidural anesthesia:This method consists of threading an

epidural catheter into the epidural space (very frequently used with bacterial filters). They allow accurate incremental dosing and infusions with prolonged analgesia; e.g., in the post operative period and in obstetrics for providing labour analgesia.

Patient controlled analgesia:With a specially designed device, the

patient controls the drug dose delivery into the epidural catheter, according to the depth of pain felt by him.

Caudal anaesthesia I Extradural sacral block:Positioning: Lateral decubitus position.

Prone position with pillow under the pelvis.

Confirmation: Whoosh test Paediatric central neuraxial blockade:

Undertaken by skilled personnel with adequate sedation.

Combined epidural and spinal anesthesia:Single and double space technique

PHARMACOKINETICS AND PHARMACODYNAMICS OF DRUGS USED IN CENTRAL NEURAXIAL BLOCKADE

This will be covered under the following headings:1. INTRODUCTION.2. PHYSIOLOGY OF NEURAL BLOCKADE3. PHARMACOKINETICS & PHARMA

CODYNAMICS OF LOCAL ANAESTHETIC INCNB.

A) PHYSIOCHEMICAL PROPERTIES OF LOCAL ANAESTHETICB) MECHANISM OF ACTIONC) PHARMACOKINETICS & CLINICAL



PROPERTIES.D) VOLUME & CONCENTRATION OFDRUG.E) FATE OF INJECTION IN SUB

ARACHNOID AND EPIDURAL SPACES

4. NEURAXIAL OPIOIDS.5. OTHER DRUGS USED IN CNS.

INTRODUCTIONPharmacokinetics is the quantitative

study of drug distribution, metabolism & excretion from the site of injection.

Pharmacodynamics is the study of the actions of the drug on the body.

Currently, the drugs most commonly used in central neuraxial blockade are local anaesthetics, viz lignocaine, bupivacaine and ropivacaine, opioids and other drugs like midazolam, ketamine, neostigmine, clonidine etc.

Local anaesthetics have the remarkable property of producing a reversible blockade of impulse conduction in the nerve fibre.

Local anaesthetics impede sodium ion access to the axon interior by occluding the transmembrane sodium channels, thus denying the process of depolarization & the axon remains polarized. Local anaesthetics block is a nondepolarizing block.

Ion Trapping:A concentration difference of the total

drug can develop on two sides of a membrane that separates fluids with different pH.

The non-ionized iipid fraction of the drug equilibrates across the cell membranes, but the total concentration of the drug is different on each side of the membrane because of the impact of the pH on the fraction of the drug that exists in the ionic form.

For example: when a local anaesthetic is given in a pregnant patient, (the iocal anaesthetic, basic drug) crosses the placenta from the mother to the foetus because the pH of

the foetus is lower than the maternal pH. The lipid soluble non -ionized fraction of the local anaesthetic crosses the placenta and is converted to the poorly lipid soluble ionized fraction in the more acidic environment of the foetus. The ionized fraction in the foetus cannot easily cross the placenta to the maternal circulation and thus is effectively trapped in the foetus. At the same time, conversion of the non- ionized to the ionized fraction maintains a gradient for continued passage of local anaesthetic into the foetus and is further accentuated by the acidosis that accompanies foetal distress.

PHYSIOLOGY OF NEURAL BLOCKADE:All local anaesthetics are salts of basic

substances. The free base is essential for penetration & the cation form is the pharmacologically active component, which determines the degree of blockade.

The physiology of neural blockade includes 3 phases.1. Delivery Phase2. Induction Phase3. Recovery Phase

Delivery Phase:Drug molecules diffuse through many

layers of fibrous & other tissue barriers before they ultimately reach the individual axon. The first step in moving the anaesthetic towards its target is by “mass movement” like in the subarachnoid space; spread is above & below the site of injection, depending on the baricity.

induction phase:After the local anaesthetic has been

deposited near a nerve trunk, it diffuses from the nerve’s outer surface (mantle fibres) towards the nerve centre (core fibres). Core fibres innervate the distal parts. So, the onset of analgesia is from the proximal to the distal region.

Recovery Phase:During recovery, the diffusion gradient is

reversed. The nerves’ core retains a higher concentration of anaesthetic than the outer fibre. So, regression of analgesia is from the proximal



Fig 7 This shows a nerve trunk with the peripheral mantle fibers attaining drug initially with no drug in the core fiber. So, the proximal territory of the nerve is anaesthetised.

Fig 8 Equilibrium attained, Intra & Extra concentrations are equal

neural

Fig 9 Reversal Gradient: As the extra neural drug reservoir is depleted, the concentration is reversed & the local anaesthetic diffuses out of the nerve.

Fig 10 Recovery: Mantle bundles, being closest to the surface of the nerve, lose their local anaesthetic content faster than the core fibers; a comfortable anaesthetic margin remains in the core after the anaesthetic concentration in the mantle has dropped. Normal function returns to the proximally innervated territory.

to the distal areas.

PHYSICOCHEMICAL PROPERTIES OF LOCALANAESTHETICSMolecular Weight:

Dural permeability and the movement of local anaesthetics through the sodium channel of the nerve membrane is claimed to be more dependent on molecular weight than lipophilicity. Molecular Weight of the agents spans a relatively small range from 220 to 290. This indicates that differences in their aqueous diffusion co-efficients will also be small; as these values are related to the inverse of the square root of the molecular weight Smaller molecules diffuse faster. Most local anaesthetics are small molecules.

Lipid Solubility:A high lipid solubility promotes diffusion

through the membranes, thereby speeding the onset of action and also increasing the potency & duration of effect.

Higher the Aqueous/ Lipid solubility coefficient, rapid is the entry into the lipid membrane & longer is the duration. E.g. Bupivacaine & Etidocaine.

Ionization:The esters have higher pKa values (8.6 - 9.3)

than the amides (7.8 - 8.7) & will therefore be more ionized at a physiological pH.• The unionized base form is important for

penetration.• The ionized cationic form is an active

component for blockage.• By promoting ionisation, a higher

pKa (ipH, Ibase) would be expected to delay diffusion, there by prolonging the onset of


155

action.

Protien binding:Besides being lipid soluble, the longer

acting local anaesthetics also exhibit a higher degree of protein binding.

Features common to all local anaesthetics:1. They are all weak bases with a pKa > 7.4

(free base is poorly water soluble).So they are dispensed as acidic solutions with HCI salts with the pH between 4-7.

receptor for local anaesthetic molecules. Failure of sodium ion channel permeability to increase slows the rate of depolarization such that threshold potential is not reached & thus an action potential is not propagated. Local anaesthetics do not alter the resting membrane potential or threshold potential.Sodium Channel

• Open Activated• Inactive Close• Rested Closed

In the resting nerve membrane, the Na+

Agent Mol. Wt. pKa 25°C DistributionCo-efficient

Protein binding (%)

EstersPROCAINE 236 9.0 1.7 5.8AmidesLIDOCAINE 234 7.7 43 65BUPIVACAINE 288 8.1 346 95ROPIVACAINE 277 8.1 115 90

Table 1: Physicochemical properties of commonly used local anaesthetics:

These commercial preparations are water soluble and highly ionized.

2. They exist in solution as an equilibrium mixture of non-ionized lipid soluble freebase & ionized water-soluble cationic form.

3. Body buffers raise the pH and therefore increase the amount of freebase present.

4. The lipid soluble form crosses the axonal membrane.

channels are distributed in equilibrium between the rested-closed & inactivated closed state. By selective binding to the Na channels in the inactivated closed states, local anaesthetic molecules stabilize these channels in this configuration & prevent their change to the rested closed & activated open states, in response to nerve impulses.

MECHANISM OF ACTION OF LOCAL ANAESTHETICS:

Covino, more recently Butterworth & Strichtartz provide seminal reviews of the electrophysiologica! & molecular mechanisms of local anaesthetic action.

Electrophysialogical effects & Ionic effects:Local anaesthetics prevent transmission

of nerve impulses (conduction blockade), by inhibiting the passage of sodium ions through ion- selective sodium channels in the nerve membrane.

The Na+ channel itself is a specific


Local anaesthetics bind to specific sites located on the inner portion of the sodium channel (internal gate or H gate) as well as obstruct sodium channels near their external opening, to maintain these channels in the inactivated closed state.

Frequency - dependent blockade:An increase in the frequency of nerve

stimulation has been shown to enhance the effect of local anaesthetics on sodium conduction & action potential Resting nerve is less sensitive than the nerve that has been repeatedly stimulated.

Etidocaine characteristically blocks motor nerves before sensory, because of frequency dependent blockade. The pharmacological effects of other drugs, including anticonvulsants, & barbiturates, in addition to local anaesthetics, may reflect frequency dependent blockade.

Effects on Age & Pregency:There will be increased sensitivity to local

anaesthetic-induced conduction block in paediatric, geriatric, & pregnant patients. In pregnancy, the dose should be reduced by 30% due to increased absorption, venous engorgement and increased sensitivity of the nerve fibres due to the effect of progesterone.

PHARMACOKINETICS OF LOCAL ANAESTHETICS:

Pharmacokinetics is the study of drug distribution, metabolism & excretion from the site of injection. Local anaesthetics are weak bases that have pKa valves somewhat above the physiologic pH. As a result, <50% of the local anaesthetic exists in the lipid soluble non ionized form at a physiological pH. Local anaesthetics with a pKa nearest to the physiologic pH have the most rapid onset of action, (e.g., lignocaine), reflecting the presence of an optimal ratio of ionized to non ionized drug fraction.

Absorption & Distribution:Absorption of local anaesthetic from its

site of injection into the systemic circulation is influenced by the site of injection, dosage, use of

epinephrine and lipid solubility. The ultimate plasma concentration is determined by the rate of tissue distribution & rate of clearance of drugs. Initially, they are distributed to the highly perfused tissues - brain, heart, kidney and later to the poorly perfused tissues - skeletal muscle, fat. In addition to tissue blood flow & lipid solubility of local anaesthetics, patient related factors such as age, CVS status and hepatic function will also have an influence. Ultimately the local anaesthetic is eliminated from the plasma by metabolism & excretion.

Metabolism:METABOLISM OF ESTER LOCAL ANAESTHETICS:

Ester local anaesthetics undergo hydrolysis by cholinesterase enzyme principally in the plasma & to a lesser extent in the liver. Cocaine undergoes significant metabolism in the liver.

METABOLISM OF AMIDE LOCAL ANAESTHETICS:

Amide local anaesthetics undergo metabolism by microsomal enzymes primarily in

Most Rapid Intermediate Slowest.Prilocaine Lidocaine & Etidocaine

Mepivacaine Bupivacaine & Ropivacaine.

the liver.

BUPIVACAINE:Possible pathways: aromatic

hydroxylation, N-dealkylation, Amide hydrolysis. Only the N-dealkylation metabolite, N-desbutyl bupivacaine, has been measured in the blood or urine after epidural or spinal anaesthesia. a1 -acid glycoprotein is the most important plasma protein binding site of bupivacaine.

ROPIVACAINEThe principle metabolite of ropivacaine

is 3-hydroxy ropivacaine.

Renal elimination:Excretion occurs by the kidney. Less

than 5% of the unchanged drug is excreted via



the kidney into the urine. The renal clearance of the amide agents appears to be inversely related to the protein binding capacity.

CLINICAL PROPERTIES OF LOCAL ANAESTHETICS & USES

Local anaesthetics have differing physicochemical properties like partition coefficient, protein binding, and pKa, which play an important role in neural blockade such as latency, duration of action, potential toxicity & ability to cross lipid barriers.

Lidocaine• Lidocaine has a low mol wt, is easily diffusible.• pKa is close to physiological pH, so it has

a rapid onset of action.• Moderate lipid solubility.• Excellent spreading capability.• So, it is the ideal agent where rapid onset

is required.• Has anti arrhythmic property.

Bupivacaine• pKa is more (8.1), so there is less base

form and less penetration.

• Highly lipid soluble i.e. partition coefficient of 28.

• 90-95% bound to plasma proteins.• So, it has a slow onset & longer duration

of action.

Ropivacaine• Lipid solubility is intermediate between

idocaine & bupivacaine.• Protein binding is slightly less than

bupivacaine with an identical pKa• Clearance is higher than bupivacaine

Bupivacaine & Ropivacaine at similar concentrations (0.5% to 0.75%), produce similar prolonged sensory anesthesia (ropivacaine has a greater tendency to block Ad & C - fibres) when used for epidural anesthesia, but the motor anesthesia produced by ropivacaine is less intense and of a shorter duration. This characteristic of ropivacaine may be advantageous for obstetric patients in labour.

VOLUME CONCENTRATION & DOSE OF



Drug Potency Onset Duration Max Toxic VD Clearance Elimination(mts) Single Plasma (Its) —e (I/m) half time

Dose Level minutes.(mg) (ng/ml)

EstersPROCAINE 1 Slow 45-60 500 — — — ___

AmideLIDOCAINE 1 Rapid 60-120 300 >5 95 0.95 96BUPIVACAINE 4 Slow 240-480 175 > 1.5 75 0.45 210ROPIVACAINE 4 Slow 240-480 200 >4 40 0.44 108

ONSET OF Mepivacaine > Lidocaine > Etido > Ropi > Bupi > Tetra > Chiorprocainelocalanaesthetics

Duration of Bupi > Ropi > Mepi > Lidocainelocalanaesthetics

Table2. Comparative Pharmacology of local anaesthetics

LOCAL ANAESTHETICS IN CNBIncrease in dosage of a drug results in a

linear increase in the degree of sensory block & the duration of epidural block, while increasing the concentration results in a reduction in the onset time & the intensity of motor blockade. - With regard to motor blockade, dosage becomes less important when dilute solutions are employed. Below a concentration of 1 % lidocaine, motor block is very minimal, regardless of the dose. The dose of epidural local anaesthetic agents is largely determined by the number of spinal segments to be blocked & the volume necessary to reach & effectively bathe those segments. The usual drug concentration is 2% lidocaine, 0.5% bupivacaine, 1% ropivacaine, both age & height should be considered.

• In obstetric patients, a 30% reduction in dose is required.

• In patients with arteriosclerosis, a 50% reduction in dose is required.

• For single injection technique, the dose ranges from 15-20 ml while fora continuous technique, the initial dosage should be 8-12 ml & subsequent dosage should be 5-7 ml every hour.

• In poor risk, debilitated, frail or very old patients, the volume should be halved.

FATE OF INJECTED AGENTS IN THE SUBARACHNOID SPACE

When the drug is injected into the subarachnoid space, immediately there is a fall in concentration, this is due to 4 pharmacokinetic processes:• Dilution & mixing in the CSF.• Diffusion & distribution to the neural tissue.• Uptake & fixation by neural tissue.• Vascular absorption & elimination:

a) Through arachnoid villib) Directly from the capillary bed of the parenchyma

In 1936, Koster demonstrated graphically, the rate of disappearance of procaine from the CSF at the site of injection.

Dilution:This occurs in the first 1 to 2 minutes

after injection. This is due to mixing & dilution, that is governed by the force with which a solution is injected and the amount of fluid in the spinal subarachnoid space. Rapid rates of injection set up turbulent currents in the spinal fluid and help


Neuraxial Blockade 159 D.Anil Kumar, S.K.Arif Pasha & Rani Manjusha

Table3. Volume Concentration & Dose of Local Anaesthetics in CNB

to mix and dilute.

Diffusion:Within 2-6 minutes of injection, this

decrease in concentration is caused primarily by the diffusion of the agent in the spinal fluid by virtue of its molecular motion. At the same time, some of the agent is being adsorbed onto nervous tissue and this contributes to the second phase of decreasing concentration.

Distribution:Once the local anaesthetics are mixed

and diluted with the CSF after injection, they are

anaesthetic agent to gain access to the nerve tissues, and to bathe both the gray and the white matter. Blockade of nerve impulses follows. The uptake & concentration of the agent at different areas of the spinal cord are related to several factors, which include:1. Concentration of the agent.2. The degree of exposure of the nerve tissue to

the agent.3. Lipid make up of the nervous tissue and the

myelin sheath. (The lateral and posterior spinal cord tracts and the anterior corticospinal tract are heavily myelinated. Hence the concentration of local anaesthetic

distributed by diffusion along a concentration gradient to 3 sites:

Diffusion from the spinal fluid into the substance of the spinal cord has been well demonstrated by auto radiography & radio assay.

Tissue Uptake:The distribution process permits the local

is greater in such areas).4. Molecular weight of the agent; diffusion

is related inversely to the square root of the molecular weight.

5. Structure of the local anaesthetic; Stoichometrically, (i.e. molecular configuration or volume), spherical molecules diffuse more slowly than chain-extended molecules (fentanyl); long molecules diffuse rapidly.



6. Blood flow.

Tissue Fixation:It is a process where in the

anaesthetic becomes adsorbed onto nervous tissue. It is a surface phenomenon. Molecules of the anaesthetic agent provide a large, free surface and these come in contact with the nerve fibres.

Vascular Absorption:Uptake of local anaesthetics from the

spinal fluid and from the nerve fibres into the vascular compartment accounts for the 3rd phase of slow decrease in the total concentration of the agent in the spinal fluid. Disappearance from the subarachnoid space is by way of 2 routes; through the arachnoid villi and directly into the capillary or lymphatic channels of the nerve bundle and into the capillaries of the nerve tissue parenchyma. The disappearance was studied by radioactive dibromo-procaine and determined that a greater portion of the drug leaves the subarachnoid space

through venous drainage while a smaller portion leaves through small lymphatic channels. The residual concentration of the anaesthetics in the subarachnoid space is removed by 2 routes:• Direct passage into the venous drainage in

the piameter and then to spinal segmental veins.

• Diffusion through the duramater into the epidural space.

Elimination:The rate of Elimination is governed by

diffusion and is proportional toa. The Concentration gradientb. Chemical characteristic of the drug i.e. Lipid

solubilityc. Physicochemical characteristic

PLASMA LEVELS OF LOCAL ANAESTHETICS AFTER SUBARACHANOID ADMINISTRATION:

The plasma concentration curves reflect



the pharmacokinetic processes of absorption, distribution, redistribution and elimination. In a study by Burm;

For hyperbaric lidocaine 75 mg in 7.5 % dextrose,• Peak Concentration time (tmax):

66 min (25-120 min)• Peak Concentration (Cmax):

444 ng/ml (290-860)• Apparent elimination Vz time:

2+ 0.3 hrs [1.5-2.4 hrs]

For hyperbaric bupivacaine 15 mg (0.5%),• Peak Concentration time (tmax):

53 min [40 - 75 min]• Peak Concentration (Cmax):

63 ng/ml (+ 22 mg)• Apparent elimination 1/4 time:

3.6 hrs + 4

There are two presumed mechanisms:1. Local anaesthetic diffuses across the duramater to act on the nerve roots & spinal cord as it does when injected directly into the SAS.2. Local anaesthetics the diffuse into the paravertebral area through intervertebral foramina producing multiple paravertebral nerve block.

It takes 15-30 mts for the drug to settle down and act. The thickness of the nerve and their coverings, dictate that a higher concentration is required if somatosensory & motor blockade are desired. Epidural injection deposits local anaesthetics some distance from the neural targets; so, the diffusion across tissue barriers is of great importance. Thus local anaesthetics with equal lipid solubility and water solubility i.e., a pKa close to the physiological pH (e.g., lidocaine) are most effective and rapid in onset.

Epidural fat provides a potential reservoir for the deposition of fat-soluble local anaesthetics. Thus, accumulation of long acting fat-soluble agents, such as bupivacaine, occurs in epidural fat. So, with repeated injection of bupivacaine, epidural fat concentration rises, but blood concentration tends to remain the same, provided the dosage is appropriate; with less fat soluble drugs like lidocaine, repeated injection results in little accumulation in fat with a potential for gradually increasing blood concentration.

The epidural venous system provides a rich network for the rapid absorption of local anaesthetics. Rapid injection into an epidural system. The inclusion of epinephrine in the local anaesthetic solution may greatly reduce vascular absorption, and thus enhance neural blocking properties and reduce the likelihood of systemic toxicity after epidural injection. The time profile of local anaesthetic absorption indicates a peak blood level at 10-20 minutes after injection; so, surveillance is necessary for at least 30 minutes after injection. Plasma protein binding greatly influences the amount of free local anaesthetics available for action on the CNS after systemic absorption from the epidural space.

NEURAXIAL OPIOIDS:Neuraxial opioid analgesia is that

condition obtained when small amounts of exogenous narcotics or endogenous ligands are introduced into the intrathecal or epidural space. The effect of regional narcotics is reversible and is exerted directly on the spinal cord neurons in Rexed’s lamina I, II & V of the dorsal horn, known to be rich in opioid binding sites. Here, the nociceptive input, which is transmitted through the A-delta and C pain fibres, is selectively inhibited. In the spinal cord, the n binding sites

DRUG Mol Wt. pKa (25°) PartitionCo-efficient

%ofnon ionized at pH 7.4.

Proteinbinding.

Morphine 285 7.9 1 - 23 35Pethidine 247 8.5 32 7 70Buprenorphine 8.24 120Fentanyl 336 8.4 950 8.5 85

Table. 5 Fhysico - chemical properties of commonly used opioids



are found along the entire cord in the superficial layers of the dorsal horns, the delta sites occupy the gray matter of the cervicothoracic part, and the kappa receptors appear in dense formation in the lumbosacral region. The opioid/receptor binding is followed by both a pre-synaptic & a postsynaptic effect involving the opioid as well as the descending non-opioid pain pathways.

Spinal Action of OpioidsPresynaptic: Control of high

threshold primary afferents, by blockade of pain transmitter release.

Postsynaptic: Inhibition of nociceptive neuronal cell excitation.

Descending inhibitory opioid and nonopioid pain systems: Activation of opioid, serotonergic, noradrenergic & GABA neurons.

Analgesia produced by neuraxial opioids, in contrast to IV administration of opioids or regional anesthesia with local anaesthetics, is not associated with sympathetic nervous system denervation, skeletal muscle weakness, or loss of proprioception. Analgesia is dose related (epidural requires 5-10 times the dose as spinal) and specific for visceral rather than somatic pain. Morphine is the only opioid for which the safety & efficiency of epidural administration has been

somniferum (Hydrophilic Opiate). The Octanol/ water Co-efficient is 1.4 at a pH of 7.4 and 37°C. It has an ampholytic nature because of the presence of both a tertiary amine group (pKa: 7.9) & a phenol group (pKa9.6) in the molecule. Thus, it is predominantly ionized at a physiological pH. Although the base is sparingly soluble in water, the HCI & the S04 salts are readily soluble in water.

Morphine kinetics after Epidural Administration

The epidural Space is highly vascularized & contains loose connective tissue & adipose tissue. There are 3 main competing structures, when drugs are injected into the epidural space:

• Diffusion across the meninges.• Distribution into epidural fat.• Vascular absorption.

Plasma concentration:Morphine injected into the epidural space

is rapidly absorbed into the general circulation. Absorption is so fast that the plasma concentration-time profile closely resembles those obtained after IM or IV administration.

The mechanism of postoperative analgesia produced by epidural administration of highly lipophilic opioids (Fentanyl, Sufentanil) is primarily a reflection of systemic absorption.

Route & Drug Dose (mg) Onset (min) Duration (hours) Infusion rate (mg/hr)

EPIDURALMorphine 1-10 30 6.24 0.1-1.0Pethidine 20-200 5 6-8 5-20Fentanyl 0.025-0.15 5 4-6 0.025-0.1

INTRATHECALMorphine 0.1 -0.5 15 8-24Pethidine 10-30 5 10-30Fentanyl 5-25 5 3-5Pentazocine 15 5 5-8Table.6 Doses, latency & duration of commonly used drugs

substantially documented. We take morphine as Poorly lipid-soluble opioids such as morphine have the prototype for our discussion. a slower onset of analgesia but a longer duration

of action than the lipid soluble opioids.Chemical properties of Morphine:

Morphine is produced from Papaver As the epidural space contains an



extensive venous plexus, vascular absorption is extensive.'After epidural administration, fentanyl blood concentration peaks in 5-10 minutes; in contrast, the blood concentration of morphine peaks after 10-15 minutefe.

Chauvin & colleagues found no significant differences in the areas under the curves after IM, epidural & intrathecal administration of the same dose. This finding suggests that availability is complete, when morphine is administered epidurally or intrathecally.

Bromage & associates reported that simultaneous co-administration of epinephrine, reduced the systemic uptake of morphine in healthy volunteers, whereas Youngstorm & colleagues found that this regimen produced no change in obstetric patients.

CSF Concentration:Epidural administration of opioids

produces considerable CSF concentrations of the drug. To gain access to spinal opioid receptors, the drug must cioss several diffusion barriers, such as the meninges and the neural tissues. Penetration of the dura is considerably influenced by lipid solubility and molecular weight. Fentanyl and Sufentanil are respectively, approximately 800 & 1600 times as lipid soluble as morphine.

After epidural administration, the CSF concentration of fentanyl peaks in about 20 minutes & Sufentanil in 6 minutes. In contract, the CSF concentration of morphine, after epidural administration, peaks after 1-4 hrs. Furthermore, only about 3% of the dose of morphine administered epidurally crosses the dura to enter the CSF.

Morphine kinetics after Intrathecal administration

The intrathecal route of administration circumvents the meningeal diffusion barriers and considerably lower doses of morphine are necessary to produce the same degree of analgesia as that induced by the epidural route.

Cephalad movement of opioids in the

CSF principally depends on lipid solubility.For e.g., lipid soluble opioids such as fentanyl & sufentanil are limited in their cephalad migration by uptake into the spinal cord, whereas the less lipid soluble morphine remains in the CSF for transfer to more cephalad locations.

After lumbar intrathecal morphine administration, appreciable cervical CSF concentration occur 1 to 5 hrs after the injection, whereas cervical CSF concentration of highly lipid-soluble opioids are minimal after their epidural administration.

The underlying cause of ascension of morphine is bulk flow of CSF. CSF ascends in a cephalad direction from the lumbar region reaching the cisterna magna in 1 - 2 hrs, the 4th and lateral ventricle by 3-6 hrs (Chaney, 1995). Coughing or straining, but not body position can affect the movement of CSF.

Relationship between Morphine concentration & analgesic response:

The most outstanding feature of epidural morphine is its ability to produce excellent, long- lasting regional analgesia from doses that are only 20 - 40% of the normal IV dose. I ntrathecal administration of morphine is even more potent, requiring only about 8% of the standard 10 mg IV dose. Clinical experience has shown that analgesic onset of action of epidural morphine is slow (45-60 minutes) compared with that of !V morphine. This delay is due to the physiochemical properties of morphine and the location of the receptors in relation to the site of administration. Being hydrophilic, morphine penetrates the different diffusion barriers much more slowly than the more lipophilic molecules such as fentanyl.

The duration of action of morphine is governed by 2 factors.a) The rate of morphine removal from receptor

sites.b) The magnitude of morphine concentration

surrounding the receptors.

The duration of analgesia varies considerably among patients; due in part to pronounced inter individual differences in pharmacokinetics. Duration is dose dependent,



and the usual 4 mg dose is commonly reported to have a duration of 10-17 hrs.

Epidural & Intrathecal Morphine Kinectics in Relation to Adverse Effects

Side effects of neuraxial opioids are caused by the presence of the drug in the CSF or the systemic circulation. The most feared adverse reaction is late respiratory depression, usually due to rostral spread of morphine in the CSF, and is extremely rare. One recent Swedish retrospective study comprising about 10,000 patients, reported an incidence of 0.25 - 0.4%.

The reasons for the rostral spread of morphine may be:a) Bulk flow of CSF.b) Physical activities such as coughing could

cause the CSF pressure wave, capable of moving a substance in a rostral direction.

c) Epidurally injected drugs could be absorbed into the valveless vasculature of the epidural space and subsequently transported to the veins in the brain.

A review of 229 patients in different controlled double-blind studies using 2-5 mg of epidural morphine showed that the three most common side effects were

• Pruritus (14%)• Urinary retention (12)• Nausea & Vomiting (11%)

A most promising study in this context, reported by Rawal & co-workers showed that continuous intravenous infusion of low-dose naloxone could be used to counteract the side effects of epidural morphine, without reducing the analgesia.

OTHER DRUGS USED IN CNBThe other relatively uncommon drugs

used in CNB are1) Benzodiazepines e.g. Midazolam.2) Ketamine3) Clonidine4) Neostigmine5) Steroids.

Spinal GABA System:The spinal GABA system has been used

as a target for newer Benzodiazepines e.g.,

midazolam, and certain neuro active steroids like alphadalone20.

NMDA Receptors and Ketamine:The pain relieving effect of ketamine has

been attributed to blockade of NMDA excitatory neurons; Mccartely, Naguit et al have used ketamine from 30mg to 50mg intrathecally and epidurally with varying results.

Clonidine:Clonidine, an alpha 2 - adrenergic

agonist, is most commonly used centrally to produce relief. It is believed to act on the adrenergic receptors, the opioid receptors and by modulation of G proteins and Substance P. Dose range - 1 to 1.5 (mcg/kg).

Neostigmine:Neostigmine is a familiar drug in the

anaesthesiologist’s armamentarium, which is being used to produce analgesia by inhibiting the breakdown of acetylcholine. The drug has been used epidurally and intrathecally in the dose range of 500 - 750 (meg /kg) and has been found to have dose dependent side effects like nausea and vomiting.

COMPLICATIONS, CLINICAL CONTROVERSIES AND RECENT ADVANCES OF CENTRAL NEURAXIAL BLOCKADE COMPLICATIONS OF CENTRAL NEURAXIAL BLOCKADE:The complications of Central Neuraxial Blockade can be classified as:• Complications due to Spinal anaesthesia.• Complications due to Epidural anaesthesia

COMPLICATIONS OF SPINAL ANAESTHESIAThese can be:During the procedure or immediate complications:A) HYPOTENSION:

Due to the decrease in cardiac output which is due to decreased venous return because of sympathetic block or due to block of sympathetic cardiac fibres.Management: Adequate preloading, head down position, vasopressors and administration of oxygen.



B) TOTAL SPINAL ANALGESIA:Characterized by marked hypotension,

apnoea, dilated pupils, loss of consciousness and bradycardia.Management: Intubation and ventilation with 100% oxygen, elevation of the legs, vasopressors and intravenous fluids. The operation can then proceed and spontaneous respiration will probably recommence within an hour, unpleasant sequelae being unlikely.

C) TOXICITY:Due to intravascular injection or by fast

absorption of local anaesthetics. Both CNS and CVS complications occur. Signs are excitement, disorientation, twitching, convulsions, apnoea and severe cardiac depression.Management: Injecting diazepam into the drip, oxygen by IPPV, protection of patient’s teeth and tongue from trauma at the time of convulsions.

D) HYPOVENTILATION:Due to brainstem hypoxia and block of

phrenic nerve roots.Management: Ltngs are ventilated with 100% Oxygen.

E) ALLERGIC RESPONSE TO INJECTED DRUG.Management: Oxygen, I.V. adrenaline,

I.V. Colloid infusion.

F) HYPOTHERMIA:Should be managed by adequately

covering the patient and infusing of warm IV fluids.

G) NAUSEA & VOMITING:As a result of

• Sudden change in position• Hypotension• Parasympathetic mediated traction• Opioid administration.

Management: Exclude hypoxia, take care of hypotension, shift the patient slowly and gently, antiemetic drugs.

H) AFFECTIVE DYSPNOEA:With block of sensory input, patient may

complain of difficulty in breathing. Mechanism is inappropriate response (ventilatory volume) to muscular effort.

Management: Encourage the patient to take deep breaths, provide supplemental oxygen, inhaling of smelling salts like aromatic salts of ammonia and applying pressure over the lower chest helps.

I) APPREHENSION:Attention to premedication is important

in prophylaxis.

J) DIFFICULT SPINAL PUNCTURE.

K) TRAUMATIC SPINAL PUNCTURE:Repeated attempts to achieve a spinal

tap may result in direct trauma to the nerves, the periosteum of the vertebra and to the intervertebral discs. Paraesthesia is noted and may persist. Transient or permanent neurological deficits may ensue.

L) BROKEN NEEDLE OR CATHETERS:Management: Removal of the needle

fragment should be attempted as soon as possible. The proximal part of the stylet should if possible be left in space to serve as a guide to the distal part. If the catheter breaks, it should be noted and the neurosurgeon informed. It is seldom justified to carry out an exploration.

Post operative or late complications of spinal anaesthesia1) POST DURAL PUNCTURE HEADACHE:

It is postural, beginning within 6 to 12 hours after lumbar puncture (but may take 3 days), often occipital and is associated with pain and stiffness of the neck.

Mechanism: It is related to the persistence of dural puncture, with leakage of CSF into surrounding soft tissues leading to lowering of the CSF pressure. This exerts downward traction on the structures of the CNS and on the blood vessels that are attached to the dura and the cranium as well as the brainstem. The result is a headache similar to acute vascular cluster headache Increased incidence is noted

• In young and female patients.• In pregnancy• If needle size is large• With the midline approach• Increased concentration of glucose

Differential diagnosis - Migraine,



meningitis, tumour, dehydration, hyponatremia. Management:Avoid in unsuitable patients, with frequent headache.

• Use of fine needles• Prevention of dehydration, strain,

coughing.• Choice of needlepoint: Whitacre, Sprotte

• Epidural blood patch

2) BACKACHE:Due to obliteration of lumbar lordosis and

stretching of ligaments, reflex muscle spasm, positioning and small haematomas. Management: A small pillow under the lumbar region reduces the incidence of backache. Skeletal muscle relaxants and analgesics, reassurance and heat will usually rectify the problem.

3) MAJOR NEUROLOGICAL INJURIES:Cranial nerve disturbances: Paralysis of

every cranial nerve except 1,9 and 10 has been reported.

The primary cause of this is due to CSF dynamics consequent to lumbar puncture. It is basically the same as the cause of headache.

Abducens nerve palsy - it has the longest intracranial course and is more vulnerable to dynamic changes in the CSF.Symptoms: Internal strabismus, blurring, diplopia and difficulty in focussing.Management: 50% cases recover within 1 month, if condition persists, dark glasses may be worn.

Urinary retention: Blockade of S2-S4 is associated with loss of bladder tone and inhibition of voiding reflex leading to overfilling of bladder. Even after resolution of blockade, voiding may be difficult. These problems are more common in male patients and in extreme cases can result in neurogenic bladder requiring intermittent catheterisation.

For prolonged Central Neuraxial Blockade, it is probably wise to avoid this problem by inserting a bladder catheter.

Cauda equina syndrome: - Characterised

by abnormalities of leg reflexes, incontinence of faeces, retention of urine, loss of sexual function, sensory loss in the lumbo sacral plexus distribution and a temporary paralysis of peroneal nerves. Most of them clear spontaneously.

Traction nerve paresis or paralysis; lithotomy position and stirrup pressure may produce peroneal nerve palsies,

4) MENINGITIS OR ARACHNOIDITIS:This may occur even with a seemingly

flawless technique. Aseptic meningitis has been reported.

Contamination with chemical antiseptics, starch powder of gloves, detergents, higher concentration of drugs and variation in pH has been blamed. The need remains for careful adherence to an aseptic technique.

5) ANTERIOR SPINAL ARTERY SYNDROME:Due to spinal cord ischaemia, due to

severe hypotension.

6) VASCULAR INJURY:In patients with coagulation disorders or

on anticoagulants.

COMPLICATIONS OF EPIDURAL ANAESTHESIA: a) Inadvertent dural puncture:

It has been recommended that when this occurs, plan for epidural anaesthesia is stopped and simple spinal / GA is administered. Objective studies indicated that this is unnecessary and we can go for epidural in another inter space or can opt for continuous spinal anaesthesia.

b) Total spinal:Due to accidental sub arachnoid

injection.

c) Neural damage:The incidence is low, but the neurological

deficits are due to trauma, anterior spinal artery syndrome and epidural haematomas.

d) Hypotension:The degree of hypotension is less in EA

than SA, because the onset of action of local



anaesthetic drugs in epidural is delayed and by that time adequate preloading is done so that the incidence and degree of hypotension is reduced.

e) Urinary retention:

f) Toxicity:As relatively large doses of local

anaesthetic drugs are required for EA, and epidural space contains numerous venous plexus, which may be penetrated by epidural needle or catheter, there is more chance of local anaesthetic toxicity with EA.

g) Catheter complications:It may be inserted directly into the blood

vessel or subarachnoid space or breaking of the catheter in the epidural space may occur. No attempt is made to withdraw the catheter through the needle.

h) Failure:

i) Epidural abscess:Following SA or EA, abscess formation

is superficial requiring limited surgical drainage and intravenous antibiotics.

j) Effect of rapid injection:Sensation such as headache, vertigo,

and paraesthesia may be seen when the anaesthetic solution is injected rapidly, as rapid injection increases the CSF pressure. This effect lasts for 3-5 minutes, during which headache is prominent.

RECENT ADVANCES IN REGIONAL ANAESTHESIA

Over the last two decades, there have been considerable innovations in materials, drugs, and techniques of central neuraxial blockade, which have contributed to improving the quality and safety of central neuraxial block. The following are a few of them.

Equipment:1. Use of 25 G epidural needle systems with a modified tip lowers the incidence of post dural puncture headache in the event of an unintentional dural puncture and causes less tissue trauma.

2. The limiting factors for the use of smaller gauge spinal needles are reduced back flow of CSF and decreased tensile strength. But new manufacturing has increased the internal diameter of small gauge needles as well, improving the back flow without a notable decrease in tensile strength. Some needles taper from a 22-gauge shaft to a 24 gauge tip.

3. Another development in neuraxial block technique is the development of effective methods of combining epidural and spinal anaesthesia via a single needle system.

