Local Anaesthetics — Classification, Mechanism, Maximum Doses and Toxicity (LAST)

A nerve impulse travels when voltage-gated sodium channels open and sodium rushes in. Local anaesthetics block these channels, so the membrane cannot depolarise and the impulse stops — while the patient stays conscious. The drug exists in both ionised and non-ionised forms; only the non-ionised form crosses the nerve membrane, and once inside, the drug blocks the channel.

That pH dependence explains a classic exam point: infected or inflamed tissue is acidic, more drug stays ionised, and the block works poorly. Conversely, adding sodium bicarbonate raises the non-ionised fraction and can speed the onset.

• Order of block: small autonomic fibres first, then sensory fibres, then motor fibres at higher concentrations.
• Cardiac effect: they also block cardiac sodium channels, so they are class I antiarrhythmics — lidocaine is the class IB prototype.
• Vascular effect: all local anaesthetics are vasodilators except cocaine, which blocks noradrenaline reuptake and so constricts vessels.

Adrenaline is added to amides because vasoconstriction slows systemic absorption, prolongs the block and raises the safe dose. StatPearls still lists end-artery sites — nose, ears, digits and penis — as places where adrenaline-containing solutions are contraindicated.

Bupivacaine is a long-acting amide used for surgical, obstetric and postoperative blocks. It binds cardiac sodium channels with high affinity and dissociates slowly, so the block persists between heartbeats and builds up — causing ventricular arrhythmias and cardiac arrest that are hard to resuscitate. It is highly lipophilic and protein-bound, which also prolongs toxicity.

• The 0.75% concentration is not recommended in obstetric anaesthesia because of cardiac arrest after accidental intravenous injection.
• Most toxicity comes from unintended direct IV injection or rapid vascular uptake.
• Case reports of lipid emulsion rescue describe profound cardiovascular collapse after nerve blocks with bupivacaine and ropivacaine.

LAST happens when the unbound plasma level rises high enough to affect the brain and heart — usually from inadvertent intravascular injection, excessive dose, or rapid absorption from a highly vascular site. Blocking inhibitory pathways first causes CNS excitation, then depression; cardiac sodium-channel block then causes conduction failure and collapse.

1. Stop all local anaesthetic (including infusion pumps), call for help, get the LAST rescue kit, and ventilate with 100% oxygen — hypoxaemia, hypercapnia and acidosis potentiate cardiotoxicity.
2. Seizures: benzodiazepines are first line. Avoid large doses of propofol if circulation is unstable.
3. 20% lipid emulsion early for serious neurological or cardiovascular features.
4. Modified ACLS: adrenaline in smaller doses (start at 1 mcg/kg or less); avoid vasopressin, beta-blockers, calcium channel blockers and more local anaesthetic.
5. Refractory collapse: early contact with a centre for cardiopulmonary bypass or VA-ECMO.

The same dose is not equally safe in every patient. Anything that raises the free (unbound) drug level or slows its clearance raises the risk. Local anaesthetics are bound to plasma proteins, so neonates, pregnant women and patients with low protein levels or acidosis have more free drug. Acidosis also reduces bupivacaine binding and worsens tissue toxicity.

• Prevention: calculate the dose by weight, inject incrementally, aspirate before each injection, use ultrasound guidance, and monitor the patient during and after the block.
• Delayed toxicity: symptoms appear within minutes after direct intravascular injection but can be delayed with continuous infusions, slow absorption or sustained-release formulations, so observation continues after the block.
• Falling incidence: rates dropped between 2006 and 2014, a change linked to wider ultrasound use, lower doses and better prevention.
• Documentation: record the agent, concentration, total dose, site, timing, use of adrenaline and any other local anaesthetic given.

EMLA (eutectic mixture of local anaesthetics) is a cream of 2.5% lidocaine and 2.5% prilocaine that penetrates intact skin. It is used to numb the skin before venepuncture, IV cannulation, port access and lumbar puncture.

Prilocaine and benzocaine are direct oxidising agents that turn haemoglobin into methaemoglobin. Prilocaine alone or as EMLA can cause methaemoglobinaemia, especially in neonates and infants younger than 3 months. Benzocaine accounts for about two-thirds of local anaesthetic-related cases (for example, throat sprays before endoscopy).

• Clue: cyanosis with a pulse oximetry reading stuck near 85% despite adequate oxygen, and chocolate-brown blood.
• Diagnosis: co-oximetry.
• Treatment: remove the drug; methylene blue 1–2 mg/kg IV over 5 minutes, which can be repeated (maximum 7 mg/kg). Use cautiously in G6PD deficiency — it is not absolutely contraindicated. Alternatives: ascorbic acid, exchange transfusion, hyperbaric oxygen.