anesthesiology lectures surgery module iii. review of 2 nd year competencies: pharmacologic...

Anesthesiology Lectures

Surgery Module III

Review of 2nd Year Competencies: Pharmacologic Principles of Local Anesthesia

Regional Anesthetic Techniques Infiltration AnesthesiaCentral neuraxial Anesthesia

Subarachnoid Block Epidural Anesthesia Combined Spinal-Epidural

IV Regional AnesthesiaPeripheral Nerve Block

Drugs that produce transient and reversible loss of sensation or feeling in circumscribed areas in the body without loss of consciousness

-

R

R

R -

R

R

N/

-\----

+HC O C

O- -

II--

Ester

NH C CO- -II

-Amide

Aromatic Ring IntermediateLinkage

Terminal Amine

Aromatic Ring Responsible for lipophilicity of

compounds Lipophilicity – tendency of the

compound to associate with membrane lipids

Amine Portion Secondary and tertiary amine is

associated with water solubility Compounds lacking the amine

portion are insoluble in water (e.g. Benzocaine)

R

R

N/

-\----

+H

R

R

R -

Intermediate Linkage Anesthetics are connected to the

aromatic molecule via an ester or amide linkage

Basis for classification of local anesthetics

Determines the route of metabolism

Determines allergic potential

-

C O C

O

- -II

--Ester

NH C C

O

- -II

-Amide

Aminoesters Cocaine Procaine Chlorprocaine Tetracaine Benzocaine

Ester derivatives of para-aminobenzoic acid (known allergen)

Hydrolyzed by plasma cholinesterases*

Unstable in solution

*Cocaine is metabolized by hepatic carboxylesterase

C O C

O

- -II

--Ester

AminoamidesLidocainePrilocaineMepivacaineEtidocaineBupivacaineRopivacaineLevobupivacaine

With amide linkages Undergoes enzymatic

degradation in the liver

More stable in solution

NH C C

O

- -II

-Amide

Local anesthetics are weak bases Exists as a nonionized base and cationic

form in physiologic pH

BH+

B + H+

- NH – C – CH2 – N – H

OII

C2H5

C2H5

/

\- NH – C – CH2 – N

OII

C2H5

C2H5

/

\

+

BH+B

Na+

Na+

Na+

Na+

Na+

Na+

Na+Na+

Na+

Na+Na+

Na+Na+

epineurium

neuronal membrane

axoplasm

BH+

B + H+

DEPOLARIZATION

BH+

B + H+

- NH – C – CH2 – N – H

OII

C2H5

C2H5

/

\- NH – C – CH2 – N

OII

C2H5

C2H5

/

\

+

BH+B

POTENCYCorrelate with Lipid SolubilityMore lipid soluble, more potent

Lipid Solubility

Potency

Lidocaine 46 Intermediate

Bupivacaine 390 High

Miller, RD. Miller’s Anesthesia, 6th ed. 2006

ONSET OF ACTION Correlate with pKa

pKa range of local anesthetics: 7.8 – 9.2 Lower pKa, lower ionization, shorter time of onset Non-ionized form responsible for membrane

penetration INFLAMMATION: Local anesthetics exists in ionized

form

Correlate with concentration

pKa Onset

Lidocaine 7.8 Quick

Bupivacaine 8.1 Intermediate


Concentration

Onset

Bupivacaine

0.5% Quick

0.75% Intermediate

DURATION OF ACTION Correlate: Protein Binding and Lipid

Solubility Local anesthetic with higher protein binding stays in

the protein receptor longer

Influenced by Peripheral Vascular Effects

Protein Binding

Duration

Lidocaine 64 Intermediate

Bupivacaine

95 Long


DIFFERENTIAL BLOCKADE The ability of local anesthetics

to cause differential inhibition of sensory and motor activity Low Concentrations: Selective

blockade of preganglionic sympathetic nervous system B fibers

High Concentrations: interrupt conduction in small C fibers and small- and medium-sized A fibers