These methods use epidural needle placement followed by insertion of a spinal needle through either a side lumen on the epidural needle, or directly via the epidural needle lumen. This combined technique allows flexibility in a number of clinical settings.

Techniques:1. VERIFICATION OF NEEDLE AND CATHETER INSERTION:

More recently, techniques to aid in location of the epidural space have been reported including the use of1. Auditory amplification of the sound made by the epidural needle as it traverses the interspinous ligament and ligamentum flavum.

• Doppler guidance and• Pressure transducer methods

2. Use of fluoroscopic guidance for epidural needle placement and injection of non-ionic radiopaque contrast solution through the epidural catheter producing the typical epiduralgram appearance. This may also be used to confirm epidural needle (or) catheter placement.

3. Recently low current electrical stimulation resulting in truncal (or) limb motor responses is regarded as a simple, objective and reliable technique for confirmation of epidural catheter placement.

II.EPIDURAL RADIOGRAPHS AND EPIDUROSCOPY: -

Use of epidural radiographic techniques and epiduroscopy have enhanced the knowledge of anatomic characteristics and fluid dynamics within the epidural space & the effect of previous epidural anaesthetic procedures on the cephalad



spread of sensory block during lumbar epidural anaesthesia.

It was noted by epiduroscopy that patients with a history of previous epidural anaesthesia had aseptic inflammatory changes within the epidural space such as, narrowing of epidural space, proliferation of connective tissue and adhesions between the duramater and ligamentum flavum. These changes are responsible for the reduction in cephalad spread of sensory blockade in patients with previous history of epidural anaesthetic producers.

III. METHODS OF DETERMINING THE EXTENT OF EPIDURAL ANAESTHESIA:1. Skin vasomotor reflex testing, using changes in skin blood flow, as measured by laser Doppler, in response to tetanic electrical stimulus.2. Somatosensory evoked potentials in response to electrical and argon laser stimulation have been used to determine the extent of sensory neural blockade during EA & SA.

IV. ANAESTHETIC TECHNIQUES:1. Unilateral epidural analgesic techniques: Insertion of epidural catheters using fluoroscopic guidance has demonstrated the relative ease with which catheters may be directed within the epidural space through changes in location and bevel orientation of the epidural needle and producing unilateral epidural analgesia.

Technique: - Selectively, relatively unilateral distribution of analgesia may be obtained through a technique involving slight angulation (approximately 5 degrees in the horizontal plane) of the epidural needle towards the intended side of location and orientation of the needle bevel between 45 degrees and 135 degrees from the cephalad direction laterally. With this needle location and bevel orientation, the epidural catheter tip is directed to lie in the lateral epidural space.

2. The technique of postoperative epidural administration of 20ml of normal saline hastening the return of motor function from EA has been described. This is related to a dilutional (washout) effect, an ion trapping effect produced by the injection of saline with a relatively low pH and increased uptake of local anaesthetic by greater

area of distribution.

3. Anaesthesia for Ambulatory surgery: Ambulatory surgery demands good surgical anaesthesia with rapid recovery from sensory and motor block & recovery of the ability to void. As lidocaine has been questioned with the possibility of neurotoxicity, hypobaric, hyperbaric and near isobaric bupivacaine solutions are used for ambulatory surgeries.

4. Patient controlled analgesia: Use of microprocessor controlled epidural infusion pumps, with patient activated dosing capability, has become the postoperative pain management technique of choice, as compared with intermittent bolus dose administration method. With this PCEA, it has been noted that there is overall reduced dose requirement and patient satisfaction.

5. Mobile epidurals have already gained popularity in the field of obstetric analgesia as they allow normal mobility with high quality of pain relief.

6. Central neural blockade in children is providing excellent intraoperative and postoperative analgesia. The paediatric regional anaesthetic techniques are greatly reducing the morbidity associated with surgery and anaesthesia in selected groups of patients and can favourably influence the postoperative course.

Drugs: -1. Separation of stereoisomers allowed the development of improved local anaesthetics for safer use, e.g.: Ropivacaine & levobupivacaine which are S.enantiomers of bupivacaine. It has been demonstrated that they have potency almost similar to bupivacaine (less with ropivacaine) while exerting significantly less CNS & CVS toxicity.

2. The most exciting new development in Central Neuraxial Block is the introduction of novel analgesic drugs (nonopioid, nonlocal anaesthetic), analgesic adjuvant medications, and new epidural anaesthetic and analgesic formulations eg.adenosine, midazolam, verapamil, ketorolac and others which are in various stages of clinical (or) preclinical study for



possible spinal analgesic utility.

3. Novel drug formulations and epidural delivery systems may soon include the use of liposome- encapsulated local anaesthetics (or) opioid analgesics capable of, producing an extended duration of analgesic effect from a single epidural dose.

CLINICAL CONTROVERSIESInspite of the many years that neuraxial

blockade techniques have been used, there remain a number of controversies about the appropriate use of these techniques.

1. Related to systemic toxicity of local anaesthetics and premedication.

Inspite of the widely held belief that benzodiazepines should be used with regional anaesthesia to minimize systemic toxicity as they elevate the seizure threshold, it has been shown that benzodiazepines cover up one of the early signs of systemic toxicity (i.e., seizure). Thus resuscitation may be more difficult after cardiovascular collapse, delaying potentially the definitive therapv.

2. Most controversy surrounds the use of epinephrine in obstetric patients in which uterine blood flow may be decreased by intravascular injection there by putting the foetus at risk, but many anaesthesiologists believe epinephrine - containing epidural test doses are useful in obstetric anaesthesia.

3. Some continue to suggest that spinal anaesthesia is inappropriate for out patients because of the occurrence of post dural puncture headache, yet there are data that the occasional headache can be successfully treated even in the out patients and considerable other data are available supporting the use of this technique in out patients.

4. The use of epidural anaesthesia for patients receiving anticoagulants is less clear because epidural anaesthesia is often avoided in these patients but there are studies, which used continuous epidural anaesthesia in vascular operations, in patients receiving preoperative oral anticoagulants without any problem. The acceptable magnitude of preoperative anticoagulation and risk benefit ratio of performing epidural anaesthesia remains undetermined by this time.

The time duration accepted between anti coagulation prophylaxis and Central Neuraxial Block is as follows:

• Low molecular weight heparin-12 hours after the last dose and the same rule applies for the insertion and removal of the catheter.

• Heparin infusion- 4 hours after the cessation of the infusion.

• Warfarin intake- An INR of less than 1.5 is accepted for performing Central Neuraxial Block. Again, it is the element of risk benefit ratio to be kept in mind when such patients are subjected to Central Neuraxial Block

REFERENCES:Anatomy for anaesthetists - Harrold Ellis, Stanely feildman, 6th editionPrinciples of anaesthesiology- Collins, 3rd edition, 1993Indian journal of anaesthesiology Dec 2001 45(6), 414,430Pharmacology and physiology in anaesthetic practice- Stoelting, 3rd edition 1999 Pharmacological basis of therapeutics - Goodman and Gillman Anaesthesia by R.D Miller, 5th edition Lee synopsis of anaesthesia- 13th edition Anaesthesiology clinics of North America - June 2000.


Patient Positioning 170 Trivandrum Medical College

INTRODUCTIONThe prone position is also called

‘concorde’ position, ‘face down’ position or the position wherein the ventral surface of the body lies on some surface supporting the body weight. In the Classic prone position the face, chest, abdomen, front of thighs, knees, toes and some surface of hands and arms all touch the supporting surface. People sleep in this posture using crooked arms to hold the face off the bed to prevent pressure on nose.

Patients under GA - Problems :1. Body weight against abdominal wall leads

to decreased diaphragmatic movement and decreased tidal volume

2. Increased intra-abdominal pressure causes decreased venous return

3. Pressure on toes and bony prominences can cause pressure injuries

4. Care must be taken in keeping the head in safe relation with the rest of the body

MODIFICATIONS OF PRONE POSITION :1. Jack knife position :This is used for anorectal surgeries. The patient lies on a flexed operating table with pelvis at the flexion point. Surgical field is clearly visible and the abdominal viscera move cephalad in response to gravity. Arms are beyond the top of the head and face turned to one side.

2. Knee-chest position : This is an exaggeration of jack knife position. Knee and chest are supported, Neck is extended and face turned to one side. Gynaecological examination is facilitated. Uterus and other viscera fall ventrally and cephalad.

3. Buie position : This is a modification of the prone position providing satisfactory exposure

for proctological work. The patient kneels on a wide padded shelf, bends forward over a 90 degree table, placing his chest on the table proper. When the table is tilted into a head down position, gravity moves viscera and venous blood away from the perineum. The operative field exposure is good, blood loss is minimal, proctoscopy greatly simplified and the patient is in a reasonable position for either hypobaric spinal or caudal anaesthesia.

4. Georgia position This is a modification of the knee- chest position. The patient’s weight is supported on his knees and chest. The knees are on a shelf, chest is on a stack of folded sheets. The height of the knee support and the height of stack of sheets are adjusted to leave abdomen free of pressure. Good exposure for perineal and rectal work is obtained, if table is tilted head down.

5. Smith’s recent modification of Georgia position: In this position specially built supports are used to raise the pelvis to a height sufficient to leave abdominal wall completely pressure free. The chest is elevated by stack of folded sheets. The chest and pelvis are elevated, usually to the same height

6. Overholt position : This is used for surgical management of specific thoracic problems to prevent drainage of infected material and blood from the involved lung into the other lung in the course of surgery. Now minimally used since double lumen tubes are available. Exception is a small child whose airway is too small to accommodate the double lumen tube. However, in such a case bronchial blockers can be used rather than Overholt position.

7. Sellor-Brown position : In this position placing the lower part of body, including abdomen



are placed in one plane and the chest, neck and head are on a lower plane. Intent is same as that of the overholt position i.e. to drain blood and infected material from the uninvolved lung.

8. Crouching or ‘carpenter’s rule’ position :In this position knees and hips are flexed

maximally. Patient’s weight rests on the back of the legs. Abdomen on the front of the thighs, back is flexed well to eliminate the lordotic curve. Problems associated in this position are possible knee injury, femoral vein obstruction, free abdominal movement restriction.

INDICATIONS FOR THE PRONE POSITION:1. Spine surgeries like laminectomy, spinal

fusion, scoliosis correction2. Posterior cervical and occipital surgeries3. Adrenal exploration and renal biopsies4. Thoracotomy by posterior approach5. Surgeries on the back of the leg eg.

Varicose vein stripping, tendon repair6. Prone ventilation for ARDS

CONTRAINDICATIONS:1. Patient with contused heart2. Crush injury to the chest3. Full flail chest4. Severe pectus excavatum

TECHNIQUE OF POSITIONING:Turning the anaesthetised patient is

potentially dangerous because1. The autonomic compensatory mechanisms are obtunded by the anaesthetic agents2. There is no muscle tone to protect the joints

Principles:1. The patient should be anaesthetised & turned on the operating table. Trying to control the patient at arms length across the bed is highly inefficient2. The patient is more safely turned if he is very lightly anaesthetised and paralysed. The cardiovascular response to stimulation should be hypertension , not hypotension. This is possible, if he has a functioning vascular control mechanism to oppose the effects of gravity. Heavy premedication with narcotics and deep anaesthesia obtund this mechanism and cause hypotension.3. Before turning -

a. The head end of the table is depressed by 5 -10 degrees. In the head down position, the venous return from lower 2/3rd of the body is maintained even if the upper 1 /3rd of the body is elevated for the turn.b. The anaesthesiologist should manage the head and neck,unless there is a cervical spine fracture . If the neck is unstable, neurosurgeon help should be sought.c. Avoid injury to eyes by the clamps or other objects.d. Avoid damage to intravenous (IV) infusion systems. Use the arm that will be on top of the body as the preferred infusion sitee. BP apparatus should be ready for an immediate measurement after positioningf. The anaesthesiologist directs the turning and must arrange to disconnect the patient from the breathing circuit for the shortest possible period of time4. Skill is more important than strength. Everyone should know what they have to do and how to do it safely.5. The steps involved in positioning the patient are:a. Move the patient towards one side of the table and roll him up onto one side. Two persons should make the lift from back to the side one at his shoulders, one at his hips, both parts to be moved at the same speed. Anaesthesiologist keeps the face in the proper plane. Now the patient is in the lateral decubitus position with one arm under the body and upper arm close to his uppermost side. At least one person should receive the body on the other side of the table.b. Patient now is rolled into 3/-«?h prone position. The underarm is freed of his weight, moved to a position behind him and lowered over the side of the table (without stress on the shoulder). The upper arm is swung forwards to hang free over the other side of the table.c. The hips and the shoulders are lifted back towards the starting edge of the table to return the patient to the middle of the table.d. As the turn is completed, the person controlling the shoulders has an arm under the chest pulling the patient back towards the middle of the table. This person should continue to hold upper part of the patient off the table while anaesthetist gets the head in a safe position, reconnects the breathing circuit, ventilates the



patient vigorously for a few breaths and measures blood pressure (BP). After that the supporting arm can be removed from under the chest.e. Now the patient is prone with the head turned to one side, both arms hanging down besides the operating table.f. Any modification of prone position can now be effected.g. After all the movements are completed bring the table back to the horizontal position.

Light plane of anaesthesia, head down tilt etc will decrease the tendency for hypotension. Paraplegics and quadriplegics require IV vasopressor drugs before the turn to avoid severe hypotension. Careful handling during turn decreases the likelihood of injury to the back, neck, shoulders, elbow, wrists and face. Turning requires an anaesthesiologist and at least 3 capable persons !f the patient is very obese additional help may be needed.

PHYSIOLOGICAL EFFECTS: 1. Cardiovascular System (cvs)a. Pressure on the inferior vena cava (IVC) and femoral vein cause decreased venous return and hypotension.The engorged epidural venous plexus cause increased intraoperative blood loss. Avoidance of pressure on the IVC are accomplished by Relton-Hall and Andrews variants of spinal surgery frames.b. Hypotension secondary to spinal, epidural or deep general anaesthesia (GA)c. If the body is properly supported on the chest wall, impairment of cardiac efficiency will not occurd. If the patient is grossly obese it is better to turn the patient into that position during his preoperative visit to see the effect on BP. Those positions which make the patient faint, nauseated or develop headache are to be avoided as these may be the symptoms of hypoxia or hypotension or both.e. Avoid pressure on the carotid sinus when the head is turned to one side as serious arrythmias and hypotension may develop. Pads, rolls can be used to keep the head stablef. The venous return from the head must not be obstructed as engorged (eye vessels, eyelid oedema, post operative headache and even subglottic edema can result.g. Blood supply to the brain must be protected. Severe twisting or extension of neck may impede flow through the vertebral artery.

2. Respiratory system:The abdominal wall should be free to move.

Less airway pressure is required to ventilate obese patients in the prone than supine, as weight of chest and abdomen wall does not have to be lifted. If abdominal wall is not free in prone position, the patient will hypoventilate. Also with every inflation of lung, the entire back will rise. Surgery will be affected on a moving target. Even with perfect positioning upper back will move detectably with artificial ventilation but the upper body weight on the sternum will limit it’s movement. However, back from T 10 down can be kept still, if the patient is properly positioned. Patient’s thorax and pelvis should be raised by supports. In grossly obese patients, lateral decubitus position might be an easier choice.

Now, prone position is utilised to treat ICU patients in acute respiratory failure. Unrestricted abdominal movement is essential. A hand should pass between abdomen & bed.Patient positioned prone with proper support from the supine position, showed market increase in the oxygen tension for the same tidal volume, Fi02and PEEP.

COMPLICATIONS: 1. Neurological Injuries:

Neurological injuries may result from pressure against bones, against hard substances in the operating area, or due to stretching.a. Eyes may be injured during turning or may suffer protracted pressure in the prone position.b. Brachial plexus injury can occur by stretching, during turning or by pressure from an improperly placed support.c. Facial nerve injury can occur by pressure over the infraparotid regiond. Jack knife position may injure the femoral nerve.e. Lateral femoral cutaneous nerve injury can occur while compression against the supporting mechanisms under the pelvis resulting in a symptom complex called meralgia paraesthetica.f. Injury to the nerves and the tendons of the dorsum of foot can occur if the foot rests against the metal edge of the tableg. Ulnar nerve is at risk of injury against sharp edges of supporting devices when the arms are positioned above the head. Flexion of the elbow makes the danger more acute.



h. While turning the patient, the hips and shoulders should be on the same plane at all times because improper turning of anaesthetised patient involving relaxation of musculature can result in spine injury.

2. OTHER INJURIESa. Male genitalia should be protected. Precaution are necessary so that electrocautery, grounding plate should not touch them.b. In the female, care must be taken so that the breasts are padded well. Large breasts, can usually be moved laterally, so that the patients weight do not injure themc. Ears must not be folded over and held there by the weight of the head as the elastic cartilage are readily damaged and slow to heal. So pad the ear as well.d. Neck should be turned only after flexion. Turning an extended head leads to protracted neck muscle spasm and headache post operatively (due to pressure on C2 nerve while emerging between the atlas and the axis)e. Skin overlying the bony prominences such as the iliac crest must be protectedf. Toes should be protected from pressure injury using pillows under the anklesg. Air embolism is a risk in any surgical position in which the operating field is higher than the heart, permitting open veins for air entry.h. In moving the patient’s arms from besides the body to beyond the top of the head, the arms are first lowered towards the floor and then swung upwards carefully in a natural arc so as to rest beyond top of the head. Such care prevents shoulder dislocation, brachial plexus injury and tear of ligaments and tendons.i. Nasotracheal tubes must be positioned to avoid pressure on nasal cartilage in the anterior margin.j. Eyes must be protected with no pressure on them. Orbital compression can cause retinal ischaemia leading to blindness. Eyes are to be examined very frequently, and must not be kept open. Head movements may alter the relationship between the eyes and the head support and can cause pressure injury resulting in blindness. To prevent head movements, stabilise it using skull pins in a rigid holder.k. Chest supporting devices must not block the venous return from the neck.lt should be

possible to pass a hand between the base of flexed neck and chest support.I. Injuries to the joints can occur, while turning from supine to prone or, back from prone to supine, m. Varying degrees of pressure necrosis of maxillae and forehead can occur in prolonged spinal procedures.n. In cervical and posterior fossa procedures, flexion of the patient’s neck causes decreased anteroposterior dimension of the hypopharynx that leads to compression ischaemia of base of tongue, macroglossia and unexpected post extubation airway obstruction

3. Accidental extubation:In the prone position there isa. Poor access to the airwayb. Traction from the head movements due to bone drills or saws and also traction from the circuit itself.c. Loosening of the adhesive tapes used to secure the tubes which can be sweated or salivated loose.

SUPINE POSITION

PHYSIOLOGICAL CHANGES IN NORMAL CONCIOUS HUMAN SUBJECT ON CHANGING FROM THE ERECT TO THE SUPINE POSITION

1. Cardiovascular system(CVS) :Human arterial blood pressure remains

within the normal ranges throughout a variety of changes in body position. The principal factors maintaining relatively unaltered systemic blood pressure(BP) on assumption of supine position from erect are,a. Venous and arterial reflexes :As the body shifts from the erect to the supine position, venous return to the heart increases because sympathetic and parasympathetic tone of splanchnic and peripheral arteriolar and venous vessels decrease.This causes increased right atrial filling, increased right ventricular stroke volume, increased pulmonary circulation, increased left ventricle (LV) stroke volume and increased heart rate. This cardioacceleration was attributed to baroreceptors in the great veins and right atrium (Bainbridge 1915). This response is prevented by bilateral vagotomy.b. Pressorecepetor reflexes and autonomic control.



The raised cardiac output caused by increased venous return on assuming the supine position, initially tends to increase the arterial BP. Carotid and aortic baroreceptors are stimulated via nerve of Hering to IXth cranial nerve and via vagus respectively to the vasomotor centre and cardiac centre of medulla. From these centre, efferent parasympathetic impulses travel via the vagus to the heart and act on the sinoatrial (SA) node and myocardium. This diminishes the heart rate,stroke volume and decreases the strength of myocardial contraction. Also efferent sympathetic discharge to the heart is decreased and hence decreased heart rate and myocardial contractility.c. Ward and Korner studied the combined reflex effects on changing from the erect to the supine position ,1. MAP, heart rate and peripheral resistance

decreased2. cardiac output and stroke volume increased3. Systolic BP remained the same while

diastolic BP decreased so there was widening of pulse pressure.

2. Respiratory system:a. Pulmonary ventilation: Expansion of the lung during normal quiet inspiration is mainly due to the downward movement of the diaphragm and to a lesser extent by the bucket handle outward movement of the ribs. In the supine position, the abdominal contents limit the diaphragmatic excursion and force the diaphragm cephalad thus decreasing functional residual capacity (FRC) and total lung capacity (TLC). The posterior part of the diaphragm is forced cephalad more than the anterior part owing to the gravitational effect of the abdominal viscera. They are therefore stretched to a greater length and is capable of greater shortening. So, more ventilation of the adjacent posterior segments at the lung base. This has the advantage that dependent lung regions are perfused preferentially, this preferential ventilation makes for more efficient gas exchange.b. Pulmonary circulation: Alveolar capillaries tend to collapse when the external pressure within the alveoli exceeds the internal pressure within the vessels. It occurs more in the apex of the lung in either supine or erect position. The effect is a differential perfusion of the lung at the base than at the apex. This can be explained by dividing the lung into 3 zones.

Zone 1 : At apex pA>pa>pv : no blood flow Zone 2 : pa>pA>pv : flow determined by arterio- alveolar pressure difference Zone 3 : pa>pv>PA: flow dependent on arteriovenous pressure difference Where pA-alveolar pressure

pa-pulmonary arterial pressure pv- pulmonary venous pressure

With the patient in the supine position, the anterior part of the lung lies above the left atrium and the plane from the hilum to the base of the lung lies at the level of the left atrium and these parts function as Zone 2. Posterior part of the entire lung from the apex to the base becomes Zone 3.c. Closing volume increases, FRC decreases.

3. Other systems:a. Blood volume : On changing from erect to supine position, a significant decrease in packed cell volume (PCV) occurs in 5 minutes, maximal decrease of 10 to 20 percent of the erect value at 20 minutes. Also a lowering of serum calcium (7%); total protein (9%) and albumin (6%), PBI (16.3%), cholesterol & triglycerides.b. Renin angiotensin aldosterone axis: There is increase in blood volume and BP decreases. Renin causes decrease in aldosterone secretion and so a 25% increase in sodium excretion.c. Oesophageal sphincter tone decreases.

VARIANTS OF SUPINE POSITION LITHOTOMY POSITION

It is the position in which the patient is on his back with the legs and thighs flexed to right angles.

Indications:Perineal, rectal .vaginal and urological operations

History:William Jones first described the position

in 1839.

Technique of Positioning:First the patient is placed supine with the

gluteal folds at the caudal table break. Anaesthesia is instituted then. The patient’s arms are restrained appropriately by taping the arm



containing the IV needle to an arm board and by wrapping the arm containing the BP cuff in a sheet to the patient’s sides. Now the patient’s legs are elevated together, flexed together and positioned in stirrups. The stirrups can be either of the ankle strapped variety or a part of the total leg support system. Knee supports are rotated medially to facilitate the rotation of the thigh. Thighs are flexed about 90 degrees to the abdomen. Then outward rotation of thigh is accomplished by abducting the knee brace and rotating the thigh by rotating the supporting rods cephalad, flexing the thigh onto the abdomen. Care is taken to cushion the ankle and knee against pressure from metal stirrups.

Disengagement of the Paitent after the procedure:

Stirrup rods with the legs should be brought together to a relatively neutral plane relieving the flexion , abduction and rotation components . Legs lifted and lowered together slowly to avoid a sudden decrease in cardiac output.

Complications1. Venous stasisAny patient placed for more than 15 minutes in lithotomy position should have their legs protected by elastic stockings2. Peripheral nerve injuries:-a. Obturator nerve (L 2,3,4) -Acute flexion of thigh to the groin may result in nerve compression and trauma leading to weakness or paralysis of the adductors of the thigh .b. Saphenous nerve- Sensory to the medial portion of the leg. Legs may get compressed to the medial aspect of the knee brace leading to loss of sensation to the medial aspect of leg.c. Femoral nerve- Injured by acute thigh flexion with angulation against the underlying surface of the pubic ramus. Manifests as abnormal gait and numbness or paraesthesia.d. Common peroneal nerve- L4,5 S1,2 Injured by pressure at the head of fibula. Results in weakness of intrinsic muscles of foot and sensory loss in sole of foot. Foot drop due to palsy of Tibialis Anterior.3. Damage to the hip and knee especially of elder women.4. Injury to the hand and fingers when the caudal portion of the table is lowered .

VARIANTS OF LITHOTOMY POSITION:1. For combined vaginal -abdominal approach to pelvic viscera. Leg elevation is less and flexion of thigh to abduction is less than 90 degrees.2. Walcher position for obstetrics: Thighs pressed firmly onto the trunk and legs kept dangling.3. ForTURP (Blandy’s position): Here the legs are supported in such a way that the thighs create an obtuse rather than an acute angle with the body.

Physiological Changes:1. RESPIRATORY SYSTEM:a. The vital capacity- decreases by 18 % ,the reason being restriction of the movement of diaphragm as well as restriction of volumetric expansion of lungs because of increased pulmonary blood volume.b. Increase in the postoperative respiratory complications due to paralysis of the abdominal wall muscles with resultant inability to cough forcefully during spinal or epidural anaesthesia.c. Tidal volume decreases by 3%d. FEV1 increases by 9% due to the weight of abdominal viscera and flexion of the thighs on abdomen acting as a belt to improve the resting position of diaphragm which increases the inspiratory reserve and added force to maximum expiratory effort.

2. CIRCULATORY SYSTEM:Lower extremities are major

reservoirs of blood. Sudden lowering can cause significant lowering of BP So slow and deliberate lowering of legs should be done in a light plane of anaesthesia.

THE TRENDELENBURG POSITION Introduction:

Historically , the Trendelenburg position describes a supine patient whose head is lower than his heart and whose legs and pelvis are elevated to facilitate surgical access to the lower abdomen and pelvic viscera. Friederich Trendelenburg used this position for urological procedures as early as 1870. The position was originally achieved by placing the patients knees over the shoulders of an orderly while Dr.Trendelenburg operated.



Trendelenburg position today implies a head down tilt so that the head is below the horizontal plane. The head down tilt may be anywhere between 1 and 45 degrees, the most common being 10 - 20 degrees tilt.

Advantages:1. Improvement in exposure of the surgical field for pelvic or lower abdominal surgery2. With the surgical field positioned superior to the rest of the body, arterial perfusion pressure at the site of operation is lowered, resulting in less bleeding. Also shed blood falls away from the surgical field enhancing surgeons visualisation. Thus surgical time is decreased.3. Trendelenburg’s position causes engorgement of dependent neck veins thus facilitating the IV placement of needles or catheters.4. Protection of trachea from regurgitated material since they drain by gravity into the more dependent pharynx. So a steep Trendelenburg position might be selected for crash induction to a patient with full stomach.

Disadvantages:1. Displacement of abdominal contents into the surgical field with ventilatory excursions due to rigorous IPPV.2. Tendency of the position to mask unrecognised blood loss through it’s enhancement of central venous return of blood and a preserved cardiac output.3. Cyanosis of the patients face secondary to venous engorgement which makes evaluation of cardiovascular and respiratory status during anaesthesia more difficult.

Anaesthetic Considerations:1. x RESPIRATORY SYSTEM:a. Increase in work of breathing- Abdominal contents are pushed cephalad against the diaphragm so that the diaphragm not only must ventilate the lungs but also lift the abdominal contents .So in obese patients, the added weight of abdominal contents and the weight of the chest wall further decreases compliance and increases the risks of atelectasis and hypoxemia.b. Pulmonary compliance and FRC are decreased - Increase in the pulmonary blood volume and gravitational force on the mediastinal

structures being the causesc. Vital capacity decreasesd. Increase in pulmonary congestion and pulmonary oedema-ln steep Trendelenburg position , most of the lungs becomes zone 3, as most of the lung then lies below the left atrium. In zone 3 , an excessive increase in LAP over the alveolar pressure will enhance fluid transudation into the alveoli increasing pulmonary congestion leading to pulmonary oedema. Hence patients with chronically elevated LAP as in Mitral stenosis tolerate this position poorly.

2. CARDIOVASCULAR SYSTEM:. When the patient is put in the Trendelenburg position, the following things happen .There is autotransfusion of 500-1000 ml of blood from the lower extremities to the central circulation. This increase in volume of blood is pumped from the heart manifesting as an intial increase in cardiac output. There is an increase in the hydrostatic pressure in the arch of aorta and carotid bifurcation. Stimulation of the baroreceptors causes a generalized reflex vasodilatation. This causes decrease in stroke volume,cardiac output and decreased perfusion to vital organ. In a patient with heart disease, this added volume in the central circulation and increased pulmonary blood, flow may cause heart failure.

3. CENTRAL NERVOUS SYSTEM:This position produces an increase in the

intrathoracic pressure thus increasing the central venous pressure leading to an increase in the CSF pressure. At the same time this position decreases cardiac output by sino-aortic reflex thus decreasing cerebral blood flow. Too aggressive use of IPPV to expand the lung will further decrease cerebral blood flow and dangerously increase the CSF pressure while insufficient ventilation will increase the PaC02 which in turn increases CBF and intracranial pressure(ICP).

Technique of positioning:First the patient is placed supine with the

knees placed at the leg section hinge of the table. The operating table mattress must be fixed to the table with adhesive tapes. Ankle straps are secured at the foot of the table with proper



padding of the ankle to protect pressure points .IV cannulae are securely placed and the patients arms are restrained across the chest or placed at the sides taking care to protect the pressure points on the radial and ulnar nerves and that the angle of the arm to the body is less than 90 degrees.

After the patient is anaesthetised, the table is tilted to the desired plane. Concomitantly, the leg piece of the table may be dropped so that the patients knees flex 90 degrees or less. A slight flexion of the hips and small pillows placed under the lumbar and cervical areas may prevent pressure pains and ligament strains. The position of the endotracheal tube should be reconfirmed once the Trendelenburg position has been achieved as the mediastinum may shift cephalad , causing an endobronchial intubation.

If Trendelenburg is combined with lithotomy position, steps are essentially the same except that the feet are placed in stirrups or the legs in leg holders prior to tilting the table. Care should be taken to see that the angle of the thigh with the body is not less than 90 degrees. This position ensures good venous return from the legs.

Disengagement of the Patient:After the procedure, the patient is slowly

returned to the horizontal position, legs slowly straightened allowing for a gradual shunting of central blood volume back into the lower extremities. This will decrease the incidence of sudden hypotension.

Complications:1. Hypotension due to baroreceptor mediated generalized vasodilatation and decrease in cardiac output. These c#n predispose to cardiac arrythmias.2. Venous air embolism by air entrainment into the open pelvic or abdominal veins can occur.3. This position may hide unrecognised blood loss4. Increase in cerebral venous pressure can cause venous thrombosis of cerebral blood vessels, retinal detachment and cerebral oedema.5. Accidental endobronchial intubation.6. Nerve injuries (brachial plexus, superficial peroneal nerve, ulnar and radial) can occur.

Patient in Fracture Table:INDICATION Femur fractures.

This table has a body plate which supports the head and the thorax, a sacral plate for the pelvis, adjustable foot plates and a perineal post. After anaesthetising the patient, the patient is transferred to this table taking care to protect the genitalia against pressure from the perineal post and fibular head protected to avoid pressure on peroneal nerves. Care should be taken to avoid injury to arms, axillary neurovascular bundle and cervical spine.

Lateral Decubitus positionINTRODUCTION

Fron Latin means act of lying on one’s side .The position is conventionally referred to as right or left lateral.INDICATIONS:1. Thoracotomya. Lung surgeries - pneumonectomy, lobectomy, decorticationb. Cardiac surgeries- PDA ligation, CMVc. Mediastinal surgeries- Thymoma, neurogenic tumours2. Laparotomy

In carcinoma of gastrointestinal tract(GIT), strictures, diaphragmatic hernias3. Urological surgeries

Pyeloplasty

HISTORY:Thorek in 1913 described this position for

oesophageal resection for a case of carcinoma oesophagus.

TECHNIQUE OF POSITIONING:

EFFECTING THE LATERAL DECUBITUS POSITION

After induction of anaesthesia and securing all IV and electrical circuits, the patient is turned from supine to the lateral decubitus position . The back should be perpendicular to the end of the table, epigastrium at the level of the kidney rest, the thigh of the dependent lower extremity is flexed upon the trunk to stabilize the pelvis and the knee is flexed. The nondependent lower



extremity is kept straight. Two pillows are placed between the two lower extremities to minimize pressure points. Now the patients trunk is stabilised in the manner that will prevent it’s rolling either forward or backward. Similarly the thighs and buttocks are also stabilised by taping to the sides of the table.

Both forearms are flexed at the elbow and kept out of the operating field and a pillow is kept in between . Another pillow is kept below the dependent axilla to prevent compression of the neurovascular bundle. Excessive abduction on the arms should be avoided to prevent brachial plexus injury. Head is supported on an appropriate sized pillow and the indifferent electrode of the ECG is placed on the upper thigh.

ACHIEVING THE LATERAL DECUBITUS POSITION

Atleast three persons are needed for positioning.a. Patient is supine and intended down arm is abducted.b. Anaesthesiologist is the co-ordinator standing at the head end. He should control turning of head and preservation of airway and the endotracheal tube.c. If the patient is to be turned to the left, anaesthesiologist turns the patients head on its pillow to the left. The two assistants stand on the right at the hip and shoulders of the patient. Assistant 1 at the shoulders places his left hand behind the neck of the patient to grasp the left shoulder and places his right hand on the patients right shoulder. Assistant 2 places his right hand under the patients thighs to grasp the pelvis in the region of the anterior part of left iliac crest

and his left hand on the right iliac crest. On receiving an affirmative reply from both the assistants, anaesthesiologist gives the command “turn”. Then the lateral position is achieved by simultaneously pulling on the patients left hip and left shoulder and pushing on right hip and right shoulder. Once the patient is in the lateral position, a hand on the shoulder of the patient will maintain stability while the limbs are positioned.

PRECAUTIONS1. Care must be taken to control the relaxed head, neck and extremities.2. Possibility of a whiplash injury to the neck should be remembered.3. Avoid pressure on dependent eye and ear.4. Care of the airway, IV lines and monitors.

ADVANTAGES OF LATERAL DECUBITUS POSITION1. Most complete access to one hemithorax2. Best approach for intra pericardial control of hilar vessels.3. Obstetrics -To prevent supine hypotension.

DISADVANTAGES1. Inherently unstable, needs restraints and supports to maintain the desired position which may cause pressure and nerve injuries or interfere with normal blood flow. Overzealously applied restraints across the chest may impair the ventilation of the lungs.2. If IV lines are on dependent limbs interference with free flow may occur.3. If the BP cuff is placed on the dependent limb it can interfere with BP measurement. Also

DO’S DON’TS

Take as many personnel as needed, at least 3 Try to move unconscious patient with

inadequate number of turners

Take care in moving, use smooth movements Use jerky, uncontrolled movements

Have a co-ordinator to call the shots Be satisfied with restraints too tight or

misplaced padding

Pad and restrain adequately Forget that lateral position is unstable

Table 1 Precautions in positioning



can interfere with CVP measurement through a peripherally placed central venous catheter.4. Alteration of the Einthoven triangle between peripherally placed electrodes.5. Atelectasis of lower lung6. Nerve injuries-Brachial plexus

MODIFICATIONS OF LATERAL DECUBITUS POSITION1. Semi supine position for Closed Mitral Valvotomy:

Here the upper leg is straightened; arm is raised by flexing the elbow over the face and the trunk lean back on a small pillow2. Semi prone positionLower leg straightened and trunk rolls forward onto a pillow at the chest.

Physiology of the Lateral Decubitus Position:1. Respira tory system:a. Mechanics of ventilation :

Spontaneously breathing - Dependentlung has better ventilation because with a reduced volume and FRC of the lower lung, the diaphragm on the dependent side lies higher in the chest and is more stretched. This hemidiaphragm has a better mechanical efficiency and produces better ventilation.

Mechanically ventilated patient - The tidal volume is differentially distributed to the non dependent lung because it is more compliant. Reduced FRC in the dependent lung predisposes to alveolar collapse. Also muscle paralysis allows abdominal contents to rise further up against the dependent hemidiaphragm and impede the ventilation of the lower lung. Finally, opening the nondependent side of the chest further accentuates the difference in compliance between the two sides because the upper lung is now less restricted in movement. All these worsen the ventilation perfusion(V/Q) mismatch and predispose to hypoxemia.b. Pulmonary blood flow:

In the lateral position both in spontaneously breathing and mechanically ventilated patients the dependent lung is preferentially perfused to a slightly greater extent because of the effect of gravity. So there is an increase in the zone of nonperfusion of alveoli leading to increase in physiologic dead space on the nondependent side.

2. CVS:In the lateral position, cardiac output is

unchanged unless venous return is obstructed (eg:- use of a kidney rest). Arterial blood pressure may fall as a result of decreased vascular resistance.

COMPLICATIONS:1. Atelectasis : Atelectasis of the dependent lung occurs due to thechanges in the distribution of inspired gas and blood flow more so with controlled ventilation. Prevention is by using large tidal volume >15 ml/Kg and slow rate 10/min with sighs. Postoperative deep breathing exercises, chest physiotherapy and incentive spirometry are recommended.2. Nerve injuries especially of the brachial plexus because of the weight of the body pressing On the lower arm and axilla.

