How should acute propofol toxicity be managed, including airway protection, hemodynamic support, and treatment of propofol infusion syndrome?

Management of Acute Propofol Toxicity and Propofol Infusion Syndrome

Immediate Actions for Acute Propofol Overdose

Immediately discontinue propofol infusion at the first sign of toxicity—this is the single most critical intervention that determines survival. 1, 2

Airway and Respiratory Management

• Establish definitive airway control with endotracheal intubation if respiratory depression occurs, as propofol overdose causes dose-dependent respiratory depression that may progress to apnea. 1
• Provide artificial ventilation with 100% oxygen immediately upon recognition of respiratory depression 1
• If intubation is required, use rapid sequence induction with ketamine 1-2 mg/kg (to avoid worsening cardiovascular instability) and rocuronium 1.2 mg/kg 3
• Ensure full neuromuscular blockade before attempting intubation to prevent coughing and aspiration 3
• Use bag-mask ventilation with two-person technique (VE-grip) if immediate intubation is not feasible 3

Hemodynamic Support Protocol

Cardiovascular depression from propofol requires aggressive repositioning and fluid resuscitation before vasopressors. 1

• Immediately raise the patient's legs to improve venous return 1
• Administer rapid bolus of 10-20 mL/kg balanced crystalloid solution 3
• If hypotension persists after fluid bolus, initiate phenylephrine infusion at 0.1 mcg/kg/min 3
• Have ephedrine or metaraminol immediately available for bolus administration 3, 4
• Consider anticholinergic agents (atropine 0.5-1 mg IV) if bradycardia accompanies hypotension 1

Recognition and Management of Propofol Infusion Syndrome (PRIS)

Propofol Infusion Syndrome is a fatal constellation of metabolic acidosis, rhabdomyolysis, cardiac failure, and renal failure that occurs with doses >70 mcg/kg/min (>5 mg/kg/h) for >48 hours, though cases have been reported at doses as low as 1.9-2.6 mg/kg/h. 5, 2, 6

Diagnostic Criteria for PRIS

Monitor for the following constellation of findings 1, 2, 6, 7:

• Severe metabolic acidosis with elevated anion gap and lactate >5 mmol/L
• Rhabdomyolysis with creatine kinase >5000 U/L and myoglobinuria
• Hyperkalemia >5.5 mEq/L
• Cardiac dysfunction: bradycardia, heart failure, or Brugada-pattern ECG changes (coved ST elevation)
• Hepatomegaly with elevated transaminases
• Acute kidney injury with rising creatinine
• Hypertriglyceridemia >400 mg/dL

Major Risk Factors for PRIS Development

The following factors dramatically increase PRIS risk 1, 2, 6, 7:

• Propofol infusion >5 mg/kg/h (>70 mcg/kg/min) for >48 hours
• Concomitant catecholamine infusions (norepinephrine, epinephrine, dopamine)
• Concurrent high-dose corticosteroid therapy
• Acute neurological injury (traumatic brain injury, stroke, status epilepticus)
• Sepsis or severe systemic inflammation
• Carbohydrate depletion or inadequate caloric intake
• Young age (particularly children <3 years, though adults are also susceptible)

Immediate Management of Suspected PRIS

Stop propofol infusion immediately—do not wait for confirmatory laboratory results, as mortality approaches 33% even with aggressive treatment. 5, 2, 7

1. Discontinue propofol and transition to alternative sedation (benzodiazepines such as midazolam 0.1-0.2 mg/kg, or dexmedetomidine 0.2-0.7 mcg/kg/h) 3, 2

2. Initiate continuous cardiac monitoring with 12-lead ECG to detect Brugada-pattern changes, arrhythmias, or heart block 1, 7

3. Draw immediate laboratory panel: arterial blood gas, lactate, creatine kinase, comprehensive metabolic panel including potassium, liver enzymes, triglycerides, and urinalysis for myoglobin 7

4. Provide aggressive hemodynamic support:

   • Fluid resuscitation with balanced crystalloids 20-30 mL/kg 3
   • Initiate inotropic support with dobutamine or milrinone (avoid high-dose catecholamines if possible, as they worsen PRIS) 6
   • Consider early vasopressin (0.03-0.04 units/min) to reduce catecholamine requirements 6

5. Treat severe metabolic acidosis:

   • Initiate continuous renal replacement therapy (CRRT) for pH <7.1 or lactate >10 mmol/L 2, 7
   • Sodium bicarbonate infusion is temporizing only—definitive treatment requires propofol discontinuation and dialysis 2

6. Manage hyperkalemia aggressively (if K+ >6.0 mEq/L):

   • Calcium gluconate 1-2 grams IV over 5 minutes for cardiac membrane stabilization 7
   • Insulin 10 units IV with dextrose 50 grams (D50W) 7
   • Initiate CRRT if refractory 2

7. Consider extracorporeal membrane oxygenation (ECMO) for refractory cardiac failure or cardiovascular collapse unresponsive to maximal medical therapy 2, 7

8. Provide adequate caloric support with carbohydrate-based nutrition (not lipid-based) to restore mitochondrial substrate availability 6, 7

Prevention Strategies: Critical Dosing Limits

The best management of PRIS is prevention—never exceed 5 mg/kg/h (70 mcg/kg/min) for more than 48 hours in any patient. 1, 2, 6

• For ICU sedation, maintain propofol infusion at 5-50 mcg/kg/min, with most patients adequately sedated at 25-50 mcg/kg/min 5
• If sedation requirements increase or metabolic acidosis develops during propofol infusion, immediately transition to alternative sedation (midazolam, dexmedetomidine) rather than escalating propofol dose 1, 2
• Avoid propofol entirely in patients receiving high-dose catecholamines, high-dose steroids, or with severe neurological injury if alternative sedation is feasible 6
• Monitor daily: creatine kinase, lactate, triglycerides, and liver enzymes in any patient receiving propofol >48 hours 7

Common Pitfalls to Avoid

• Never continue propofol infusion when increasing doses are required to maintain sedation—this is an early warning sign of PRIS development 1, 2
• Do not abruptly discontinue propofol without transitioning to alternative sedation, as this causes rapid awakening with agitation and ventilator dyssynchrony 1
• Do not delay CRRT initiation in suspected PRIS—early dialysis improves survival by removing propofol metabolites and correcting acidosis 2, 7
• Avoid using propofol in patients with egg, soy, or sulfite allergies, as anaphylaxis can mimic or complicate acute toxicity 1, 5
• Do not use lipid emulsion therapy for propofol toxicity (unlike local anesthetic toxicity)—propofol is already in lipid emulsion and additional lipid worsens the syndrome 3, 2