Local Anaesthetics

Question 1

What is the order in which functions are affected?

Answer 1

Autonomic
Pain 
Temperature
Touch
Deep pressure
Motor

Question 2

What is the mechanism of action for LA?

Answer 2

Local anaesthetics inhibit preferentially bind to Na+ channels in the open or inactivated state and prevent ion conduction. When local anaesthetic molecules have bound to a sufficient number of Na+ channels, the membrane is unable to depolarise sufficiently to reach the threshold potential, and generation of an action potential is prevented

Question 3

What is the structure of an LA?

Answer 3

• Lipophilic aromatic group
• Hydrophilic tertiary amine group
• Intermediate chain – determines classification into either ester or amide

Question 4

what is the example of amines?

Answer 4

lignocaine, ropivacaine, bupivacaine, prilocaine, mepivacaine

Question 5

how are amines metabolised?

Answer 5

• metabolised by microsomal enzymes (CYP) in liver
• Drug activity prolonged in (1) liver disease, (2) conditions with reduced hepatic blood flow, e.g. congestive heart failure (CHF), hypovolaemia

Question 6

what is the example of esters?

Answer 6

2-chloroprocaine, procaine, tetracaine, cocaine

Question 7

how are esters metabolised?

Answer 7

• primarily metabolised by pseudocholinesterase in plasma (exception is cocaine, which is partially metabolised by liver and partially excreted unchanged by kidneys)
• Drug activity prolonged in (1) neonates, (2) atypical plasma pseudocholinesterase, (3) presence of anticholinesterase (AChE inhibitors)

Question 8

why are amines more commonly used then esters?

Answer 8

Ester linkage is more easily broken; esters are relatively unstable in solution.

Body has abundant esterase (e.g. pseudocholinesterase in plasma), vs amides which must be transported to liver for metabolism 🡪 shorter duration of action for most esters (generally 1-2 h)

Metabolism of most esters cause production of para-aminobenzoic acid (PABA), which is associated with allergic reactions and may progress to anaphylaxis (but rare in amides)

Question 9

What is the ideal LA characteristics?

Answer 9

• Non-irritating, no pain on injection
• Inexpensive
• No neurotoxicity (CNS)
• No systemic toxicity, especially cardiotoxicity (CVS)
• Effective as injection or local application
• Customisable duration of actions, i.e. by adjusting concentration

Question 10

what are the CNS signs of LA toxicity?

Answer 10

LA first inhibits the descending cortical inhibitory pathway, leading to CNS excitation

• Early: tachycardia (first sign!), light-headedness/dizziness, circumoral or tongue numbness, metallic taste
• Higher levels: tinnitus, visual dysfunction, agitation, anxiety, tremors, tonic-clonic seizures

At higher plasma concentrations: LA also inhibits ascending cortical pathways, leading to CNS depression
- Drowsiness, loss of consciousness (LOC), respiratory arrest, coma

Question 11

What are the CVS signs of LA toxicity?

Answer 11

If blood concentrations rise high enough, LA can bind to Na+ channels present on myocardial cells 🡪 reduces myocardial automaticity, and shortens refractory period 🡪 cardiac arrhythmias, depressed contractility, cardiac arrest (i.e. dose dependent negative inotropic effect)

In general, high potency agents (e.g. bupivacaine, ropivacaine) have greater cardiotoxicity than the low potency agents. Of note, cardiotoxic effects of bupivacaine and ropivacaine have been observed to occur without promontory CNS effects

Question 12

How does one manage cardiac toxicity?

Answer 12

Immediately stop LA; call for help, secure ABCD

Immediate management

• Airway: secure with adjuncts, intubate if required
• Breathing: give 100% O2, ensure adequate lung ventilation (hyperventilation by help improve LA-induced seizures, or compensate for metabolic acidosis) and oxygenation
• Circulation: assess cardiovascular status, ensure IV access, start vasopressors if needed
• Disability: abort anaesthetic-induced seizure using benzodiazepine, thiopentone, or propofol (in small incremental doses)

If circulatory arrest present:

• Start CPR
• Manage arrhythmia according to standard protocol
• Start IV 20% lipid emulsion “Intralipid” as CPR continues: sequesters lipid-soluble fraction of LA from plasma 🡪 can reverse CVS toxicity
• Propofol will not be suitable, due to risk of profound hypotension
• Recovery from LA-induced cardiac arrest may take > 1 hour

If no circulatory arrest:: Use conventional therapies to treat hypotension, bradycardia and tachyarrhythmias

Follow up

• Transfer to ICU for continuous monitoring
• Exclude lipid emulsion induced pancreatitis (rare S/E) by regular clinical review