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Local Anesthetic Systemic Toxicity (LAST)

Kristin Barkley, DNP, CRNA

Quick Facts
Procedure Guide
SCOPe Guide
Media
References

Local Anesthetic Systemic Toxicity (LAST)

  • LAST is a potentially fatal complication of local anesthetic (LA) administration causing central nervous system (CNS) and/or cardiovascular (CV) toxicity.
  • Mechanism: at toxic levels, LAs depress voltage-gated sodium (Na+), potassium (K+), and calcium (Ca2+) channels in excitable tissues of the CNS and CV systems.
  • Incidence varies by block type and setting; registry estimates ~0.3 per 1,000 peripheral nerve blocks, with neuraxial generally lower. A notable proportion occur outside the hospital.
  • Most LAs are lipophilic and highly protein-bound; longer-acting, more lipophilic agents tend to be more cardiotoxic.

 

Procedure Guide

Types of Blocks (risk/order varies by site & vascularity)

  • Common sites/techniques (approx. frequency in many practices, not exhaustive): circumcision; neuraxial; upper extremity; head & neck; topical/infiltration; transversus abdominis plane (TAP); intravenous regional anesthesia.
  • Higher systemic absorption risk with more vascular sites; consider tailored dosing and vigilance by block site.

 

Local Anesthetics – Mechanism of Action

  • LAs block voltage-gated Na+ channels from the intracellular side, preventing depolarization and action potential propagation → analgesia/anesthesia.
  • Shorter-acting agents are generally less cardiotoxic than longer-acting agents.
  • Greater potency ↔ higher lipophilicity and protein binding (e.g., bupivacaine > lidocaine for cardiotoxic risk).
  • Large-volume blocks are higher risk if dosing/absorption are not carefully controlled.
  • pKa & pH: lower pKa → more nonionized fraction → faster membrane transit.

 

Clinical Presentation – CNS (most common initial)

  • Subjective prodrome: agitation, tinnitus, circumoral numbness, blurred vision, metallic taste.
  • Progression: excitatory → depression (muscle twitching, seizures, unconsciousness).
  • Advanced: respiratory arrest; CV involvement may follow.

 

Clinical Presentation – Cardiovascular

  • Can be the first/only sign in severe LAST.
  • Typical sequence (most to least frequent): dysrhythmias, conduction delay, cardiac arrest, bradycardia/hypotension.

 

Presentation Mix & Onset

  • Approximate distribution at recognition: CNS-only, CV-only, or combined presentations.
  • Onset: ~75% within 10 minutes of injection; may be delayed with infusions/continuous techniques.

 

Block Site & Relative Risk of Systemic Absorption

  • Higher risk with intercostal and paravertebral (highly vascular) > caudal/epidural > interfascial plane blocks (abdominal wall) > psoas compartment > sciatic > brachial plexus/cervical (varies) > subcutaneous/intra-articular.

 

Exparel (Liposomal Bupivacaine) – Compatibility Notes

  • May be admixed only with bupivacaine HCl; total bupivacaine HCl dose should not exceed a 1:2 ratio relative to Exparel.
  • Do not admix with non-bupivacaine LAs (e.g., lidocaine) due to rapid release; Exparel may follow lidocaine after ≥20 minutes.

 

Lipid Emulsion – Rationale

  • “Lipid sink/shuttle”: sequesters LA away from heart/brain for subsequent metabolism/elimination.
  • May also exert direct cardiotonic and metabolic effects (Na+ channels, fatty-acid utilization, mitochondria).
  • Rare complications: pancreatitis, DVT—monitor labs post-treatment.

 

SCOPe Guide

Strategies – Treatment (ASRA Checklist-guided)

Initial

  • Call for help.
  • Airway & Breathing: 100% O2; manage ventilation/oxygenation early.
  • Seizure suppression: benzodiazepines preferred; if only propofol is available, use small, titrated doses.
  • BLS/ACLS with LAST-specific modifications (see below).

20% Intravenous Lipid Emulsion (use lean/ideal body weight if applicable)

  • <70 kg: Bolus 1.5 mL/kg over 2–3 min → infusion 0.25–0.5 mL/kg/min.
  • Repeat bolus up to 3× for persistent CV collapse; consider doubling infusion if unstable.
  • Continue infusion ≥10 min after achieving hemodynamic stability.
  • Recommended upper limit over first 30 min ≈ 12 mL/kg.
  • ≥70 kg (adult): Bolus 100 mL over 2–3 min → infusion 200–250 mL over 10–20 min.

AVOID / MODIFY

  • Avoid: vasopressin, beta blockers, calcium channel blockers, additional local anesthetic.
  • Epinephrine: use smaller doses; start <1 mcg/kg per dose during resuscitation.
  • Avoid propofol as an anticonvulsant in CV instability.

Escalation

  • Prepare for cardiopulmonary bypass/ECMO when available for refractory collapse.

Clinical Optimization – Prevention & Detection

  • Preparation: When using LAs, stock a LAST kit and post the treatment algorithm where blocks are performed.
  • Risk reduction: lowest effective dose; frequent aspiration; test doses; incremental dosing; ultrasound guidance; keep patient lightly sedated to allow feedback.
  • Patient factors increasing risk: advanced age; hepatic/renal disease; conduction abnormalities; low plasma protein (↑ free drug); metabolic/respiratory acidosis; heart failure; pregnancy; mitochondrial disorders.
  • Monitoring: observe during and ≥30 minutes after injection; consider LAST with any new neurologic changes or hemodynamic instability after regional anesthesia.
  • CV progression cue: early hyperdynamic signs (tachycardia, hypertension, ventricular ectopy) can precede hypotension, conduction block, bradycardia, VT/TdP/VF, or arrest.

Pearls

  • Know where lipid emulsion is stored before starting blocks; check expiration volume.
  • Initiate the LAST protocol early and titrate to clinical severity and speed of progression.
  • Use lean/ideal body weight for dosing when appropriate.
  • High-risk patients/blocks warrant extra vigilance and extended observation.

 

Media

Copyright © 2020 by the American Society of Regional Anesthesia and Pain Medicine.

 

References

Media Attributions

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License

Icon for the Creative Commons Attribution-NonCommercial 4.0 International License

The Scope Copyright © by Bailey Freeman, DNP, CRNA; Angela Mordecai, DNP, CRNA; Brian Cornelius, DNP, CRNA; and Kristin Barkley, DNP, CRNA is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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