Local Anesthetic Systemic Toxicity (LAST): Recognition + Lipid Rescue

Regional + neuraxial blocks place gram-quantity local anesthetic next to vessels. Inadvertent intravascular injection (esp. bupivacaine) → CNS-cardiac toxicity continuum. Bupivacaine's twist: it binds the cardiac sodium channel for orders of magnitude longer than it stays bound to a regular peripheral nerve channel — so you can have CNS recovery + lethal cardiac arrhythmia simultaneously. ASRA reports LAST in roughly 1-2 per 1,000 peripheral blocks (lower with US guidance + aspiration before injection).

Subjective + early: circumoral or tongue numbness, metallic taste, tinnitus or muffled hearing, lightheadedness, restlessness, agitation. Objective + intermediate: muscle twitching, dysarthria, confusion. STOP injecting at any of these — they buy you minutes before seizure + cardiotoxicity. Late + severe: tonic-clonic seizure → CNS depression → coma → bradyarrhythmia → wide-complex tachycardia (Na-channel blockade signature of bupivacaine) → asystole or VF.

1. STOP injection. 2. Call for help + LAST cart. 3. Manage airway: 100% O₂, ventilate, intubate if seizing/obtunded. 4. Suppress seizure with benzodiazepine (midazolam 1-2 mg IV) — AVOID propofol if hemodynamically unstable. 5. ALERT pump-availability + cardiopulmonary bypass capability if available. 6. Lipid emulsion 20% — bolus 1.5 mL/kg over 1 min (lean body weight, ~100 mL adult) → start infusion 0.25 mL/kg/min → titrate to 0.5 mL/kg/min if hemodynamics persist → MAX 12 mL/kg cumulative. 7. ACLS modified: epinephrine ≤1 mcg/kg per dose (NOT the standard 1 mg ACLS dose). AVOID vasopressin, calcium-channel blockers, beta-blockers, lidocaine.

Standard ACLS epinephrine 1 mg IV: in LAST, this worsens outcomes (animal models + clinical reports) — pure-α adrenergic effect with bupivacaine-bound Na channels triggers refractory arrhythmias. Reduce to 1 mcg/kg (≈ 70 mcg adult). Vasopressin: associated with worse outcomes; off the list. Lidocaine: same Na-channel mechanism as bupivacaine — adds toxicity rather than treating arrhythmia. Amiodarone is preferred if antiarrhythmic needed.

Three proposed mechanisms: (1) lipid sink — extracts lipophilic local anesthetic from cardiac tissue back into the plasma compartment. (2) metabolic effect — provides fatty acid substrate for the energy-depleted myocardium. (3) ion channel modulation — direct effect on cardiac sodium channels. Clinical effect: ROSC rates dramatically improved; cases of resuscitation after >60 min of CPR documented in the registry. The lipid is the cardiotoxicity treatment; everything else is supportive.

Aspirate before every injection (intermittent aspiration during slow injection too). Use ultrasound to confirm needle tip position outside vessels. Use the lowest effective dose — adult bupivacaine max 2.5 mg/kg (3 mg/kg with epinephrine), ropivacaine 3 mg/kg, lidocaine 4.5 mg/kg (7 with epi). Add epinephrine 1:200,000 to detect intravascular injection (HR ↑20 bpm within 1 min = positive test). Inject slowly — fast injection raises peak plasma concentration even if total dose is safe. Have a stocked LAST cart visible at every block location.