total intravenous anaesthesia
TRANSCRIPT
TOTAL INTRAVENOUS ANESTHESIA
Dr Brijesh Savidhan,Department of Anaesthesiology,Travancore Medical College.
INTRODUCTION Total intravenous anesthesia
Technique of GA
Anesthesia via intravenous agents (propofol, narcotics, muscle relaxants)
In boluses/drips
No volatile agents
DEFINITION Method of inducing and maintaining GA exclusively by IV admd
drugs , without simultaneous admn of any inhalnl agents.
Search for suitable drugs and techniques to meet changing demands of advanced diagnostic and therapeutic modalities requiring alleviation of patient discomfort
Safe anaesthesia with rapid pt turnover as in ambulatory care setting, to maximise no of patients
WHY TIVA?
Anaesthesia in non operative locations where inhalational anaesthetics are difficult
Availability of rapid, short acting, easily titratable analgesic and relaxant drugs
Pharmaco-kinetic and -dynamic based IV delivery systems which are portable Eg.TCI
o Monitors to measure the depth of the hypnotic component of the anaesthetic state Eg.entropy
TIVA EQUIPMENTS
ADVANTAGES
Easy titratability of drugs
Superior recovery profile and early discharge
Portable delivery system
Less operating room pollution
No risk of MH
Less PONV
Preserves HPV
Avoid distention air filled spaces in the patient’s body- so better operating conditions for surgeons
Better hemodynamic control
Improved V/Q matching
Better preservation of cerebral autoregulation
Reduced stress response
SPECIFIC INDICATIONS
Airway procedures
Remote locations
MH susceptible
Neurosurgery
Neuro monitoring
PONV risk
Short procedures-CT,MRI
PHARMACOKINETICS AND TIVA
There are different types of pharmacokinetic models -
1. Compartmental models.
2. Physiological models.
3. Hybrid models.
THREE COMPARTMENT MODEL
do not represent any real anatomical entities.
quantify drug movement mathematically
drug is distributed to different tissues within the body at different rates -declining exponential processes- by drug elimination , drug distribution.
Rate constants - describe the rate of these separate exponential processes
The rate constants describe the rate of movement by the drug between the central compartment and each of the other compartments and also the rate of elimination, usually from the central compartment.
LIMITATIONS inter individual pharmacokinetic variability.
They assume immediate mixing of drug in the compartments and therefore cannot be used to describe lung uptake
In practice, a dose of drug given IV does not equilibrate instantaneously
‘static’ model
does not incorporate -altered protein binding, blood loss, haemodilution, which are aspects of the dynamic state
Physiological models
describes drug uptake in the different tissues and the influence of circulation and recirculation on drug distribution.
adjusts the model to the pathological state of the patient.
require a large set of mostly unknown parameters not expected much use outside the research envt.
Hybrid models compartmental models adjusted to physiological parameters
such as cardiac output
Using pharmacokinetic compartmental modeling , computer programs can simulate profiles of drug distribution and elimination.
different pharmacokinetic profiles can grossly affect drug suitability for use by TIVA.
CONTEXT SENSITIVE HALF TIME The time in which the plasma concentration of the drug reduces by
50% after discontinuing an infusion ; ie in the ‘context’ of a specified duration of infusion.
short CSHT desirable if a drug is to be used for TIVA, as it would infer a quick recovery following anesthesia
The time a pt takes to recover from a drug does not necessarily correlate with a in plasma conc. of 50%- practically CSHT -poor predictor of recovery
The plasma concentration at this point may not be one where recovery expected.
EFFECT SITE EQUILIBRIUM lag time between achieving a specific plasma conc. and
observing a particular clinical response.
mathematical or temporal relationship between the conc. in the plasma and the clinical response observed- time taken to equilibrate described by a rate constant (Keo).
time to equilibrate with the effect site -different for different drugs
physical properties of the drug , receptor binding properties influence the delay between achieving plasma concentrations and observing a response .
effect site decrement time, the time taken for the effect site concentration to decrease by a specified percentage- used to predict recovery.
CLINICAL APPLICATION OF TIVATo achieve and maintain a constant plasma conc. over a period
of time
A bolus dose (B) calculated to fill the central compartment to the required concentration.
A constant-rate infusion to replace drug lost by elimination (E) and
An exponentially decreasing infusion that will replace drug lost from the plasma by transfer or distribution (T) to peripheral tissues.