Modifications of the Lateral Position:A. KIDNEY POSITION:

This refers to the posture of a laterally recumbent patient whose spine is flexed laterally to separate the iliac crest of the upper side from the costal margin. This improves the surgical access to the kidney and urinary tract of the exposed flank.

To establish the kidney position, the patient is placed on his side in the middle of the operating table. The break in the table should be at the level of the iliac crest. A pillow is placed between the legs. The lower leg is flexed at the knee and thigh flexed to 90 degrees. Lower thigh and leg are flexed and upper leg remains straight. Table is then flexed or broken so that the muscles of the loin are taut. Final step is the use of a kidney elevator to make the loin muscles extremely taut. Patient is maintained in this position with adhesive tapes. Eyes and arms are well protected.

ANAESTHETIC CONSIDERATIONS:1. Respiratory system:a. Vital capacity decreases by 14.5% due to the restriction of thoracic cage in all the directions. Lateral expansion and diaphragmatic excursion more affected than the anteroposterior expansion.b. Tidal volume decreases by 14%c. Dependent lung prone for atelectasis.d. Surgically induced pneumothorax especially if the surgeon resects the 12th rib



2. Cardiovascular System (CVS) :a. Cardiovascular collapse: This is the most dangerous complication when an anaesthetised patient is turned from supine to either right or left lateral position. So slow and deliberate positioning with constant checking of BP should be done in light planes of anaesthesia.b. Hypotension:1. Morphine frequently given as premedication for renal procedures causes peripheral vasodilatation2. Halothane if used depresses the myocardium and decreases cardiac output.3. G A depresses carotid and aortic sinus reflexes so there is no compensation for cardiovascular instability4. Lateral position especially left lateral, shifts the mediastinum and rotates the heart and interfere with venous return and decreases cardiac output.5. Kidney position produces pooling of blood in both lower extremities. Also there is distortion of upper quadrant of abdomen and obstructs blood flow from lower extremities via inferior vena cava.

COMPLICATIONS OF KIDNEY POSITION.

1. Adhesive tapes - Compression necrosis of the head of femur

2. Injury to the brachial plexus3. Pressure necrosis of the ankle, knees and

feet4. Injury to eyes, ears and cervical spine

B. LATERAL POSITION FOR TOTAL HIP REPLACEMENT:

Anaesthesia is induced in supine position and then turned laterally with the affected hip up. Two pads are kept the first in front of the symphysis pubis to avoid pressure on the genitalia, second is secured posteriorly distal to the iliac crest. Lower leg is flexed at the knee and hip. Additional pads are placed -A. distal to the fibular head to protect the

common peroneal nerveB. under the lateral malleolus of the ankleC. between the kneeD. beneath the dependent axillae

COMPLICATIONS:1. Injury to the dependent hip and leg leading to rhabdomyolysis, myoglobinuria and renal failure.2. Arterial insufficiency of dependent limb and massive swelling of the thigh.

SITTING POSITION INTRODUCTION:

The history of the sitting position for surgical purposes is uncertain, but undeniably lengthy. Barlow, in 1830, reported an episode of air embolism that occurred during the removal of a facial tumor while the patient was in a chair. Dentists seated patients to extract teeth decades before that.The first public demonstration of ether, by W.T.G. Morton in 1846,involved a seated patient undergoing jaw surgery.

The term sitting position describes the posture of the neurosurgical patient whose back is elevated towards the vertical, thighs are flexed on the trunk, legs flexed on the thighs and at the level of his heart.

A much less marked elevation of the head, with the hips and knees only slightly flexed , is used by many surgeons for operations about the jaws, neck and thyroid gland. This is essentially a Lawn chair position with the long axis of the body much more nearly supine than is the classical sitting position.

For pneumoencephalography, the patient is placed in a full sitting position with the spine vertical for a few moments during which air introduced into the lumbar cistern, floats into the skull and initial erect X Ray films of the ventricular system are taken. Surgical procedures, however, are rarely done with the patient in this position.

ANALYSIS:Opinion is divided about the use of sitting

position in Neurosurgery. The sitting and prone positions compete as a means of access to the posterior cranial fossa and cervical spine, whereas the usual choice for approaching the middle cranial fossa is between the sitting and the lateral decubitus positions.

Advantages of the sitting position afe-



1. It allows a better physical access to the operative site from directly behind the wound, rather than from above and to one side, as is the case in prone position.2. Because the head is not weight bearing, this position will permit greater torsion of the head and neck than will prone. This allows the surgeon a more lateral approach to the cerebellopontine angle than could be accomplished with the patient prone.3. Accumulated blood drains out of and away from the operative site, thereby offering more rapid access to the bleeding points, a cleaner surgical field and a technically more favourable operative access.4. The sitting position allows an unobstructed view of the patients face, so that the anaesthesia team may observe motor responses from stimulated cranial nerves.5. Suitable head holders for the sitting position remove the hazard of pressure upon the eyeballs, by the circular or horse shoe shaped face pieces commonly used for prone position.6. Because there is free access to the anterior chest wall in the sitting position than in the prone position, resuscitative measures can be instituted more rapidly if cardiovascular collapse occurs.7. The amount of intrathoracic pressure needed for IPPV is less in the sitting position than in the prone position. A patient who is prone must be lifted off his anterior chest wall by each passive inflation of his lung. This increases venous distension in the wound during expansion of the lung and constitutes a major annoyance to the surgical team if venous bleeding is hard to control.8. Relatively unobstructed access to the chest wall for monitoring purposes or therapeutic needs.9. Arm vessels are more readily available for monitoring, fluid administration or obtaining arterial blood samples.10. Urinary catheter obstructions which upset fluid balance calculations are less likely.11. Sudden dislocation of ETT is unlikely since direct access to the airway by the anaesthesiologist is maintained.

INDICATIONS:1. Posterior cranial fossa surgeries2. Cervical laminectomy3. Suboccipital craniectomy

RELATIVE CONTRAINDICATIONS :1. Ventriculoatrial shunt in position and open2. Cerebral ischemia in the upright awake patient3. LAP<RAP4. Platypnoea-orthodeoxia5. Cervical spine degeneration6. Pre operative demonstration of PFO or right to left shunt7. Cardiac instability8. Extremes of age

PHYSIOLOGICAL EFFECTS OF SITTING POSITION 1. Cardiovascular System (CVS) :

The force of gravity assumes a prominent role in cardiovascular function depending upon the extent to which the long axis of the body becomes vertical in the sitting position, Massaging action of leg muscles useful iri returning dependent venous blood to IVC are absent under anaesthesia and the blood volume in the legs may increase by more than 500 ml as a result. With IPPV there is an additional impedence to the venous return. These forces act to diminish systemic perfusion by decreasing venous return and cardiac output.

Above the level of heart, venous return is aided by gravity. The higher the surgical field is located above the heart, the greater is the pressure differential and the more easily is air entrained in partially severed or patulous vessels. In addition the structure of the dural sinuses is that they do not expand under pressure or collapse when their internal pressure is low. The entrainment capacity of these structures is obvious.

In the arterial tree, gravity antagonises the upward flow of blood into the elevated head and augments it’s accumulation in the dependent lower extremities. With unrestricted arterial pathways cerebral perfusion decreases 2 mm Hg /vertical inch (2.54 cms) of elevation above the heart. 60% of lateral rotation of the head begins to reduce the flow in the contralateral vertebral artery and 80% of rotation obstructs it. Opposing this is a proportional increase in the ipsilateral vertebral artery flow. Another safeguard is the reversal of the normal cephalad flow through the basilar



arteries if the vertebral arteries become ineffective: Brainstem perfusion is then supplied caudal from the circle of Willis.. However any signs of impaired brainstem perfusion (such as unexpected change in BP or appearance of bradyarrhythmias or PVCs) should be recognised early and responded to promptly. Predictable cardiovascular response to tilt includes -1. Increase in heart rate (upto 19%)2. Decrease in stroke volume3. Decrease in cardiac output.(cardiac index <14%)4. Little variation in SBP but an elevation of both DBP and MAP(increase 9-38%)5. Increase in peripheral vascular resistance calculated from the fall in cardiac output and rise in MAP (40%)6. Lengthening of pre ejection period due either to need to open the aortic valve against a higher diastolic pressure or to a reduction in the contractility of the myocardium.

2. Respiratory System(RS):The anaesthetized patient has the benefits

of an almost unimpeded RS when placed in the sitting position. Unlike supine position, in which abdominal viscera tend to restrict the caudad motion of the diaphragm or compress it cephalad at rest, the sitting position permits the downward displacement of the abdominal contents and freer diaphragmatic motion. This should promote better ventilation of the lung bases.

If IPPV is used, the pressures required to expand the lungs of a patient are much less if the patient is in the sitting position than the prone. Since the intrathoracic pressure patterns affect venous return, the pressure of IPPV that is transmitted to the surgical field is less, resulting in less bleeding.

The lung volume at which the small airways begins to close during exhalation has been termed “closing volume”. In healthy adults, Closing Volume(CV) occurs between functional residual capacity (FRC) and residual volume (RV). Both these values are increased in sitting position , but the degree of increase in FRC is more than that of the CV. Hence there is a significant reduction in the volume of trapped gas (VTG) in the sitting position.

A potential detriment of the sitting position was reported by Gurtner & Fowler in 1971. They found a reduction in the diffusing capacity for 02 (A-a D02) in the sitting position because of decreased perfusion of the upper zones of the lung.

3. CNS:The normal CSF pressure in the supine

position is 8-12 mm Hg(100-165 mm H20). With the patient in the sitting position this pressure becomes about 30 mm Hg (400 mm H20) in the lumbar cistern , while at the vertex of the skull it is subatmospheric at -5 mm Hg (-65mmH20). This reduces one force composing the ICP and results in more effective perfusion at lower arterial pressures.

4. Other considerations:a. Pregnancy : Should this position be required in the last trimester of pregnancy, the uterus can impair the two major advantages of this posture - by encroaching upon the downward movement of the diaphragm and compressing the IVC. Careful attention to ventilation and gentle lateral displacement of the uterus should improve the situation.b. Temperature variations : Can be hard to control in the seated patient.

TECHNICAL ASPECTS:The operating table should have a

removable head platform and separate controls for the leg section, for the back and for flexion.

If a thermal mattress or a Gardner-Dohn antigravity suit (G-suit) is used, they should be placed on the table prior to placing the patient on it. 1 or 2 pillows are placed in the thigh section of the table. This serves to elevate the patients seat in the final sitting position, so that when the head platform is removed , the edge of the table corresponds to the 2nd/3rd thoracic vertebra.

Endotracheal intubation in these patients is safest with a non kinkable tube which permits the unusual head position occasionally required for access to the cerebellopontine angle. Tube compression by biting can be prevented by inserting a properly made bite block between the patient’s teeth; a conventional oral airway fails



to separate the teeth widely enough to protect the ETT.

Large calibre IV lines, a right atrial catheter when indicated, an arterial cannula, an esophageal stethoscope, ECG leads, urinary catheter and thermal probes are all put in place with the patient supine. The lower extremities are wrapped with compression stockings or elastic bandages, if needed. Any hypotension associated with induction of anaesthesia is corrected and ventilation is stabilised.

To establish the sitting position, first the table is flexed fully. The foot section is lowered by at least 45 degrees. The thigh straps are loosened temporarily to prevent injuries to the thighs or restricting motion of the table top. The back section is slowly elevated while the chassis is being inclined towards the Trendelenburg position. This combined manoeuvre is coordinated to produce further flexion of the thighs on the trunk. During these manoeuvres BP should be monitored repeatedly.

Continued elevation of the back section will now place the patient in the desired degree of sitting position with the legs at about the level of the heart. The knees should be flexed upon the thighs to prevent stretching of the sciatic nerve or its branches. Slowed elevation of the head and judicious use of a balanced vaspressor, such as ephedrine or mephenteramine, are indicated to ensure BP levels that provide adequate cerebral perfusion.

The traditional method of securing the head was to use a horse shoe shaped head rest placed against the face & to tape the head to it. They, however, seldom fit the face and thereby threaten the eyes, cheeks and the supraorbital nerve with excessive pressure. The strapping can also be sweated loose or ripped off by sustained traction .

The most successful head holder is some form of skull pin & clamp device. There are two versions- the Gardner version and the Mayfield version. Each of these models consists of 3 sterile pins, which firmly penetrate the outer table of the skull & fits into a C shaped skull clamp. The

clamp is then attached to a long supporting arm that is attached to a U shaped brace fastened tightly to the rails of the operating table.

Once the patient’s head is stabilised, the head section of the table is removed. The elbows of the patient are supported by pillows or pads. The patient’s hands are crossed in his laps. Bony prominences are padded and the legs wrapped to mid thigh in elastic bandages to augment venous return.

VARIATIONS:A useful variation was reported by Garcia-

Bengochea & colleagues. They described a position in which the patient was placed in a chair fixed to the operating table in such a way that Durant’s left lateral position can be rapidly established simply by lowering the control end of the table chassis. By arranging the table top in the form of a chair ( back elevated, foot section down), placing a back rest for the patient at 90 degrees to the right edge of the elevated back section, they stabilized the patient in a sitting posture that allowed varied head torsion. Should hypotension or air embolism occur, the usual head end of the table chassis can be lowered rapidly by turning a single crank and the Durant’s position can be attained without losing control of or contaminating the wound.

COMPLICATIONS, PREVENTION AND TREATMENT: 1. Hypotension :

Hypotension in the seated anaesthetised patient is indicative of cerebral hypoperfusion. It is probably the most frequent complication of this position.lt requires rapid detection and prompt correction.a. Fluid volume deficits should be corrected before surgery.b. Vasopressors such as ephedrine or mephenteramine.c. The G suit, though cumbersome, has been shown to be useful in the immediate treatment.d. Alert replacement of intraoperative blood loss.

2. Endotracheal tube migration :An unexpected complication is the

migration of the tip of the ETT into the right



mainstream bronchus. Elevation of the diaphragm produced by the sitting position can easily raise the carina cephalad and cause the tip to migrate. Auscultation of each hemithorax is a must after the positioning and the ETT must be adjusted so that all lung fields are ventilated equally.

Firm tape fixation of the ETT & bite block are mandatory to prevent the ETT from being dislodged by head motion from bone drills or saws or by traction from the breathing circuit itself.

3. Air embolism :Venous air embolism(VAE) is detectable

in the sitting position by precordial Doppler in 40% of patients & in 76% of patients using transesophageal echocardiography.Common sources:The common sources of major VAE are1. Major cerebral venous sinuses

a. transverse sinusb. sigmoid sinusc. posterior half of the sagittal sinus

2. Emissary veinsa. to the suboccipital musculatureb. diploic space of the skull

3. Cervical epidural veins

EFFECTS OF AIR EMBOLISM :Effects depend on the total volume &

perhaps more importantly on the rate of air entry. The air bubbles may pass from the right atrium into the right ventricle, where they may be churned up into froth before being ejected into the pulmonary artery. Pulmonary hypertension with right ventricular strain develops due to mechanical blockage of the pulmonary vessels and neurogenic effect.The cardiac output and BP fall & dysrhythmias including VF, may be precipitated.

Air can then pass into the systemic circulation either through the pulmonary vascular bed or through intracardiac defects like Patent Foramen Ovale. The dangers of systemic air are that it may enter the coronary artery & provoke VF or enter the cerebral vessels & produce permanent neurological damage.

The effect of air embolism is aggravated if the patient is receiving N20 at that time. N20 which is 30 times more soluble than N2, would

diffuse quickly into the bubbles & appreciably increase their size.

MONITORS:1. TEE : This can detect air embolism in 8- 75% of patients in the sitting position. It is a highly sensitive monitor. Emboli as small as 2 microns can be detected. It has the advantage of identifying right to left shunting of air.2. Doppler ultrasound : One of the more sensitive methods to detect air embolism. The receiver is placed over the tricupid valve. The combination of precordial Doppler with ETC02 monitoring is the current standard of care in the sitting position.3. Auscultation : Faintly audible high pitched tinkling sounds can be heard at first. 30 ml of air produces the characteristic mill-wheel murmur. The changes are earlier appreciated with an esophageal stethoscope.4. ECG : Changes are best seen in V1 & comprise of signs of right heart strain(RBBB, T wave depression &tall peaked P waves in the right chest leads)5. ETC02: Sudden falls in ETC02 is produced due to an increase in alveolar dead space secondary to the development of venoarterial shunts in the lung.6. CVS monitoring : There is hypotension secondary to low cardiac output , tachycardia and increase in bothCVPand PAP.7. ETN2: Theoretically attractive, but its use in anything less than catastrophic VAE is small.

MANAGEMENT:1. Prevent further air entrya. Notify the surgeon- compress or ligate the

vessel. If this is not possible flood the wound with saline or pack with saline soaked pads.

b. Apply Jugular compressionc. Change the position of the patient (lower

the patient’s head)2. Support circulation :

External Cardiac Massage (ECM), 100%02, Vasopressors.

3. Removal of air :The classical description is that turning

the patient to the left side head down (Durant’s position) places the right atrium & tricuspid valve above the right ventricle & tends to delay the passage of air into the pulmonary artery. Air can



then be aspirated through a right atrial monitoring catheter. Natural absorption of air is hastened by ventilation with 100% oxygen. Whole body compression of the patient may be valuable to force the gas into solution.

4. Quadriplegia :The sitting position per se has been

implicated as a cause of rare instances of unexplained post operative quadriplegia. It has been hypothesized that neck flexion, which is a common concomitant of the seated position, may result in stretching or compression of the cervical spinal cord. This possibility represents a relative especially when there is evidence of associated cerebral vascular disease.

5. Macroglossia :Swelling of the pharyngeal structures

including the soft palate, post wall, pharynx & base of the tongue have been observed. These have been attributed to trauma/ischemia occurring as a result of foreign body (usually oral airways) causing pressure on these structures in lengthy procedures with sustained neck flexion. It is ideal to maintain at least a finger breadth’s distance between the chin & sternum to prevent excessive reduction of the AP diameter of the oropharynx.

6. Arrythmias :Arrythmias in the seated patients are

classified as perfusing and nonperfusing.

A non perfusing arrythmia is one which causes or accompanies a fall in perfusion pressure & is an emergency. Treatment must be prompt.a. Cessation of the surgical stimulus alone

may be enoughb. Prompt use of vasopressorsc. Restoration of depleted blood volumed. Inflation of the G suit.e. Aspiration of intracardiac air.f. Use of supportive drugs.g- Cardiac massage as needed

A perfusing arrythmmia , that is one notaccompanied by hypotension, may also result from surgical manipulation. If surgical stimulation is not the cause and air embolism can be ruled out, the most frequent cause seems to be C02 excess when blood gases are not being monitored. Other extracardiac causes like electrolyte disturbances should be sought and corrected.

8. Miscellaneous complications :a. Tension pneumocephalusb. Sciatic nerve injury due to prolonged extension of the knees.c. Foot drop due to pressure on the common peroneal nerve.Severe flexion and lateral rotation of the rieck can be traumatic to an arthritic cervical spine.


HOW I DO IT?

A 20 year old Primi with severe MS requires Labour Analgesia 186 R.Bharathi

There is no question that labour and delivery are extremely painful experiences for most women. Unfortunately, many believe that labour pain has an important biological function and should not be relieved and there is a general belief that methods of pain relief are dangerous to the mother and newborn.

IS THERE A NEED TO RELIEVE PAIN?ASOG statement

“Labour results in severe pain for many women. There is no other circumstance, where it is considered acceptable for a person to experience severe pain amenable to safe intervention, while under physician’s care. Maternal request is a sufficient justification for pain relief during labour".

As stated by Hippocrates “Divine is the task to relieve pain”. This is truer than ever when we are considering two lives and we must take every effort to honour the patient’s request for labour analgesia.

When confronted with the patient’s cardiac problem, the anaesthetist must answer the following questions:

1) What are the anatomic abnormalities in mitral stenosis (MS)?2) What changes in preload, afterload, heart rate and contractility will optimise the patient with MS especially with relation to pressure volume loop.3) What are the treatment options for MS?4) What are the important considerations in planning the anaesthetic management of a patient with MS?5) What are the special considerations for anaesthetic management of labour and delivery in MS anticipating haemodynamic swings?6) What are the complications and limitations

of regional anaesthesia in MS?

Although rheumatic heart disease is decreasing worldwide and has become a rare complication of pregnancy in affluent societies, it is still prevalent in poor countries like India and remains an important cause of maternal mortality, MS being the commonest lesion. The overall mortality associated with MS is reported to be 1% but increases to 5% in Class III and IV of the NYHA classification. In the presence of atrial fibrillation, maternal mortality is 14-17%. Similarly, perinatal mortality rates are low in Class I and II, but increase in Class III and IV to 12-31%.

PATHOPHYSIOLOGY:MS causes physiologic abnormalities

both proximal and distal to the abnormal valve. Distally, there is a “protected” or underloaded left ventricle (LV), which may have contractile abnormalities. Proximally, a pressure gradient develops between the left atrium (LA) and LV in order to force blood across the obstruction of the narrowed valve orifices. This elevated LA pressure causes alterations in LA size, compliance and function. In addition, the pressure is reflected back into the pulmonary veins causing changes in pulmonary and right ventricle (RV) function. The area of the valve orifice is the key to the flow, and as the orifice gets smaller, the turbulent flow increases across the valve and total resistance to flow increases.

Diagramatic representation of the transmitral blood flow velocity:

Left ventricular (LV) filling starts with the opening of the mitral valve and continues during the early (rapid) and late (slow) filling phases while atrial blood rushes through the mitral valve into the ventricular cavity. The pressure gradient tends to accelerate the blood flow in the LV cavity.



The haemodynamic deterioration that occurs when a patient with MS becomes tachycardic is dictated by this relationship between the atrioventricular pressure gradient and the flow rate. Since tachycardia shortens diastole proportionately more than the systole, it decreases the over all time available for trans mitral flow.

The main factors that determine transmitral blood flow are the rate of rise of the transmitral pressure gradient and the LV diastolic compliance or stiffness.

Effects of the determinants of the transmitral pressure gradient on transmitral blood flow velocity are shown in Table 1.

The normal mitral valve area is 4-6cm2. With progressive narrowing of the mitral valve orifice, diastolic inflow into the LV can only be maintained by the development of an elevated

pressure gradient across the mitral valve.

Gorlin’s formula (determinants of transvalvular flow);

Rearranging this, when valve area is constant, the pressure gradient varies greatly as the square

of the transvalvular flow rate.

Pressure gradient ~ (transvalvular flow rate)2 =

(Cardiac output \2

Diastolic filling time )Thus the shorter the diastolic filling time (i.e. rapid heart rate), greater the transvalvular

gradient (i.e. increased LA pressure).Pressure -Volume loop:

During pregnancy, blood volume increases by an average of 40% above nonpregnant levels. Cardiac output (CO) begins to increase during the first trimester and by 28 - 32 weeks, it has increased by up to 40% above non-pregnant levels. The increase in CO is due to an increase in both stroke volume (SV) and heart rate (HR), but as term approaches, CO and SV decrease somewhat and HR increases. Normally, there is no increase in pulmonary artery pressure (PAP) in pregnant patients, despite the increase in blood volume.

Determinant Change in peak transmitral blood flow velocity

High atrial pressure IncreaseSlow ventricular relaxation Small decreaseIncreased myocardial stiffness DecreaseIncreased systolic function Unchanged

Table 1. Effects of the determinants of the transmitral pressure gradient on transmitral blood flow velocity.



In the patient with MS, pregnancy is associated with an increase in CO. There is also an increase in pulmonary artery pressure (PAP), which is probably due to increase in blood volume. If there is pre-existent pulmonary hypertension, the increase in PAP may lead to pulmonary congestion and it may be necessary to initiate diuretic therapy. Symptoms from even mild to moderate MS may become severe as the pregnancy progresses. These haemodynamic changes account for the 25% incidence of pulmonary congestion and 5-17 % mortality rate in the puerperium.

Tachycardia is not well tolerated by patients with MS as it decreases LV diastolic filling time. LA dilatation as a result of increase in central blood volume may lead to atrial fibrillation, which will further impair LV filling. Digoxin is often given prophylactically during pregnancy with MS to prevent tachycardia and atrial fibrillation. Beta- blockers may also be used.

Labour and delivery impose additional stresses on the CVS. In the normal patient, there is a progressive increase in CO during the peripartal period, which is accompanied by an increase in both HR and SV. The increase in CO is due to increased sympathetic stimulation secondary to pain and increased metabolic demand. Uterine contractions cause a further 15- 20% increase in CO, due to blood being transfused from the uterus into the central veins. When the term pregnant patient is turned from the supine to the lateral position aortocaval compression is relieved and CO is increased by 30%

CO and HR are maximal during the immediate postpartum period at which time, CO is approximately 80% above nonpregnant levels (due to disappearance of aortocaval compression and autotransfusion of blood to the central veins by the contracted uterus), This increase in intravascular volume and heart rate makes the MS patient particularly vulnerable to the development of pulmonary oedema at this time.

PAIN PATHWAYS DURING LABOUR:Pain during the first stage of labour is

mainly due to uterine contractions and cervical

dilatation. In the first stage, pain is transmitted via visceral afferents that accompany sympathetic nerve fibres and enter the spinal cord at T10, 11,12 and L1 segments. Visceral pain is severe, dull aching and poorly localized and is easier to block than somatic fibres. Opioids are useful in relieving the pain. In the late first stage and second stage of labour, pain is due to distension of the pelvic floor, vagina and perineum. Opioids are not useful for second stage and local anaesthetic is needed.

WHY PAIN RELIEF?Pain and fear are the main reasons for

maternal hyperventilation during labour, which can lead to respiratory alkalosis, increased oxygen consumption and lactate accumulation. This may not affect a healthy parturient but will affect the parturient with limited cardiac reserve as in mitral stenosis who cannot increase oxygen delivery.

Acid base balance: Inadequate pain relief leads to progressively increasing metabolic acidosis and the foetus becomes more distressed. Failure to relieve labour pain can lead to maternal exhaustion and reduction in the efficacy of uterine work. Maternal pain and stress reduce uterine blood flow secondary to the release of endogenous norepinephrine. There is an increase in cardiac output (25% in the late first stage and 40% during second stage) due to increase in sympathetic activity. This increase in cardiac output is 10-15% less in those who receive labour analgesia, which is beneficial with a narrow mitral valve. Epidural analgesia decreases plasma catecholamine concentrations and attenuates the increase in cardiac output seen in the labouring parturient.

MITRAL STENOSIS:ANAESTHETIC MANAGEMENT IN LABOUR:

Patients with MS often tolerate the haemodynamic changes of pregnancy poorly. Because of the increases in blood volume and cardiac output associated with pregnancy, symptoms from even mild to moderate MS may become severe as the pregnancy progresses. These haemodynamic changes account for the 25% incidence of pulmonary congestion and 5- 17 % mortality rate in the puerperium.



ObjectiveTo minimize left ventricular end diastolic

pressure (LVEDP) and impedance to forward flow and to maximize left ventricular end diastolic volume (LVEDV) and facilitate movement of this relatively fixed CO toward the periphery.

1) Oxygen administration, left lateral position2) Antibiotic prophylaxis - (not necessary for

vaginal delivery as per AHA guidelines)3) Fluid restriction (with monitoring to maintain

preload)4) Slow heart rate: Beta blockade, analgesia,

phenylephrine (not ephedrine?) for hypotension

5) Prevention/Treatment of AF: Digoxin, Verapamil, Beta blockade, DC Cardioversion

MonitoringECG, Pulse oximetry, CVP (use of PA

Catheter is controversial as PCWP does not reflect the left atrial pressure), peripheral arterial line and foetal heart monitoring.

AnaesthesiaREGIONAL ANAESTHESIA FOR LABOUR:

Epidural or CSE the aim is to avoid abrupt decrease in SVR. Suplimental dose will be required during the second stage of labour for elective forceps delivery.

CAESAREAN SECTION:Elective: Epidural probably preferred.

Maintain filling pressures. Emergency: General anaesthesia with

endotracheal intubation. Postpartum high-risk period

First 1-2 hrs critical Possible use of epidural post-op postpartum.

Primi with critical MS for Labour AnalgesiaA 30-year-old primigravida with severe

mitral stenosis (mitral valve area-0.9cm2) requests labour analgesia.

The management begins with a detailed history including prior hospitalisation, drug therapy and decreased exercise tolerance during this pregnancy. I will do a complete physical examination of the cardiovascular and respiratory

systems with particular reference to evidence of cardiac failure (elevated jugular venous pressure, pedal oedema, basal crepitation) and arrhythmias (atrial fibrillation). Airway assessment and spine examination will complete my physical examination.

Investigations that I would like to have will include haemoglobin%, serum electrolytes, blood urea nitrogen, serum creatinine, electrocardiogram and a recent echocardiogram.

I will interact with the obstetrician regarding the progress of labour (cervical dilatation) for the timing of the labour analgesia.

My plan for this patient is combined spinal epidural analgesia.

I will explain to the patient about the benefits of labour analgesia and obtain written consent for the same.

Preparation before the procedure.The patient is given oxygen at 6l/mt and

a wedge kept under the right hip for left uterine displacement. After establishing monitoring including electrocardiogram (ECG), pulseoximetry (Sp02), I will cannulate the left radial artery for invasive pressure measurement and central venous line through the right cubital fossa for central venous pressure monitoring.

Emergency resuscitation trolley, a good working laryngoscope and a working suction are kept ready and the following drugs are loaded before the procedure:1) Thiopentone sodium2) Suxamethonium.3) Atropine.4) Esmolol.5) Phenylepherine.6) Frusemide.7) Fentanyl.

I will explain in detail about the wholeprocedure and allay the patients fear if any.

Combined spinal epidural techniqueNo preloading of intravenous fluid will be

given but ringer lactate will be given at 75 ml/hr



as maintenance fluid. After putting the patient in the left lateral position, the procedure is done as described below. The epidural space is identified with a 16 G tuohy needle in the L3-L4 interspace using loss of resistance to air. Using a needle through needle technique fentanyl 10 meg is given intrathecally with a 26G spinal needle. Alternatively, a separate spinal injection can be given at a lower space. A16 G epidural catheter is inserted 6 cms into the epidural space. All the while, the foetal heart is monitored.

No test dose is givenAn epidural infusion of bupivacaine

0.0625% and fentanyl 2mcg/ml is started at 6 ml/hr. The infusion rate may be increased up to 12 ml/hr so as to achieve a block up to T10 level. Additional doses of fentanyl 25 meg may be given so as to augment analgesia when necessary, as during maximal cervical dilatation. Epidural analgesia facilitates a controlled second stage of labour and can be shortened by the elective use of either vacuum extraction or forceps delivery. During this period, epidural boluses of 0.1% bupivacaine with fentanyl 25 meg can be given in slow incremental doses over a period of 10 to 20 minutes, so as to prevent hypotension. If there is any hypotension during this period, I will manage it with phenylepherine rather than ephedrine, as it will cause tachycardia. There is no evidence that the use of phenylepherine compromises uterine blood flow.

After delivery of the baby, I will give oxytocin 10 units slowly as an infusion over 15 to 20 minutes in order to minimize reflex tachycardia. Since these patients are at risk of developing pulmonary oedema, precipitated by autotransfusion in the postpartum period, I will give frusemide 20 mg in divided doses and as well continue the epidural bupivacaine and fentanyl infusion.

Advantages of combined spinal epidural techniqueINTRATHECAL FENTANYL:

Intrathecal fentanyl alone is effective in early labour (cervical dilatation < 5 cm) conferring the advantage of profound analgesia with complete absence of motor block, greater patient satisfaction and greater reliability. Intrathecal

fentanyl in the range of 5 - 25 meg produces a dose dependent increase in the duration of analgesia (45 -90 mins). Fentanyl doses more than 50mcg do not prolong the analgesic duration. There is a similar analgesic effects, onset, intensity and duration with a smaller dose of fentanyl (15-25mcg) compared to a larger dose (50mcg). There is a modest decrease in maternal blood pressure, likely due to analgesia rather than sympathetic block.

High block, respiratory depression and dysphagia can occur. Ventilatory depression is characterized by reduced tidal volume rather than decreased rate and it can be delayed in onset (30 minutes or more).

Lateral positioning during intrathecal administration may limit the rostral redistribution and limiting the maximum intrathecal dose to 25mcg is likely to reduce these complications.

Appropriate monitoring (Patient observation and pulse oximetry) is strongly recommended when intrathecal techniques are used.

Nausea and pruritis are very common dose dependant side effects. They require treatment infrequently and resolve before the analgesic effect wanes.

There is a low incidence of foetal heart rate (FHR) abnormalities (6-12 %) seen with intrathecal fentanyl 25mcg compared to 30% incidence with 50mcg fentanyl where more of the FHR changes resulted in the need for caesarean delivery. These are transient and resolve spontaneously and are not accompanied by maternal hypotension or emergent interventional delivery.

Foetal bradycardia following the onset of intrathecal analgesia most often is associated with rapid cervical dilatation, or nuchal or prolapsed umbilical cord. Uterine hypertonus can be due to abrupt elimination of beta-adrenergic mediated inhibition of uterine contraction thereby reducing intervillous blood flow.

Epidural testdose1) From the safety point of view, the most

important characteristic of any test to



detect IV or intrathecal catheter malposition is its negative predictive value. This is because the larger therapeutic dose is administered only after the negative test result is obtained. At the same time, a low false positive rate is highly desirable to prevent unnecessary catheter replacement and delay in providing analgesia.

2) Traditional test dose of 45 mg Lignocaine with 15mcg epinephrine is not recommended as there is a risk of high spinal block associated with unrecognised intrathecal catheter malposition, which is hazardous in a labouring cardiac patient as well as tachycardia if it is intravascular, which is detrimental.

3) Unintentional intravascular placement of epidural catheters has been reported to occur with the frequency of 2-9% and is associated with serious outcomes.

Aspiration for blood alone is 98% sensitive in detecting intravascular placement of multiorifice epidural catheters.

Does the air test work for multiport catheter?Inject 1 ml of air through the epidural

catheter and listen for maternal heart sound changes for 15 seconds using a Doppler probe. The test is considered positive if a loud swishing sound lasting atleast 5 seconds is heard in addition to or in place of the normal “lub-dub” heart sounds.

Air test may be less reliable in multiport than in single orifice catheters because gases, to a greater extent than liquids, preferentially exit through the most proximal catheter hole.

Fentanyl test doseAfter 100 meg epidural fentanyl if the

patient has any increased sedation, dizziness or light headedness within the first 5 minutes then it should be interpreted as a positive response for intravascular injection. No adverse foetal outcome has been observed with this method. Yet there may be maternal desaturation, which will require 02 supplementation.

Low dose mixtures of opioid and local anaesthetic are used as a ‘test dose’ combining observation and incremental dosage. At best, intravascular injection results in minimal analgesia

and minimal effects in the mother and the foetus. If the injection is intrathecal, the worst scenario is an increasing degree of slow - onset motor blockade with minimal loss of sympathetic tone.

DisadvantagesEpidural analgesia has potential

disadvantages. A rapid onset of epidural blockade may cause a sudden reduction in SVR. As well as potentially compromising uteroplacental perfusion, marked reduction in SVR can cause a compensatory tachycardia.

Therefore, I chose to use CSA. Intrathecal fentanyl provided rapid initial analgesia without adverse haemodynamic effects. This enabled analgesic maintenance to be established gradually using an infusion of dilute bupivacaine- fentanyl mixture, with the avoidance of large or rapid boluses of local anaesthetic. Epidural infusion has less incidence of hypotension compared to intermittent top ups. Thus sympathetic block and potential haemodynamic changes are likely to be of slow onset and amenable to controlled and titrated management.

If analgesia is insufficient for delivery, pudendal nerve block can be added rather than increase the concentration of local anaesthetic boluses.

In the early postpartum period, the patient is at risk of developing pulmonary oedema, which will be exacerbated by cessation of epidural analgesia and the return of sympathetic tone. Hence, I would like to continue epidural analgesia in the postpartum period.

Patient undergoing Caesarean section for obstetric IndicationFOETAL DISTRESS:-

As there is no time for establishing epidural blockade, general anaesthesia is preferred. Epidural catheter is left for post-op analgesia.

NON-PROGRESSION OF LABOUR: -Incremental injection of boluses of 5ml

of 0.5% bupivacaine are given over 15 minutes interval with careful attention to patient’s mental status (every reinjection is a test dose). CSE is associated with more rapid cervical dilatation



compared to standard epidural analgesia. Obstetric and neonatal outcome are the same with both techniques.

Compared with epidural, the advantages of combined spinal epidural (CSE) are

• Rapid and improved analgesia• Reduced initial and total dose of drugs• An objective procedural end point (CSF)• Nil or minimal motor blockade• Minimal autonomic (sympathetic)

blockade• Selective sensory blockade• Ambulation is possible and safe.

Controversies about CSE:1) Risk of penetration through the dural hole

It is impossible to force a 16G or 18G epidural catheter through a dural hole after a single dural puncture with a 25G spinal needle

2) Perceived increased risk of neurotrauma No evidence that paresthesia on CSE needle

or catheter placement is likely to result in a neurologic deficit.

3) Risk of meningitis is extremely low

4) CSE block and decreased risk of post dural puncture headache (PDPH):

Reasons may bea) The use of a very fine diameter spinal needleb) Tuohy needle as an introducer allows meticulous puncture of the duramaterc) CSF leakage through the dural hole is decreased by the increased pressure from epidural anaesthetic solutions (splints the dura from the arachnoid membrane)d) With the single segment CSE technique, the spinal needle is deflected somewhat, as it exits through the Tuohy needle, approaching the dura at an angle, hence both holes do not overlap.

5) Epidural and intrathecal opioids are prophylactic against PDPH.

