Amide Local Anaesthetics

Amide local anaesthetics have an amide link between the aromatic and amine groups, are metabolised in the liver and rarely cause true allergy. They are the main agents for infiltration, peripheral nerve block, spinal and epidural anaesthesia. They differ in onset, duration, motor block and cardiotoxicity.

Mechanism. Block of intracellular sodium channels in the open and inactivated state, with greater affinity for rapidly firing fibres. Bupivacaine dissociates slowly from cardiac channels, explaining severe cardiotoxicity; ropivacaine and levobupivacaine are single isomers with less cardiac binding.

Pharmacokinetics. Absorption depends on vascularity (intercostal and caudal blocks highest, then epidural, brachial plexus, sciatic, subcutaneous). Binding to alpha-1 acid glycoprotein (rises after surgery and trauma) lowers free drug. Half-life: lidocaine 1.5 to 2 hours, bupivacaine 3 to 4 hours, ropivacaine 2 hours.

Lidocaine. Infiltration and blocks 0.5 to 2%; spinal not advised because of transient neurological symptoms; topical 2 to 5%; intravenous regional anaesthesia 0.5% at 3 mg/kg; antiarrhythmic 1 to 1.5 mg/kg intravenously then 1 to 4 mg/min. Maximum plain 3 to 4.5 mg/kg (200 to 300 mg); with adrenaline 7 mg/kg (500 mg). Toxicity from plasma levels over about 5 micrograms/mL.

Bupivacaine.

• Infiltration and blocks 0.25 to 0.5%; epidural 0.25 to 0.5%; labour epidural 0.0625 to 0.125% with fentanyl 2 micrograms/mL.
• Spinal hyperbaric 0.5%: 10 to 15 mg for lower limb and abdominal surgery; 10 to 12.5 mg with fentanyl 10 to 25 micrograms for caesarean section.
• Maximum 2 mg/kg (150 mg); 0.75% is contraindicated in obstetric epidural.

Levobupivacaine. Same concentrations and maximum dose as bupivacaine (2 mg/kg, 150 mg), with lower cardiac and central nervous system toxicity.

Ropivacaine. 0.2% for infusion and postoperative analgesia (6 to 14 mL/h epidural); 0.5 to 0.75% for surgical block; maximum 3 mg/kg (about 200 to 225 mg). Less motor block, so suited to labour and ambulation.

Prilocaine. 6 mg/kg plain (maximum 400 mg), 8 mg/kg with felypressin; intravenous regional anaesthesia 0.5% where licensed; methaemoglobinaemia over 600 mg.

Mepivacaine and articaine. Mepivacaine 3% dental, 1 to 1.5% blocks (maximum 4.5 mg/kg, 300 to 400 mg); articaine 4% dental, maximum 7 mg/kg, rapid onset with good bone penetration.

• First-line. Lidocaine for infiltration and short procedures; bupivacaine or levobupivacaine for long blocks, spinal and epidural; ropivacaine for continuous infusions and labour.
• Alternative. Prilocaine or articaine for dental work; mepivacaine for intermediate duration blocks.
• Specialist. Intravenous lidocaine infusion for perioperative analgesia and refractory arrhythmia; continuous plexus catheters.
• Emergency. Lidocaine for ventricular tachycardia when amiodarone is unavailable; blocks for hip fracture (fascia iliaca or femoral nerve block with bupivacaine 0.25% to 0.5%, 20 to 30 mL).

Selection. Use ropivacaine where motor sparing matters; use bupivacaine hyperbaric for spinal; avoid lidocaine spinal; reduce doses in older adults and in advanced pregnancy (epidural spread is higher).

Contraindications. Hypersensitivity to amides; infection at the site; coagulopathy; severe hypovolaemia for neuraxial block; raised intracranial pressure for spinal block; heart block and severe bradycardia for lidocaine antiarrhythmic use; bupivacaine 0.75% in obstetrics; prilocaine in methaemoglobinaemia, anaemia and glucose-6-phosphate dehydrogenase deficiency.

Serious adverse effects. Systemic toxicity (central nervous system then cardiovascular), high spinal and total spinal block, hypotension, bradycardia, nerve injury, methaemoglobinaemia with prilocaine, myotoxicity with prolonged bupivacaine infusion, chondrolysis with intra-articular infusion.

Major interactions. Beta-blockers, cimetidine and amiodarone raise lidocaine levels; fluvoxamine reduces ropivacaine clearance; other antiarrhythmics add to cardiac depression; anticoagulants raise haematoma risk with neuraxial and deep blocks.

Common prescribing errors.

• Using bupivacaine 0.75% in obstetrics.
• Confusing hyperbaric and plain spinal solutions.
• Epidural solutions injected intravenously.
• Not reducing the dose in the elderly or in pregnancy.
• Exceeding maximum dose when repeated blocks are performed.

Special groups.

• Pregnancy: avoid bupivacaine 0.75% in obstetric epidural; reduce spinal dose near term.
• Breastfeeding: compatible.
• Children: bupivacaine and ropivacaine 2 mg/kg and 3 mg/kg limits; use weight-adjusted concentrations.
• Older adults: reduce neuraxial doses by 20 to 30%.
• Kidney: caution with prolonged infusion.
• Liver: reduce infusion rates and total dose.
• East Africa: avoid reuse of opened single-dose ampoules; confirm that spinal ampoules are labelled hyperbaric or plain.

Monitoring. ECG, blood pressure and saturation during and after block; motor and sensory level; plasma level is not routine; watch infusions beyond 48 hours for toxicity.

Referral and escalation. Systemic toxicity, high block with respiratory compromise, new neurological deficit, back pain or infection after neuraxial block.

Comparison with alternative classes. Compared with ester agents, amides last longer and rarely cause allergy but need hepatic clearance and carry a higher risk of accumulation and cardiotoxicity.