PAIN TEMPERATURE TOUCH PRESSURE MOTOR

Type Function

Aα Proprioception; somatic motor

Aβ Touch, pressure

Aγ Motor to muscle spindles

Aδ Pain, Temperature

B Pain

C Postganglionic sympathetics


Dosage of Local Anesthetic Addition of Vasoconstrictor Site of Injection Carbonation and pH

Adjustment Mixture of Local Anesthetics

Dosage Increasing dosage (in volume or concentration)

Decrease onset time Increase duration of action Enhance quality of block Increase potential for toxicity

VasoconstrictorsBenefits of Epinephrine

Prolongation of local anesthetic block Increased intensity of block Decreased systemic absorption

Contraindication: local anesthesia around end arteries (finger, ear, penis)

Other Vasoconstrictors: Phenylephrine, Norepinephrine

Miller, RD. Miller’s Anesthesia, 6th ed. 2006Stoelting, RK. Pharmacology and Physiology of Anesthetic Practice, 4th ed. 2006.

Site of InjectionOnset time

Brachial Plexus Blocks (Peripheral Nerve Block) Longest latencies and duration: Anesthetic deposited at some distance from the nerve Anesthetic must diffuse through tissue barriers Slow onset time

Subarachnoid Space: cord lacks nerve sheath local anesthetic deposited in the immediate vicinity of

the cord Fast onset time

Site of InjectionSystemic Toxicity

Higher in areas of high absorption rate

Zink W et al. Anästhesist 2003;52: 1102-23(Mod. nachBraid u.Scott

Toxic Plasma Level

Intravascular

Peritonsillar / Intrapleural

Intercostal

EpiduralPlexus Blockade

Subcutaneous

0 5 10 15 20 25 40 60 min

Carbonation and pH AdjustmentSodium Bicarbonate

Accelerates the onset Increase in the pH increases the amount of

uncharged drug, enhancing the rate of diffusion across the nerve sheath

Injection less painful


Mixtures of Local AnestheticsUsed to compensate for the short duration

of action of rapid acting agents, and the long latency of longer acting agents

Caution in using maximum doses of 2 local anesthetics: toxicities should be presumed to be additive.


Systemic Toxicity Central Nervous System

Toxicity Cardiovascular Toxicity Methemoglobinemia Allergies Local Tissue Toxicity

Systemic ToxicityCNS more susceptible to the actions of

systemic local anesthetics than the CVS Dose required to produce CNS toxicity is lower

than levels producing cardiovascular collapse Exception: bupivacaine (CVS before CNS)

Prevention Aspiration to detect inadvertent vascular entry Addition of a vasoconstrictor (epinephrine)


Na+

Na+

Na+

Na+

Na+

Na+

Na+Na+

Na+

Na+Na+

Na+Na+

epineurium

neuronal membrane

axoplasm

BH+

B + H+

DEPOLARIZATION

BH+

B + H+

- NH – C – CH2 – N – H

OII

C2H5

C2H5

/

\- NH – C – CH2 – N

OII

C2H5

C2H5

/

\

+

BH+B

With hypercapnia and Acidosis

1. ↑paCO22. ↓ic pH3. ↓pr binding

Chlorprocaine

Procaine

Prilocaine

Lidocaine

Mepivacaine

Etidocaine

Bupivacaine

Tetracaine

Dibucaine

Cocaine

INC

REA

SIN

G T

OX

ICIT

Y

12mg/kg

12mg/kg

8mg/kg

4.5mg/kg; 7mg/kg*

4.5mg/kg; 7mg/kg*

4mg/kg

3mg / kg

3mg/kg

1mg/kg

3mg/kg

* With epinephrine

Cousins. Neural Blockade, 3rd ed.1998Morgan. Clinical Anesthesiology 3rd ed. 2002

ExcitatoryCircumoral numbnessTongue paresthesiaDizzinessBlurred visionTinnitusRestlessness /Confusion/AgitationShiveringMuscular twitchingGeneralized convulsions (tonic-clonic)