ALTERNATIVE METHODSThese include but not limited to

intramuscular opioids, entonox, ketamine and hypnosis’

Regional analgesia is the only effective way of providing complete pain relief, if that is what is desired.

CONCLUSIONPhysiological changes associated with

increased metabolic demand can lead to functional deterioration in women with MS who become pregnant. This is exacerbated in labour when pain, bearing down and autotransfusion can lead to tachycardia, elevations of pulmonary vascular resistance and increases in central blood volume, all of which may be poorly tolerated. Successful management of parturients with MS depends on a multidisciplinary approach and is facilitated by early referral to the cardiology and anaesthesia teams and the use of preoperative echocardiography to delineate the valvular lesion before formulation of the delivery plan.

REFERENCES1) Combined Spinal-Epidural analgesia in the management of labouring parturients with mitral stenosis. W.D Ngankee, J.Shen, A.T.O Chiu, I.Lok, K.S.Khaw. Anaesthesia Intensive Care 1999 27; 523-526.

2) Combined Spinal-Epidural anaesthesia in G.primigravida with valvular heart disease. Tomas VanHelder, Kari G. Smeastad, Can J. Anaesthesia 1998/ 45:5 /488-490.

3) Mitral stenosis in pregnancy: a four-year experience at king Edward VIII hospital, Durban South Africa. British Journal of Obstetrics and Gynaecology. Aug 2000, 107: 953-958.

4) Pain management in the critically ill obstetric patients. Chandra Jayasinghe, Norman H Blass, crit care clinics 1999; Jan 15(1): 201-28

5) Multiport epidural catheter. Barbara et al. Anaesthesiology 2000; 92:1617-20

6) Regional Anaesthesia for the pregnant Cardiac patient Mitterschiffhaler Regional Anaesthesia. Acta anaesthesio scan suppl 1996: 109:180-4



7) The incidence of foetal heart changes after intrathecal fentanyl labour analgesia. Craig M Palmer et al. Anaes analg 1999:88:577-81

8) Can Parturients distinguish between intravenous and epidural fentanyl? Morris GF et al. Can J Anaes: 1994:41: 667-72

9) The parturients with cardiac disease. Ridley Smiley Anaesthesiolo Clin? North Ame 1998:16:430-32

10) Labour Epidural Analgesia without an intravascular “Test Dose” Mark C Noris et al. Anaesthesiology

1998:88:1495-501

11) Regional Anaesthesia for obstetrics Anaesthesiolo Clini North Ame 2000:Vol184

12) The Combined Spinal Epidural technique Narinder Rawal, Bjon Holmstrom et al. Anaesthesiology clinics of North America June 2000:V18: 267-288

13) Invasive Monitoring for anaesthetic management of parturient with mitral stenosis. G.T Hemmings et al. Can J Anaest 1987/34:2 182-5


A 25 year old otherwise healthy male with Ludwig’sangina is posted for abscess drinage

194 Manjunath Prabhu

Ludwig’s angina is a potentially lethal, rapidly spreading cellulitis involving the sublingual and submaxillary spaces. It is manifested by brawny suprahyoid induration, tender swelling in the floor of the mouth, and elevation and posterior displacement of the tongue. This condition is a therapeutic emergency because of inherent life threatening airway obstruction. In 1836, Wilhelm Friedrich von Ludwig described this condition as rapidly spreading cellulitis which produced well defined, woody oedema of the submandibular and sublingual areas with minimal throat inflammation, absence of submandibular lymph node involvement and lack of suppuration. A dental focus of infection can be an initiating factor in the majority of cases. Young adult males are more commonly affected than others. The mortality has come down significantly with the use of early intravenous antibiotics. The most common causative agents are streptococci and staphylococci with anaerobes involving in the mixed infection.

MANAGEMENTAirway obstruction has long been

recognised as the most frequent cause of death in Ludwig’s angina (LA) patients. Airway protection is imperative in the successful treatment plan. Early intravenous antibiotic therapy and exploration of the submandibular spaces in those patients who develop abscesses or fail to respond to initial conservative treatment is important. Continuous observation of the respiratory status is mandatory, as progressive soft tissue oedema compromises the airway insidiously, and total obstruction or laryngospasm secondary to aspiration can be abrupt. In cases of rapidly advancing cellulitis, emergency tracheostomy may be life saving. Nuchal rigidity, trismus and gross distortion of the normal anatomy along with grossly enlarged tongue and pooled secretions

can not only make intubation difficult but also make it traumatic and potentially hazardous.

Prior to detailed examination of the patient a proper planning is a must. Preoperative evaluation of the general condition of the patient and airway examination in particular can give a lot of information that can be of great help in deciding the actual anaesthetic plan. Preinduction intubation may be an ideal way of airway management in these patients. Fibreoptic assisted intubation can be a useful option, but it demands greater skills, a cooperative patient and a Clearfield. These prerequisites are not often encountered in usual clinical settings. Blind nasal intubation can be traumatic causing damage to the inflamed surrounding structures and may precipitate airway obstruction.

Earlier recommendations were for early tracheostomy under local anaesthesia before proceeding with incision and drainage. In recent literature, there are enough evidences suggesting that tracheostomy can be avoided in a large number of patients with careful airway management. In 1982, Patterson etal reported 20 cases of Ludwig’s angina patients and 9 patients underwent surgical exploration.1 Tracheostomy was performed in four patients and in the remaining 5 patients, It was avoided. They reported successful treatment in all 20 patients with the use of antibiotics, surgical drainage and proper airway management. In 1985, Loughnan and colleagues reported successful airway management of nine patients with Ludwig’s angina coming for emergency surgery without tracheostomy.2 Most of their patients had trismus and they were induced with inhalational agents and then intubated under direct vision. Mehrotra et al reported a case report where they have used cervical plexus block and


A 25 year old otherwise healthy male with Ludwig’sangina is posted for abscess drinage 195

Manjunath Prabhu

then successfully managed the drainage procedure in a military field hospital in Delhi.3 There are reports of people losing the airway suddenly both while intubating awake as well as under inhalational agents.4 Probably intravenous induction and muscle paralysis before securing the airway may not be a safe technique. After going through the literature it is clear that the airway management is quite tricky in this group of patients and there are more than one way of doing it correctly.

HOW I DO IT:The management of these emergency

cases depends on the actual clinical settings and the available options. The important steps to be remembered are a good skilled assistant, proper planning and option for immediate tracheostomy. In the following part, I have explained the way I would like to manage a young, otherwise healthy Ludwig’s angina patient with no acute airway obstruction coming for abscess drainage.

Starting of intravenous antibiotic will be the first step in the management in these patients. The antibiotics should be active against streptococcus and anaerobes. Minimal blood investigations are needed including haemoglobin and blood grouping. Chest and neck radiographic pictures will be asked for. The neck X- rays will give information regarding the soft tissue swelling and its effect on the upper airway structures. Deviated larynx and trachea or a narrow laryngeal passage would indicate a possible difficulty in airway management.

The preoperative evaluation should include a detailed history and airway examination. Trismus can be a common finding and this may lead to restriction on mouth opening until pain is fully controlled. The space available inside the mouth, with the floor of the mouth pushed upwards and swollen tongue should be assessed. Reassuring the patient and explaining the proposed plan can be very useful since proper airway management and early antibiotic therapy can avoid the mortality in most cases. The preoperative advice include written consent for anaesthesia as well as tracheostomy (elective or emergency), starvation orders and continuation of antibiotic therapy. My premedication includes

intramuscularly administered glycopyrrolate for its antisialogogue effect. I will not administer any sedatives until the patient is under my direct observation in the operating room or in the ICU.

Prior to administration of any anaesthetic to the patient, I would like to keep the difficult airway trolley ready. These include, but not limited to, properly illuminated laryngoscopes, appropriate sized cuffed endotracheal tubes, gum elastic bougie, emergency cricothyrotomy set, emergency tracheostomy set etc. Monitors will include pulseoximeter and capnograph in addition to electrocardiogram and noninvasive blood pressure. Emergency resuscitation drugs and equipments will be kept ready. A good suction apparatus with wide bore suction catheters like Yankauer suckers will be kept ready.

Following establishment of IV fluids and connecting the patient to preinduction monitors,I would like to nebulise lignocaine solution in order to provide topical anaesthesia of the upper airway. Nebulisation of lignocaine should make subsequent airway management less painful and helps in the release of trismus. If the patient is having relatively stable vitals, satisfactory mouth opening and is not in acute airway obstruction, then I would induce the patient with inhalational anaesthetic sevoflurane in oxygen. The rapid induction and rapid emergence property of sevoflurane would be the major advantage over other inhalational anaesthetics. A small dose of a short acting narcotic like fentanyl 100 pgm will be administered slowly before induction. As patient is induced, gentle attempts to assist ventilation will be made. In case of necessity, a soft well lubricated nasal airway will be introduced with minimal force. Once the patient is induced as indicated by regular shallow respiration, trismus is likely to disappear and then laryngoscopy will be tried. Tracheal intubation will be done using Machintosh blade if glottic visualisation is possible. In case of difficulty in passing the tube due to inadequate glottic exposure, a gum elastic bougie will be used as a guide for intubation. I would use a size smaller than the usual cuffed endotracheal tube (6.5 or 7.0 mm ID tube). The important steps to be followed are optimum position of the patient and first laryngoscopy by an experienced person using



Manjunath Prabhu

a well illuminated laryngoscope with appropriate size blade. The first attempt at laryngoscopy should be considered as the best attempt and so all the efforts should be made to optimise the first attempt. After confirming proper placement of the endotracheal tube with auscultation and capnography, muscle relaxant will be administered. A close monitoring of oxygen saturation will be done throughout and all attempts will be made to maintain oxygen saturation in the safe range. A skilled surgeon and a assisting nurse should be ready from the beginning of induction so that an emergency tracheostomy will be done immediately if the need arises.

Following successful airway management surgical drainage will be allowed. A proper drainage with proper exploration of the surrounding spaces is encouraged. Pus will be collected and send for culture and sensitivity test. The antibiotic therapy will be continued intraoperatively. Considering the possibility of post operative airway oedema endotracheal tube will be retained for a variable time which will be decided by the further course of the disease.

Postoperatively, the patient will be kept under the direct observation of the anaesthesiologist in a high dependency area. Supplemental oxygen, analgesics (narcotic infusion), antibiotics and adequate intravenous fluids will be administered. Following surgery, the patient will be reassessed on the first postoperative day. The general condition of the patient, airway oedema and other likely complications like pneumonia or spread of infection to the surrounding tissue will be assessed. If the patient is awake, well oriented with improved general condition and decreased airway oedema then extubation is considered. The equipments for intubation along with monitors like capnograph and pulseoximeter will be kept ready. In the presence of a skilled assistant, extubation will be performed over a tube exchanger which will also have option for oxygen therapy. Following extubation, I will closely observe the patient atleast for an hour before removing the tube exchanger. The patient will be kept under observation for a further 24 hours. Postoperative spread of infection to other tissue planes, to the

lungs and mediastinum is assessed. If the recovery is satisfactory and there is no danger of further airway problems then the patient will be sent to the surgical ward.

THE ALTERNATIVE METHODS OF AIRWAY MAINTENANCE INCLUDE:Elective tracheostomy under local anaesthesia:

Even though this was recommended earlier, many clinicians have shown successful airway management without tracheostomy. If we can avoid this in a relatively short lasting crisis, then we can avoid all the morbidity associated with tracheostomy. In more sick patients with significant airway compromise, this can still be a life saving option either as an elective procedure or as an emergency. The technique is difficult considering the distorted anatomy and abnormal feel of the structures. There are enough reports about infection spreading to deeper planes or to the mediastinum.

Awake fibreoptic guided intubation:Awake fibreoptic intubation can be a

useful alternative method of securing the airway in these patients. This requires a skilled operator and the main limiting factors can be an uncooperative patient with partial airway obstruction and possible secretions, pus or blood which may make it impossible to view through the scope.

Awake direct laryngoscopy and intubation:This technique may sound safer but it

has got its own limitations. A compromised difficult airway in a patient with pain and trismus can make direct visualisation impossible. Direct trauma to the inflammed structures in a struggling patient can lead to airway obstruction or laryngospam requiring emergency tracheostomy. Direct trauma and sudden release of pus may precipitate aspiration and related complications.

Blind nasal intubation :Even though experienced persons can

use this technique, it may not be an easy option in a distorted airway anatomy and compromised airway. Possibility of airway trauma and aspiration should be kept in mind.


A 25 year old otherwise healthy male with Ludwig’sangina is posted for abscess drinage 197 Manjunath Prabhu

Intubation following intravenous induction and muscle relaxation:

This technique may not be advisable in the majority of patients with Ludwig’s angina. Sudden loss of airway following IV induction can lead to a major crisis. This technique can be applied by experienced people when there is no airway compromise.

Thus a patient coming with Ludwig’s angina for abscess drainage poses several challenges and a management dilemma to the anaesthesiologist. Proper preoperative assessment and adequate preparation can make all the difference. Carefully planned airway management can not only help in avoiding tracheostomy, it can also prevent the possible major complications and help in patient’s recovery.

REFERENCES:

1. Patterson HC, Kelly JH and Strome M. Ludwig’s angina: an update. Laryngoscope 1982; 92: 370 - 7.

2. Loughnan TE, Allen DE. Ludwig’s angina. The anaesthetic management of nine cases. Anaesthesia 1985; 40: 295-7.

3. Allen D, Loughnan TE, Ord RA. A re-evaluation of the role of tracheostomy in Ludwig’s angina. J Oral Maxillofac Surg 1985; 43: 436-9.

4. Mehrotra M and Mehrotra S. Decompression of Ludwig’s angina under cervical block. Anesthesiology 2002; 97: 1625-6.

5. Neff SPW, Merry AF and Anderson B. Airway management in Ludwig’s angina. Anaesth Intensive Care 1999; 27: 659-61.

6. Mostafa SM, Atherton AMJ. Sevoflurane for difficult tracheal intubation. Br J Anaesth 1997; 79: 392-93.

7. Moreland LW, Corey J and McKenzie R. Ludwig’s angina report of a case and review of literature. Arch Intern Med 1988; 148: 461-6.

8. Sparks CJ. Ludwig’s angina causing respiratory arrest in the Solomon Islands. Anaesth Intensive Care 1993; 21: 460-2.


PROS & CONS

Induced hypotension is contraindicated in children 198 A. Rajamanoharan

“The use of deliberate hypotension for paediatric procedures has been more limited because the hazards are relatively high”. At present anaesthesiologists are in a “real dangerous position”. We are "pressurized" from many sides to employ this method in order to save blood or facilitate the work of the surgeon! At the same time we are deeply concerned about our lack of knowledge of the haemodyamics involved and by the unexpected complications.- Robert M.Smith, Anaesthesia for infants and children 4th edition, 268

The mechanism of action of hypotensive drugs differ and produce complex changes in the auto regulatory reflexes, and subsequently blood flow to various organs. Because deliberate hypotension is not without risk, the advantages and disadvantages must be weighed. The “intelligent use" of deliberate hypotension has advantages for "certain” procedures that “may” promote surgical success.- Edward D. Miller Jr- Miller 5th edition, 1470

“As the inappropriate use of induced hypotension can result in irreversible cardiac or brain damage”.- George A. Gregory, Text book on Paediatric anaesthesia,

“Thus a systolic blood pressure of less than 70 mm of Hg is a cause for concern at any age”.- Wylie Churchill Davidson

From the above quotations it is more than clear that induced hypotension in children is to be totally discouraged. Let us see in detail why the text books deliver such “danger signals” on deliberate hypotension.

1. Death rate of induced hypotension of 1 in 1802 as stated by Hugovan Aken (Miller) may be statistically insignificant, but totally avoidable and objectionable, because please remember it is deliberate.

2. The decision to induce hypotension has often been controversial, primarily because of our inability to define the lowest safe MAP with confidence.

3. Most clinical studies do not support the belief that deliberate hypotension decreases operating room time.

4. Patient positioning and attention to ventilation, both of which influence venous return play an important role in minimizing blood loss. Clinical experience suggests that blood loss can be decreased with less or no degree of hypotension and that attention to the surgical field may be a better monitor than the absolute value for MAP.

5. The advantages and contraindications must be weighed carefully when induced hypotension is used, as the inappropriate use of induced hypotension can result in irreversible cardiac or brain damage.

6. Further more, significant deviation from the (routine) management may result in organ damage.

7. Body temperature must be carefully monitored because drug-induced generalized vasoconstriction and vasodilatation may increase heat loss. Normothermia should be maintained, if not, deliberate hypotension is contraindicated.

8. An indwelling arterial cannulation is mandatory as rapid and profound changes in the arterial pressure may require immediate intervention as well as determination of arterial blood gases, electrolytes and glucose level.



9. In Pulseoximetry, the reduced size of the pulse waveform is an indicator of reduced pulse volume.

10. If the patient is positioned in head-up, pressure transducer is placed at the level of the he^d and the CVP at the level of right atrium. Both transducers are to be adjusted.

11. The effects of body position and positive pressure ventilation on blood pressure must be evaluated before induced hypotension is started.

12. Urinary catheter should be inserted after induction of anaesthesia but before induced hypotensaion, and care should be taken to maintain a urine output of 0.5 to 2ml/kg/hr throughout anaesthesia

13. In one study, death from controlled hypotension was mainly due to postoperative complications. So, meticulous care imust be directed to the postoperative period besides the routine monitoring.

14. To minimize the risk of cerebral hypoperfusion, hypocapnia is to be avoided during controlled hypotension.

15. The arterial P02 should be maintained above 300mm of Hg at all times during controlled hypotension which may require

i discontinuation of nitrous oxideL16. Thus a systolic blood pressure of less than

70 mm of Hg is a cause for concern at any age.

17. Parasympathetic control of CVS is well developed at birth and sympathetic control is immature.

18. Decreased sympathetic output may explain the normally low blood pressure in human infants and their INCREASED SUSCEPTIBILITY to bradycardia and hypotension.

19. A low level of baroreceptor activity in infants may reduce their ability to ADAPT to hypotension by an increase in heart rate.

20. Even when a clear indication exists, several relative contraindications abort and out-model the usage of induced hypotension.

21. The usefulness of controlled hypotension during clip ligation of cerebral aneurysm is controversial because wall stress at any given pressure depends on the thinness of the aneurysm sac. Better will be temporary occlusion of the proximal vessel.

22. Farmer et al argue that deliberate hypotension

increases the incidence of vasospasm seriously and compromises border line ischemic brain tissue and impairs cerebral auto regulation. Thus controlled hypotension may place focal areas and the entire brain at a risk of ischaemia.

23. Resistance and development of tachyphylaxis.

24. Rebound haemorrhage in the postoperative period.

CONTRA INDICATIONS TO CONTROLLED HYPOTENSION1. Physicians’ lack of understanding of the

technique; lack of technical expertise or inability to monitor the patient’s condition adequately.

2. Inadequate postoperative care3. Local or generalized, decreased organ blood

flow4. Elevated intracranial pressure.5. Anaemia, haemoglobinopathy and

polycythemia6. Allergy or hypersensitivity to hypotensive

agents7. Hypovolemia8. Cerebrovascular disease9. Ischaemic heart disease10. Peripheral vascular disease11. Severe obstructive lung disease12. Renal impairment or hypertension

COMPLICATIONS OF SODIUM NITROPRUSSIDE

For several years, SNP was believed to be devoid of major toxicity. Side effects were seen infrequently, consisting of nausea, vomiting, twitching, sweating, and apprehension, all of which were believed to be the result of overdosage that could be relieved by decreasing the rate of SNP infusion. Chronic overdosage is reported to have caused hypothyroidism in one patient (Katz and Wolf).

The first abnormal response, thought to be tachyphylaxis, is found in patients whose arterial pressure falls with initial administration of SNP but, on continuation of the drug, rises within 30 to 40 minutes, to be controlled only by increasing dosages. This has been seen several times and is believed to be due to the initial presence of adequate tissue rhodanase and



sodium thiosulfate, followed by early depletion of one, probably the thiosulfate. When this response develops gradually, Davies and associates have been successful in treating the condition with intravenous administration of 150mg of sodium thiosulfate over a period of 15minutes and subsequently proceeding with SNP.

The second abnormal response is seen in patients whose arterial pressure falls with administration of SNP but who require a high dose from the start (over 3.5fig/kg/min).

The third abnormal response consists of such resistance to SNP that hypotension is unobtainable even with greatly increased dosage. Davies and associates believe that patients who show either of the last two responses are in danger of developing metabolic acidosis and cyanide poisoning, and they recommend discontinuation of the drug.

Special contraindications to the use of SNP• Vitamin B12 deficiency• Leber’s optic atrophy• Tobacco amblyopia

Signs suggesting hypoxia or cyanide poisoning during induced hypotension

• Tachycardia, bradycardia, arrhythmias• Metabolic acidosis• High dose requirement

• Increased mixed venous oxygen content• Decreased arterial - mixed venous

oxygen difference• Dilated pupils• High blood cyanide content• Marked hypothermia

The above said contraindications negate the use of induced hypotension. But more importantly, some of these adverse situations may arise during the intraoperative period, in otherwise normal patients. Such a situation becomes very much complex and complicated.

CONCLUSIONSmooth induction, proper choice of

anaesthetic drugs, maintenance of correct plane of anaesthesia, attention to adequate ventilation, proper posture and unimpeded gravity aided venous return will all benefit the surgeon and even more importantly the paediatric patient from undue surgical bleeding and thereby obviate the relative hazards of deliberate hypotension.Primum non nocere - “first of all do no harm”

REFERENCES

1. Robert M.Smith, Anaesthesia for infants and children 4th edition, 268

2. Edward D.Miller Jr - Miller 5th edition, 1470

3. George A. Gregory, Text book on Paediatric anaesthesia,

4. Text book of Anaesthesia by Wylie Churchill Davidson

5. MacRae, W.R.and Owen, M.: Severe metabolic acidosis following hypotension induced with sodium nitroprusside, Br. J. Anaesth. 46:795.

6. McDowall D. G. Keaney, N.P. Turner, J.M, and others; The toxicity of sodium nitroprusside, Br. J. Anaesth. 46:327

7. McHugh, R.D, Berry, F.A, Jr. and Longnecker, D.E,: Dose requirement of sodium nitroprusside during anaesthesia in children, abstract, annual meeting of the American Society of Anaesthesiologists, Chicago.

8. Ivankovich, A.D, Miletich, D.J, Albrecht, R.F, and Zabed, B: Sodium nitroprusside and cerebral blood flow in the anaesthetized and unanaesthetized goat, Anaesthesiology, 44:21.


Induced Hypotension is not contraindicated in children 201 Lakshmi Vas

Hypotension is an entity that is defined by the normal blood pressure or normotension. As such it is a relative value. The normal blood pressure in paediatrics does not lie within a fixed range as it does in adults, but varies depending on the age, prematurity etc. The range that is normal for a premature neonate would be considered as hypotension in an older infant or child. Thus before considering hypotension, we have to define the normal ranges for different ages ( Table 1)\ Conversely, in a patient used to a high blood pressure as in pheochromocytoma or adrenal cortical tumours, reduction of blood pressure to ‘normal’ levels can upset their delicate

balance to cause end organ ischaemia. In both adults and children the ‘Normal’ blood pressure is lower during states of sleep and higher during wakefulness. This prevails or gets slightly exaggerated during the sleep of surgical plane of anaesthesia.

In the past (prior to the 1970s), there were many fears regarding the effects of hypotension in children. These fears were quite valid because blood supply to various vital organs like brain, heart, lungs and kidney are dependant on an adequate perfusion pressure. When the hypotension goes below the range of the

AGE Heart Blood pressure Arterial blood gas valuesrate (mms of Hg) (mms of Hg)(BPM)

Systolic Diastolic Pa°2 Paco2 PHPre term 150 + 20 50 + 3 30 + 2 60 + 8 37 + 6 7.37 + 0.03Term 133 + 18 67 + 3 42 + 4 70 + 11 39 + 7 7.40 + 0.026mo 120 + 20 89 + 29 60 + 10 95 + 8 40 + 6 7.41+0.0412mo 120 + 20 96 + 30 66 + 25 93 + 10 4 1 + 7 7.39 + 0.032Y 90 +10 99 + 25 64 + 25 Comparable to adult values5Y 150 + 20 94 + 14 55 + 912Y 70 + 17 109 + 16 58 + 923Y 70 + 5 122 + 30 75 + 20

% Change in BP with halothaneAGE 1 MAC 1.5 MACNewborn 27 + 8 38 + 11Adult 5 + 5 15 + 5

Table 1: Changes with age in heart rate, blood pressure and arterial blood gas values (From Paediatric anaesthesia edited by George A. Gregory)



autoregulation for that organ, there can be disastrous consequences of end organ hypoxia. Results of injudicious hypotension could be brain damage and or spinal cord damage in the CNS, renal failure in the kidney, splanchnic ischemia with resultant septicemia in the intestines and so on and so forth.

But all these complications result from an incompetent use of a valuable technique and not as a consequence of its judicious scientific use. It use has to be restricted to specific indications with optimal perioperative monitoring. The general principle is to maintain the highest BP to achieve the desired effect and no lower. The end point is usually a MAP 2/3 the baseline level. The minimum allowable MAP is 55mms of Hg.The onset of hypotension should be gradual over 10-15minutes to allow maximal dilatation of cerebral, coronary and renal vasculature to maintain perfusion pressure and tissue perfusion.

Deliberate or controlled hypotension is a manipulation of the cardiovascular system for:1) Reduction of blood and component loss,

avoiding the risks of blood transfusion and reducing the surgical time.2) Providing a better visibility in the surgical field which is essential for microscopic surgery and procedures inside a narrow or deep cavity that can be flooded by blood (spine) obscuring the whole field including the bleeding vessel.

The common indications are neurosurgery, craniofacial surgery(40% reduction of blood loss), spine surgery , major vascular abnormalities, ENT disorders and burns debridement (1'5)

The contraindications are more discretionary than absolute. Inappropriate use of this good technique can lead to irreversible cardiac and neurological damage. This does not preclude its 3ppropriate scientific use. Obviously the procedure cannot be performed (i) by an inexperienced anaesthesiogist without an understanding of the technique or of paediatric physiology, (ii) when there is lack of technical expertise or (iii) an inability to monitor the patients’ condition adequately ( Table 2) or (iv) an inadequate postoperative care facility.

The relative contraindications applicable to the general patient, both adult and paediatric are focal and generalized reduction of organ blood flow, elevated intracranial pressure, anaemia, haemoglobinopathies (sickle cell anaemia), polycythaemia and allergy or sensitivity to the hypotensive agent.

The mandatory prerequisite for hypotensive anaesthesia is a thorough understanding of the hypotensive agents in a paediatric patient and alteration of physiology by hypotension perse. The hypotensive agents can be subdivided into two types, the volatile agents and the vasodilators.

The anaesthetic agents bring about mild hypotension by maintaing the correct surgical plane of anaesthesia that obtunds any painful stimuli that might cause a haemodynamic response. Their major hypotensive effect is by their effect on the cardiovascular system (negative ionotropy) and/or vasodilatation and depression of central and peripheral sympathetic nerves. Halothane has both effects while isoflurane which has a predominant effect on the peripheral vasculature is preferred. Even nitrous oxide, a weak anaesthetic can cause some hypotension in infants, particularly when their fluid balance is marginal. An initial concentration of 3-4 % and a maintenance level of 2% Isoflurane produces a smooth induction of hypotension, particularly with a reverse Trendelenberg tilt of 20°.

The vasodilators can be subdivided into those that act directly on the vessels (Sodium nitroprusside and nitroglycerin), those that act indirectly, on the sympathetic ganglia (pentolinium) and those that have both direct and indirect actions like Trimethaphan.

THE PHYSIOLOGICAL EFFECTS OF INDUCED HYPOTENSION:Central nervous system:

Most of the data on CBF and metabolism in children have been extrapolated from studies in adults. All volatile agents abolish autoregulation of cerebral blood flow in a dose dependant manner with the effect more pronounced with halothane>enflurane >isoflurane>desflurane. Since we have only halothane and isoflurane in



our country, the obvious choice is isoflurane. It also has the advantage that it reduces the cerebral metabolic rate of oxygen more than it reduces the cerebral blood flow, regardless of hypocapnia.

Hypocapnia reduces the CBF in normotensive subjects by 2% for every 1 mmof Hg reduction of PaC02.6 In hypotensive subjects this effect is attenuated or abolished.8,9 If the reduction in CBF is greater than the reduction in CMR02, cerebral ischaemia may develop. EEG changes occur when CBF is reduced to 40-50% of control values and is isoelectric when it is 60% . Vasodilators like nitroprusside and nitroglycerin dilate cerebral vessels directly without affecting the CMR02. Electrical cortical activity and cortical blood flow are preserved better with nitroprusside than with trimethaphan.(10)

To minimize risks of cerebral ischaemia during controlled hypotension, it has been recommended that MAP should be above 55 mms of Hg and that Isoflurane is the agent of choice with nitroprusside or nitroglycerin as adjuncts. A head up tilt may decrease the cerebral perfusion pressure by2mmHg for every 2.5cm the head is above the arterial transducer.

Respiratory system:Controlled hypotension increases the

alveolar dead space and the intrapulmonary shunt. Head up tilt increases the zone 1 and the VdA/t discrepancy, though to a lesser extent than in adults. This has been attributed to a decrease in pulmonary artery pressure, an increase in zone 3 and a reversal of hypoxic pulmonary vasoconstriction. This reversal is in the order of nitroprusside>nitroglycerin> isoflurane. Nitroprusside directly relaxes the pulmonary vasculature with a reduction of right ventricular afterload. Base line ABG and lactate measurements before and after head up tilt and every 30-60 minutes thereafter are essential to ensure adequate oxygenation and normocapnia.

Cardiovascular system:Hypotensive agents reduce

predominantly the afterload and to a lesser extent

preload. The former improves the left ventricular function so long as there is no exaggerated reduction of preload to compromise the left ventricular filling volume. Fortunately, coronary flow is rarely compromised in children (with the exception of muco polyscharidoses and glycogenoses where IHD is reported). So myocardial ischaemia is not a worry. Reflex tachycardia is a common drawback which can be prevented or treated with (3 blockers, propranolol 60ng/kg in small increments or esmolol infusion 500 fig/kg over 2-3 minutes followed by 300 fig/kg/min are useful.

THE HYPOTENSIVE AGENTS:Can be used in conjunction with volatile

anaesthetics or by themselves in patients where volatile agents have to be withheld for malignant hyperthermia or for SSEP or EEG . In these cases a narcotic , relaxant technique with or without propofol is used with hypotensive agents.

Sodium nitroprusside:This is commonly used in children. Its

action, safe doses, toxicity and its treatment have to be thoroughly understood before embarking on its use in children. It is a direct acting arterial dilator and to a lesser extent venous dilator with a rapid onset of action (1-2mins), a brief duration of action and no myocardial depression. It acts via the release of nitric oxide and cyclic GMP. However, overdose produces cyanide toxicity. It is administered as a 0.01% solution ( 50 mg in 500ml) with an infusion rate starting at 0.1 ng/kg/ min and going up to 8-10 ^g/kg/min. The maximal recommended dose is 2-3 mg/kg/day. As it reduces afterload, preload and myocardial oxygen consumption without reducing contractility, it may increase the cardiac output or decrease it or leave it unchanged. Tachycardia as a common baroreceptor response may reduce its effectiveness and necessitate increasing doses and toxicity. To avoid this, p blockers like IV propranolol 0.015 mg/kg or esmolol 0.2-0.3 mg/ kg/h have been used.

TOXICITY:Cyanide is a toxic metabolite which is

metabolized by the rhodanase enzyme system in the liver(80%) and the methaemoglobin



pathway in the RBC(20%). Each molecule of nitroprusside produces 5 ions of cyanide. This combines with thiosulphate or hydroxycobalamin ( both are sulphur atom donors) to form thiocyanate which is excreted by the kidney. However if an overdose is given, the detoxification pathways are overwhelmed and the cyanide binds with the cytochrome oxidases of mitochondria to cause cytotoxic hypoxia. As a result, the cells are unable to utilize the available oxygen and the mixed venous oxygen level rises. As a result of anaerobic metabolism of substrates, the level of lactate rises as the pH decreases.

Immediate treatment comprises stopping the infusion of nitroprusside, administration of 100% oxygen to maximize its cellular availability and sodium nitrite (10mg/kg bolus and 5mg/kg over 30 mins). This drug binds with haemoglobin to form methaemoglobin which has a higher affinity for cyanide than the cytochrome oxidase and so is a temporary measure to release the cytochrome oxidase to relieve the cellular hypoxia. Simultaneously sodium thiosulphate 150mg/kg is also administered to transfer cyanide from cyanmethaemoglobin to form thiocyanate, hydrogen cyanide and methaemoglobin. This methaemoglobin is free to leech some more cyanide from the cytochrome oxidases or is converted to normal haemoglobin by glutathione reductase. Caution has to be exercised to avoid too much nitrite to form excessive methaemoglobin which itself can cause cellular hypoxia. Because the level of haemoglobin is so important in avoiding the toxicity and its treatment, anaemia is a definite contraindication to the use of nitroprusside.

Precautions to be taken with nitroprusside administration are monitoring of oxygenation by oximetry and ABG and lactate levels, direct arterial BP, constant watch for unexplained tachycardia and tachyphylaxis. To avoid tachyphylaxis, hypotension can be augmented by coadministration of isoflurane, captopril, aminophylline and p blockers to reduce the dose of nitroprusside. It should be infused through a central line or a dedicated venous line directly into the hub of the cannula to minimize dead space and delayed response to changes

in infusion rate. Use of an infusion pump ensures accuracy and avoids accidental overdose. The IV Bottle should be shielded, though the IV line need not be shielded as the decomposition takes hours and not minutes that the solution is exposed to light in the tubing.

Nitroglycerin:This is a direct acting venous

capacitance dilator and secondarily an arterial dilator and its action is via nitric oxide. It is a potent coronary vasodilator that decreases cardiac output and pulmonary artery pressure. The onset of hypotension is smooth and gradual without precipitous hypotension. The dose is 1-10 jig/kg/min. All the precautions taken with nitroprusside are applicable to nitroglycerin too, except the shielding of the bottle. A controlled double blind study showed that nitroprusside 6-8 fig/kg/m in produced effective hypotension with a mild increase in A-a Do2 and a mild base deficit. Nitroglycerin was less effective in producing hypotension. The metabolites of nitroglycerin are nitrates and nitrites which have less potent vasodilatory effect and no toxic effect. There is no rebound hypertension either. However, tachyphylaxis, and rarely resistance are common as they are baroreceptor mediated in response to hypotension.

Trimethaphan:This rapidly reduces the systolic BP by

decreasing the systemic vascular resistance. The effect has been attributed to ganglionic blockade, (arterial and venular) direct vasodilatation and in high doses, a adrenergic blockade. All the precautions taken with nitroprusside are applicable.

The dose ranges from 10-200 jig/kg/min. Pressure begins to decrease in 5 minutes and reaches minimal values in 10 minutes. A head up tilt helps the hypotension.

Trimethaphan decreases Cardiac output by either ganglionic blockade or negative inotropic effect. Disadvantages include tachyphylaxis , tachycardia, histamine release, inhibition of pseudocholinesterase activity, mild myoneural blockade, fixed dilated pupils(upto 24 h), urinary



retention and gastrointestinal disturbances as an extension of ganglionic blockade.

Pentolinium:This was used in a dose of 0.1 mg/kg

bolus and> repeated to a maximum of 0.3mg/kg. Its onset of action is in 5 minutes reaching a maximum in 30 minutes. The effect is augmented by headhigh tilt, volatile anaesthetics and p blockers, A single dose lasts for 1 -4hrs and can be reversed at the end by change of position to horizontal, stopping the augmenting effect of volatile anaesthetics and p blockers and volume replacement. It has been replaced in paediatric anaesthesia by other better drugs as it has the disadvantages of trimethaphan.

Adenosine:It is an a/a2 agonist. There are a1

receptors in the SA and AV nodes which can cause bradycardia and transient AV block, and those in the kidney that cause renal vasoconstriction. The a2 action causes systemic and pulmonary vasodilation comparable to nitroprusside in the rapidity of and reliability of action but without the disadvantages of tachyphylaxis and rebound hypertension or toxic metabolites. Preload and cardiac output are unchanged or increased. There is no myocardial ischaemia . Both CBF and CMR02 are maintained unlike with nitroprusside. Nor does the hypocapnia cause lowering of CBF to ischaemic levels. However, its a1 action precludes its use. Presently, selective a2 blockers are being developed for clinical use.

Miscellaneous drugs:Likeclonidine, an a2 agonist that is used

for its sedative and hypotensive effects, as an adjunct to isoflurane / metoprolol anaesthesia, magnesium sulphate is being investigated. However, it causes postoperative sedation, coagulation abnormalities and weakness that are a cause for concern, p blockers and calcium channel blockers and propofol have also been used as adjuncts.

ANAESTHETIC MANAGEMENT OF HYPOTENSIVE ANAESTHESIA:

Combined haemodilution (to 30- 20% Hct), hypotension and hypothermia (to 30° C )

have been studied. At lower temperatures, the metabolic demand and oxygen consumption are lower. At 31° C and an FI02of 1, the dissolved oxygen in blood increases to 2ml/100ml representing 30% of Ca02 However these are esoteric techniques to be tried in special centers . In our country, the decision to use controlled hypotension has to be dictated by a favourable risk : benefit ratio and a proper planning of strategies is mandatory. A Hb of 10g/ dl is recommended, though haemodilution with hypotension has been studied.

Premedication can include a venodilator and a ganglion blocker like morphine, droperidol, clonidine (4-8|ig/kg)orchlorpromazine. Vagolytics are avoided.