MANUALLY CONTROLLED INFUSION
Bristol infusion regimen for propofol (‘10-8-6’) based on LBW plasma conc of 3.5 µg/ml- adeq. for body surface surgery
premed -3 µg/kg fentanyl – indn with1.0 mg/kg bolus of propofol infusion of 10 mg/kg/h - 10 minutes , 8 mg/kg/h -10 minutes 6 mg/kg/h.
Recovery after procedures lasting up to 90 minutes -5-10 mins
MANUAL INFUSION SCHEMES
Anesthesia Sedation or Analgesia
DrugLoading Dose (µg/kg)
Maintenance Infusion (µg/kg/min)
Loading Dose (µg/kg)
Maintenance Infusion (µg/kg/min)
Alfentanil 50–150 0.5–3 10–25 0.25–1
Fentanyl 5–15 0.03–0.1 1–3 0.01–0.03
Sufentanil 1–5 0.01–0.05 0.1–0.5 0.005–0.01
Remifentanil 0.5–1.0 0.1–0.4 † 0.025–0.1
Ketamine 1500–2500 25–75 500–1000 10–20
Propofol 1000–2000 50–150 250–1000 10–50
Midazolam 50–150 0.25–1.5 25–100 0.25–1
Methohexital 1500–2500 50–150 250–1000 10–50
TARGET CONTROLLED INFUSION
Computer driven infusion device used to achieve a pre-set target plasma concentration of drug
For predictability of drug effect, a specific PK model and control algorithm devpd eg: Diprifusor.
Has dual microprocessor component incorporated into an infusion pump enables to deliver propofol in TCI mode.
Pt body wt, target conc. entered. Visual display- calculated conc. for plasma and
effect compartment, and actual infusion rate.
Total dose infused recorded
Target level selected for induction - adjusted in response to clinical signs -maintain adeq. anesthetic depth.
no need for a bolus induction -initial plasma conc. set
Depth of anesthesia - changed rapidly selecting a new target blood concentration, similar to adjusting a vapouriser during volatile anesthesia.
microprocessor makes relvnt calculns of bolus increment or alterns in the infusion rate to achieve, maintain and alter the blood concentration to any target level.
PUMPS Safe and continuous admn of IV anesthetics - reliable
delivery system, vigilant anesthetist
A simple gravity intravenous infusion can be “piggy-backed” to a carrier line
Pump offers the adv. of more precise dose selection, lower risk of overdose, minimal flow variation from changes in venous pressure or bag height
TYPE OF PUMPS Syringe Pumps:
Use a driver that pushes fluid out of a syringe by advancing its plunger while the barrel is kept stationary.
Small units, light weight, cordless, accurate at very low flow rates. May have program library
Volumetric Pumps:
Use a disposable cassette within IV system that controls rate by a variety of methods
Larger size, added cost of cassette tubing, more susceptible to air bubbles
IDEAL PROPERTIES OF DRUGS USED IN TIVA
Water-soluble to minimize toxicity associated with the solvent
Stable in solution
No perivascular sloughing if extravasated
Given in conc. soln to avoid fluid overloading
Not absorbed by plastics
Does not promote bacterial growth
Rapid onset of action
rapid and predictable recovery
Devoid of adverse side effects
Potent and lipid-soluble
Relatively cheap
Chemically compatible with other drugs.
DRUGS USED IN TIVA Individually or in combination, depending upon the Patient and
Procedure:
Hypnotics Propofol, Ketamine, Benzodiazepines, Etomidate, Barbiturates
Analgesics fentanyl, Remifentanyl, sufentanil, alfentanil,
Muscle relaxants Atracurium, Vecuronium
HYPNOTICS Propofol- most commonly used hypnotic for TIVA No active metabolites
Short CSHT(8 minutes)
Rapid onset
Antiemetic
Not an MH trigger
CBF: Autoregulation and CO2 responsiveness not affected.
Proportional Reduction in CMRO2 and CBF, decrease in ICP
Free radical scavenging-prevention of free radical induced lipid peroxidation
Membrane stabilisation
Anticonvulsant
Induction dose is 0.5 to 1.5mg/kg for loss of consciousness with a maintenance infusion of 80 to 120 µg/kg/min
DISADVANTAGES Propofol related infusion syndrome -Metabolic acidosis, cardiac dysfunction, rhabdomyolysis,
hypertriglyceridemia
Myoclonic phenomenon-imbalance between excitatory and inhibitory phenomena
Pain on injection
Allergic reactions
Bacterial growth
Etomidate – maintains a good cardiopulmonary function and has been used in tiva.
Initial i.v dose 1-2 mg/kg Maintainence 0.02-0.3 mg/kg/min
infusion may be terminated 10 to 15 minutes before the anticipated end of the surgical procedure.