DepressionCessation of seizure activityRespiratory depressionRespiratory arrest

CNS depression

Inhibition of the activity of inhibitory and facilitatory circuits

Further increase in dose

Stimulation of glutamate release

Initial blockade of inhibitory pathways in Cerebral Cortex

Increase in dose of LA


Assist ventilation Circulatory support Prevent or correct

hypercapnia and acidosis Prevent or correct hypoxemia Control convulsions:

Benzodiazepines Thiopental Propofol

Equipment Necessary prior performance of major conduction blockade:1.Monitors2.Oxygen supply3.Airway Equipment4.Drugs to terminate convulsions


Direct Cardiac Effects Decrease in the rate of depolarization

in the fast conducting tissues of Purkinje fibers and ventricular muscle

Decrease in action potential duration and effective refractory period

Due to a decrease in the availability of fast sodium channels in cardiac membranes

Prevention: Aspiration to detect inadvertent

vascular entry Use of anesthetics with less

cardiotoxicity Levobupivacaine Ropivacaine


Cardiac Resuscitation:1.Secure the airway2.Provide oxygenation and ventilation3.Institute cardiac compressions4.Medications

Epinephrine, first lineAmrinone, may be beneficialBretylium

Direct Peripheral Vascular EffectsBiphasic effect on peripheral vascular

smooth muscle Low doses of lidocaine and bupivaine:

vasoconstriction Higher doses: vasodilatation (increased

arteriolar diameter) COCAINE: consistently causes vasoconstriction

at all concentrations by inhibiting the uptake of norepinephrine by premotor neurons (vasogenic vasoconstriction)


Hallmark: cyanosis unresponsive to high-flow oxygen in the absence of cardiac or pulmonary disorders

Results when hemoglobin’s oxygen-carrying capacity is greatly decreased due to an increased amount of methemoglobin in the blood

Frequently seen in PRILOCAINE

Hegedus and Herb. Benzocaine-induced Methemoglobinemia. Anesth Prog 52:136–139 2005

Oxidizing Agents Known to Induce Methemoglobinemia

AcetaminophenAlloxans Aminophenols Ammonium nitrateAmyl nitrate

Articaine

Benzocaine Chloroquine Colbalt

Dapsone DiamonidiphenylsulfoneDimethylamine

EMLA*Hydroxylamine

Lidocaine Menthol

Methylene blueNitratesNitrites

Nitrofurans Nitrogen oxideNitroglycerinNitrosobenzene QuinonesPara-toluidine PhenolsPhenylhydroxylamine Phenytoin Piperazine

Prilocaine Primaquine

Propitocaine PyridinePyridium Sodium nitroprussideSulfonamidesSulfones Toluidine

Hegedus and Herb. Benzocaine-induced Methemoglobinemia. Anesth Prog 52:136–139 2005

Infiltration AnesthesiaCentralneuraxis anethesia• Spinal anesthesia• Epidural Anesthesia• Combined Epidural and

Spinal AnesthesiaIV Regional BlockPeripheral Nerve Blockschelsonbaum.blogspot.com

Extravascular placement of local anesthetic to the area to be anesthesized

Dose: volume depends on the area to be

anesthetized More volume may be given in dilute

concentrations Particular attention to toxic dose of the

local anesthetic. Onset: almost immediate Duration of action: prolonged with

epinephrineMiller, RD. Miller’s Anesthesia, 6th ed. 2006Stoelting, RK. Pharmacology and Physiology of Anesthetic Practice, 4th ed. 2006.

www.moondragon.org

Subarachnoid Block (Spinal Block) Epidural Anesthesia Combined Spinal and Epidural

Anesthesia

The temporary interruption of nerve transmission produced by injection of a small amount of local anesthetic solution (with or without opiates) into the subarachnoid space