Intraoperatively, light anaesthesia has to be avoided to prevent hypertension and tachycardia in response to surgical stimulus. Vecuronium is preferred for its slow heart rate. In our country, the best technique to provide analgesia would be an epidural or a regional block if the surgical location permits it. It helps in providing a steady, reliable and total analgesia that is non fluctuant. In addition, the pulse rate goes down as does the blood pressure, to some extent, particularly in children above 6-7 yrs. The vasodilatation associated with epidural also helps in haemodilution . Alternatively, opioids like fentanyl 3 jag/kg stat followed by morphine 0.1 mg/ kg provide a stable level. Positioning with a head up tilt helps with most hypotensive agents.

Intravascular volume should be restored by infusion of colloids (either gelatins or starch) and/or balanced salt solution. A large bore peripheral cannula for replacement of blood loss and a dedicated line for hypotensive infusion is necessary. An arterial line is mandatory for both monitoring and repeated electrolyte, sugar (especially if p blockers like esmolol, metoprolol or labetalol are given), ABG and lactate estimations. An NIBP can both underestimate or overestimate the BP. A dorsalis pedis line may overestimate BP with nitroprusside and underestimate it with isoflurane; so a radial or axillary line is preferred. A central venous line is recommended as right sided filling pressures parallel left sided pressures in children. PA



catheters are not commonly used. Blood loss estimation and replacement have to be diligent. Nitrous oxide may have to be replaced with air if the Pao2 has to be maintained around 300 mm Hg.

Postoperatively intensive monitoring in the ICU is indicated in all cases of hypotensive anaesthesia. Proper positioning, urine output and serial ABG monitoring have to continue to ensure a zero mortality and morbidity

RISKS:Sudden blood loss, occult or overt, can

cause severe hypotension and this has to be corrected by timely and rapid replacement as well

as a temporary discontinuation of hypotension to restore BP. Rebound hypertension may have to be managed with other drugs. Blindness has been reported with severe haemodilution and hypotension in scoliosis attributed to anaemia, hypotension and dependency of the eye in the prone position.

In conclusion, hypotensive anaesthesia is a demanding technique to be practised with expertise, elaborate monitoring, immaculate planning and execution. Safety is assured if these criteria are met and no child should be deprived of this extremely useful technique due to ill founded prejudices.

Parameters Absolutely essentialECGOesophageal stethoscope

Temperature monitoring

Oximeter

EtCo2

Direct arterial blood pressure

Arterial blood gases

Serum lactate levels

Urine output

As a minimum mandatory safety monitor of the heart As the failsafe monitor of heart, circulation, hypovolaemia and breath sounds.As a sensitive indicator of circulation, metabolic heat production, particularly if mild/moderate/deep hypothermia is to be combined with hypotension to control blood loss.To know that the Fio2 and ventilation are maintaining the shunting effect (VD/VT) of hypotension within acceptable limits. To know expired C02 reflects the adequacy of ventilation and to avoid hypocapnia that can reduce cerebral blood flow.To know the accurate real time BP at any given point of time, and any possible rapid fluctuations for a coherent manipulation of BP. Titrate patient safety to surgical demands To know Spo2 & to know whether expired C02 reflects the arterial values and that there is no respiratory or metabolic acidosis.For prolonged procedures, particularly when nitroprusside is the chosen agent.Most sensitive physiological monitor which is custom designed for the patient irrespective of standard, predicted, absolute haemodynamic values. 0.5-2ml/kg/h is recommended.

Relatively necessaryCentral venous pressure

EEG, BIS

To know the adequacy of fluid replacement vis-a-vis the expanded vascular bed and preload .For research purposes

Table: 2 Monitoring for hypotensive anesthesia



References

1. Jerrold Lerman In Special techniques ( acute normovolemic haemodilution, controlled hypotension and hypothermia, and ECMO in Paediatric anaesthesia edited by George A . Gregory 4th edition Churchill Livingstone New York, Edinburgh .London, Philadelphia.

2. DiazJH. Lockhart CH: Hypotensive anaesthesia for craniectomy in an infancy. Br.J.Anaesth 51: 233, 1979.

3. Viguera MG., Terry RN., Induced hypotension for an extensive surgery in an infant Anesthesiology 27: 701, 1966.

4. Fairbairn ML., Eltringhamrj, Young PN Robinson JM. Hypotensive anaesthesia for microsurgery of the middle ear A comparison between halothane and isoflurane. Anaesthesia 41: 637 1986

5. Szyfelbein SK Ryan JF Use of controlled hypotension for primary surgical excision in an extensively burned child. Anesthesiology 41:501 1974

6. HarpJR. Wollman H : Cerebral metabolic effects of of

hyperventilation and deliberate hypotension.Br.J.Anaesth 45:256.1973.

7. Artru AA: Partial preservation of cerebral vascular responsiveness to hypocapnia during isoflurane induced hypotension in dogs Anesth Analg 65:660,1986.

8. ArtruAA. Colley PS. Cerebral blood flow response to hypocapnia during hypotension. Strokel 5:878,1984.

9. ArtruAA. . Cerebral vascular response to hypocapnia during nitroglycerin induced hypotension. Neurosurgery 16:468.1985.

10. Thomas WA, Cole PV Etherinton NJ et al.: Electrical activity of the cerebral cortex during induced hypotension in man: a comparison of sodium nitroprusside and trimethaphan Br.J.Anaesth 57:134.1985

11. YasterM., Simmons RS., ToloVT. Etal: A comparison of nitroprusside and nitroglycerin for inducing hypotension in children : a double blind study. Anesthesiology. 65:175, 1986

12. Jean Camboulives in the chapter on Fluid, Transfusion, and blood sparing techniques in PEDIATRIC ANAESTHESIA .Principles and practice edited by Bruno Bisonetteand Bernard Dalens McGraw -Hill.


Strict Preoperative Blood Sugar Control to a FBS of200 mgs% is Mandatory Before Elective Surgery 208 Naheed Azhar

INTRODUCTIONBlood glucose management during the

peri-operative period still continues to be an unending topic of heated debate between various specialties of medicine. Party to these arguments are the physicians, diabetologists, intensivists, surgeons and finally the anaesthesiologists. Even among the anaesthesiologists a definite consensus seems to be elusive, which only adds to the confusion.

The current accepted norm by anaesthetists for elective surgeries is to aim for a fasting blood sugar of less than 200 mg/dl (11.1mmol/L) prior to surgery. To support this viewpoint we have to try and understand the scientific material on the basis of which this figure was reached. The understanding of this issue can

be simplified if we aim to find answers to 4 cardinal questions. In the answer to these questions lies the basis for evolving such criteria. The questions are1. What are the effects of anaesthesia,

surgery, and stress on blood glucose levels?

2. Does hyperglycaemia produce adverse effects in the intra-operative period?

3. Does hyperglycaemia adversely affect the post-operative period?

4. What are the reasonable expectations of an elective surgery?

EFFECT OF ANAESTHESIA, SURGERY, STRESS ON BLOOD GLUCOSE LEVELS

Surgery evokes a series of well- characterized changes in hormonal secretion and

ORGAN INCREASED INCREASED/DECREASED DECREASEDSECRETION SECRETION SECRETION

Pituitary ACTH(3-EndorphinGHProlactinAVP

TSHFSH/LH

Adrenal gland CatecholaminesCortisolAldosterone

Pancreas Glucagon Insulin

Others Testosterone/OestradiolTriiodothyronine

Table: 1. Hormonal Responses to Surgery



substrate mobilization commonly referred to as “stress response” to surgery. This was a survival aid necessary for animal survival in a primitive environment.

Kehlet et al consider this response as an “epiphenomenona” and hypothesized that its deliberate prevention, or attenuation may be beneficial in reducing post-operative morbidity and mortality.

Surgery, stress and anaesthesia have an overbearing role on glucose metabolism leading to a hyperglycaemic response. Glucose production by the liver is increased initially and later by gluconeogenesis together with a decline in glucose uptake peripherally lead to hyperglycaemia.The sympathoadrenal activation, release of counter regulatory hormones, raised cortisol production, increased catecholamine secretion along with insulin suppression produce hyperglycaemia even in the absence of extraneous intravenous glucose.

Role of counter-regulatory hormones:Triiodothyronine

Table 1 reflects the hormonal response

produced by the body to the stress produced by anaesthesia and surgery. A majority of hormones released under the effect of stress have a diabetogenic effect and tend to produce hyperglycaemia. These counter regulatory hormones have a profound catabolic effect. The effects of Growth hormone are mediated through somatomedins or IGF factors.

The vairous metabolic effects of the major anabolic and catabolic hormones of the body are given in table 2.

ACTH and cortisol release during surgery reaches values close to the maximal secretory capacity of the human body and thus impairs the ability of the body tissues to deal with extra glucose. Hepatic glucose metabolism, endocrine pancreatic secretion and adrenal medullary secretion are regulated by several mechanisms under the control of the ANS. It is well- documented fact that stress produces an increase in the plasma concentration of glucose raising (counter- regulatory) hormones producing glucose tolerance during anaesthesia.

Nakamura et al demonstrated increases

HORMONE ANABOLIC EFFECTS CATABOLIC EFFECTS

Glycogenesis Lipogenesis ProteinSynthesis

Glycogenolysis Lipolysis Proteolysis

Insulin + + + - - -

Epinephrine - 0 0 + + -

Glucagon - 0 0 + ?* +

Cortisol +/- - - - + +!

Growth

Hormone 0 0 + - + + !

+

+/-*!

: Stimulatory effect : Inhibitory effect: Stimulatory in presence of insulin & inhibitory in the absence of insulin : Effects increased with nonphysiological concentrations : Effects important in the absence of insulin

Table:2. The various metabolic effects of the major anabolic and catabolic hormones of the body.



in epinephrine and norepinephrine concentrations during surgery resulting from afferent painful stimuli. This leads to a disturbance in the metabolism of glucose and NEFA.

Dounia et al reported that despite the use of glucose free maintenance solutions, plasma glucose concentration increased significantly, 5 minutes after induction with Thiopentone (5.3 ± 0.4 vs. 4.5 ± 0.9 mmol/L). This increase persisted throughout the period of surgery.

Walts et al studied diabetic patients undergoing anaesthesia and found that all patients developed rising plasma glucose concentrations beginning with the start of anaesthesia. The mean rate of increase was 22 mg/dl/hour in the “no insulin - no glucose” group to 17 mg/dl/hour in patients who received one- fourth of the usual insulin dose. Eight percent of the patients achieved plasma glucose concentrations greater than 400 mg/dl, and all these patients had pre-operative blood sugar more than 200 mg/dl.

CHANGE IN MEAN PLASMA GLUCOSE CONCENTRATION WITH TIME WITH VARIOUS REGIMES OF MANAGEMENT-WALTS ET AL(Figure 1)

Under halothane anaesthesia, early increase in glucose production with no change in

peripheral glucose uptake leads to an early postinduction rise in plasma glucose concentration. This was due to stimulation of glycogenolysis and increased glucose production related to the release of catecholamines.

Glucose utilization under anaesthesia decreased by 17 to 20% in the peripheral tissues. 20% of glucose utilization in post-absorptive adults is accounted for by muscle uptake. Loss of muscular activity as a consequence of anaesthesia could contribute to increased glucose levels. The imbalance between glucose production and utilization is reflected by significant decreases in “glucose fractional disappearance rate” under anaesthesia.

BLUNTED INSULIN RESPONSEInsulin is a primary anabolic hormone,

which promotes glucose uptake, glycogen formation, fatty acid transport, triglyceride synthesis, and amino acid transport and protein synthesis in the muscle. It also has significant anticatabolic effects like inhibition of glycogenolysis, gluconeogenesis, and ketogenesis in the liver, inhibition of lipolysis in adipose tissue and protein catabolism in the muscle.

Under anaesthesia there is a significant blunting of the insulin response to hyperglycaemiaa. Circulating insulin levels are



inappropriately low for the prevailing blood glucose values, reflecting a relative lack of circulating insulin during surgery. The factors responsible for this are unclear, but it seems that circulating catecholamines released during surgery have a direct inhibitory effect on the p cells of the pancreas, acting through the a adrenoreceptors.

Desborough et al demonstrated decline in insulin secretion after the induction of anaesthesia, and before the onset of surgery. This inhibition implicated the role of the anaesthetic agents, either directly or indirectly by altering splanchnic blood flow.

Kehlet et al reported increased blood lactate concentrations during surgery under GA.

Desborough et al also demonstrated that inhibition of insulin secretion by halothane, enflurane and isoflurane in clinical concentrations by their inhibitory effect on the stimulus-secretion coupling in the p cells of pancreas and impairment in uptake of glucose in both skeletal and hepatic tissues.

Brandi et al demonstrated that in days after surgery or trauma, circulating insulin values increase above normal values, but the hormone is ineffective metabolically. This period presenting with hyperglycaemia is called the “phase of insulin resistance”. It is related to the effects of catabolic hormones like cortisol and cytokines on insulin receptors along with a post-receptor defect. The moderate resistance to insulin may also be attributable to alteration in the distribution space and serum clearance of insulin.

CONCLUSION NO: 1Anaesthesia and surgery conclusively

produce a hyperglycaemic response due to increased secretion of counter regulatory hormones and relative insulin resistance. This is attributable to decreased glucose tolerance induced by any of the following mechanisms:1. Impaired insulin secretion.2. Decreased biologic response of tissues to

insulin such as diminished peripheral glucose utilization.

3. Impaired gluconeogenesis and /or glycogenolysis.

4. Increased hepatic glucose output and / or

splanchnic release of glucose due to increased anabolic process.

5. Decreased peripheral uptake of glucose.

ADVERSE EFFECTS OF HYPERGLYCAEMIA IN THE INTRA-OPERATIVE PERIOD

Inadequate control of blood glucose and hyperglycaemia in the intra-operative period leads to1. Ketosis.2. Acidemia.3. Electrolyte abnormalities.4. Volume depletion from osmotic diuresis.5. Hyperosmolality.6. Thrombogenesis.7. Lactic Acidosis.8. Disruption of autoregulation.

The renal threshold for glucose is 10 mmol/L. At levels greater than this, the glycosuria causes an osmotic diuresis, with loss of water and electrolytes. High levels of blood glucose can cause severe cellular dehydration due to osmotic transfer of water out of the cells. During renal glycosuria, the osmotic effect on the renal tubules decreases tubular reabsorption of fluids. This leads to massive loss of fluid in the urine causing ECF dehydration, and ultimately compensatory dehydration of the ICF.

Intra-operative hyperglycaemia leads to hyperosmolality. Each mOsmol / L of any substance exerts an osmotic pressure of 19.3 mm Hg. Blood glucose at normal concentrations of 5.6 mmol / L (100 mg / dl) exerts a pressure of 108 mm Hg. The osmotic pressure of plasma is 5443 mm Hg, which is 20 mm Hg more than the pressure of the ECF and ICF, which is 5423 mm Hg. A rise in blood glucose to 20 mmol / L can change the osmotic pressure by as much as 400 mm Hg producing deleterious effects on water and electrolyte homeostasis.

The maximum reabsorptive capacity of renal tubules for glucose averages 320 mg / min. When the tubular load rises above 220 mg / min (plasma glucose = 180 mg / dl), a small amount of glucose begins to appear in the urine, termed as glucose threshold. This glucose excretion keeps rising between plasma levels of 180 to 250 mg / dl. Beyond plasma glucose of 250 mg /dl the absorptive capacity of all nephrons is exceeded showing a steep rise in glycosuria.



Osmotic diuresis is accompanied by a continual loss of electrolytes particularly sodium. Sodium loss is around 150 mmol / L of urine and potassium around 5 mmol / L. Progressive sodium depletion activates the Renin - Angiotensin system and Aldosterone secretion increases, leading to increased sodium resorption from tubules. High aldosterone concentrations reduce potassium resorption and increase urinary potassium excretion. Hyponatremia and Hypokalemia can occur. In rare instances, when oliguria and uremia occur inspite of a substantial osmolar load, potassium starts leaking out of cells into ECF, but can no longer be excreted by diuresis. So although the total potassium stores are depleted the patients may have dangerously high plasma potassium.

Hyperosmolality and dehydration can produce haemodynamic instability and depressed mental state leading to recovery problems. Sodium and potassium derangements may produce arrhythmias and delayed recovery. Hyperglycaemia may increase the viscosity of blood by increasing the osmolal load. Increased viscosity favors slow flow of blood in the blood vessels. Slowflcwing blood causes concentration of pro-coagulants to rise high enough in certain local areas to initiate clotting and thrombogenesis. This is more likely to occur if conditions like dehydration, pre-existing atherosclerosis, high haematocrit, cold induced peripheral vasoconstriction, myocardial depression and hyperglycaemia are present. Controlling peri-operative blood glucose to < 10 mmol / L (200 mg / dl) can eliminate some of the precipitating causes.

Hyperglycaemia increases production of macroglobulins by the liver. They increase the viscosity and promote intracellular swelling by favoring production of non-diffusible molecules like sorbitol.

Hyperglycaemia also disrupts autoregulation. Glucose induced vasodilatation prevents vital target organs from protection against increases in systemic blood pressures. Different degrees of hyperglycaemia may be required before different vascular beds are affected.

Hyperglycaemia promotes lactic acidosis and academia. The increased viscosity and dehydration are major contributory factors

towards it. Acidosis may impair cardiac contractility, provoke arrhythmias, hypotension and interfere with the action and metabolism of drugs. Acidoc s depresses not only the myocardial function but also respiration. Bicarbonate therapy to rapidly correct acidosis is fraught with dangers in alteration of CNS structure and function due to paradoxical CSF and CNS acidosis, decreased CBF, altered CNS oxygenation and development of unfavorable osmotic gradients.

A study of 340 diabetics undergoing open-heart surgery revealed an increases in operative mortality (1.8% vs. 0.6%). During the study a number of cases were reported where inotropic agents were ineffective in maintaining cardiac contractility, although filling pressures, sinus rhythm, serum electrolytes and blood gases were adequate. The blood sugar was high in each of this case. After IV infusion of insulin, effective myocardial contractions returned, allowing easy and rapid bypass weaning.

Intra-operative use of drugs like corticosteroids, p agonists and adrenergic agents all increase the likelihood of intra-operative hyperglycaemia.

CONCLUSION NO: 2Hyperglycaemia is definitely undesirable

during the intra-operative period. The adverse effects of hyperglycaemia are directly or indirectly related to increased blood glucose levels producing1) Ketosis.2) Lactic Acidosis and Acidemia.3) Electrolyte abnormalities.4) Volume depletion from osmotic diuresis.5) Hyperosmolality.6) Thrombogenesis.7) Impaired myocardial contractility.8) Haemodynamic instability.9) Arrythmogenicity.10) Altered drug pharmacodynamics and

pharmacokinetics.11) Disrupted autoregulation of vascular beds.

IMPLICATION OF HYPERGLYCAEMIA IN THE POST/PERI-OPERATIVE PERIOD

Hyperglycaemia during the peri-operative period leads to an increased incidence of infection and delayed wound healing.



Hirsch et al report that impaired wound strength and wound healing occur when plasma glucose levels exceed 11.1 mmol /L (200 mg / dl). Hyperglycaemia interferes with leukocyte chemotaxis, opsonization, phagocytosis, granulocyte adherence and depresses bactericidal activity.

Hyperglycaemia depresses the immune response of the body to infection by producing short-term glycosylation of immunoglobulins thereby inactivating them. Glycosylation of C3 component of complement occurs at its opsonic site, rendering it impotent and unable to bind to the surface of the invading bacteria.

Rassias et al demonstrated that neutrophil phagocytic activity was less depressed when blood sugar was tightly controlled during the peri-operative period (75% vs. 47%). They demonstrated that hyperglycaemia depresses the white cell function and increases the risk of infection after surgery.

Researchers showed that anastomotic healing in both ileum and colon of diabetic animals was better if hyperglycaemia is tightly controlled starting from 4 days before surgery and extending into the entire peri-operative period. Hyperglycaemic animals showed qualitative change in the newly formed collagen causing reduction in wound strength.

Studies reveal that hyperglycaemia results in impaired wound healing due to 1) Accelerated non-enzymatic glycosylation of body proteins due to addition of glucose molecules to the exposed lysine residues on extra cellular proteins. 2) Glycosylation of newly synthesized collagen associated with increased collagenase activity and decreased wound collagen content.

CONCLUSION NO: 3Hyperglycaemia increases the incidence

of infection by interfering with leukocyte function. It also impairs wound healing by altering collagen activity and strength.

GOALS OF ELECTIVE SURGERYAnaesthesia and surgery carry a certain

amount of risk even for the normal patient. The lowest class in ASA classification is Class 1,

with its attendant risks. A class 0 does not exist in anaesthesia. Unanticipated, undesirable events can occur during anaesthesia and these can range from mere hypotension, myocardial depression to the much dreaded arrhythmias, anaphylaxis and failed intubation situations.

During elective surgery, the aim is to plan and to be prepared to minimize these risks to as low as possible. Even if unforeseen complications arise, we should be able to leave the patient undergoing elective surgery with the least possible risk of suffering morbidity or mortality. Uncontrolled hyperglycaemia in the peri-operative period precludes our ability to offer this advantage to the patient undergoing elective surgery.

Hyperglycaemia worsens the neurological outcome in patients who have suffered global CNS ischaemia / hypoxia. Hirsch et al recommend tight control of blood sugar in patients undergoing neurosurgical procedures. Werner et al recommend a plasma glucose of 100 to150 mg / dl for better outcome of patients with stroke or neurotrauma.

Roizen et al recommend blood glucose of less than 200 mg / dl during periods of ischaemia in diabetic patients about to undergo surgery in which hypotension or reduced cerebral blood flow occurs. Hyperglycaemia also worsens neurological outcome after regional CNS blood flow alterations and ischaemia.

In a study of 430 consecutive patients resuscitated after out-of-hospital cardiac arrest, mean blood glucose values were found to be higher in patients who never awakened (341 ± 13 mg / dl) than in those who did (262 ± 7 mg / dl). Among patients who awakened, those with persistent neurological deficits had higher mean glucose levels (286 ± 15 mg / dl) than did those without deficits (251 ± 7 mg / dl). These results are consistent with the findings that hyperglycaemia during stroke is associated with poorer short- and long-term neurological outcomes.

Roizen et al advocate that blood glucose is a major determinant of brain damage following ischaemia. They recommend that until better data is available blood glucose levels should be maintained below 200 mg / dl during periods of likely cerebral ischaemia.



Hyperglycaemia in the pregnant diabetic affects her adversely, as well as her offspring. Maternal hyperglycaemia may stimulate insulin secretion in the fetus leading to neonatal hypoglycaemia and delayed release of glucagons. Hypotension in the presence of hypoglycaemia in this sub-sect of patients produced maternal lactic acidosis and consequent fetal acidosis.

Conclusion No: 4During elective surgery enough time is

available to adequately stabilize the patient. This should be utilized to minimize the risk of morbidity and mortality due to anaesthesia and / or surgery. Unanticipated, critical events, if they occur (as they could during anaesthesia) it has been conclusively proven that hyperglycaemia are associated with poor outcome.

CURRENT MOST PRACTISED PROTOCOL FOR DIABETIC MANAGEMENT

Before the advent of bedside glucosimetry, hypoglycaemia being greatly feared, majority of the anaesthetists accepted a moderate hyperglycaemia in the peri-operative period. Since early 1970’s evidence has been accumulating against the harmful effects of even moderate hyperglycaemia.

Dunnet et al in 1985 surveyed the protocols used by anaesthetists in the diabetic management in the peri-operative period. Most of the anaesthetists aimed to maintain the blood glucose in the range of 7 to 10 mmol/L. 35% of respondents chose a value greater than 11 mmol/L.

Eldridge et al restudied the same parameters in 1993. They now found that 26% preferred to maintain blood glucose between 4- to7 mmol/L. 63% preferred a range of 7 to 10 mmol/L. Only 9% selected a range greater than11 mmol/L.

These gross changes amongst the attitude of anaesthesiologists, in their practice of managing blood glucose during the peri-operative period, clearly indicates the emerging trends based on the scientific data that has been made available by recent research. Undoubtedly there is an emerging need to control blood sugar within the normoglycaemic range. The starting point in

this endeavor is to start with pre-operative blood sugar below 200 mg / dl.

CONCLUSIONIn our attempt to seek an answer for

what would be an appropriate pre-operative blood sugar value in a fasting state in an individual posted for elective surgery, we ended up searching the literature to find answers for 4 questions. The search yielded important conclusions, which need to be re-considered at this stage. They are■ Anaesthesia and surgery definitely produce a hyperglycaemic response.• Hyperglycaemia produces undesirable adverse effects in the intra-operative period.■ Hyperglycaemia increases the risk of infection and delays wound healing.■ Unanticipated critical events if they occur in the presence of hyperglycaemia are associated with poor outcome.■ The current approach to blood glucose management in the peri-operative period is to maintain blood glucose within the normoglycaemic range.

The adequate management of blood sugar for the entire peri-operative period should begin with adequate control in the pre-operative period. Fasting blood sugar in elective surgeries, if not all, should strictly be maintained in the normoglycaemic range.

Amongst the majority of workers who have done hall mark studies in peri-operative management of blood glucose, Hirsch, Rassias, Kehletand Roizen all recommend blood glucose to be maintained between 140 to 180 mg/dl. Alberti et al give us the liberty of accepting fasting blood sugar of 180 to 200 mg / dl as an indicator of adequate control.

On the basis of the scientific data available to us at this point of time, it seems reasonable to aim for peri-operative blood sugar in the normoglycaemic range, it would be appropriate to begin this with a fasting blood sugar of less than 200 mg /dl being mandatory for elective surgeries.


Strict Preoperative Control of Blood Sugar to an FBS of 200mg%is NOT Mandatory Before Elective Surgery 215 Kalyan Chakravarthy

INTRODUCTION:Diabetes Mellitus (DM) with its

devastating consequences has assumed epidemic proportions in many countries of the world. Spectacular increase in the incidence and prevalence of this chronic disease is destined to have enormous impact on mortality, morbidity and health care resources. India would rank first in sharing the global burden of diabetes in the next two decades1. Epidemiological transition including improved socio-economic status, rural to urban migration, adoption to sedentary habit and stress of modern life style is largely responsible for this cataclysmic shift in the burden of diabetes2.

DEFINITION OF DIABETES MELLITUS (DM):Diabetes Mellitus is a syndrome

characterised by chronic hyperglycaemia and disturbances of carbohydrate, fat and protein metabolism associated with absolute or relative deficiencies in insulin secretion and /or insulin action. When fully expressed, diabetes is characterised by fasting hyperglycaemia, but the disease can also be recognised during less overt stages and before fasting hyperglycaemia appears, most usually by the presence of glucose intolerance3.

CURRENT DIAGNOSTIC CRITERIA:The 1997 American Diabetic Association

(ADA) expert committee on the diagnosis and classification of diabetes mellitus and the provisional report of the WHO consultation focus on fasting plasma glucose (FPG) that is 126mg% or greater and confirmed on subsequent day as the preferred criterion for the diagnosis of diabetes mellitus4. This criterion is supported by studies demonstrating that this threshold accurately

differentiates between non-diabetic and diabetic populations and is associated with the development of specific diabetic microvascular complications.

The following points must be remembered while the diagnosis of diabetes mellitus is made.

1. The diagnosis of DM must be based on blood glucose estimations.

2. Urine glucose testing must not be used to diagnose diabetes.

3. True blood glucose should be estimated using enzymatic methods like the glucose oxidase method.

4. Plasma glucose >200mg%, confirmed on repeat testing, in a patient with characteristic signs and symptoms of diabetes is diagnostic.

5. Doing a GTT in a known diabetic patient is not necessary.

6. In all other persons, a GTT must be carried out in order to exclude diabetes.

CLASSIFICATION OF DIABETES MELLITUS5:Diabetes is classified into four major

categories:• Type-1 —IDDM• Type-ll-MODY• Gestational• Secondary

DOES GOOD GLYCAEMIC CONTROL MATTER:

Improved control of blood sugar is protective and this has been confirmed in humans. The Diabetes Control and Complications Trial (DCCT) in the USA compared standard and intensive insulin therapy in a prospective controlled trial of young patients with IDDM6. Even

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Strict Preoperative Control of Blood Sugar to an FBS of 2Q0mg%is NOT Mandatory Before Elective Surgery________________________ Kalyan Chakravarthy

in those with intensive therapy, mean blood glucose levels were 40% above the non-diabetic range, but this level of control reduced the risk of progression to retinopathy by 60%, nephropathy by 30% and neuropathy by 20% over seven years of the study.

CELLULAR AND MOLECULAR BASIS OF LONG TERM DIABETIC COMPLICATIONS7:

The complications of DM are attributable to tissue damage due to vascular disease involving micro and macro vasculature. The most common pathology of micro vessels occurs in the retina, kidney, peripheral arteries of the lower limbs, in the coronary vessels and the cerebral arteries.

RELATIONSHIP BETWEEN DIABETIC CONTROL AND COMPLICATIONS:

Patients with type-1 DM have more chance of developing duration dependent complications of disease with better survival. Patients with type-11 DM may have microvascular and macrovascular complications of the disease at the time of detection.

The (UKPDS) UK Prospective Diabetes Study was started in 1977 and included 5702 patients with NIDDM over a period of 20 years6. Summary is:1. Good glycaemic control is necessary for type II diabetes mellitus.2. Early intervention to modify risk factors, and obtain good glycaemic control.3. Control of hypertension in patients with typeII DM needs intensive treatment.4. UKPDS confirms the efficacy of existing treatment for type II DM.

UKPDS and nephropathy - Renal failure and death from renal disease did not differ between the conventional group and the intensive group

UKPDS and neuropathy - No significant difference was seen in the incidence of absent knee and ankle reflexes. Incidence of impotence, abnormal cardiac autonomic functions also did not differ significantly between the groups.

UKPDS and macrovascular complications - The incidence of fatal Ml, heart failure, angina, stroke, amputation and death from

PVD was not lowered significantly.

While a close control of blood glucose is normally mandatory to avoid progressive organ failure, during the peri-operative period, well- standardised insulin protocols appear to be sufficient to manage the diabetic patient7

The peri-operative care of diabetic patients is less dependent on blood glucose control, which needs to be exceptionally tight, and is usually easily obtained thanks to pharmacological improvements, human insulins and analogues, technical progress with blood glucose monitoring at the bedside and infusion with constant flow rates. More important is the influence of end organ pathology, often clinically silent, which must be carefully assessed during the pre-operative evaluation. The organ impairments concern especially the heart, but also all those organs that were modified by abnormal glycosylated proteins. The pre-existing pathology has many consequences on anaesthesia management; the anaesthetic technique depends essentially on their existence. A better long-term control of diabetes both for type I and type II by insulins, and the new oral antidiabetic drugs reduce the incidence of the end organ pathology and the risk linked to organ failure in the peri-operative period8.

Diabetes per se is not a risk factor for post-operative morbidity or mortality, after adjustment for co-morbidities like atherosclerosis. Controlled studies have shown the advantages of tight control of glycaemia, in two acute complications of atherosclerosis, i.e. Ml and CVA. These diseases have a high prevalence rate in diabetic patients, as the probability of macroangiopathy is high. Perioperative tight control of glycaemia is a probable necessity to avoid these complications, which is best achieved by a team.

Reasonable control of blood sugar can best be achieved within a few hours pre-operatively and clinical assessment can be performed on an outpatient basis. Anaesthetic management consists of assessments of control of the disease followed by evaluation of diabetic complications and their severity.

Different views are expressed regarding tight control of blood glucose vs. moderate control



when managing diabetic patients.

The importance of guarding against factors'favouring metabolic decompensation in the peri-operative period is stressed. Minor or major surgery has important implications regarding the management of diabetes. All patients scheduled for major surgery should be treated with insulin10. Strict intra-operative glucose level control was accomplished with low dose glucose infusion of 100mg/kg/hr and variable infusion rates of insulin to control serum glucose levels11.

HAZARDS OF INTENSIVE GLYCAEMIC CONTROL:• Hypoglycaemia• Weight gain• Others include

n Restriction of life style, n Increased short term cost n Inconvenience □ Discomfort etc.

Treatment to restore glycaemia to near normal should be a reasonable goal to both the patients and the treating physicians, as a longterm goal rather than just pre-operative tight control.

TYPE II DM - GLYCAEMIC CONTROL AND COMPLICATIONS:

The natural history of microvascular complications in type II DM has been difficult to define because the disease may be present for many years before it was diagnosed, and the incidence and progression of complications may be influenced by multiple confounding factors including age and hypertension.

Persons with diabetes should no longer be at a higher risk than their counterparts for poor

surgical outcomes. Coexisting complications such as neuropathy and large vessel occlusive diseases will have an impact on rates of wound healing, but no studies in humans support the long held belief that the level of blood glucose in the peri-operative period directly affects surgical success.

IMPACT OF GLYCAEMIC CONTROL ON COMPLICATIONS OF DM:

“CURE” is an appropriate future goal. The question is whether to wait for blood sugar values to be strictly below 200mg% or to accept fasting blood sugar more than 200mg% for elective surgery. We aim to see that there are no metabolic derangements like DKA. Ease of insulin administration peri-operatively with the availability of modern gadgets should make it possible to go ahead with the surgical procedure.

CLASSIC “NON-TIGHT CONTROL” REGIMEN12:Aim:

To prevent hypoglycaemia, hyperosmolar states and ketoacidosis.

Protocol:1. Day before surgery, patients should be given nothing orally after midnight. A13 ounce glass of clear orange juice should be available immediately.2. At 6.00 am on the day of surgery, institute IV fluids and a solution containing 5% Dextrose, infused at the rate of 125ml/hr/70kg.3. After institution of IV fluids give one- half of the usual morning insulin dose subcutaneously.4.Continue 5%Dextrose solution through the operative period giving at least 125ml/hr/70kg. 5.ln the recovery room, monitor blood glucose and treat on a sliding scale. Such a regimen has been found to meet its goals.

Pre-surgical blood glucose mg/dl

Intermediate acting insulin % of patients with usual insulin dose

Regularinsulin

70-150 50 none151-250 67 3-4 U251-350 75 5-8U>350 Consider cancelling surgery or consider using an insulin drip to

correct the glucose values.Table 1: Dose of insulin according to blood sugar


Strict Preoperative Control of Blood Sugar to an FBS of 200mg%is NOT Mandatory Before Elective Surgery________________________ Kalyan Chakravarthy

GENERAL GUIDELINES FOR DIABETIC PATIENTS ON THE DAY OF SURGERY13: Tab 1

For type I or type II diabetic patients on insulin therapy: Check blood glucose levels before surgery and use the following guidelines:

In conclusion, an important clinical lesson is that hyperglycaemia is the most important cause of long-term diabetic complications in both types of DM. The available methods of treatment of hyperglycaemia, is effective in achieving near normoglycaemia, which will lessen the morbidity, mortality and cost of management of diabetic complications.

REFERENCES:1. King H et al- Global burden of diabetes 1995-2025, prevalence, numerical estimates and projections. Diabetes Care 1998;21: 1414-31.

2. Ramachandran A, Snehalatha C et al - Diabetes Epidemiology Study Group in India (DESI), High prevalence of diabetes and impaired glucose tolerance in India: National Urban Diabetes Survey. Diabetologia 2001 ;44: 1094-101.3. Peter H. Bennett. Chapter 11; Diabetes definition and pathogenesis, Joslin’s Diabetes Mellitus - 13th Edn. Lippincott Williams and Wilkins 193-4, 2000.4. The Expert Committee on Diagnosis and Classification of Diabetes Mellitus.Diabetes Care 1997;20: 1183-97.5. Douglas B. Coursin, et al, Peri-operative care of the diabetic patient. ASA Refresher courses in Anesthesiology 2001 October; 29(1): 1-9.6. Ashok Kumar Das, TS Ashida. Impact of glycaemic control on complications Diabetes Mellitus- Chapter 46. RSSDI-Text book of Diabetes Mellitus, 1st Edn. 2002. 617-22.7. Minerva Anestesiologica. 67(4):258-62, 2001 Apr.8.European Journal of Anaesthesiology. 18(5):277-942001 May.9. Acta Clinica Belgica. 52(5):313-9, 1997.10. South African Journal of Surgery, 30(3);85-9,l!892 Sep.11. JAMA, 244(2): 166-8, 1980 July.12. Ronald D. Miller. Anesthetic implications of concurrent diseases, chapter 25; 5th Edition p-909.s13. Clinical Diabetes vol19, No2, 2001


Spinal Anaesthesia Is Contraindicated for Day Care Surgery 219 Elsa Varghese

The advent of newer short acting general anaesthetic drugs have made day care surgery a reality. Day care surgery involves short duration surgical procedures (not associated with significant alterations in the patient’s normal physiology) on relatively healthy patients. The improvement in surgical technique and the major advancements in anaesthesia drug research has resulted in a large number of medical centres performing the majority of surgical procedures on a day care basis.

In the recent past, the factor of economy has played a major role in increasing the popularity of providing regional anaesthesia for day care surgery. Spinal anaesthesia is being popularised by die-hard fans of this technique as the anaesthetic of choice for surgeries performed below the level of the umbilicus.

To those of us who have performed thousands of spinal anaesthetics and will continue to do so in the future, one may wonder why should there be any contraindication for surgery to be performed on a same day basis, under spinal anaesthesia. There are several reasons why, which this article will address.

