Local Anesthetics

A Case-Based Review

The Na+ Channel- Site of LA Action

www.septodont.ca/.../ english/other/cea_dh01.html

Summary

Block Na+ channels with loss of nerve conduction

Therefore we call the result of LA action…

Conduction Block

Case 1: Mom with Liver Disease

Plan is epidural for laborWhat are key concerns related to use of

0.125% bupivacaine?

Structure and metabolism

Structure: Local Anesthetics

Structure of the LA moleculeHeadTailIntermediate chain

N

Lipophilic Head(Benzene Ring)

Hydrophilic Tail(Quaternary Amide)

Intermediate Chain(Hydrocarbon)

Ester(-CO-)

Amide(-NHC-)

R

R

H+

Adopted from:Barash PG, Cullen BF, & Stoelting RK. (eds) Clinical Anesthesia 1997. J.B. Lippincott

Metabolism

LA Structures: Esters vs. Amides

Main issue: metabolic pathway Esters

Ester hydrolysis by plasma cholinesterase Amides

N-dealkylation and hydroxylation in the liver

This patient has pre-existing liver disease- we would worry about accumulation of the drug

Entiomers

Substances of opposite shape Molecules existing in mirror image forms

Left and right handed

When dissolved in solution rotate polarized light Optical isomers

Important concept in LA toxicity Right handed molecules such as bupivacaine are

more toxic

Case 2: You are working in a dental practice The next patient has an abscessed

tooth You suggest deep sedation, the

dentist insists on trying to get a decent block with local

You end up with deep sedation due to patient discomfort

Why?

Pus

ie - How they get in there and do their job

How LA’s Work

Ionized/Non-ionized Pairs

Local AnestheticMolecule

pH of site pH of solution

Intrinsic structure

pKa

Variables Affecting Ionization

Adjuncts

H+Non-H+

Local Anesthetics and Ionization: Both ionized and non-ionized forms are needed for function

In infected tissue, the LA is completely ionized and won’t work- hence the need

for sedation or GA

Onset Speed: 1/Ionization

Adopted from: Datta, S (1993) Pharmacology of Local Anesthetic Agents in Barash, PG (ed) ASA Refresher Courses in Anesthesiology, 21:241-254., Young and MacKenzie, 1994; Carpenter and Mackey, 1990; Strichartz and Covino, 1992,Stoelting Pharmacology and Physiology 1999. Hemmings 2000, pg. 295

Case 3: Differential Block

Your obstetric patient is a difficult epidural placement. On the third attempt you get the epidural and

administer a test dose with no change in BP or HR observed.

You then give a bolus dose of 8 cc of 0.125% bupivacaine. The patient begins complaining of blurred vision and a metallic taste

Her LOC then becomes depressed

Systemic Toxicity

CNS toxicity: due to peak serum local anesthetic blood levels Accidental intravascular injection is the most

common etiologic factor in severe systemic reactions

Toxicity can be gradual Same variables:

Site, vascularity, total dose, use of a vasoconstrictor….

Systemic Toxicity Symptoms: Mild neurological symptoms to coma or

death Excitatory symptoms

Selective depression of inhibitory neurons Depression of CNS

Na channel block centrally Depression of heart

Takes a much higher blood level

Lipid soluble agents are more potent and more toxic

Clinical Potency: Clinical Toxicity

Adopted from:

Mulroy, MF (1996) Pharmacology and Toxicity of Local Anesthetics in Barash, PG (ed) ASA Refresher Courses in Anesthesiology, 24:193-204.

Treatment of Toxicity

Get assistance Airway

Oxygen, ventilation, intubation or airway equipment Drugs to stop seizure

Benzodiazepines Barbiturates Other drugs/interventions

Post seizure management

Toxic Dose Ranges- AmidesAmide LA Max Dose Plain Max Dose + EpiArticaine N/A 7

Bupivacaine 2.5 3

Dibucaine 1 N/A

Etidocaine 4 N/A

Lidocaine 4.5 7

Mepivacaine 4.5 7

Prilocaine 8 N/A

Ropivacaine 3 N/A

Doses are in mg/kg, dose ranges change depending on site of injection

Toxic Dose Ranges- Esters

Ester LA Max Dose Plain

Max Dose + Epi

Chloroprocaine 12 N/A

Cocaine 3 N/A

Procaine 12 N/A

Tetracaine 3 N/A

Doses are in mg/kg, dose ranges change depending on site of injection

Site of Injection: Likelihood of Toxicity

IVTracheal

IntercostalCaudal

ParacervicalEpidural

Brachial plexusSciatic/FemoralSubcutaneous

MostMost

Least Least

Vas

cula

rity

Tox

icit

y L

ikli

hoo

dSchematic is illustrative in nature and not intended to reflect absolute correlation

Case 4: Will the Spinal Last?

Your patient presents for a BKA You administer a Lidocaine 2% (80mg) SAB

with epi The surgeon runs into trouble and the case

approaches 90 minutes

Duration = Protein Binding = Lipid Solubility

Protein binding. protein binding = duration

Lipid solubility lipid solubility= duration

Lipid Solubility: Duration

Adopted from :Datta, S (1993) Pharmacology of Local Anesthetic Agents in Barash, PG (ed) ASA Refresher Courses in Anesthesiology, 21:241-254.

Datta, S (1993) Pharmacology of Local Anesthetic Agents in Barash, PG (ed) ASA Refresher Courses in Anesthesiology, 21:241-254. Stoelting RK, Pharmacology and Physiology in Anesthetic Practice, 1999

Protein Binding: Duration

Adjuncts also Prolong Duration

Vasoconstrictors Epinephrine/Phenylephrine/ Levonordefrin

Prolong duration Minimize effect of LA vasodilatation toxicity intensity of block bleeding

Morgan 2006

Morgan 2006

And Don’t Give Me Any of Those Local Anesthetics!

Get Me the Imported Stuff!