DISADVANTAGES It suppresses the production of cortisol.
High concentration of propylene glycol in etomidate preparation causes hemolysis resulting in hemoglobinuria
Expensive
Ketamine - Ketamine has been successfully used with propofol for TIVA technique.
Loading dose 1 to 3 mg/kg Infusion dose 5 to 20 µg/kg/min
Disadvantage: seizure activity and hypertonus during recovery may occur
Midazolam - Midazolam-opioid combinations can also provide complete anesthesia
Initial i.v bolus 0.2 mg/kg IV Maintainence 8.0 g/kg/min
TIVA for major (cardiac) and/or long operations may be effectively achieved with the combination of midazolam and sufentanil
ANALGESICS
Most commonly used are fentanyl, alfentanil with propofol
Fentanyl Phenylpiperidine derivative synthetic opioid agonist
Analgesia-75-125 times more potent than morphine
Rapid onset
Short duration of action
Highly lipid soluble
Highly protein bound
Minimal pharmacological activity of fentanyl metabolites
Short CHST
Stable hemodynamics
PROPOFOL AND REMIFENTANIL Ideal combination for TIVA. Remifentanil is a very short acting opioid with a
CSHT that varies very little regardless of infusion duration.
undergoes rapid ester hydrolysis with a clearance in excess of 3L/min.
reduced plasma concentration of propofol required for adequate anaesthesia by 50%.
Typical manually controlled remifentanil infusion rate are:
1-2 µg/kg/min for induction
0.1-1.0 µg/kg/min for maintenance, adjusted according to surgical stimulation.
TCI remifentanil target levels are 4-10 ng/L depending on the nature of surgery.
Offset of action is rapid and constant - constant and short CSHT of 3.5 minutes.
remifentanil can be continued till the end of surgery, after propofol has been discontd.
Provision of post operative analgesia essential because the analgesic effects of remifentanil disappears soon after discontinuing the infusion
PROPOFOL AND FENTANYL Most commonly used
When given as an IV bolus injection, effective in 4-7 minutes
Short CSHT of fentanyl makes it possible to continue the opioid infusion even after propofol infusion has been stopped (5-10 minutes before surgery ends
Ensure adequate anesthesia and rapid awakening
Fentanyl Loading dose : 4 - 20 ug/kg , Maintenance dose: 2 - 10 ug/kg/hr Propofol Loading dose: 0.5 – 1.5 mg/kg Maintenance dose: 80- 120 ug/kg/min
DOSES OF OPIOIDS FOR TIVA
Loading Dose (µg/kg)
Maintenance Infusion Rate
Additional Boluses
Alfentanil 25–100 0.5–2 µg/kg/min 5–10 µg/kg
Sufentanil 0.25–2 0.5–1.5 µg/kg/hr 2.5–10 µg
Fentanyl 4–20 2–10 µg/kg/hr 25–100 µg
Remifentanil 1–2 0.1–1.0 µg/kg/min 0.1–1.0 µg/kg
PHARMACOKINETICS AND DRUG SELECTION Anesthesia can be maintained either with intravenous infusions
of drug or with intermittent boluses.
Infusions are preferred because- Greater hemodynamic stability
More stable depth of anaesthesia
More predictable and rapid recovery
Potential lower total dose of drug used (25%-30%)
less respiratory depression
Avoid latency in reaching effect site
Discharge times faster with infusions-30%
Faster PACU requirements -30 minutes
USES OF TIVA
General anaesthetic-neurosurgery, day care surgery
Supplement to regional, local anaesthetic
Sedation analgesia for diagnostic/therapeutic procedures
CONSTRAINTS Cost
Availability of the most suitable drugs and delivery systems
No reliable technique for monitoring plasma concentration of drugs equivalent to End Tidal inhalational agent
monitoring
Increased risk of awareness specially with concurrent use of muscle relaxants
DISADVANTAGES Acquisition costs
Set-up and use greater workload than vaporizers
Early or late respiratory depression
Opioid side-effects- biliary, muscle rigidity, GI motility, pruritus
Adverse events if IV line disrupted
SUMMARY TIVA techniques can provide numerous advantages over volatile
anesthetics.
equipment set-up and cost is greater than using existing vaporizers, appreciable long-term savings.
Improved understanding of drug kinetics, dynamics and interactions has facilitated optimal drug selection and method of administration
Modern infusion technology and TCI lends control to IV techniques to rival vaporizer use.
TIVA is ideal for Day care surgery with large patient turnover
The increasing popularity of TIVA is testament to its ease of use and perceived benefits
TIVA represents a new technique of the speciality with major advantages
THANK YOU