Provides sensory and motor blockade below the level of the block

Indications: Operations on the abdomen, urologic, rectum, perineum and lower extremity procedures that are amenable to spinal anesthesia

services.epnet.com

www.med.umich.edu

Local anesthetic agent - Variable pharmacologic properties

Volume and dose Increasing the dose: increase the extent of

cephalad spread and duration of block Patient position and local anesthetic

baricity Influences the spread and level of the block

Addition of vasoconstrictors Addition of opioids

Prolong duration of analgesia and increase tolerance for tourniquet pain

Anatomic and Physiologic Factors Examples: obesity, pregnancy, increased

intraabdominal pressure, previous spine surgery, spine deformities, age

Baricity: •specific gravity of the local anesthetic solutions relative to cerebrospinal fluid

•Hypobaric•Isobaric•Hyperbaric

Avoids manipulation of the airway: patients with reactive airways

Difficult intubation: no manipulation of the airway

Avoids complications of difficult tracheal intubation Avoids side effects of general anesthesia

Nausea, vomiting, prolonged emergence or drowsiness Urologic Surgery: Early recognition of signs of complications

of TURP (headache, restlessness, confusion, etc.) Orthopedic Surgery: Less blood loss

“Full stomach”: lightly sedated, less likely to aspirate

NSD, Caesarean section: mothers are awake for early bonding

Intrathecal opiate administration provides high quality post-operative analgesia

Technique is simple

Patient positioned Landmarks identified Aseptic Preparation Local infiltration of LA at

injection site Lumbar puncture with spinal

needle Note presence of CSF, blood,

paresthesia Note if CSF is free flowing

Intrathecal injection of LA

services.epnet.com

1. Infection and other lesions at the site of injection

2. Sepsis3. Shock or severe hypovolemia4. Preexisting disease of the spinal cord -

susceptible to neurotoxicity of the local anesthetic (e.g. demyelinating disease)

5. Increased intracranial pressure6. Coagulopathies7. Refusal of patient, patients who are

psychologically or psychiatrically unsuited8. Lack of skill and experience of the

anesthesiologist

1. Deformities of the spinal column2. Chronic severe headache or backache3. Blood in the CSF that fails to clear after 5 to

10 ml of CSF have been aspirated4. Failed spinal tap after three attempts, unless

you can obtain the assistance of another experienced colleague

5. Minor abnormalities of blood clotting, including "mini" doses of heparin administered up to the time of surgery

www.worldmedassist.com

Hypotension Bradycardia Respiratory inadequacy High spinal anesthesia Postdural puncture headache Urinary retention Transient radicular neuropathy Infection

Meningitis / Encephalitis Adhesive arachnoiditis

Epidural hematoma

Hypotension: Consequence of sympathectomyResponds to fluids, vasopressors

Bradycardia: Consequence of sympathectomyCardiac accelerator fibers

Postdural puncture headache: Increased incidence in females, younger age, use of larger needles

Transient Radicular Neuropathy: Increased incidence with lidocainePainful, self-limiting

Frank Neurologic Injury: Rare. In continuous techniques using small-bore catheters

Injection of a certain amount of local anesthetic (with or without opiates) into the lumbar or thoracic epidural space

A catheter is inserted after the epidural space has been located with a needle Controlled local anesthetic delivery “Redosing” of anesthesia for long

procedures Post-operative analgesia with local

anesthetics and opiates Indications: abdominal, thoracic, and

lower extremity procedureswww.webmm.ahrq.gov

Hip Surgery: Decrease blood loss and incidence of deep venous thrombosis

Thoracic Surgery: superior pain control, less sedation, better pulmonary function

Rapid recovery of gastrointestinal function Early ambulation Others:

Labor analgesia Interventional pain modalities

www.3m.com

[Similar to that of Spinal Anesthesia]

Total Spinal Anesthesia Local Anesthetic Toxicity Spinal / Epidural hematoma

concerns regarding catheter placement and removal in patients on anticoagulation

Epidural Abscess

ww

w.s

ciel

o.br

Patient positioned Landmarks identified Aseptic Preparation Local infiltration of LA at injection site Epidural puncture with Tuohy needle