COMPLICATIONS AND UNDESIRABLE SIDE EFFECTS OF SPINAL ANAESTHESIA

Complications and undesirable side effects associated with spinal anaesthesia require anaesthesiologists to balance potential risks against potential benefits. Everyday, anaesthesiologists are challenged to make clinical judgements as to the means and methods for ensuring the safety and comfort of their patients. In many cases the administration of spinal anaesthesia may be controversial. The relationship between perceived risk of potential

complications and administration of spinal anaesthesia is a need to be examined.1

Failure to Achieve Anticipated AnaesthesiaSpinal anaesthesia unlike general

anaesthesia is fallible! Even with modern techniques designed to enhance precision, regional anaesthesia may not completely meet the expectations of patients, surgeons or anaesthesiologists. The spectre of unreliability can prejudice its selection.

Informed Consent and Spinal AnaesthesiaWe are obliged to inform our patients of

the potential risks associated with spinal anaesthesia including local anaesthetic toxicity, haematoma, infection, cardiac arrest or death. Shivering, backache, dizziness and urinary retention are unpleasant side effects that may require disclosure.

Controversy of Hyperbaric Spinal LidocaineThe ideal spinal anaesthetic would

combine rapid and adequate surgical anaesthesia with rapid achievement of discharge criteria such as ambulation and urination. The most important determinant of both successful surgical anaesthesia and time until recovery is the dose of local anaesthetic.2

Ideally, local anaesthetics that have an appropriate duration of action with an acceptable side effect profile and the addition of adjuvants which add to the anaesthetic efficacy, without prolonged recovery need to be administered. Hyperbaric spinal lidocaine has long been the gold standard for short acting spinal anaesthesia. Lidocaine has an optimal onset and duration of action of anaesthesia for out-patients but also has the potentially unacceptable side effect of



transient neurologic symptoms (TNS).3 The incidence of TNS has been found to be highest in out-patients compared with in-patients and in patients undergoing surgery in the lithotomy position (30%) or knee arthroscopies (20%), under spinal anaesthesia.4

Reports of cauda equina neuropathy (CEN), persistent sacral nerve root irritation and unacceptable high incidence of transient neurologic symptoms (TNS) have forced a reappraisal of the safety of hyperbaric spinal lidocaine.

I) CAUDA EQUINA NEUROPATHY (CEN)Auroy et al reported 24 neurologic deficits

following 40,600 spinal anaesthetics.5 Nine of these occurred after lidocaine. CEN has been reported following repeated spinal administration, given to improve the density of a patchy or incomplete subarachnoid block.6

Since CEN can occur after uncomplicated single injections as well, the safety of hyperbaric spinal lidocaine has become controversial. There is mounting laboratory evidence supporting the possibility that a substantial risk exists for prolonged abnormal conduction when 5% Lidocaine is applied to simulated nerve roots.7

The threat of CEN and persistent sacral irritation and transient neurologic symptoms has certainly challenged the clinical decision to persist with providing appropriate spinal anaesthesia for day care surgery.

II) TRANSIENT NEUROLOGIC SYMPTOMS (TNS)

The term TNS is used to describe symptoms of backache with radiation into the buttocks or lower extremities. This syndrome is rarely seen after general anaesthesia and has been demonstrated after spinal anaesthesia. Hyperbaric heavy lidocaine is associated with an increased risk for TNS.8 The aetiology of TNS is unknown. Positioning (lithotomy and knee flexion), sacral stretch, pooling of hyperbaric spinal lidocaine following installation with small-bore pencil point needles have all been implicated as possible risk factors. TNS may occur post

operatively in 4-36% of patients undergoing hyperbaric lidocaine spinals. Alternative approaches for spinal anaesthesia especially for use in outpatients are prompted by the fear of possible neurologic effects of heavy lidocaine.2

ill) CONTROVERSY OF ALTERNATIVES TO HYPERBARIC SPINAL LIDOCAINE

Finding alternatives to hyperbaric spinal lidocaine has challenged clinicians. TNS has been reported with lower concentrations of lidocaine. The addition of epinephrine to isobaric spinal mixtures can increase the incidence of urinary retention.9

Spinal anaesthesia enthusiasts are now ‘dialling down’ the mass of local anaesthetic instilled. But unfortunately dose response data for alternatives such as bupivacaine is scant. There is renewed interest in isobaric and hypobaric alternatives. Laboratory studies suggest a comparative potency of bupivacaine to lidocaine of 9:1. Studies with 2% lidocaine (40mg and lower doses), as well as 0.5% hyperbaric spinal bupivacaine (7.5mg), though providing adequate duration of anaesthesia; have shown a discharge time often exceeding 3 hours for both drugs.1011

IV) MINI DOSE SPINAL ANAESTHESIALow dose lidocaine (20mg) or bupivacaine

6 mg with fentanyl has been advocated for day care spinals of late. Though these combinations may provide satisfactory analgesia and recovery profiles as described by some authors, these concentrations may not provide an immobile extremity during surgery.121314 Moreover, proprioception is preserved with this combination and therefore the patient has the unpleasant awareness of limb manipulation

Post-Dural Puncture Headache (PDPH)Although not a life threatening problem,

PDPH carries substantial morbidity by restricting activities of daily life. A recent survey of 75 consecutive patients suffering from PDPH revealed that approximately 18% had slight restriction of physical activity, 31 % were partially bedridden with restricted physical activity and 51% were entirely bedridden. Furthermore spontaneous resolution of PDPH takes 1 -6 weeks



after dural puncture thus resulting in frequent and prolonged restriction of daily activities.15

Because no effective non-invasive treatments exist, clinical strategies have focused on prophylactically reducing CSF lost after dural puncture. Traditionally, we have minimised needle size to decrease the size of the CSF leak in the dura, turned cutting needles longitudinally to prevent transverse cutting of longitudinally aligned dural fibres and selected pencil-point needles to maximize the parting and not cutting of dural fibres. Reina et al16 have questioned the concept of less trauma to the dura with pencil-point needles as their study observed similarly sized but more traumatic lesions to the dura with pencil- point needles compared with longitudinally aligned cutting tips.

Evaluation of Closed Claims Data BasesCheny et al17 examined closed claims

database of the American Society of Anaesthesiologists. Of 4183 claims, 16% were for anaesthesia related nerve injury. 84 claims were associated with spinal anaesthesia.

Sudden cardiac arrest during spinal anaesthesia is a significant cause of risk in current medical practice. Interestingly they have been reported in young men undergoing short surgical procedures, where the cardiac arrest occurred almost 30 to 40 minutes following the administration of the spinal anaesthetic. 41 well- documented cases of cardiac arrest have been reported, in which a circulatory mechanism played the primary role in sudden cardiac arrest during spinal or epidural anaesthesia. These arrests were vagal linked or associated with vagal- inducing stimuli like traction, movement, fear and athletic heart syndrome.

Intra-operative cardiac arrest analysis in a prospective study by Biboulet18 suggests that risks and outcomes may be less favourable under conditions of spinal anaesthesia than general anaesthesia. There is persuasive evidence that this phenomenon can occur unexpectedly under conventional conditions of practice and that the associated injury can be very severe.

More so in a situation of day care surgery where there is a rapid turnover and the anaesthetist is under stress to run a schedule in a hurried manner.

BARRIERS TO THE PRACTICE OF SPINAL ANAESTHESIA IN AMBULATORY SURGERY

In ambulatory surgery the use of spinal anaesthesia is subject to the same risk benefit analysis that applies to any anaesthetic technique. There are absolute and relative contraindications.

Patient SelectionSpinal anaesthesia involves very careful

patient selection, the careful positioning and preparation of the patient, introduction of a needle into the subarachnoid space and injection of a local anaesthetic with or without an adjuvant drug and the need to wait for the onset of action of the drug. The possibility of a patchy effect of the block is a reality. The knowledge and expertise in dealing with untoward physiological effects of the block are required. Often, for day care surgery, general anaesthesia has been the preferred anaesthetic of choice mainly for convenience of fast turn overtime and therefore maintaining the hectic OR schedule in a busy day care set up.

Patients are still anxious about being awake during a surgical procedure and more so in the day care setting where premedicant anxiolytic drugs are used minimally. So it is crucial to pick the right patient as inappropriate patients or patients with great anxiety, needle phobia, poorly controlled psychiatric disease or language barriers, are all potentially difficult situations, where though the spinal anaesthetic may provide the analgesia, the patient remains extremely restless and anxious throughout. These patients may require deep sedation, which then defeats the advantages of the technique.

An increasing number of patients are on anti platelet drugs, as the concern for deep vein thrombosis is on the rise. These medications pose an additional risk for spinal anaesthesia and an in-depth information of the medications the patient is on is essential.

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Picking the Wrong SurgeonSurgeons must be willing to wait a few

minutes for the onset of action of the block and the choice of spinal anaesthesia may be inappropriate in the outpatient setting when a large number of patients have been scheduled and you have an impatient surgeon on hand.

Picking the Wrong SurgeryPelvic Laparoscopy is a common

procedure performed on a day care basis involving carbon dioxide pneumoperitoneum and steep Trendelenburg. When these procedures are performed under spinal anaesthesia, shoulder tip pain (irritation of the diaphragm) and ascent of spinal level (steep Trendelenburg) are troublesome complications which can occur.

Discharge CriteriaPatients undergoing spinal anaesthesia

need to meet additional discharge criteria before being sent home. As yet there are still no clear- cut guidelines for patient discharge criteria following spinal anaesthesia in ambulatory surgery and they are still being evolved. The ability to void is an important discharge criterion that results in a significant delay in patient discharge after resolution of spinal anaesthesia.19,20

The patient should also be able to stand unaided, walk in a straight line and stand still without swaying. These additional tests would pose an additional strain on recovery room staff especially in a busy day care set-up.

GENERAL ANAESTHESIA FOR DAY CARE SURGERV

Newer anaesthetics have the pharmacokinetic and pharmacodynamic advantages of a shorter duration of action and a more rapid rate of recovery. These factors permit a faster emergence from anaesthesia. Less than 30 years ago, it was unthinkable that patients would be able to return home on the day of surgery. Today, advances in surgery and anaesthesia make it possible to perform surgery safely and effectively on an ambulatory basis.21

With newer agents, propofol, remifentanil, sevoflurane, rapid recovery of patients undergoing anaesthesia permits a patient to be shifted

directly from the operating room to a second stage recovery room and not necessarily the post anaesthesia care unit where nursing care is intensive.

CONCLUSION

Given the uncertainty, along with the time constraints under which day care anaesthesia has to be provided, there has to be a rethink on pushing for the increased use of spinal anaesthesia in the day care setting. There are too many variables out of our control, which does not make it the suitable anaesthetic technique of choice in day care anaesthesia.

REFERENCES

1. Gilbert HC: Complications and controversies in regional anaesthesia. ASA Refresher Course lectures October 2002: No 1232. Liu SS, McDonald SB: Current Issues in Spinal Anaesthesia. Anesthesiology 2001; 94:888-9063. Pollock JE, Neal JM, Stephenson CA et al: Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anaesthesia. Anesthesiology 1996; 84:1361-74. Freedman JM, Li DK, Drasner K, et al: Transient neurologic symptoms after spinal anesthesia. Anesthesiology 1998; 89:1633-415. Auroy Y, Narchi P, Messiah A, et al. Serious complications related to regional anesthesia. Results of a prospective survey in France. Anesthesiology 1997; 87:469-726. Rigler M, Drasur K, Krejue TC et al: Cauda equina syndrome after continuous anesthesia. Anesth Analg 1991; 72:275-817. Lambert L, Lamber D, Strichartz GR: Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology 1994; 80:10828. Hiller A, Kearjalainen K, Balk M, et al: Transient neurological symptoms after spinal anaesthesia with hyperbaric 5% lidocaine or general anaesthesia. Br J Anaesth 1999; 82:575-99. Chiu A, Liu S, Carpenter RL, et al: The effects of epinephrine on lidocaine spinal anesthesia, a crossover study. Anesth Analg 1995; 80:735-910. Hampi KF, Heinzmann-Wiender S, et al: Transient neurologic symptoms after spinal anesthesia. A lower incidence with prilocaine and bupivacaine than with lidocaine. Anesthesiology 1998; 88:629-3311. Urmey WF, Stanton J, et al: Combined spinal- epidural anesthesia for outpatient surgery. Dose response characteristics of intrathecal isobaric lidocaine using 27 gauge Whitacre spinal needle. Anesthesiology 1995; 83: 528-3412. Ben David B, Mayarsky M, Gurevetch A et al: Comparison of mini dose lidocaine -fentanyl and conventional dose lidocaine spinal anesthesia. Anesth Analg 2000; 91:856-70



13. Casati A, Fanelli G, Cappelleri G, Berglin B, et al: Low dos£ hyperbaric bupivacaine for unilateral spinal anesthesia. Can J Anesth 1998; 45:850-5414. Ben David B, Solomon E, et al: Intrathecal fentanyl with small dose dilute bupivacaine; better analgesia without prolonged recovery. Anesth Analg 1997; 85: 560-515. Lybecker H, Djernes M, Schmidt JF: Post dural puncture headache (PDPH): onset, duration, severity and associated symptoms: an analysis of 75 consecutive patients with PDPH. Acta Anaesthesiol Scand 1995; 39:605-1216. Reina MA, de Leon-Casasola OA, Lopez A, et al: an in vitro study of dural lesions produces by 25 gauge Quinke and Whitacre needles evaluated by scanning electron microscopy Reg Anesth Pain Med 2001; 25:393- 403

17. Cheny FW et al: Standard of care and anaesthesia liability. JAMA 1989; 261: 1599-160318. Biboulet P: Fatal and non-fatal cardiac arrest related to anesthesia. Can J Anesth 2001; 48:326-3219. Marshall SI, Chung F: Discharge criteria and complications after ambulatory surgery. Anesth Analg 1999; 88:508-1720. Kamphuis ET,lnonescu Tl, Kuipers PW, et al: Recovery of storage and emptying function of urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men. Anesthesiology 1998; 88:310-621. Lichter JL, Wetchler BV: Outpatient anesthesia, Clinical Anaesthesia, 3rd Edition. Edited by Barash PG, Cullen BF, Stoelting RF, Philadelphia, JP Lippencott Co 1997, pg. 1389-1412


Spinal Anaesthesia is not Contraindicated for Day Care Surgery Rathna.N.

It is 103 years since the first spinal anaesthetic was administered by Bier in August 1898 in Kiel, Germany. Spinal anaesthesia for a procedure that in many institutions would nowadays be managed on an outpatient basis was reported by Matas in December 1899.1 In spite of the widespread development of ambulatory surgery, there has been relatively little critical evaluation of the role of spinal anaesthesia in outpatients. ‘

Over the past 20 years, the most dramatic change in the delivery of surgical care in the United States has been the shift from inpatient to outpatient and short-stay surgical procedures. Ambulatory surgery in the 1990s, with its demonstrated efforts at cost containment has been enthusiastically accepted by all segments of,health care. Consequently, 65% of all surgical procedures are outpatient based and 35% are in-patients, which in turn has had an impact on the manner in which both surgeons and anaesthesiologists practice.2

“What is an ideal outpatient Anaesthetic”?An ideal outpatient anaesthetic should

provide a safe, simple technique with a quick start (onset of action), rapid stop (offset of effects), minimal postoperative side effects with residual analgesia in the postoperative period. Can spinal anesthesia provide all these? “YES” with selective Spinal anaesthesia.

Why do we think conventional Spinal anaesthesia is contraindicated in ambulatory Surgery?

It is because of the belief and fact that Conventional Dose Spinal Anaesthesia (CDSA)

involves a technique that initiates a block lasting long, with a long time to recovery. Since the time of conventional technique to now, with the better understanding of neurological anatomy, physiology, molecular pharmacology and receptor pharmacology and devices, we have embarked into an era of precision where “selectivity” is the rule with excellent results and benefits, with minimum side effects, which has resulted in a practice of a changed spinal anaesthesia, while exploiting the good aspects of it and succeeding in making it “walk in and walk out” technique for ambulatory surgery.

Professional concernsA survey of 3,651 anaesthetists revealed

that 68 % would choose regional anaesthesia for their own surgery.3 Among the reasons given were ease of administration, fewer complications, pleasant recovery, good operating conditions and less difficulty in the recovery room. More recently, 91 % of anaesthetists who experienced both spinal and epidural anaesthesia expressed a preference for regional anaesthesia.4 Thus, there appears to be a “double standard” within the profession which has lead to pleas that anaesthetists treat their patients as they themselves would like to be treated. Interestingly, 50% of outpatients are afraid of not waking up after anaesthesia. Even though patients’ main preferences are mental clarity and freedom from emesis, pain, dysphoria and myalgias, there is evidence to indicate that administration of general anaesthesia leads to these very problems which may persist for up to 28 days postoperatively.5 Patients’ attitudes towards regional anaesthesia is either favorable(46%) or indifferent (45%), and their main fears are needle pain, backache, seeing and


Spinal Anaesthesia is not Contraindicated for Day Care Surgery 225 Rathna.N.

hearing things, paralysis and the possibility of failure. Thus , a majority of patients would be amenable to regional techniques.

Spinal anaesthesia is not contraindicated for day care surgeries

Regional anaesthesia like spinal and epidural anaesthesia can offer many advantages for the ambulatory patients. In addition to limiting the anaesthetized area, the common side effects of general anaesthesia like nausea, vomiting, dizziness, lethargy etc can be avoided.6 It is said that patients with GA are either “sore, sick or sleepy”. Furthermore, the risks of aspiration, pneumonitis and other side effects of tracheal intubation are avoided. Other advantages include decreased post-operative intensity of care, decreased recovery times, increased mobility, (and) increased post-operative alertness7 and postoperative analgesia. Recently published outcome data have suggested that patients undergoing spinal / epidural anaesthesia alone or combined with general anaesthesia may actually have decreased morbidity and mortality when compared to patients undergoing general anaesthesia alone.8

Minor morbidity, patient satisfaction and costThere are few well-structured

comparisons of regional and general anaesthesia in outpatients. Although general anesthesia continues to be offered as the anaesthetic of choice to most outpatients, its role is being questioned. It is now becoming apparent that minor morbidity is of serious concern. The reported incidence of minor symptoms after outpatient propofol- based general anaesthesia were: hoarse voice (26%), sore throat (24%), headache (10%), backache (20%), emesis (12%), loss of appetite (18%), anxiety (12%), tiredness (28%), delayed recovery of normal function (37%) and postoperative pain (55%).6 A randomised comparison of spinal and general anaesthesia in 433 patients revealed that general anaesthesia was associated with a higher incidence of nausea and vomiting, sore throat, a longer stay in the recovery room with an increased need for opioids, and increased cost.9 Other studies have confirmed a shorter discharge time and decreased cost after spinal anaesthesia. Finally, studies of spinal anaesthesia in outpatients consistently demonstrate that patient satisfaction remains high (>90%).10

Should we abandon conventional dose spinal anaesthesia (CDSA) in outpatients?

A comparison of GA (propofol) and CDSA (15 mg bupivacaine) showed that 180 min after surgery, 15% of GA patients fulfilled home discharge criteria but none of the CDSA patients were able td walk due to residual motor block11. Recently, Vaghadia et al ^demonstrated that small-dose spinal lidocaine was associated with shorter discharge times than CDSA. They have remarked thatthere is a price to be paid for CDSA and the data also revealed what some of us may have suspected - propofol GA may not be the panacea for outpatients. The large standard deviations seen with GA reflect large inter-patient variability depending on whether postoperative complications such as emesis and pain develop, and delay discharge. Interestingly, the short acting spinal anaesthetics have small standard deviations and this suggests that their use will be associated with a more predictable discharge profile, particularly when they are employed with small dose techniques.12

So, conventional dose spinal anaesthesia may not be suitable for routine use in outpatients and anaesthetists need to familiarise themselves with techniques that are associated with a rapid recovery profile.

SELECTIVE SPINAL ANAESTHESIA (SSA)

Definition“ The practice of employing minimal

doses of intrathecal agents so that only the nerve roots supplying a specific area and only the modalities that require to be anaesthetised are affected.”

Drugs used:

LOCAL ANAESTHETICS:

LIDOCAINE:

Investigators have assessed various doses, baricity and concentration. The quality of block, maximum block height and duration are summarised in Table -I. Adjuvants such as fentanyl and sufentanil facilitate reductions in the dose of lidocaine and prolong the sensory block without delaying time to void. In addition, they improve tolerance to visceral sensations such as bladder distension and peritoneal stretch. Addition of



Solution Block Height Quality of motor block Durationf min)5% lidocaine (1.5 ml) in dextrose7.5%,hyperbaric

t6 Good 130

1.5% lidocaine plain (3.3 ml) Isobaric

t6 Good 100

1.5% lidocaine (5 ml) in dextrose7.5%hyperbaric

T< Good 150

1% lidocaine (2.5 ml) + fentanyl (0.5ml), hypobaric

t8 Good 60

0.5% lidocaine in saline (5 ml) isobaric

T,o Good 30

0.5% lidocaine in water (8 ml) hypobaric

T,0 Not specified 116

1% lidocaine(1 ml)+ sufentanil (0.2 ml),+ water (1.8 ml) hypobaric

t5 Nil 30

Table I. Characteristics of spinal anaesthesia with various doses of Lidocaine

epinephrine prolongs sensory analgesia by about 30 min but prolongs time to void by up to 80 min. As the dose of lidocaine is reduced to < 25 mg modalities such as light touch and proprioception will be preserved, but pin prick analgesia will still occur. With a dose < 10 mg, there will be no motor block and patients will be able to perform deep knee bends immediately after surgery lasting < 30 min. Thus, patients and surgeons need to be aware of such selectivity and dosages should be tailored for the procedure and the surgeon depending on the requirements.

BUPIVACAINE1314

For longer outpatient procedures bupivacaine may be preferable. Dose response characteristics are better defined for hyperbaric bupivacaine and are summarised in Table 2. In the supine position, hyperbaric solutions spread more cephalad than hypobaric and isobaric

solutions. Weak solutions (0.1%) prepared by mixing plain bupivacaine with sterile water, provide selective sensory block for perineal procedures

OPIOIDSMEPERIDINE 15’16

Preservative free meperidine 5% has been used as a sole spinal anaesthetic for urological, gynaecological and orthopaedic procedures. A dose of 0.5-1 mg.kg1 is associated with an onset time of four to eight minutes and a duration of sensory and motor block of 80-100 min. Duration of postoperative analgesia is about 3.5 hr. Motor block will only occur in 70% of patients with plain meperidine but addition of local anaesthetics will increase this to 100%. Lower doses can be used for selective spinal block. A dose of 1 mg. kg1 is associated with plasma concentrations one third to one sixth those reported to produce respiratory depression and a

Variable Duration per mg spinal bupivacaine (min)Duration of Sensory block at:Ankle 15Knee 13Pubis 7Umbilicus 5Duration of Motor block at:Quadriceps 10Gastrocnemius 6Duration of tolerance to thigh tourniquet 7Time to achieve discharge criteria 21

Table 2. Duration of sensory and motor block per milligram of Spinal bupivacaine



plasma T1/2 p of five hours. A small dose (10mg) of intrathecal meperidine is equivalent to sufentanil (5 ng) or fentanyl (10 jig) and provides analgesia for approximately 60-90 min.

LIPOPHILIC OPIOIDS LIKE FENTANYL AND SUFENTANIL

These have a more favorable clinical profile of fast onset (minutes) modest durations(1 -4 hours), and little risk of delayed respiratory depression.17 Compared to sufentanil, fentanyl is less lipid soluble and will maintain modest spinal selectivity when injected intrathecaliy.18 Addition of fentanyl to spinal anaesthesia produces synergistic analgesia for somatic and visceral pain without increased somatic block.17 In addition, it decreases the baricity of the local anaesthetic solution and may alter the distribution of agents in the CSF. Studies suggest that spinal fentanyl alone provides dose-dependent analgesia with a minimally effective dose of approximately 10|ag with risk of early respiratory depression occurring in doses greater than 25^g19. Hence the best risk-benefitdose range would be addition of 10-25ng of fentanyl. Numerous studies have shown that addition of fentanyl, allows use of less local anaesthetic and does not prolong duration until discharge.20

oc2- ADRENERGIC AGONISTSClonidine is the best characteristized

a2 adrenegeric agonist which provides dose dependent analgesia and causes side effects like hypotension, bradycardia and sedation . It is not associated with side-effects of spinal opioids like respiratory depression and urinary retention.21 Clonidine attenuates nociceptic input from A and C fibers and acts synergistically with spinal local anaesthetics.22 Oral clonidine has almost 100% bioavailability as it is well absorbed and may be a useful premedication for sedation,sympathetic attenuation and augmentation of ambulatory spinal anaesthesia. A dose of 150-200fig oral

clonidine administered 1-3 hrs before spinal anesthesia can augment sensory and motor block without delaying achievement of discharge criteria.23 Spinal clonidine in a dose of 15-45ng is an optimal dose which has been shown to improve anaesthetic success of 8 mg ropivacaine from 60% to 100% for ambulatory knee arthroscopy without prolonging recovery.24

Adjuvant techniquesINTRATHECAL 12’19’20

Epinephrine and opioids (fentanyl and sufentanii) are common adjuvants added to intrathecal local anaesthetics. Epinephrine 0.2 mg prolongs lidocaine and bupivacaine spinal anaesthesia by approximately 30 min but delays time to voiding by 50-80 min. Fentanyl 20-25 ng prolongs lidocaine and bupivacaine sensory block by 30 min without effect on motor block or bladder function. The onset of fentanyl effect is within four minutes and dose response data are summarised in Table 3. There appears to be little benefit above a dose of 40 fig. Sufentanil (10fig) provides pin prick analgesia for 30 min. Dose response studies in volunteers suggest that there is no additional benefit to using doses larger than 12.5|ag. The mean residence time in CSF is one hour. A dose of 10(ag sufentanil prolongs bupivacaine analgesia by 60 min. Recently, sufentanil alone has been found to provide satisfactory anaesthesia for minor outpatient procedures such as extracorporeal Shockwave lithotripsy. Clinically important respiratory depression after single doses of intrathecal fentanyl and sufentanil has not been described. At Vancouver General Hospital, experience with >100 outpatients who received either intrathecal fentanyl or sufentanil as adjuvants for spinal anaesthesia during outpatient laparoscopy, respiratory depression was not seen. However, the incidence of mild but self-limiting pruritus may be 60-70%. Reassurance and intravenous

Fentanyl dose pg Duration of analgesiaMin

5 3010 6020 12040 30050 300

Table 3. Duration of analgesia after intrathecal fentanyl



TABLE IV Increase in level of spinal analgesia 10 min after systemic administration of opioidsSystemic opioid dose Increase in Level of spinal block (cm)

Fentanyl:50ng 2100ng 3150wg 4

Nalbuphine:10 mg 215 mg 320 mg 4

Table 4. Increase in level of spinal analgesia 10min after systemic admistration of opioids

diphenhydramine are preferable to naloxone because of the risk of reversing opioid analgesia. SYSTEMIC25

Systemic opioids enhance the spread of sensory analgesia produced by intrathecal local anaesthetics. This effect is dose dependent (Table 4) and naloxone reversible and may be clinically useful when a spinal block appears to be dissipating before completion of surgery. Regression of sensory but not motor block is also delayed by systemic opioids.

Oral clonidine also prolongs the action of spinal local anaesthetics. A dose of 0.2 mg clonidine po 1.5 hour before spinal anaesthesia prolongs motor and sensory block with lidocaine by about 30 min. However, the incidence of sedation is 50% and patients develop a slight decrease in systolic blood pressure (13 mmHg) and heart rate (13 beats-min1)

Inhalation of nitrous oxide 50% for 10 min increased the level of sensory block with spinal lidocaine by 2 cm compared with baseline and in a net benefit of 5 cm when compared with a control group breathing nitrogen 50%.

Thus, anaesthetists unfamiliar with low dose spinal techniques may take comfort from the fact that systemic administration of opioids, clonidine and nitrous oxide may help to “stretch out” a spinal in the event of unanticipated delays with surgery.

New techniquesDosage is more important than

concentration or volume with respect to spread of spinal anaesthesia particularly when solutions

have the same baricity. Posture should be used to control the spread of hypobaric and hyperbaric solutions. Large volumes (> 6-8 ml) of weak solutions will result in high blocks (>T^ and hypotension. Hypobaric solutions produce less motor block and less hypotension. In the supine position, hyperbaric solutions spread further cephalad than isobaric and hypobaric solutions due to the anatomical configuration of the lumbar spine.26 New techniques focus on the use of lower doses of intrathecal agents with or without intrathecal or systemic adjuvants. The main aim is to provide spinal anesthesia with greater precision and selectivity so that return of function occurs rapidly.

A. CURRENT CONCEPTS:1. Newer needles

Introduction of small gauge pencil point spinal needles like Whitacre side-port, Sprotte’s and Green pencil point, has reduced the risk of postdural puncture headache [PDPH] to approximately 1%27, few failed blocks, a low incidence of backache and high patient acceptance. Hence, the use of spinal anaesthesia for ambulatory surgery has become more popular. To minimize the CSF leak in the dura, smaller gauge needles with longitudinal cutting bevels have been developed which prevent transverse cutting of longitudinally aligned dural fibres and pencil-point needles to maximize the parting and not cutting of the dural fibers. Other reasons to use pencil-point needles include fewer manufacturing flaws, less susceptibility to tip damage after bony contact, and less likelihood of deposition of tissue cores into CSF than cutting needles.28



2. Drugs- Local Anaesthetics:A. LIDOCAINE: Spinal lidocaine has long been a popular choice for ambulatory spinal anaesthesia. Although it has enjoyed a long history of safety and popularity since its introduction in 1945, it has come under recent scrutiny because of transient ‘neurologic symptoms [TNS], which has shown to be clearly associated with the spinal lidocaine, with an approximate incidence of 20% in the ambulatory setting.29

B. BUPIVACAINE: TNS is virtually absent in all clinical studies with spinal bupivacaine. Recent studies indicate that small doses [<1 Omg] can be used for ambulatory anaesthesia with time until discharge comparable to lidocaine.30

C. ROPIVACAINE: It is a new local anaesthetic released in the USA in 1996, which is lipid soluble and is approximately 50-60% as potent as spinal bupivacaine with little risk of TNS. Studies have shown that equipotent doses [2:1] of ropivacaine have similar recovery times as bupivacaine.31

D. PRILOCAINE: It is an amide local anaesthetic with pharmacologic properties similar to lidocaine. Recent studies suggest that prilocaine is approximately equipotent to lidocaine with a dose range of 40-70mg and thus may have suitable characteristics for ambulatory spinal anaesthesia with minimal risk of TNS.32

3. Combined Spinal- Epidural Anaesthesia [CSEA]

Has become increasingly popular as its advantages include rapid onset, profound neuraxial block, the ability to titrate or prolong blockade, and lower total drug dosage. Various techniques have been described and technology has provided multiple needle configurations like:

1. Needle through-needle technique

2. Eldor “double barrel” needle

3. Hanaoka “back eye” needle4. Coombs needle.

Availability of the epidural catheter for a rescue anaesthetic allows use of marginal doses of spinal local anaesthetic with resultant rapid recovery and discharge and represents an alternative or complimentary strategy to use of

analgesic additives. However, induction of a CSEA technique probably takes more time than conventional spinal anesthesia, and no current data are available to assess relative cost benefit of increased induction time versus decreased recovery time with CSEA.33

4.. Continuous Spinal Anaesthesia [CSA]The continuous spinal anaesthetic

technique is regaining acceptance in the anaesthesia community. Various needle and catheter designs are available for CSA. Microcatheter (< 24G) and epidural needles and macrocatheters (18-22G) can be used. Newer kits provide an over- the- needle method in which the smaller gauge spinal needle acts as a guide over which the larger gauge catheter ''an be introduced. This needle was designed to reduce the risk of PDPH by not promoting CSF leak. The incidence of PDPH with this technique is 0- 3%.34

One of the advantages of CSA over conventional spinal anaesthesia is the ability to titrate local anaesthetic doses. This slow titration is particularly beneficial in the haemodynamically unstable patient, such as in the elderly or in those with valvular heart disease or trauma.35,36 A number of clinical studies have compared CSA with conventional spinal anaesthesia, demonstrating fewer episodes of hypotension and lesser need for vasopressor with CSA. Another advantage of CSA is the ability to prolong anaesthesia for long surgical cases or even for postoperative analgesia. The ability to use lower anaesthetic doses can lead to faster recovery times, and thus CSA may have applicability to the ambulatory setting, especially in the elderly who are less prone to PDPH.37

TECHNICAL CONSIDERATIONSRecently, it has become apparent that

the pattern of innervation of muscles and deeper structures does not conform strictly to the overlying dermatomes. It has been shown that traditional assumption of a spinal block up to T10 being a prerequisite for urological surgery may not be correct and a mid-lumbar(>L1) level is quite adequate for TURP if bladder pressure is kept <15 mmHg. Systemic adjuvants may also help to improve the adequacy rate of such low block techniques.

The injection rate through a non-cutting



needle (Whitacre) also determines the block height achieved and is important when using low dose techniques. A fast injection rate (0.5 ml.sec-1) results in a greater cephalad spread of spinal anaesthesia (approximately three to four segments) than a slow injection rate (0.02 ml.sec*1).

Continuous spinal anaesthesia with microcatheters would appear a logical method of facilitating selective spinal anaesthesia in outpatients while leaving open the option of further “top ups” as required. An alternative approach is to administer combined spinal-epidural anaesthesia (CSE) with the minimal intrathecal dose required for surgery and utilize the epidural route for back up as necessary. Using a 40 mg initial dose of 2% lidocaine for outpatient arthroscopy, CSE was found to be a reliable technique and was associated with earlier recovery and discharge. Only 10% of patients required intra operative epidural supplementation.

DISCHARGE CRITERIA:Using the newer techniques of spinal

anaesthesia, the patient’s recovery is hastened and the patient can be directly shifted to the step- down recovery by bypassing the Post Anaesthesia Care Unit (PACU). This process is known as “fast tracking” after ambulatory surgery.38lf the patients are awake and oriented in the OR, transfer of these patients directly to the step down unit (Fast tracking) is recommended. The criteria are awake, oriented patients, stable vital signs, minimal pain or bleeding, minimal nausea and vomiting, complete reversal of neuromuscular agents, and oxygen saturation of >94% on room air or resumption to baseline levels. In countries where most or all of the hospital costs are borne by the insurance companies, it results in a significant saving because the major determinant of PACU costs is personnel.39

After spinal anaesthesia, the outpatients must meet the same discharge criteria as patients recovering from general anaesthesia like stable vital signs, ambulation with or without support; no or minimal nausea and vomiting, minimal pain and minimal surgical bleeding.40 In addition, these patients should have prior to ambulation, normal perianal (S4-S5) sensation, the ability to plantar

flex the foot, and proprioception of the big toe as also the ability to void i.e., recovery of sensory, motor and sympathetic nervous functions.40 Patients may be discharged earlier if voiding is not a discharge requirement; however there must be appropriate measures in place if the inability to void persists after discharge.41

POSTOPERATIVE PAIN AND EMESISTwo of the most common problems seen

in the ambulatory surgery patient are pain, and nausea and vomiting. Opioids (e.g., fentanyl, Demerol, morphine) are still the most common and effective method of treating acute, moderate to severe postoperative pain.

Perhaps, as troubling as postoperative pain, is the occurrence of postoperative nausea and vomiting (PONV). For the most susceptible patients (patients with previous history of nausea/ vomiting, motion sickness, women in the luteal phase of the menstrual cycle), prophylactic antiemetic therapy should be considered. The type of surgical procedure also influences PONV; specifically, strabismus repair, laparoscopy, middle ear surgery and orchidopexy are all associated with a relatively high incidence of postoperative vomiting. Despite significant improvement in the pharmacological management of PONV, single drug treatment is not completely effective. However, a multimodal approach has proved successful, including a 92% complete treatment achieved with a combination of droperidol and ondansetron.42 Regional anaesthesia is proven to be associated with a minimal incidence of nausea and vomiting, thereby ameliorating the need for therapeutic interference with drugs.

A LOOK INTO THE FUTURE 43

Experience with new techniques has opened up the possibility of providing “walk-in walk-out” spinal anaesthesia with a real possibility of fast tracking outpatients through the recovery process. Current research is aimed at evaluating the feasibility of bypassing the recovery room after selective spinal anaesthesia (SSA). It has also become apparent that traditional assumptions about the sequence of return of neurological function after spinal anaesthesia (sympathetic, pinprick, motor and finally



propioception) may not apply with SSA. Experience with SSA has demonstrated that pinprick analgesia suitable for surgery can be provided while light touch, proprioception, motor and sympathetic functions are preserved.

CONCLUSIONAmbulatory anaesthesia is continuing to

evolve and has become a recognized anaesthesia subspeciality as more and more surgeries are being performed on an outpatient basis. Ambulatory surgery today represents a new challenge for the anaesthetist as the focus has been shifted and the bottom line is: cost containment and competitive quality care. Spinal anaesthesia with low dose local anaesthetics and analgesic additives provide the double advantage of faster recovery of the central neuraxial blockade and also good postoperative analgesia. New local anaesthetics, analgesic additives, and techniques are being investigated for different applications as the practice of medicine focuses on outpatient care. Safety of spinal agents and complications from spinal anaesthesia continue to be examined and reexamined to improve safety.

With the aforesaid insights into spinal anaesthesia, like• Selective Spinal anesthesia• Modification of techniques - hypobaric and

low dose, adjuvant narcotics• Finer pencil point needles, with an almost

non existent PDPH and• Opportunity for fast tracking the patients• Good post operative analgesia• NoPONV• High acceptance

“ Is Spinal Anaesthesia Contraindicated in Outpatient Surgery”?The answer is a Definite “NO”

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34 clonidine prolongs lidocaine spinal anesthesia

35 Anaesthesiology 1995;82:1353-1359.

36 Dekock M, Gautier PE, Intrathecal ropivacaine and clonindine for 37 ambulatory knee arthroscopy : A dose response study (abstract).

