01Mechanism of Action
LAs disrupt nerve conduction by blocking voltage-gated sodium channels: - Reversibly bind the intracellular α-subunit - Inhibit Na⁺ influx → block action potential - Resting and threshold potentials unchanged
Steps: 1. Nonionized (base, lipid-soluble) form crosses the axonal lipid bilayer 2. Re-equilibrates in axoplasm 3. Ionized (cationic) form binds the Na channel
| Characteristic | Determined by |
|---|---|
| Speed of onset | pKa (degree of ionization) and concentration |
| Potency | Lipid solubility |
| Duration of action | Protein binding (α1-AAG) |
Procaine and chlorprocaine have HIGH pKa but fast onset due to high concentration use. In infected (acidic) tissue, pKa is further from environmental pH → slower onset.
02Categories
Esters — metabolized by plasma pseudocholinesterase / RBC esterase - Cocaine, 2-chloroprocaine, procaine, tetracaine - Methylparaben preservative → PABA → allergic reactions in small percentage
Amides ("i" before "-caine" — AmIde has 2 I's) — metabolized by liver (aromatic hydroxylation, N-dealkylation, amide hydrolysis) - Lidocaine, bupivacaine, ropivacaine, mepivacaine, etidocaine, levobupivacaine
| Amide | pKa | Ester | pKa | |
|---|---|---|---|---|
| Lidocaine | 7.9 | Procaine | 8.9 | |
| Mepivacaine | 7.6 | Chloroprocaine | 8.7 | |
| Prilocaine | 7.9 | Tetracaine | 8.5 | |
| Bupivacaine | 8.1 | |||
| Ropivacaine | 8.1 |
03Maximum Doses
| Drug | Onset | Max (mg/kg) | Max with Epi |
|---|---|---|---|
| Lidocaine | Rapid | 4.5 | 7 |
| Mepivacaine | Medium | 5 | 7 |
| Bupivacaine | Slow | 2.5 | 3 |
| Ropivacaine | Slow | 3 | — |
| Tetracaine | Slow | 1.5 | — |
| Chloroprocaine | Rapid | 10 | 15 |
Bupivacaine 0.25% (2.5 mg/mL) at max 2.5 mg/kg → max 1 mL/kg (70-kg patient ≈ 70 mL).
04Routes of Delivery
- Topical (cocaine, EMLA, viscous lidocaine)
- IV (systemic lidocaine infusion 1 mg/kg/h):
- Anti-inflammatory
- Blunts response to laryngoscopy
- ↓ Postop pain and opioid use
- Reduces MAC up to 40%
- Epidural / spinal (neuraxial)
- Perineural (regional nerve blocks)
- Small diameter A-delta and myelinated nerves are most susceptible → sensory loss before motor
05LAST — Local Anesthetic Systemic Toxicity
Vascularity of injection site (ICEBALLS, decreasing absorption): Intravenous > Intercostal > Caudal > Epidural > Brachial > Axillary > Lower-extremity > Leg subcutaneous > Subcutaneous
Risk depends on: 1. Dose 2. Drug's intrinsic kinetics 3. Addition of vasoactive (epi)
Bupivacaine is more cardiotoxic than equipotent lidocaine — higher binding to resting/inactivated Na channels and slower dissociation during diastole.
CNS toxicity (progression): Lightheadedness → tinnitus → tongue numbness → metallic taste → CNS excitation (block inhibitory pathways first) → CNS depression → seizure → coma
CV toxicity: Bradycardia → ventricular dysrhythmias → ↓ contractility → CV collapse (refractory in bupivacaine).
06LAST Management
1. Get help; manage airway with 100% O₂ — hypoxemia and acidosis worsen toxicity.
2. Stop seizures with benzodiazepine. Small doses of propofol if benzo unavailable, but avoid propofol if CV unstable.
3. Lipid emulsion 20%: - 1.5 mL/kg bolus over 1 min (~100 mL in adult) - Infusion 0.25 mL/kg/min (up to 10 mL/kg over 30 min) - Repeat bolus q3–5 min for persistent cardiovascular collapse
4. Modified ACLS: - ↓ epinephrine doses to ≤ 1 mcg/kg - AVOID vasopressin, calcium channel blockers, β-blockers, local-anesthetic antiarrhythmics (lidocaine, procainamide) - Amiodarone preferred for ventricular arrhythmia
5. If refractory: cardiopulmonary bypass / ECMO.
Continue monitoring at least 4–6 h after resolution.