What is the treatment for Local Anesthetic Systemic Toxicity (LAST) caused by Exparel (bupivacaine)

Treatment of Local Anesthetic Systemic Toxicity (LAST) from Exparel (Liposomal Bupivacaine)

Treat LAST from Exparel identically to conventional bupivacaine toxicity with immediate 20% intravenous lipid emulsion (ILE) administration as the cornerstone therapy, combined with aggressive airway management and standard resuscitation measures. 1

Immediate Management Algorithm

Step 1: Stop and Call for Help

• Immediately discontinue any ongoing local anesthetic administration 1, 2
• Alert the nearest facility with cardiopulmonary bypass capability 1
• Request assistance and prepare for prolonged resuscitation efforts 1

Step 2: Airway and Oxygenation (Priority #1)

• Secure the airway and provide 100% oxygen ventilation 1, 2
• Perform early advanced airway placement if needed, as hypoxia and acidemia worsen cardiotoxicity 1
• Maintain adequate ventilation to prevent progression from CNS to cardiovascular toxicity 1

Step 3: Lipid Emulsion Therapy (Class I Recommendation)

Initial Bolus:

• Administer 1.5 mL/kg of 20% lipid emulsion over approximately 1 minute 1
• For adults >70 kg, give 100 mL bolus 3
• Repeat bolus once or twice for persistent cardiovascular collapse 1

Continuous Infusion:

• Start 0.25 mL/kg per minute infusion immediately after bolus 1
• Double the infusion rate if blood pressure remains low 1
• Continue for at least 10 minutes after attaining circulatory stability 1
• Maximum recommended dose: approximately 10 mL/kg over the first hour 1

Step 4: Seizure Management

• Use benzodiazepines as first-line therapy (e.g., intravenous midazolam 0.1-0.2 mg/kg) 1
• Avoid propofol if cardiovascular instability is present 1
• Seizure control prevents worsening hypoxia and acidemia that accelerate cardiotoxicity 1

Step 5: Cardiovascular Support

For Bradycardia:

• Administer atropine (Class IIa recommendation) 1

For Wide-Complex Tachycardia:

• Give sodium bicarbonate to overcome sodium channel blockade (Class IIa recommendation) 1

For Hypotension:

• Administer 10-20 mL/kg balanced salt solution fluid bolus 1
• Start phenylephrine infusion at 0.1 μg/kg per minute to correct peripheral vasodilation 1
• Reduce epinephrine doses compared to standard ACLS protocols 1

Critical Medication Avoidance:

• Do NOT use vasopressin, calcium channel blockers, or β-blockers 1
• Do NOT administer additional local anesthetic 1

Step 6: Refractory Cases

• Consider VA-ECMO for refractory cardiogenic shock (Class IIa recommendation) 1
• Be prepared for prolonged resuscitation efforts, as recovery may take extended time 1

Exparel-Specific Considerations

Liposomal bupivacaine carries the same cardiotoxic risk as conventional bupivacaine because bupivacaine has greater affinity and longer binding duration to cardiac sodium channels compared to other local anesthetics, causing reentry dysrhythmias, conduction suppression, and calcium channel blockade. 1, 4

The liposomal formulation does not reduce toxicity risk—LAST with cardiac arrest has been documented with Exparel during transversus abdominis plane blocks. 4

Post-Resuscitation Monitoring

• Observe for minimum 24 hours after stabilization 5
• Monitor for biphasic toxicity, as liposomal formulations create extended-release depots that can take hours to reach peak plasma levels 3
• Continue cardiovascular and neurologic monitoring even after apparent recovery 5

Critical Pitfalls to Avoid

• Do not delay ILE therapy while waiting for definitive diagnosis—administer at first sign of serious systemic toxicity 1, 3
• Do not assume the liposomal formulation is safer—it carries identical cardiotoxic potential to conventional bupivacaine 1, 4
• Do not discharge early—extended observation is essential due to prolonged absorption kinetics 5, 3
• Do not use standard epinephrine dosing—complex pharmacodynamic interactions exist between ILE and vasopressors 1

Prevention Strategies

• Calculate maximum safe dose before injection (2.5 mg/kg bupivacaine without epinephrine for peripheral blocks) 1, 6
• Perform aspiration test before each injection 7
• Use fractionated dosing with slow injection 1, 7
• Have 20% lipid emulsion immediately available at bedside before starting the procedure 6, 8
• Monitor continuously for CNS symptoms (perioral numbness, tinnitus, metallic taste, visual changes) that precede cardiovascular collapse 8, 7