38 Anaesthesiology 2000;93:A6.

39 Sarantipoulos C, Fassoulaki A, Systemic opioids enhance the spread of sensory

40 analgesia produced by intrathecal lidocaine . Anesth Analg 1994;79:94-7.

41 Vaghadia H, Spinal anesthesia for outpatients Controversies and new

42 techniques. Can J Anes.1998;45:R64-R50.

43 Halpan S, Preston R: Post dural puncture headache and spinal needle design:

44 Metganalysis. Anesthesiology 1994; 8:1376- 1383.

45 Greenberg CP, Walit A, Roth JM: Costconscious anesthetic choice for

46 ambulatory surgery (abstract), Anaesthesiology 1994; 81:A1202.

47 Freedman JM,Lid K, Drasner K, Jaskela MC, Larsen B, Wis: Transient

48 neurologic symptoms after spinal anesthesia: An epidemiologic study of 1863

49 patients. Anesthesiology 1998: 89:633-641.

50 Kamphuis ET, Jonscu Tl, Kuipers PW, de Grier J, van vennooij GE, Boon TA:

51 Recovery of storage and ing functions of the urinary bladder after spinal

52 anesthesia with lidocaine and with dupivacaine in men. Anesthesiology 1998;

53 88:310-6.

54 Gautier PF, Dekock M, Vansteenberge A: Intrathecal ropivacine for ambulatory

55 surgery: A comparison between intrathecal dupivaciane and intrathecal

56 ropivacaine for time arthoscopy Anesthesiology 1999; 91:1239-45.

57 Hampl KF, Heinzmann-Weidmen S, Lugmin buch I, Seeberger M, Schneider

58 MC, Drasner K: Transient neurologic sysmptoms after spinal anesthesia: A lower



incidence with prilocaine and bupivacaine than with lidocaine. Anesthesiology 1998; 88:629-33.

59 Liu SS, McDonald SB. Current Issues is spinal Anesthesia. Anesthesiology

60 2001;94:888-906.

61 Muralidhar V, Kaul HL .Mallick P: Over the needle versus microcatheter through needle technique for continuous spinal anesthesia: A prelimnary study.Reg Anesth Pain Med 1999;24:417-21.

62 Collard CD, Eappren S, Lynch EP, conception M: Continuous spinal anaesthesia with invasive hemodynamic monitoring for surgical repair of the hip in 2 patients with severe aortic stenosis Anesth Analy 1995;81:195-198.

63 Wilhelm S, Standi T, Burmeister M, Kessler G, Schulte am Essch J: Comparison of

continuous spinal- epidural anesthesia using plain bupivacaine 0.59% in trauma patients . Anaesth Analg 1997; 85:69-74.

64 Favarel-Garrigues JF, Sztark F, Petitjean MF, Thicoipe M, Larsic P, Dauadic

P:Hemodynamic effects of spinal anesthesia in the elderly: Single dose versus titration through a cather. Anaeth. Analg 196; 82:312-6.

65 Lubarsky DA: Fast track in the post anesthesia care unit:Unlimited possibilities? J Clin Anesth 1996; 8:705.

66 Dexter F, Tinen JH: Analysis of strategies to decrease post anesthesia care unit costs. Anaesthesiology 1995; 82:94.

67 Chung F: Are discharge criteria changing? J Clin Anesth 1993; 5:645.

68 Chung F: Discharge criteria: A new trend. Can J Anaesth 1995; 42:1056.

69 McKenzie R, Lim Uy NT, Riley TJ, Hamilton DL. Droperidol/Ondensetron combination controls nausea and vomiting after tubal ligation. Anesth Analg 1996;83:1081-3.

70 Viskari D.Berril A,Vaghadia H. Walk-in walkout spinal anaesthsia for outpatient laparoscopy: evalution of hreehypobaric solutions. Can J Anaesth 1997; 44: A26-B.


DEBATE

Invasive Monitoring in ASA III and ASA IV patientswill Influence the Outcome of Surgery._______________ 234 Ashok Badhe

The role of Invasive Monitoring in ASA III and ASA IV patients for surgery is quite established by now. Invasive monitoring is quite routinely practsiced in these patients. To single out the influence of invasive monitoring on the outcome of surgery is quite difficult. The outcome of surgery in these groups of patients is influenced by a variety of factors. The factors influencing the outcome of surgery can be broadly categorized as:

1) The patient’s disease2) The Surgery3) Anaesthesia.

The perioperative variables also interact with each other and it is quite difficult to separate the contribution of each to perioperative morbidity and mortality and the postoperative outcome.

To recapitulate (ASA III and IV patients)

ASA classification:1) ASA III - A patient with a severe systemic

disease that limits activity but is not incapacitating.

2) ASA IV - A patient with an incapacitating systemic disease that is a constant threat to life.

The role of monitoring during surgery is not questioned by anybody in the present anaesthesia practice. The basic purpose of monitoring is to help us to know the haemodynamic status and also to guide us about the therapeutic measures to be taken to correct the derangement. Most of the haemodynamic parameters can be monitored by noninvasive techniques, but one must keep in mind the limitations of these techniques in patients of ASAIII and ASA IV. The focus is on this subset of

patients. One must keep in mind that these patients need more intensive and more or less continuous and accurate monitoring which cannot be achieved by noninvasive monitoring techniques. For example, pulse oximetry, one of the most commonly used, and quite useful monitor, can be affected by hypotension, hypothermia and peripheral vasoconstriction which are quite commonly seen in ASA III and ASA IV patients undergoing major surgery.

VARIOUS INVASIVE MONITORING TECHNIQUES : employed during the perioperative period are:

i) Urine output monitoringii) Invasive Arterial Blood Pressure

monitoring.iii) Central Venous Pressure monitoring.iv) Pulmonary Artery Pressure monitoring.

i) Urine Output Monitoring:This is one of the least invasive of all the

monitoring methods. Hourly urine output is quite important in ASA III and ASA IV patients posted for major surgeries. This helps us to know the perfusion of the vital organs and also guides us about the therapeutic modalities. These therapeutic modalities can have an important bearing on the outcome of the surgery.

ii) Invasive Arterial Blood Pressure Monitoring:

Accurate, correct, continuous blood pressure monitoring is mandatory in these groups of patients. Direct Intra-arterial Blood pressure remains the gold standard technique. It provides a beat to beat indication and the waveform. In these patients, wide-swings of arterial pressures may be seen because of surgical manipulations, intravascular volume shifts, effects of anaesthetic agents and arrhythmias. It also helps to obtain



repeated blood gas assessment.Indications in these patients:

I. Major surgical procedures involving large fluid shifts, and blood loss.

II. Pulmonary disease patient requiring frequent ABG analysis.

III. Patients with hypovolemic, cardiogenic or septic shock or with multiple organ failure.

IV. Massive TraumaV. Patients requiring Inotropes.VI. Patients with electrolyte and metabolic

disturbances requiring frequent arterial sampling.

VII. Inability to measure arterial pressure noninvasively (morbid obesity).

The indications during cardiovascular, thoracic, and urosurgeries, are not mentioned here.

COMPLICATIONS:1) Infections: This potential common

complication is common to all invasive monitoring techniques. The incidence can be reduced by using a proper aseptic technique and avoiding prolonged catheterization at the same site.

2) Hemorrhage: this is a potential risk because of disconnection. This can be reduced by Luer lock connections and having low pressure alarms.

3) Thrombosis and Distal Ischaemia: Factors that correlate with increased incidence of thrombosis are prolonged cannulation and larger catheters in smaller vessels. This complication is seen in a negligible number of cases and can be reduced by removing arterial catheters with continuous aspiration of catheter by syringe during proximal and distal occlusion of the vessel.

iii) Central venous Pressure Monitoring:Accurate measurements are possible if

the distal end of the catheter lies within one of the large intrathoracic veins or the right atrium. This is quite a useful invasive monitor if the factors affecting it and its limitations are understood. Serial measurements are more useful than a singular measurement and the response of the CVP to a volume infusion is a useful test of right ventricular function. This mainly indicates

intravascular volume.Indications for CVP monitoring include

• Major surgeries involving large fluid shifts and blood loss.

• Intravascular volume assessment when urine output is not reliable or unavailable (Prostate surgery, Renal failure).

• Major trauma• Venous access for vasoactive irritating drugs.• Inadequate peripheral venous access. These

are some of the indications in ASA III and ASAIV patients in the perioperative period.

COMPLICATIONS:A) Arterial Puncture: This is because the veins lie in the close proximity of arteries. This can be minimized by meticulous technique and by using a small gauge (22G) needle initially, to localize the vein.B) PneumothoraxC) Nerve InjuryD) Arrhythmias: Transient atrial and or ventricular arrhythmias commonly occur as the guide wire is passed into the right atrium.

iv) Pulmonary Arterial Pressure Monitoring:The population of patients with multiple

systemic disease is likely to benefit from this “leap” in monitoring. It gives important diagnostic information to decide about the therapeutic management.

INDICATIONS FOR PULMONARY ARTERY CATHETER MONITORING:• Patients with recurrent myocardial infarctions

or unstable angina.• Patients with left ventricular dysfunction

(congestive heart failure).• Patients in hypovolemic, cardiogenic or

septic shock with multiple organ failure.• Patients with massive ascites.• Major procedures involving large fluid shifts

in patients with coronary artery disease.

COMPLICATIONS:1 Unintended arteriotomy2 Pneumothorax3 Arrhythmias4 Sepsis



5 Potentially fatal haemorrhage.PAC MONITORING HAS WELL KNOWN POTENTIAL BENEFITS:1. Ability to measure important haemodynamic

indices.2. Additional information regarding fluid

management and drug therapy.3. Also helpful in determining whether it is safe,

for high risk patients to proceed with surgery.

This is one invasive monitoring about which a lot of claims and counter claims appear in the literature by both the technophiles and technophobes. But one must keep in mind that the PAC monitoring is a useful adjunct but it cannot replace the vigilant anaesthetist.

The question most commonly asked is, ‘Does invasive monitoring influence the surgical outcome?’ When one asks a question like this, it is implicit in the question that it does contribute to the surgical outcome atleast in principle. The technology is a discrete, separate feature of our environment; hence we are inclined to think that it can be treated as a single factor and its contribution can be measured or atleast estimated. But in practice it is not so, various prospective and retrospective studies are not able to decide the influence of PAC on the outcome of surgery because most of the studies are not conducted with standard methodology and there are various lacunae in the studies like patient selection, selection of controls etc. ASA established a task force on PAC an 1991 to examine the evidence for benefits and risks from PAC catheters. This report summarizes the task force recommendations based on scientific evidence and experts’ opinions. If you look into statistical analysis, the benefit and the influence

on the outcome of surgery is negative but if you clinically look in to the findings it is quite suggestive that patients do benefit from PAC and it may have influence on the outcome of surgery.

CONCLUSION:To conclude, the principle function of

invasive monitoring technology is to amplify or augment human operator expertise. The benefits of invasive monitoring can be reaped maximum by adequate training, experience and expertise.

REFERENCES:1 Report by ASA Task force on PAC

Anaesthesiology Feb.93, vol.78 No.2

2 Friend and Foe: Why can’t we agree about the effects of new technology in patient safety - Richard I Cook, ASA Refresher course series 2002.

3 Cardiac Anaesthesia - Joel A Kaplan.

4 Bedford RF: Removal of radial artery thrombi following percutaneous cannulation for monitoring. Anaesthesiology 46: 430, 1977.

5 Bedford R.F, Ashfor T.P.: Aspirin pretreatment prevents post cannulation radial

Aspirin pretreatment prevents post cannulation radial artery thrombosis. Anaesthesiology 51: 176, 1979.

6 U. Wolter M.D. et al. - ASA classification and perioperative variables in predictors of post operative outcome. BJA August 1996 Vol.77 No.2.

7 A practice of Anaesthesia - Wylie and Churchil Davidson’s. Edited by Thomas E.J. Healy & Peter Cohen.

8 Anaesthesia Providers, Patient outcome & costs: Anaesth. Analgesia. Jun 1996 Vol.82 No.6 p.1273.


Invasive Monitoring in ASA III & ASA IV patientswill not Influence the Outcome of surgery__________ 237 A. Rajamanoharan

Monitoring forms the base or the basis of the conduct and safety of anaesthesia. Measurement is a single observation and monitoring is a serial evaluation. Under anaesthesia the vital parameters must be maintained within the safe limits. The ideal monitoring should be r'mple to apply and observe, cost effective, dynamic, accurate, error free and safe.

The simplicity, safety and the advances in the microprocessor, servo mechanical control technology and photoplethysmography have enabled the non-invasive techniques to be the choice to provide a nearly continuous, correct and accurate assessment of blood flow and pressure.

Invasive monitors without exception carry real dangers and are only used as temporary devices while successful and continued efforts are being made to replace them. Two of the least appreciated disadvantages of extensive monitoring are prolonged immobilisation and the anguish that accompanies it.

Measurement of cardiac output has traditionally been the poor relation to pressure monitoring because of the perceived risks, complexity and expense of pulmonary artery catheterisation. The latest National Confidential Enquiry into Perioperative Deaths highlighted how only a small minority of the reviewed patients had intraoperative pulmonary artery catheter monitoring, yet over three-quarters were classified as being ASA Grade III or higher. No mention was made as to whether cardiac output was actually measured during the operation. The onset of significant haemodynamic deterioration and organ dysfunction is often the cue for its introduction; this belated insertion may partly explain the difficulty in demonstrating any benefit in the critically ill patient. Indeed, a recently

published retrospective analysis has actually suggested possible detriment. This paper has generated considerable debate as to when, how and in whom this invasive approach should be used. It has also given added impetus to the development of alternative flow monitoring techniques that are either non- or minimally invasive and, with advances in technology, increasingly reliable and user-friendly. Many of these techniques also provide additional information on circulatory status, e.g. cardiac preload, ventricular contractility and extravascular lung water, which can further assist therapeutic decision-making. The particular benefits that could arise from non-invasive flow assessment are early identification and either prevention, or faster correction, of circulatory derangements before a significant tissue oxygen debt has been allowed to develop. This proactive philosophy may impact significantly upon postoperative outcome.

Any blinding enthusiasm for non-invasive techniques should be tempered by awareness of the limitations of both the machine and the technology being utilised. Not infrequently, poor equipment design, over-stated abilities and/or inadequate user education have generated unfavourable studies. This may contribute more to an understandable wariness on the part of the clinician rather than to any inherent problem with the technique itself, which is often discredited in the process. It thus behoves prospective users to familiarise themselves fully with both theory and practice underlying a particular device, to develop sufficient expertise to recognise unreliable or erroneous signals, and to be aware of any limitations. All technologies have flaws, and data derived from different methods do not necessarily correlate well. Techniques may often be better at monitoring change rather than delineating absolute output itself. So, let us replace the out-modelled and more harmful



invasive monitoring with non-invasive monitoring equipments and see how they are better, dependable, accurate, totally harmless and user- friendly.

PULSE OXIMETERPulseoximetry (PO) has been arguably

called the most significant technological advance ever made in monitoring the safety of patients during anaesthesia. Prior to the advent of Pulse oximetry, the only monitor for adequate oxygenation of the patient was the “trained” eye of the anaesthesiologist observing skin colour for cyanosis. The pulse oximeter has now become a mandatory intraoperative monitor and in October 1989, the American Society of Anaesthesiologists voted to mandate the use of Pulse oximetry in all anaesthetics after January 1990.

Pulse Oximetry is made possible by the combination of two simple physical principles:1. Every substance has a unique absorbance spectrum2. Of all light absorbing substance in the living tissues, only arterial blood is pulsatile.

Clinical applications1. MONITORING OXYGENATION

- Provides warning of hypoxemia in the operating room (OR), post anaesthesia care unit (PACU), during transport between OR and PACU, and during out-of-hospital transport.

2. MONITORING OXYGEN THERAPY• Helps to titrate supplemental oxygen

in mechanically ventilated patients and patients receiving oxygen therapy by Venturi device. Trends of Sp02 by pulse oximetry should be periodically confirmed by blood gas analysis.

• Pulse oximetry can also be used as a supplement to arterial blood gas analysis to monitor hyperoxia in premature infants

3. ASSESSMENT OF PERFUSIONPresence of pulsatile signal

appropriately tracks the viability of the tissue monitored.

4. MONITORING VASCULAR VOLUME• The amplitude of plethysmographic

waveform provides information about

hypovolaemia during positive pressure ventilation.

Pulse oximeter occupies a unique place among the present day monitors as it provides vital patient information continuously and noninvasively. It also scores over other monitors, as it requires little training for its use and no calibration, making it extremely user-friendly. By helping to detect hypoxemia early, it helps the anaesthesiologist in providing safe patient care in the operating room as well as the intensive care unit.

CAPNOGRAPHYCapnography, the measurement of the

carbon dioxide (C02) content in respired gases, has become part of basic monitoring in anaesthesia and intensive care. Capnographs can provide information regarding the production, transport and excretion of C02. A closed claims study in 1989 has concluded that about 93% of anaesthetic mishaps could have been prevented if capnograph and pulse oximeter had been used as monitors

Indications and uses of capnography• Verification of endotracheal tube placement.• Difficult airway■ Blind nasal intubation• Proper positioning of double lumen tube• Validation of reported end tidal values• Indirect assessment of partial pressure of arterial carbon dioxide tension (normal (a-ET) PC02 varies from 2 to 5mmHg and increases with age, pulmonary disorders like emphysema, pulmonary embolism, decreasing cardiac output, hypovolaemia and general anaesthesia.

■Adequacy of spontaneous ventilation under general endotracheal anaesthesia and also in the awake intubated patient in the recovery room/ICU and in a patient under regional anaesthesia, (apnoea monitor).• Assessment of ventilator, breathing circuit and gas sampling integrity.• Circuit leaks and adjustments of fresh gas flow.■ Instantaneous disconnection, total occlusion and accidental extubation.■ Carbondioxide retention due to faulty circuit (Bains).■ Exhausted carbondioxide absorbent in a semi


/nvasive Monitoring in ASA III & ASA IV patientswill not Influence the Outcome of surgery__________ 239 A. Rajamanoharan

closed circle absorber system.■ Malfunction of valves.• Assessment of patient airway integrity• Obstructive airway disease and its response to treatment

Hypermetabolic states• Cardiopulmonary resuscitation• Venous carbon dioxide embolism• High frequency jet ventilation.

Thus capnography has got several applications in the operating room as well as intensive care units. When it is used to its fullest potential it can make patient care much more safe.

DOPPLER ULTRASONOGRAPHYThe velocity of a moving object can be

calculated from the shift in reflected frequency of a sound wave of known frequency..V = (Df*C)(2ftxcosq)

corpuscles; Df=Doppler frequency shift; C=Sound velocity in tissue; ft = transmitted frequency; and 0 = angle between ultrasound beam and the flow direction.

For blood flow measurement, high frequency ultrasound waves are directed at moving erythrocytes. These Doppler frequency shift signals can undergo fast Fourier transform spectral analysis and be displayed in real time as velocity-time waveforms on a monitor.

Doppler measurement of aortic blood flow was first described in the 1960s initially via a transthoracic approach and then from a probe

placed in the suprasternal notch directed at either the ascending or arch portions of the aorta. Validations performed against reference techniques, such as thermodilution, have confirmed its accuracy. It is quick, easy to perform, totally non-invasive and painless. However, up to 5% of patients cannot be readily measured due to either anatomical (e.g. short neck) or pathological (e.g. emphysema, mediastinal air, postcardiothoracic surgery, aortic valve disease) factors.

A 6 mm diameter 4 MHz continuous wave Doppler transducer is inserted orally into the distal oesophagus to a depth of 35-40 cm. A characteristic blood flow signal from the descending thoracic aorta is readily distinguishable on the monitor. Insertion and correct positioning take a matter of minutes. The area of each velocity-time waveform - the stroke distance - is a representation of stroke volume flowing down the descending thoracic aorta.

Only aortic coarctation, use of an intra- aortic balloon pump and, possibly, thoracic aortic aneurysms provide no meaningful signals. Moderate or severe aortic regurgitation produces a characteristic reverse flow throughout the whole of diastole. Caution should be observed in patients with oesophageal varices or other local pathology, and in those with marked coagulopathies. However, no serious adverse event has yet been reported.

Starling like curves can be constructed to optimise fluid and dilator therapy Whereas preload changes predominantly affect the FTc, inotropic changes mainly affect the peak velocity while afterload changes have an intermediate effect. The effects of therapy can thus be readily appreciated on a beat-by-beat basis.

ECHOCARDIOGRAPHIC EVALUATIONEchocardiographic techniques (either

transthoracic or transoesophageal) can be used to estimate cardiac output in one of two ways: Combined use of imaging with Doppler signal derivation

Two steps are required. The Doppler flow velocity is measured as described above though, with the echocardiographic technique, the flow


Invasive Monitoring in ASA III & ASA IV patientswill not Influence the Outcome of surgery 240 A. Rajamanoharan

being interrogated is usually in or close to the heart, e.g. across the mitral valve or, commonly, in the aortic root. Echocardiographic measurement of cross-sectional area at this point will allow calculation of cardiac output as the product of blood velocity averaged over a minute and cross-sectional area. Planimetric measurement, enhanced by recently developed edge-detection technology, may improve the accuracy of calculated cardiac outputs although it may still prove difficult to obtain accurate short- axis views.

The use of combined transoesophageal echocardiographic imaging and Doppler probes allows estimation of cardiac output in the critically ill more readily than transthoracic imaging techniques.

Calculation from ventricular volumesIf ventricular volume at end-systole and

end-diastole are measured, stroke volume can be calculated as the difference between these two values, and cardiac output as the product of this stroke volume and heart rate.

Recently developed technology allows 3- dimensional reconstruction of images of the left ventricle. Routinely, however, ventricular volumes will still be calculated from 2-D and M-Mode images although these often rely upon assumptions about LV shape, namely:

Transthoracic impedanceIn 1966, Kubicek described the thorax

as a cylinder evenly perfused with blood of specific resistivity ‘p’, itself related to the haematocrit. Pulsatile thoracic aortic blood flow caused negative impedance changes (measured from a steady state mean base impedance (Z), with a maximum rate of change [(dZ/dt)m J of Zm during systole between pairs of electrodes placed around the neck and upper abdomen.

SV=p(L2/Z2)ZmWhere SV = stroke volume; p=electrical

resistivity of the blood; L=mean separation of the inner pair of electrodes; Zm = maximum rate of change of impedence (dZ/dt)maxduring systole, and Z = basic impedance between the inner electrodes.

The original Kubicek equation consistently overestimated SV. Furthermore, it

was subsequently shown that the thorax behaves electrically more as a truncated cone rather than as a cylinder. . This, and the application of new technology, renders transthoracic impedance of potential clinical use and the new equations have been incorporated into commercial systems such as the NCCOM-3 (Biomed Medical Manufacturing Ltd, Irvine, CA, USA). Common systems have involved the application of a sensing electrode to either side of the neck root and to opposite sides of the body in a mid-coronal plane at the xiphisternum level. Two pairs of transmitting electrodes are placed 5 cm above the neck sensors and 5 cm below the thoracic sensors, respectively. Accurate electrode placement is crucial using such systems.

Although data derived from this system may, under some circumstances, correlate well with those derived from thermodilution (and even prove more reproducible in individual subjects), the varying impedance technologies and derived equations have yet to be validated in individuals of both sexes and of diverse age and habitus in varied clinical situations. Adoption of the technique in the ICU setting cannot yet be recommended. Its use in the emergency room (to allow rapid and non-invasive monitoring of responses to resuscitation) or on the operating table may prove more readily acceptable.

Pulse Contour AnalysisSince the rate at which blood flows from

arteries to veins is proportional to the rate of fall of arterial pressure, analysis of the contour of the aortic pulse-wave allows determination of cardiac output. The area of the arterial waveform (or pulse contour) was first described as a means of monitoring cardiac output by Frank in 1899. This pulse contour cardiac output technique (PCCO) can be performed non-invasively from a finger pressure waveform using a Finapres device or from an indwelling arterial cannula which is being pressure transduced. However, it cannot be used for quantitation of cardiac output unless a calibration tool such as thermodilution is used. Over the last two decades, various equations have been developed by different researchers for monitoring stroke volume.

The Bradley MethodA clinical means for estimating cardiac



output and peripheral vascular resistance was revised by Bradley. In experienced hands, this has been shown to be a reliable technique, however, a validation study showing good agreement when compared against thermodilution has only been published in abstract form and it has to be shown to be readily transferable to novices.

It relies upon a version of Ohm’s law where the voltage gradient across a circuit equals the product of current and resistance. In the systemic circulation, the pressure gradient across the circuit (mean arterial pressure minus central venous pressure) measured in mmHg equals the product of cardiac output (in 1 /min) and peripheral vascular resistance (in Wood units).

COMPLICATIONS OF INVASIVE MONITORING Complications of arterial puncture

• Infection• Haemorrhage• Thrombosis and distal ischaemia

Skin necrosis EmbolizationHaematoma Neurologic injuryLate complications like pseudoaneurysm and AV fistula

Complications of central venous cannulationsArterial puncturePneumothorax/hydrothoraxChylothoraxPericardial effusion/tamponade

• Venous air embolism Nerve injury Arrhythmias

Complications of pulmonary artery catheterisation

All complications of internal jugular vein cannulation and in addition:

• Complete heart block (in patients with LBBB)Endobronchial haemorrhage Pulmonary infarction Valvular damage Thrombocytopenia

• Thrombus formation Incorrect placement

Balloon rupture

CONCLUSIONKISS the well known acronym for “Keep

it simple, stupid” is often taken to be good advice for life in general. Editorial by C.E. Hahn BJA volume 86-4 April 2001.

Moreover, for the trainee, there is a galaxy of advice, opinion and controversies to be digested. Monitoring has become the sixth sense of the clinician and has contributed in a major way to a safer anaesthetic practice.

Invasive monitoring is time consuming, needs technical expertise, definitely damaging, necessitates immobilization and is vulnerable for disturbances and inaccurate results. Let us eradicate “invasion” anywhere in the universe. To quote Mahatma Gandhi “non-violence”’ (noninvasion) is the strongest but still the most successful method. So let us be non-invasive in monitoring our ASA III & IV patients.

REFERENCES

1. Noninvasive monitoring of cardiac output, Hugh Montgomery, Mervyn Singer, 163, Recent advances in anaesthesia and analgesia 20 by A.P.Adams, J.N.Cashman.

2. Edward D.Miller Jr - Miller 5th edition, 14703. Text book of Anaesthesia by Wylie Churchill Davidson4. Tinker JH, Dull DL, Caplan RA, Ward RJ, Cheney FW.

Monitoring devices in preventing of anaesthetic mishaps: a closed claims analysis. Anaesthesiology 1989; 71:51-46.

5. Shankar KB, Moseley H, Kumar AY, Delph Y, Capnometry and anaesthesia:Can J Anaesth 1992; 39:617-32.

6. Eichhom JH, Prevention of intraoperative Anaesthesia Accidents and Related Severe injury through safety monitoring. Anaesthesiology 1989; 70:572-7.

7. Stock MC, Capnography for Adults. Critical Care Clinics 1995; 11:219-32.

8. Severinghaus JW,, Kelleher JF. Recent developments in pulse oximetry Anaesthesiology 1992; 76:1018-38.

9. Moon RE, Camporesi EM, Respiratory Monitoring. In Miller RD, eds. Anaesthesia. 5th ed.California:Churchill ivingstone; 2000:1:1269-77.

10. Dorsch JA, Dorsch SE Pulseoximetry in: Understanding Anaesthesia Equipment 4th ed. Baltimore:Williams and Wilkins; 1998; 811-48.

11. Wahr JA, Tremper KK.Pulseoximetry. ln:Blitt CD, Hines RL, eds. Monitoring in anaesthesia and critical care medicine.3rd ed. Newyork:Churchill Livingstone; 1995;385-406.

12. RACE 2000 - Postgraduate symposium on Non-invasive monitoring.



• Significant increase in ICP occurs with both.

• EEG: No evidence of spike or seizure activity.

RESPIRATORY SYSTEMInhalational induction is rapid and pleasant without causing breath holding or coughing. Respiratory depressant Decrease in tidal volume with increasing depth of anaesthesia although respiratory rate is increased.BronchodilationInhibits hypoxic pulmonary vasoconstriction response in a dose dependent manner

CARDIOVASCULAR SYSTEMHalogenated anaesthetic: cardiovascular depressant

• Myocardial depression: More with sevoflurane than isoflurane but less than that with halothane anaesthesia.

• Systemic Vascular Resistance: Decreases SVR but to a lesser degree than isoflurane

• Mean Arterial Pressure: Effect similar to isoflurane.

• Heart Rate: Lesser rise in heart rate as compared to isoflurane

• Does not sensitize myocardial to the arrhythmogenic effects of catecholamines.

METABOLISM AND TOXICITYLacks the stability of halothane or isofluraneRate of degradation at22°C is 6.5% per hour for each degree rise in temperature. Renal effects of prolonged exposure to sevoflurane.• Serum inorganic fluoride levels: 22.1 (± 6.1) mmol/L after 1 hour exposure.• The inorganic fluoride levels associated

with prolonged sevoflurane exposure declined rapidly to less than half the maximal level by 48 hours after cessation of anaesthesia. This is related to a low blood gas partition coefficient, which allows rapid elimination of sevoflurane via the lungs, leaving a little drug to be metabolized after cessation of anaesthesia delivery.

LOCAL ANAESTHETICS Ropivacaine

Ropivacaine was developed in response to the reports of cardiovascular toxicity after accidental intravascular injection of bupivacaine. The main differences from bupivacaine lie in its

• Pure enantiomeric formulation• Improved toxic profile• Lower lipid solubility

ENANTIOMERIC FORMULATIONSubstitution of propyl for the butyl group in the piperidine ring’s tertiary nitrogen atom. Ropivacaine consists of a single enantiomer, the S-stereoisomer• This renders ropivacaine less intrinsically

cardiotoxic.• It is cleared more rapidly from circulation

if injected intravenously which however cannot be substantiated as S- enantiomers are metabolized by the liver more slowly than the corresponding R- enantiomers17.

TOXIC PROFILE CardiotoxicityCardiovascular toxicity of local anaesthetics has effects directly on the myocardium, vascular smooth muscle, and central innervations of the heart.• In both neuronal and cardiac Na+

channels, the S-isomers of the piperidine containing local anaesthetics are less potent than R-isomers. The stereo potency of cardiovascular effects mediated through the vascular tissue and the CNS is unknown18.

• The smaller propyl substitution in (S-) ropivacaine makes it slightly less potent than S-bupivacaine in its effect on single Na+ channels and isolated nerve action potentials19.



• Very slow reversal of Na+ channel blockade after cardiac action potential is a hallmark of bupivacaine. This reversal is considerably faster with ropivacaine20.

• A greater therapeutic index for ropivacaine than bupivacaine, particularly with regard to cardiotoxicity.

CNS Toxicity• Convulsing doses of ropivacaine are

larger than those of bupivacaine but less than those of lignocaine.

LIPID SOLUBILITY21

• Ropivacaine’s low lipid solubility may result in reduced penetration of the large myelinated A<x motor fibres, so that initially these fibres are relatively spared. However during continuous infusions they get blocked. Therefore, motor block produced with ropivacaine has

• A slower onset with ropivacaine• Less dense• Shorter duration when compared to

bupivacaine.

KINETICSRopivacaine is metabolized in liver by

aromatic hydroxylation, mainly to 3-hydroxy- ropivacaine, but also to 4-hydroxy-ropivacaine, both of which have some local anaesthetic activity21.

LevobupivacaineCLINICAL POTENTIAL:

The S(-)enantiomer of bupivacaine, with less cardiovascular and central nervous toxicity, a slightly longer duration of sensory block, but otherwise similar to its parent.

PHARMACODYNAMICS:Compared to bupivacaine it is as

potent, with a trend towards longer sensory block; with epidural usage it produces less prolonged motor block; Differentiation not seen with peripheral placement; lethal dose 1.3 to 1.6 times higher; less cardiac effect including less depression of contractility and fewer arrhythmias; higher convulsive doses. Has not been compared at equipotent anaesthetic doses with ropivacaine.

PHARMACOKINETICS:

_Elimination t1/21.3 hours VD 67L in adult volunteers Protein binding > 97%Metabolism by CYP1A2 and 3A4 Crosses placenta No racemisation in vivo.

DOSAGE:Minimum effective concentration

0.085%; Recommended maximum dosage 150mg for single dose epidural; 12.5mg/hr (10mls/ hr of 0.125% solution) for labour epidural infusion; 18.75mg/hr (15mls/hr of 0.125% solution) for epidural infusion; and 25mg every 15 or more minutes for epidural bolus doses.

15mg for intrathecal placement. 2.5mg/kg for nerve blocks in paediatric patient.

ADVERSE EFFECTS:Potential for hypotension and

cardiac arrest: observe precautions as for all local anaesthetics. Cardiotoxicity and CNS toxicity as noted.

DRUG INTERACTION: Unknown.Of Note:(1) Don’t use 0.75% in obstetrics;(2) Not for paracervical or Bier’s block;(3) Avoid if hypersensitivity to amides (rare).

EMLA (Eutectic mixture of local anaesthetic)21When two compounds are mixed

to produce a substance that behaves with a single set of physical characteristics, it is said to be eutectic. EMLA (5%) contains mixture of crystalline bases of 2.5% lignocaine and 2.5% prilocaine in a white oil: water emulsion. The mixture has a lower melting point, being oil at room temperature, while the individual components would be crystalline solids.

PRESENTATION AND USESEMLA is presented as an

emulsion in tubes containing 5 or 30 gm. It is used to anaesthetize skin before vascular cannulation or harvesting for skin grafts. It should be applied to intact skin under an occlusive dressing for at least 60 min. to ensure adequate anaesthesia.

CAUTIONSMethaemoglobinaemia is caused

by o-toludine, a metabolite of prilocaine______RACE 2003 Ramachandra Anaesthesia Continuing Education


• Congenital or idiopathic methaemoglobinaemia• Infants less than 12 months receiving treatment with methaemoglobin-inducing drugs• Patients on drugs associated with methaemoglobinaemia (sulfonamides, phenytoin)• Do not use on mucous membranes due to rapid systemic absorption• Patients receiving Class I antiarrhythmic drugs (Tocainide, Mexilitine)

NON DEPOLARIZING MUSCLE RELAXANTS

to limit the duration of the block23.□ Avid liver uptake and elimination into bile

due to increase in the lipophillic nature of the molecule with regard tovecuronium24. At appropriate dose, enables tracheal intubation in 60 - 90 sec and may prove a substitute for succinylcholine in rapid tracheal intubation, other aspects of clinical pharmacology of rocuronium seemssimilar to properties of vecuronium25.

PHARMACODYNAMICS

Table 1: Dosage and duration of action of rocuronium


Newer Anaesthetic Agents Pankaj Kundra

received an additional dose of reversal agent. The median (range) dose of neostigmine was 0.04 (0.01 to 0.09) mg/kg and the median (range) dose of edrophonium was 0.5 (0.3 to 1.0) mg/kg. In geriatric patients (n=51) reversed with neostigmine, the median TA/T: increased from 40 to 88% in 5 min.

METABOLISM & ELIMINATIONNo metabolism of rocuronium has yet been reported. Like vecuronium dual hepatic and renal pathways of elimination exist. Unchanged drug

has been recovered from bile and urine24.

REFERENCES1. Simons PG, Cockshott ID, Douglas EJ. Blood concentrations, metabolism and elimination after subanaesthetic intravenous dose of 14C-propofol to male volunteers. Postgrad Med J 61: 64; 1985.2. Hughes MA, Jacob JR, Glass PSA. Context sensitive half time in multicompartment pharmacokinetic models for intravenous anesthesia. Anesthesiology 76: 334; 1992.3. Major E, Verniquet AJW, Waddell TK et al. A study of 3 doses of ICI 35 868 for induction and maintenance of anaesthesia. Br J Anaesth 53: 267; 1981.4. Aun CST, Short SM, Leung DHY, Oh TE. Induction dose response in unpremedicated children. Br J Anaesth 68: 64; 1992.5. McDonald NJ, Mannion D, Lee P et al. Mood evaluation and out patient anaesthesia. A comparison between propofol and thiopentone. Anaesthesia 43: 68; 1988.6. Anonymus. Convulsions after propofol. Pharm J 249: 745; 1992.7. Dwyer R, McCaughey W, Lavery J et al. Comparison of propofol and methohexitone as anesthetic agents for electroconvulsive therapy. Anaesthesia 43: 459; 1988.8. Stephan H, Sonntag H, Schenk HD, Kohlhausen S.

