Bupivacaine

Quick Answer

Bupivacaine is a potent, long-acting amide local anaesthetic widely used for neuraxial blocks (epidural, spinal), peripheral nerve blocks, and labour analgesia. Structure: Amide local anaesthetic (pipecoloxylidide), butyl group on aromatic ring (lipophilic), chiral molecule; S-enantiomer (levobupivacaine) and racemic mixture available; ropivacaine (pure S-enantiomer, propyl group) has similar but slightly less potent profile. Mechanism: Sodium channel blockade (high lipid solubility, crosses nerve membranes readily); high affinity for Na+ channels (long duration); strong protein binding (95% to α1-acid glycoprotein—longer duration, less placental transfer than less protein-bound drugs). Potency: High (4× lignocaine); lipid solubility (partition coefficient 28) high. Onset: Slow (5-10 minutes)—pKa 8.1 (15% unionized at pH 7.4, crosses nerve membrane slowly); can speed with bicarbonate or using more lipid-soluble formulations (higher concentrations). Duration: Long (2-8 hours depending on route, concentration, additives); epidural 0.5% lasts 3-6 hours; spinal hyperbaric 0.5% 1.5-3 hours; with adrenaline slightly prolonged; repeated doses have cumulative effect. Dosing: Epidural 0.25-0.75% (analgesia vs. surgical block), spinal 0.5% hyperbaric 2-3 mL, peripheral nerve block 0.25-0.5%, infiltration 0.25%, labour epidural 0.0625-0.125% (low concentration for sensory block without motor block). Maximum dose: 2 mg/kg (150 mg/70 kg without adrenaline), 3 mg/kg with adrenaline. Toxicity (LAST): CNS effects (tinnitus, perioral numbness, metallic taste, visual disturbances, seizures, coma); cardiovascular toxicity most concerning—profound cardiac depression, ventricular arrhythmias (VT, VF), cardiac arrest; bupivacaine most cardiotoxic amide due to strong Na+ channel binding (tight, long dissociation time) and direct myocardial depression; resuscitation prolonged (lipid emulsion essential—Intralipid 20% 1.5 mL/kg bolus then infusion); avoid using 0.75% bupivacaine in obstetrics (FDA warning after maternal deaths—cardiac toxicity in labouring women). Clinical pearls: 0.5% hyperbaric spinal for caesarean section (reliable, dense block); 0.25-0.375% for peripheral blocks (long duration analgesia); low concentrations (0.0625%) for labour epidural (motor sparing); racemic bupivacaine largely replaced by levobupivacaine or ropivacaine (less cardiotoxic, less motor block) in many centres; bupivacaine metabolized by CYP3A4 (inhibited by ketoconazole, azoles). Indigenous considerations: No specific alterations; careful dosing in obesity (use ideal body weight). [1-10]