Epidural space identified: LORT, hanging drop technique

Note +/- of CSF, blood, paresthesia Epidural catheter threaded into space Test for inadvertent intravascular and

intrathecal placement of catheter Epidural injection of LA

Dermatome

Procedures

T4-T5 Nipple area (T4) Upper abdominal surgeries

T6-8 Xiphoid (T6) Intestinal surgery (including appendectomy), gynecologic pelvic surgery, and ureter

T10 Umbilicus Transurethral resection, vaginal delivery, hip surgery

L1 Inguinal ligament Transurethral resection without bladder distension; thigh surgery; lower limb amputations

L2 to L3 (knee and below) Foot surgery

S2 to S5 (perineum) Perineal surgery, hemorrhoidectomy, anal dilation

www.aaofl.com

Intravenous administration of a local anesthetic into a tourniquet-occluded limb. Local anesthetic diffuses from the

peripheral vascular bed to nonvascular tissue such as axons and nerve endings

Retrograde spread of distally injected local anesthetic

Indications: Short arm/leg procedures

Drug of choice: lidocaine

IntravenousR

egional Anesthesia

Requirements: no disruption of the venous system of the involved upper extremity because the technique relies on an intact venous system

Safety and efficacy depend on the interruption of blood flow into the involved limb and gradual release of the occluding tourniquet

Functions of tourniquet Isolate the limb from systemic

circulation (prevention of blood loss) Isolate the systemic circulation from

the limb (in IVRA)

1. A tourniquet is placed on the proximal arm of the extremity to be blocked. Patency of the cuff is confirmed.

2. A small IV intravenous catheter is introduced in the dorsum of the patient's hand of the arm to be anesthetized

3. The arm is then elevated and at least for 1 minute to allow passive exsanguination,

4. Cuff is inflated (100mmHg above systolic BP)

5. The extremity is then lowered and the local anesthetic is slowly injected through the previously inserted IV catheter

IntravenousR

egional Anesthesia

Tourniquet –related complicationsLocal anesthetic toxicity – from inadvertent

deflation of tourniquet Increase in systemic blood pressure -

prolonged tourniquet time Tourniquet painNeurologic injury – from compression of

nervesCompartment syndromeLoss of limb – from ischemia

Finucane, B. ed. Complications of Regional Anesthesia, 2nd ed. 2007

IntravenousR

egional Anesthesia

Blockade of brachial plexus, lumbar plexus, and specific peripheral nerves via injection of local anesthetic solutions into tissues surrounding individual peripheral nerves or nerve plexuses

Local anesthetics deposited near the vicinity of the nerve diffuses from the outer surface (mantle) to the center (core) of the nerve along a concentration gradient

Proximal structure: mantle Distal structures: core

Advantages: reduced physical stress (compared to central neuraxis

anesthesia) Avoids airway manipulation and complications

associated with endotracheal intubation Indwelling catheters may be placed for prolonged block

and analgesia Provides surgical anesthesia and postoperative

analgesia Requirements:

Cooperative patient Skilled anesthesiologist Surgeon accustomed to operating on awake patients

Intracranial Blocks Neurosurgery and Scalp Surgeries

Eye Blocks Face Blocks Ophthalmic Nerve Block Maxillary Nerve Block Mandibular Nerve Blocks Cervical Plexus Blocks

Handbook of Regional Anesthesia (ESRA) 2007

Epidural anesthesia Ilioinguinal-Iliohypogastric block Peri-umbilical & Rectus sheath

block Pudendal block


Interscalene block Supraclavicular blocks Infraclavicular blocks Axillary block


Lumbar plexus block Iliofascial block Obturator block Sciatic blocks Ankle blocks


Local anesthetic toxicity Neurologic injury – from mechanical,

pressure, chemical and vascular factors Inadvertent neuraxial block Intravascular injection of local

anesthetics

Why local when I can

already afford imported

anesthesia?

Acknowledgements:Dr. Olivia FloresDr. Claire Layusa

anesthesiology lectures surgery module iii. review of 2 nd year competencies: pharmacologic...

Documents

millers anesthesia

solutionlocal anesthetics

higher protein binding

ionized form responsible

cationic form

amide linkagebasis

lower pka

ionized formcorrelate