Effects of disoprivan on cerebral blood flow, cerebral oxygen consumption and cerebral vascular reactivity. Anaesthesiologist 36: 60; 1987.9. Mirakhur RK, Shepherd WFI, Darrah WC. Propofol or thiopentone: effects on intraocular pressure associated with induction of anaesthesia and tracheal intubation (facilitated with suxamethonium) Br J Anaesth 59: 431; 198710. Taylor MB, Grounds RM, Dulrooney PD, Morgan M. Ventilatory effects of propofol during induction of anaesthesia. Comparison with thiopentone. Anaesthesia 41: 816; 1986.11. Goodman NW, Black AMS, Carter JA. Some ventilatory effects of propofol as a sole anaesthetic agent. Br J Anaesth 59: 1497; 1987.12. Coates DP, Monk CR, Prys-Roberts C, Turtle M. Hemodynamic effects of the infusions of the emulsion formulation of propofol during nitrous oxide anesthesia in humans. Anesth Analg 66: 64; 1987.13. Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth 60: 3; 1983.14. Hopkinson KC, Denborough M. Propofol and malignant hyperpyrexia (letter). Lancet 1: 191; 1988.15. Johnson SE. Remifentanil: A unique, short acting opioid. Advances in Anesthesia vol. 16, Chapter 4, Mosby Inc. 1999.16. Navarro JR. New Inhalational Anesthetics. Advances in Anesthesia vol. 12, Chapter 4, Mosby - Year Book Inc. 1995.17. Rutten AJ, Mather LE, Mclean CF. Cardiovascular effects and regional clearances of intravenous bupivacaine in sheep: Enantiomeric analysis. Br J Anaesth 67: 247; 1991.18. Lee-Son S, Wang GK, Concus A, et al. Seterioselective inhibition of neuronal sodium channels by local anesthetics. Anesthesiology 77: 324; 1992.19. Wang GK. Binding affinity and stereioselectivity in single batrachotoxin activated Na* channels. J Gen Physiol 96: 1105; 1990.20. Arlock P. Actions of three local anaesthetics: lignocaine, bupivacaine and ropivacaine on guinea pig papillary muscle sodium channels (Vmax). Pharmacol Toxicol 63: 1; 1988.21. Peck TE, Williams MA. Pharmacology for Anaesthesia and intensive care. 1st edition. Chapter 10. Ashford Colour Press, Great Britain.22. Wierda JMKH, Di Wit APM, Kuizenga K et al. Clinical observations of the neuromuscular blocking action of ORG 9426 a new steroidal non-depolarizing agent. Br J Anaesth 64: 521; 1990.23. Min JC, Becavak I, Glavinovic Ml et al. lontophoretic study of speed of action of various muscle relaxants. Anesthesiology 77: 351; 1992.24. Khuenl-Brady K, Castagnoli KP, Canfell PC et al. The neuromuscular blocking effets and pharmacokinetics of ORG 9426 and ORG 9616 in the cat. Anesthesiology 72: 669; 1990.25. Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine and vecuronium for rapid sequence induction of anesthesia in young adults. Anesthesiology 79: 913; 1993.*26. Muir AW, Houston J, Green KL et al. Effects of new neuromuscular blocking agents (ORG 9426) in



anesthetized cats and pigs and in isolated nerve muscle preparation. Br J Anaesth 63: 400; 1989.27. Servin FS, Lavaut E, Desmonts JM. Clinical evaluation of ORG 9426 in cirrhotic and control patients.

Anesthesiology 77: A357; 1993.Shanks CA, Fragen RJ, Ling D. Continuous intravenous infusion of rocuronium in patients receiving balanced, enflurane or isoflurane anaesthesia. Anesthesiology 78: 649; 1993.


Management of Acute Pain 22 M R. Rajagopal

INTRODUCTIONIn June 2002, a Californian jury found a

doctor “liable for reckless neglect in under-treating a man’s pain” and ordered him to pay 1.5 million US dollars to the dead man’s children1.

It has started. We cannot get away with it any more. We have always known that a doctor’s duty is to “cure sometimes, relieve often and to comfort always” but we have seldom taken it seriously. But people have started demanding pain relief now, and we better learn to satisfy them.

Unrelieved pain can cause several adverse physiological changes.1. It causes reflex skeletal muscle spasm that,

specially in upper abdominal surgery or chest surgery, can result in regional hypoventilation and result in postoperative chest complications.

2. Pain causes reflex vasoconstriction. It can possibly impair wound healing in any case, but particularly in people with compromised blood flow, this can be very damaging.

3. Pain causes stress response, with adverse circulatory consequences. This can be very detrimental in people with compromised circulation.

4. Pain prevents early mobilization with attendant complications. Pain relief during recovery from acute injury improves survival and speeds rehabilitation by promoting volitional activity2.

For all these reasons, and also because it is simply our duty to relieve suffering, acute pain has to be treated. Lack of resources is certainly not an excuse. Most pain relief

measures are relatively inexpensive. Pain relief is not necessarily something to be done with expensive electronic gadgetry. There are other options.

We will attempt to briefly review the pathophysiology of pain, and use that understanding to describe various means of pain relief. Then wc shall give attention to what could be done even with limited resources.

PATHOPHYSIOLOGY OF PAINLet us start by making some key points

pertaining to pain mechanisms.

Pain is what the patient says hurts.The International Association for Study

of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”3. It is important to remember that people are different, their emotional states could be different and that it would be necessary to take that into consideration while planning treatment.

A simpler definition is, “Pain is what the patient says, hurts”4. The emphasis is on the patient’s experience. He and no one else can assess his pain properly. Once we accept the definition, we shall escape the pit-fall of being judgemental about someone who is 'too sensitive’ or 'too fussy’ and complains 'too much’ about his or her pain.

Hence, the patient is the most appropriate person to assess the severity of his pain. The message is, “Believe the patient about



his pain.”

Pain causes more pain.Unrelieved pain results in steady

worsening of pain. The following description of pathophysiology will make this easier to understand.

Peripheral mechanisms of pain:Any injury causes stimulation of pain

sensing nerve endings, which are called nociceptors. The impulse is transmitted via the C and A-delta sensory nerve fibres to the dorsal horn of the spinai cord. There from, the impulse is transmitted to the thalamus and the sensory cortex.

The initial injury is followed by liberation of chemicals - the nociceptive substances -, which continue to stimulate the nociceptors and perpetuate pain. Of the many such substances (kinins, leukotrienes, substance P, histamine, serotonin, hydrogen and potassium ions and so on), prostaglandins deserve special mention. Prostaglandins sensitize the nociceptor to the other pain producing substances.

It has also been found that silent or sleepy nociceptors are recruited in the face of sustained stimulation. This means that for a particular stimulus, there will be progressively increasing response.

CENTRAL PAIN MECHANISMS AT THE LEVEL OF THE DORSAL HORN

There is some form of sensitization and recruitment at the level the of dorsal horn too. The phenomenon is called “wind-up” - analogous to a wound-up spring. With sustained stimulation from the periphery, the dorsal horn cells seem to get wound up so that with time, there is progressively increasing response to the peripheral stimulus. NMDA receptors are said to play a major role in the development of “windup”.

There is also a process of recruitment at the central level. With time, there is recruitment of adjacent spinal segments so that pain increases not only in intensity, but in extent as well.

In fact with prolonged, unrelieved, acute pain, there can be permanent anatomical changes in the nervous system, so that the pain gets centrally established and becomes chronic pain. It is believed that this is the mechanism of most scar pains.

This entire gamut of changes mean that the earlier pain is treated, the easier it is It also means that in elective trauma (surgery-), pain had better be prevented rather than treated. This is the concept of pre-emptive analgesia.

MANAGEMENT OF ACUTE PAIN:Let us start with some general principles

of pain management.1. All pains are not opioid-sensitive. Roughly

two thirds of acute pain can be treated successfully by opioids. This means that a multi-modal approach works best.

2. Analgesics must be administered round the clock. This may mean the use of continuous infusions or the use of drugs by the clock depending on its duration of action. For example, morphine can be administered either as a continuous subcutaneous or epidural infusion or as 4-hourly bolus doses.

Major pain relief modalities:The following three form the major

modalities of pain relief:1. Prevention of peripheral sensitization by the

use of NSAIDs.2. Application of local anaesthetics, peripherally

or centrally.3. Use of opioids, centrally or peripherally.

By judicious combinations of these, it is possible to achieve adequate analgesia without serious adverse effects. In individual cases, however, there may be other forms of treatment that can be added on. We shall come to them briefly later.

NSAIDs:By preventing sensitisation of

nociceptors and indirectly central sensitisation, NSAIDs contribute to pain relief. However, there are concerns about their safety. The major concerns are:



1. Bleeding tendency because of inhibition of platelet adhesion. There is some controversy; but there does seem to be some evidence at least that it can be a real concern. One study found them to double the bleeding during hip arthroplasty5. But the coxibs appear to be safe. If anything, there seems to be a doubt that coxibs may even have a prothrombotic tendency.

2. Renal dysfunction in those who are predisposed to it. In the surgical context, this can also be a concern in the hypovolaemic. The associated water retention has the potential to worsen hypertension and cardiac failure. It seems doubtful if the chance of this complication is any less with coxibs.

3. Gastritis. But the coxibs appear to be safer than the older generation drugs in this matter.

In spite of these disadvantages, the addition of NSAIDs does seem to improve the quality of analgesia. The combination decreases opioid requirement and decreases the chance of ileus. They are hence recommended particularly in procedures like dental extraction where chance of significant bleeding is negligible.

There is one situation where NSAIDs must be used. In people with chronic arthralgia like in osteoarthritis, rheumatoid arthritis etc, preoperative cessation of NSAIDs causes a flare up of pain (algesic flare). In such cases, it is recommended that coxibs be started and continued through the peri-operative period.

NEWER NSAIDS.Valdecoxib is said to have no effect at

all on platelet function.

Parecoxib is the only Cox-2 selective drug that is recommended for parenteral use.

Etoricoxib is the most potent second generation NSAID yet, three times more selective than rofecoxib.

LOCAL ANAESTHETICSAs used in pain relief, they have a

predominant local effect and some systemic effect (membrane stabilization). The latter,

nevertheless, may be significant when there is a neuropathic component to the pain. Conventionally, they are used most often as epidural injections. Given preoperatively, it can contribute to surgical anaesthesia and confer post-operative analgesia too. Where facilities exist, they had best be given as continuous epidural infusions. An infusion of 0.125- 0.25% bupivacaine would provide adequate analgesia, while permitting ambulation; a dose of 4-8 ml/ hour may be a good starting point. When the pain stimulus is severe, (as in ischaemic pain for example), sometimes it may be necessary to give an anaesthetic concentration of the drug (0.5%) and compromise on mobility. A syringe pump would be the standard equipment for the infusion; a Patient Controlled Analgesia (PCA) device may permit fine-tuning of analgesia.

When a syringe pump is not available, one has to resort to intermittent injections. Too frequent injections are impractical; but on the other hand, at least four hourly injections will be needed if pain relief has to be adequate. And even in that case, the sizeable dose requirement predisposes to hypotension following every bolus injection. Particularly in the context of the unstable circulatory status in many major surgical procedures, this can be quite relevant. Obviously, smaller and more frequent bolus doses are desirable.

Bupivacaine is the local anaesthetic agent used most often. Shorter acting agents like lignocaine have the disadvantage of tachyphylaxis. Ropivacaine seems to have nearly the same duration of action as bupivacaine. It may have an edge over bupivacaine in that it seems to have better selective sensory blockade. With ropivacaine, it is easier to achieve analgesia without motor blockade than with bupivacaine.

Epidural catheters function best for an average of three days. As days go by, blockage, infection, pain on injection and leaks can be problems limiting long term use6.

When epidural infusions of local anaesthetics are not feasible or practical for lack of facilities, even single dose local anaesthetic



blocks can be valuable. By avoiding the maximal pain in the immediate post-operative period, it serves to decrease the sensitization. A single dose epidural block, an interpleural or intercostal block, or a regional block as for herniorrhaphy, can all be very useful, despite the short duration of a single block.

OPIOIDSOpioids can act both centrally and

peripherally. The importance of peripheral opioid receptors is being more and more understood now. Their practical relevance is that the same dose of opioid infiltrated around the incision would be much more effective than a subcutaneous injection elsewhere, because in the former case, we can have the drug acting both on the peripheral receptors as well as systemically.

Addition of opioids to the local anaesthetic agent given epidurally, improves the quality of analgesia. The basic principle is that we are able to achieve rather high neuraxial concentrations compared to systemic drug levels, resulting in excellent analgesia with minimal side effects. Some side effects are possible however, like nausea and vomiting, delayed respiratory depression, urinary hesitancy or retention and itching.

Preservative-free morphine is the agent used most often for this purpose as it has the most opioid-sparing effect compared to IV injection. The dose required is only about one- tenth of the systemic dose. It is about one-third for fentanyl and two-third for buprenorphine. Herein lies the main advantage of morphine over the other opioids for epidural administration - small dose, thus fewer side effects. However, as a practical point, there is the problem of poor availability of preservative-free morphine. (The manufacturers should be able to provide us with this on request.)

However, buprenorphine does have an advantage. It does not have to be given at the required segmental level.

COMBINATION 0!^ DRUGSIn general, we can make the following

recommendations for post-operative analgesia.• NSAIDs, particularly the coxibs would help to

improve the quality of analgesia, but need to be used after weighing the risks and benefits.

• Combination of a local anaesthetic with an opioid would be particularly useful - simple infiltration of these drugs over the site of incision itself may go a long way towards post operative pain relief.

• Preservative free morphine is the best drug for epidural administration, if it can be applied over the segment to be blocked. If the site of administration were distant, buprenorphine would be a better choice.

ANCILLARY MEASURESSeveral other possibilities exist for relief

from acute pain.1. Though not freely available in this country,

Entonox (the compressed mixture of oxygen and nitrous oxide in 50:50 combination) is a good choice for analgesia in the emergency room.

2. It appears that pre-treatment with tricyclic antidepressants decrease opioid requirements presumably by inhibiting reuptake of serotonin and norepinephrine at the inhibitory synapses. While this may have little application as a technique for pain relief in routine practice, this strengthens the case for continuing tricyclics in the peri-operative period in those patients already on it.

3. Sub-cutaneous infusion of lignocaine may supplement analgesia in relatively opioid resistant pains, particularly in patients who have already been in pain for some time, and especially if there is a neuropathic component to the pain (like some patients with burns).

4. Subcutaneous infusion of a sub-anaesthetic dose of ketamine (for example, 5 mg per hour) may help in difficult pains by its action on the NMDA receptors in the dorsal horn of the spina! cord.

5. Transcutaneous electrical nerve stimulation (TENS) is a particularly safe form of pain relief, though it has limited application. The device itself is inexpensive, but they should be used only if sterile conducting pads are available.

RACE 2003 Kamachandra Anaesthesia Continuing Education


Organization of an acute pain serviceMore and more is talked now about the

concept of a pain-free hospital. There is a move favouring institutional commitment to pain relief- making pain the 4th vital sign in the patient’s daily hospital record of parameters. Measurement of pain of course mandates adequate control too.

Most acute pain services are anaesthesiologist-led. But it is important to remember that pain service demands teamwork. It would be impossible to achieve assessment and management of pain in a whole hospital, without adequate personnel. Most pain services depend a lot on nurses. It would be essential to have at least one nurse with special training round the clock in the hospital, who will help the staff nurses with evaluation and pain control. Needless to say, this nurse will need expertise in assessment of pain as well as in the mechanical aspects including the use of devices like infusion pumps and PCA devices. Theanaesthesiologist, then, is able to do the consultant’s job. In fact the presence of such a team is much more important than the high tech devices like PCAs. Last but not least, the importance of explanations to the patient and family cannot be overemphasized. If they know what to expect,

anxiety will be less, and that will lessen the pain experience.

REFERENCES

1. Okie.S. Californian jury finds doctor negligent in managing pain. National news', 15 June 2001, Washington.

2. Tuman KJ, Me Carthy RJ, DeLaria GA, Patel RV, Ivankovich AD. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesthesia and Analgesia 1991; 73:696-704.

3. I ASP Sub-committee on Taxonomy. Pain terms: a list with definitions and notes on usage. Pain 1980; 8:249-52.

4. Black RG. The Chronic Pain Syndrome. Surgical Clinics of North America. 1975; 55:999-1011.

5. Robinson CM, Christie J, Malcolm-Smith N. Non-steroidal anti-inflammatory drugs, perioperative blood loss and transfusion requirements in elective hip arthroplasty. J Arthroplasty 1993; 8:607-610.

6. McQuay HJ. Epidural analgesics. In: Wall PD; Melzack R, Eds. Textbook of Pain 3rd ed. Churchill Livingstone, Philadelphia. 1994: 1025-1034.


Anaesthetic Management of aPregnant Patient for Non-Qbstetric surgery 27 R. Gopinath

INTRODUCTIONEach year for about 80,000 anaesthetics

administered there are 2 % of parturients who undergo surgery. This is largely due to the increase in the endoscopic procedures undertaken to treat conditions common in the childbearing age group like trauma, ovarian masses, appendicitis, gall bladder disease, breast surgery etc. Major surgical procedures like cardiac surgical, neuro-surgical and liver transplants have been performed during pregnancy with good outcomes for both the foetus and the mother. The known problems of foetal development and drug administration to the mother during pregnancy and the risk of abortions make both the physician and the patient wary of an anaesthetic. To assess the risk one has to understand the physiological changes involved during pregnancy and that two lives are involved during the conduct of anaesthesia raising several unique concerns.

ALTERATIONS IN MATERNAL PHYSIOLOGY.All systems are involved in change but

those important to the anaesthetic management are:Respiratory:

Increased oxygen consumption, reduced functional residual capacity, hypocapnia due to increased minute ventilation, likelihood of difficult intubation and trauma to the airway due to increased vascularity of the mucosa.

Cardiovascular:Increase in both the cardiac output and

the blood volume, dilutional anaemia, decreased vascular responsiveness, increased baroreceptor responsiveness, aortocaval compression in the supine position.

Gastrointestinal:The lower oesophageal sphincter tone is usually reduced though gastric pH, volume and emptying are not much altered.

Central nervous system:Inhalational agent MAC and local

anaesthetic requirements are reduced.

Teratogenicity of anaesthetics is probably minimal and has never been conclusively demonstrated. The use of agents like nitrous oxide, which in animal studies may cause vasoconstriction of the uterine vessels and reduce uterine blood flow are of concern but this, has not been demonstrated in human beings. Benzodiazepines were associated with oro-facial abnormalities but again have not been proven in prospective studies. The inhalational agents, narcotics, intravenous agents and local anaesthetics have long been used safely during pregnancy.

There is a slight increase in miscarriages for OR personnel found during a meta-analysis of anaesthetic exposure in the workplace.

DRUGS AND PREGNANCYDrugs offered for use in pregnancy aregrouped into one of five categories:A. Controlled studies show no riskB. No risk in animal studies or no risk supported

by controlled human studiesC. Animal studies indicate a risk but no human

studies availableD. Evidence of foetal risk but benefits outweigh

risk.X Evidence of high risk to foetus, which

outweighs benefitsNA. Not applicable


Anaesthet/c Management of aPregnant Patient for Non-Obstetric surgery 28 R. Gopinath

Types of drugs taken during pregnancy• Drugs of abuse: Opioids & opiates, marijuana,

cocaine, alcohol and nicotine• Sedatives: Benzodiazepines (class D orX)• Oral contraceptives (low risk, evidence

uncertain), cardiac glycosides (safe)• Antibiotics (most class B, although

aminoglycosides can have foetal toxicity and tetracyclines may give congenital defects)

• Antiparasitics (class C, except quinine, class X)

• Anti-asthmatic drugs (GCs may have latent effects and reduce birth weight, anti-histamines may result in blindness)

• Relaxants/sympathomimetics etc (class C)• Diuretics (most class D)• Anticoagulants (not recommended)• Anti-viral drugs (most category C)

Maternal Pharmacokinetic VariablesDuring pregnancy, a number of

physiological changes occur that affect drug absorption, uptake and metabolism.These changes include:• Changes in body fluid volume• Changes in cardiovascular parameters• Changes in pulmonary function• Alterations in gastric activity• Changes in serum binding protein

concentrations and occupancy• Alterations in kidney function

These maternal variables determine the maternal and foetal therapeutic/toxic responses to drugs! Specifically:• Pregnancy is associated with increased

cardiac output (-30%) and plasma volume (-50%) = increased Vd

• Maternal aqueous and fatty tissue spaces increase dramatically in pregnancy (10-30 weeks mainly); total body water increases by -8 L (mostly extracellular water; 40% maternal, 60% foetal/placental)

• Reduction in motility of stomach and gut - increased intestinal transit time (-30-50%) (P4 effect?) and increased mucus formation = raised gut pH

• Nausea and vomiting may also affect gut

transit time and pH.• Decreased serum albumin concentrations

(-25%), but unchanged alpharacid glycoprotein. Binding sites also taken up by steroid and peptide hormones (= more free drug)

• Glomerular filtration rate increases (-50%) with renal blood flow (-50%), resulting in increased renal excretion & creatinine clearance. Rates of hepatic enzyme activity may also be increased (i.e. phenytoin metabolism) or decreased (theophylline/ caffeine) ?steroid effects

• Hyperventilation and increased pulmonary blood flow = increased alveolar uptake of inhaled drugs (i.e. anaesthetics)

Drug disposition in the maternal-foetal unitDrugs that reach the foetus are (almost)

always administered to the mother!Drug -> Mother-> Placenta -> Foetus -> Placenta-> Mother -> Excretion

Foetal Pharmacokinetic Variables• Blood flow through the placenta (maternal

side) increases during gestation (50 ml/min @ 10 weeks of pregnancy - 600 ml/min @ 38 weeks).

• Foetal plasma binding proteins differ from maternal concentrations: albumin 15% > than maternal, but alpharacid glycoprotein -37% lower (so free fractions of basic drugs such as propranalol and lidocaine are elevated)

• Foetal plasma proteins also appear to bind some drugs with lower affinity than in adults (i.e. ampicillin, benzylpenicillin)

• Ion trapping: Foetal plasma pH > maternal: base drugs (i.e. salicylate) are more ionized on the foetal side, hence lesser drug crosses the placenta back to the maternal plasma = apparent accumulation in foetal plasma. Principle also applies to metabolites (more polar, less mobile)

• Fcetal liver expresses metabolizing enzymes (i.e. CYPs), but metabolizing capacity is less than that of mother (some enzymes are foetal- specific)

• Drugs transferred across the placenta undergo first pass through the foetal liver before reaching systemic circulation (modulated by



ductus venosus shunt, 30-70% by pass)• Foetal kidney immature: GFR is reduced,

increasing with gestational age but only 2-4 ml/min at term (3% of cardiac output vs 25% in adult). Anion (i.e. penicillin) secretion very low, cation (i.e. cimetidine) secretion is efficient.

• Foetal urine enters the amniotic fluid which may be swallowed by the foetus (however, foetal renal blood flow is only 5% of the blood flow)

Placental PharmacokineticsCritical factors that affect drug transfer

across the placenta:• Physicochemical properties i.e. lipid solubility,

ionization, size, protein binding characteristics.

• Transfer of flow-limited drugs affected by placental flow.

• Compounds that alter blood flow alter maternal drug disposition and placental transfer.

• Placental metabolism (dealkylation, hydroxylatior, demethylation) affects drug transfer across the placenta (usually relatively minor effect compared to foetal or maternal liver).

• Foetal metabolism may also be significant, but may change during pregnancy.

Adverse Effects of Drugs on the Foetus DuringPregnancyMECHANISM:1. Effects on maternal tissues primarily, with

only indirect (secondary) effects on the foetus2. Direct effects on developing foetal tissues3. Indirect effects via interference with the

function of the placenta, i.e., placental transferor placental metabolism

TYPE OF EFFECTS:• Teratogenicity (i.e. thalidomide) - readily

detected at, or shortly aftet, birth• Long term latency (i.e. diethylstilbestrol -

increased risk of vaginal adenocarcinoma after puberty, or abnormalities in testicular function and semen production)

• Impaired intellectual or social development (i.e. exposure to phenobarbitone- alters

programming of the brain)• Predisposition to metabolic diseases (i.e.

Barker hypothesis - low birth weight associated with increased risk of diabetes, hypertension, heart disease in adulthood)

DRUGS KNOWN TO EXERT SIGNIFICANT EFFECTS ON THE FOETUS:

Aminopterin, aminoglycosides, barbiturates, chloramphenicol, chlorpropamide, cortisone, diazepam, diethylstilbestrol, ethanol, heroin, iodide, isotretinoin, methadone, methyltestosterone, methylthiouracil, metronidazole, norethindrone, phenytoin, tetracycline, thalidomide, trimethadione, valproic acid, warfarin

Maintenance of uterine perfusion and maternal oxygenation determine and preserve foetal oxygenation. These are of concern and vital for any anaesthetic during pregnancy. Avoid maternal hypoxia and hypotension at all costs and one should be aware of the effects of all agents used on the maternal cardiovascular system and oxygen delivery.

The most difficult perioperative problem is preterm delivery, which is the leading cause of foetal death due to preterm labour. Prevention and management of the same is very important. The anaesthetic management per se is not related as much as the disease process for the surgical intervention and surgery itself.

ANAESTHETIC MANAGEMENTPerioperative management starts with

assessment preoperatively and should include establishment of pregnancy if in doubt, counseling the patient on the risks of anaesthesia (for the foetus on continuation of pregnancy and so considering delaying surgery till the second trimester with explanation of teratogenicity) and the chances of spontaneous miscarriage, the symptoms of preterm labour and the need for uterine displacement to the left if needed. Documentation of the date of the LMP should be recorded.

Preoperative medications to allay anxiety or pain should be given as appropriate and not withheld, since elevated endogenous maternal



catecholamines will reduce uterine blood flow. Prophylaxis against aspiration should be considered and a combination of an antacid (nonparticulate), H2 -receptor blocker or metoclopramide administered. The obstetrician should be involved and perioperative tocolysis discussed. Indomethacin (oral or suppository) and magnesium sulfate as an infusion are commonly used. Indomethacin has few anaesthetic implications but magnesium use should be viewed with caution due to its interactions with neuromuscular blocking agents and the risk and management of hypotension during potential blood loss and volume replacement.

Intraoperative management is not influenced by the anaesthetic technique as long as maternal oxygenation and perfusion is maintained. A review of 49,000 consecutive pregnancies found that 0.14% required surgery during pregnancy. There was no correlation between the type of surgery, type of anaesthetic, trimester in which surgery occurred, length of surgery, estimated surgical blood loss, or the length of anaesthesia and the outcome of the pregnancy.

Monitoring should include blood pressure, oxygenation, ventilation and temperature. Blood glucose should be checked if the procedure is prolonged. If the surgical field is not a hindrance, continuous or intermittent foetal monitoring should be performed after 20-24 wks gestation to ensure the intrauterine environment is optimized. Loss of beat-to-beat variability is normal after anaesthetics are administered, but decelerations are not. They may indicate the need to increase maternal oxygenation, maintain or increase maternal blood pressure, further uterine displacement, reduce surgical retraction, or begin tocolytic drugs. Foetal monitoring can help assess the adequacy of uteroplacental circulation and foetal perfusion during cardiopulmonary bypass, induced hypotension or procedures with major blood loss and volume shifts.

General anaesthesia should include full preoxygenation and denitrogenation, rapid sequence induction with cricoid pressure, high FI02, slow reversal of relaxants to prevent acute rise in acetylcholine that might induce uterine contractions. Inhalational agents should be kept

below 2.0 MAC to prevent cardiovascular compromise. During the first trimester ketamine at doses of > 2.0 mg/kg may cause uterine hypertonus. Nitrous oxide and propofol may be used. Propofol has recently been shown to reduce oxytocin-induced contractions of the uterine smooth muscle. Early pregnancy does not decrease the concentration of propofol required for loss of consciousness. The increase in \nucosal vascularity and potential for difficult airway must be kept in mind during laryngoscopy.

Regional anaesthesia is advantageous in reducing drug administration and reducing the concerns of teratogenicity during the first trimester and minimizing changes in foetal heart rate variability later in gestation. Prevention of hypotension with adequate preload and uterine displacement and aggressive treatment with ephedrine if needed, is mandatory. The dose of local anaesthetic for central neuraxial blocks can be reduced by one-third from that for the nonpregnant patient due to the increased vascularity in the spinal canal with epidural vein engorgement. Regional anaesthesia provides excellent postoperative pain control while reducing maternal sedation needs and maintaining FHR variability.

Postoperatively, monitoring of the foetal heart rate and uterine activity should be continued. Preterm labour must be treated aggressively and at the earliest sign. The patient should be kept in a location like the labour or delivery suite and provision of nursing expertise in the surgical recovery area should be made available. Systemic pain medications will reduce the foetal heart rate variability and this should be borne in mind during monitoring. Regional techniques are thus best suited and should be used wherever feasible. The risk of thromboembolism is very high in these patients and hence they should be mobilized early, which also entails good pain relief postoperatively. In the recovery period also, good maternal oxygenation and left uterine displacement should be maintained. The help of a paediatrician should be enlisted in the management of the patients when the foetus is of a viable gestational age so that preterm labour and delivery can be managed as well as counseling for the parents.



SPECIAL SITUATIONSThere are specific anaesthetic

considerations for unusual situations like trauma, neurosurgery, foetal surgery and laparoscopic surgeries.

Emergency surgeryAppendicectomy and adnexal masses

are the most frequent conditions needing surgical treatment. In one study, parturients undergoing appendicectomy had an incidence of 18% of postoperative pulmonary oedema or ARDS. Factors of risk for the same were gestational age> 20 weeks, preoperative respiratory rate of more than 24 breaths/ min, preoperative temperature> 100.4 degrees F, a fluid load ( I/O) greater than 4 liters in the first 48 hrs, and concomitant use of tocolytic agents. Anaesthetists should be conservative in fluid management and have central venous pressure monitoring should there be a fluid overload.

TraumaTrauma is the highest cause of maternal

death. Foetal loss in these situations is due to maternal death or placental abruption. An early ultrasound should be done in the emergency room itself to determine viability of the foetus. The mother should receive all needed diagnostic tests to optimize her management, with lead shielding for the foetus when possible. Exposure to less than 5 rad does not increase the risk to the foetus. Ultrasound or MRI is safer.

There are a few indications for emergency caesarean delivery and would include:1. A stable mother with a viable foetus in distress2. Traumatic uterine rupture.3. Gravid uterus interfering with intra-abdominal

repairs in the mother.4. A mother who is unsalvageable with a viable

foetus.

If the foetus is pre-viable or dead, optimizing the mothers’ condition takes precedence. Vaginal delivery at a later date is better than an emergency caesarean section or a laparotomy.

NeurosurgeryNeurosurgical procedures such as an

aneurysm or AVM repair may be required in this age group. All the usual anaesthetics can be used safely and foetal monitoring will be helpful especially when certain techniques are planned.

Induced hypotension reduces uterine perfusion although most agents like SNP, NTG, hydralazine, esmolol, and inhalational agents have been used safely. Foetal monitoring will determine if uterine perfusion is impaired. The anaesthetist should still provide all necessary care for optimal outcome of the mother while informing the surgeon of any concerns. Hyperventilation reduces maternal cardiac output and shifts the ODC to the left thus decreasing release of oxygen to the foetus. High doses of mannitol have been shown to cause foetal dehydration in animals but should not cause concern in the clinical situation. Endovascular management of acute conditions like ruptured intracranial aneurysms has been successfully undertaken during pregnancy. Foetal shielding should be used at all times.

Foetal SurgeryFoetal surgery is performed in very few

centers and for limited indications. The major problem is postoperative preterm labour. Patients often receive preoperative indomethacin and perioperative magnesium sulfate for tocolysis. A high dose of inhalation agents are used for maternal and foetal anaesthesia and for uterine relaxation during surgery and the possibility of reduced uterine perfusion is to be kept in mind.

Laparoscopic surgeryLaparoscopic procedures have been

employed to avoid laparotomy when abdominal pain presents a diagnostic challenge during pregnancy, as well as for some surgical procedures amenable for such surgery like cholecystectomy. Animal studies have shown that pneumoperitoneum with C02 does not cause significant foetal haemodynamic changes, but does induce foetal respiratory acidosis. Normalizing maternal ETC02 produces late and incomplete correction in the foetus. It is important to maintain intra-abdominal pressure as low as possible and limit operative time to the minimum.



Arterial sampling for blood gas analysis is necessary to normalize maternal PC02 if the procedure is'prolonged or difficult. Other technical alterations during pregnancy should include foetal shielding during cholangiograms, pneumatic stockings, left lateral table tilt and an open technique for trocar insertion.

Cardiothoracic surgeryCardiothoracic surgery requiring bypass

has also been successfully performed during pregnancy. The increase in blood volume and cardiac output is maximal at 28-30 weeks and this is the time of high risk for decompensation in patients with cardiac lesions as also immediately post partum. After delivery, the release of aortocaval compression and autotransfusion of uteroplacental blood increases the cardiac output maximally. Those who have severe symptoms and are not responsive to medical management, benefit from surgical interventions, and this should, where possible, be performed in the second trimester when the major risk of teratrogenecity due to drugs, radiation and low flow states of bypass is past and pre term labour is less likely. Combined Caesarean section and bypass too have been successfully performed. Surgery should not be withheld if indicated since mortality is comparable in the mother with non-pregnant states.

After 24 weeks gestation, the foetal status should be monitored and uterine displacement maintained to optimize uterine perfusion. Optimal pressures and flow on bypass are controversial and foetal monitoring is a sensitive measure of perfusion and should be used to optimize flows on bypass. Foetal bradycardia commonly occurs during onset of bypass and slowly returns to baseline with little or no beat-to-beat variability. Hypothermia can oe used although some authors advocate warm

heart surgery. It is essential to avoid high dose vasopressors if possible, to prevent its effect on uterine blood flow, however, optimizing the mothers’ condition is the best way to ensure a good outcome for the foetus.

SUMMARYSurgery during pregnancy may be

necessary and anaesthetists should reassure the mother that anaesthetic agents and techniques do not put the foetus or the pregnancy at risk. Prevention of preterm labour is the greatest concern and may require perioperative use of tocolytics. Good postoperative pain management without sedation will aid in early diagnosis and management of preterm labour and mobilization to prevent thromboembolic complications.

REFERENCES

1. Loebstein, R, Lalkin A, Koren G. Pharmacokinetic changes during pregnancy and their clinical relevance. Clin Pharmacokinet 1997 33(5):328-343

2. organ DJ. Drug disposition in mother and fetus. Clin Exp Pharmacol Physiol 1997 24:869-873.

3. Bailey B, Shinya I. Breast-feeding and maternal drug use. Ped Clin North America 1997 44:41-54.

4. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. New Eng J Med 1998: 338(16): 1128-1137.

5. Garland M. Pharmacology of drug transfer across the placenta. Obstet Gynecol Clin Nth Am. 1998 25(1) 21-42.

6. Boiven JF. Risk of spontaneous abortion in women occupationally exposed to anaesthetic gases: a metaanalysis. Occup Environ Med 1997; 54: 541-8.

7. Friedman JM. Teratogen update: anaesthetic agents, Teratology 1988; 37: 69-77.

8. Hunter JG. Carbon dioxide pneumoperitoneum induces foetal acidosis in a pregnant ewe model. Surg Endosc 1995; 9: 272-9.

9. Rosen MA. Management of anaesthesia for the pregnant surgical patient. Anesthesiology 1999; 91: 1159-63.

10. Weiss BM. Outcome of cardiovascular surgery and pregnancy: a systemic review of the period 1984- 1996. Am J Obstet Gynecol 1998; 179: 1643-53.



The single most significant major change in the practice of paediatric anaesthesia in the last two decades has been the introduction of regional anaesthetic techniques. Acceptance of the concept that infants and children feel pain and suffer from its consequences has revolutionized the practice of paediatric anaesthesia in that regional anaesthesia and analgesia have become an integral part of paediatric anaesthesia. In children, light general anaesthesia is required to institute regional blocks. The advantages of this technique are minimal general anaesthesia, preemptive analgesia and attenuation of the stress response to surgery.

Lumbar epidural anaesthesia is very useful in children as an epidural catheter can be positioned and the local anaesthetic drug deposited close to the segment of the cord supplying the dermatomes around the proposed surgical incision. The safety is of a lower volume and dose of local anaesthetic, which by a rough formula is 0.1-0.2 ml/kg/segment to be blocked. The catheter passes quite easily in babies even to levels of the cervical cord. The exact placement can be determined by measuring the distance to be traveled, on the catheter. Recently, connecting a nerve stimulator with a metal needle to the saline filled epidural catheter and passing a current will stimulate the segments of the cord at the tip of the catheter and thus confirms the position of the catheter tip. This produces twitches in the muscles supplied by those segments. Position and spread can also be confirmed by omnipaque (iohexol) injection.

In children, the skin-epidural distance varies with age and weight. A rough guide is 1,5mm/ kg till 1 yr and 1 mm/kg thereafter. Since this is a very short distance, care has to \ be taken not to overshoot this distance and puncture

the dura. The exact technique for introducing an epidural needle in children is different from that of adults. In adults, either a hanging drop or a loss of resistance with incremental advancement of the needle identifies the epidural space. In children, hanging drop technique and incremental advancement of needle is not practicable due to the short skin-epidural distance. The needle is continuously and steadily advanced with a continuous checking for loss of resistance to saline. There is a distinct increase in resistance to the advancement of needle tip and also on the plunger of the syringe, when the needle tip enters the ligamentum flavum. The loss of resistance when the needle leaves this ligament and enters the epidural space is also unequivocally distinct.I prefer saline to elicit this, as it is very easy, obvious and avoids the risks of air embolism, which could be catastrophic considering their size and the volumes of air normally injected.

Many drugs have been used for postoperative analgesia. Various authors have used morphine, fentanyl, pethidine, buprenorphine, pentazocine, tramadol, ketamine clonidine, neostigmine and midazolam. Use of the opioid drugs in neonates and infants has to be done in an ICU setting where an anaesthesiologist is constantly available. This is a luxury many of us do not have. So in this age group we rely solely on bupivacaine in a concentration of 0.05 - 0.1- % solution. In older children, we have used ketamine 0.25-0.5 mg/kg and buprenorphine1-2 microgram/kg. Ketamine has the advantage that there is no fear of any possible respiratory depression, but the problem of unpredictability of duration of action and the possibility of hallucinations remain. Buprenorphine, with its extreme lipophilicity, is very predictable in action, lasts about 24-30 hours, and in the dose mentioned has not given any respiratory depression in any of our patients
