What is the management and prevention of Propofol (propofol) infusion syndrome?

Management and Prevention of Propofol Infusion Syndrome

Immediately discontinue propofol infusion upon suspicion of PRIS and provide supportive care, while preventing PRIS by limiting propofol to doses <70 μg/kg/min and durations <48 hours whenever possible. 1, 2

Clinical Recognition and Diagnosis

PRIS presents as a constellation of findings that should trigger immediate action:

• Metabolic acidosis with worsening base deficit is often the earliest warning sign 1, 3
• Cardiac manifestations including bradycardia progressing to asystole, arrhythmias, and myocardial failure 2, 4
• ECG changes showing coved ST segment elevation (Brugada-like pattern) or T-wave inversions may appear 24-48 hours before circulatory collapse 2, 5
• Hypertriglyceridemia (lipemic plasma) occurs in 100% of PRIS cases 3
• Rhabdomyolysis with elevated creatine kinase and myoglobinuria 1, 4
• Acute kidney injury and hepatomegaly with elevated liver enzymes 1, 6
• Hyperkalemia and increasing vasopressor requirements despite escalating support 1, 2

Critical pitfall: PRIS carries a mortality rate of 33-36.8% and is frequently underdiagnosed because its manifestations overlap with common ICU complications. 1, 3 The incidence is approximately 1-2.9% in patients receiving prolonged propofol infusions. 1, 3

Prevention Strategies

Dose and Duration Limits

• Maintain propofol infusion rates <70 μg/kg/min (ideally 5-50 μg/kg/min) 7, 1
• Avoid prolonged infusions beyond 48 hours when alternative sedation strategies are available 1, 2
• The FDA warns that PRIS has been reported with doses >5 mg/kg/h (83 μg/kg/min) for >48 hours, but can occur at lower doses and shorter durations 2
• Recent evidence shows PRIS can develop at median doses of 36.4 μg/kg/min over 147 hours, with onset at median 125 hours post-initiation 3

Monitoring Requirements

Implement daily laboratory surveillance for all patients on propofol infusions:

• Arterial blood gases to detect metabolic acidosis early 1
• Serum triglycerides (lipemia is universal in PRIS) 1, 3
• Creatine kinase for rhabdomyolysis detection 1, 8
• Renal function tests (creatinine, BUN) and liver enzymes 1
• Continuous ECG monitoring for T-wave changes, bradycardia, or Brugada-like patterns 2, 5
• Serum lactate and base deficit 8
• Urine myoglobin if rhabdomyolysis suspected 8

High-Risk Populations Requiring Extra Vigilance

• Traumatic brain injury or severe neurological illness 1, 5
• Sepsis or critical illness with decreased oxygen delivery 2
• Concomitant catecholamine infusions (vasopressors, inotropes) 2, 6
• Concurrent corticosteroid therapy 2, 6
• Young age (particularly children <3 years, though adults are also at risk) 8, 5
• Carbohydrate depletion or inadequate caloric intake 6

Alternative Sedation Strategies

For Sedation Beyond 48 Hours

Switch to dexmedetomidine (0.2-0.7 μg/kg/hr) or midazolam-based sedation after 48 hours of propofol use: 7, 1

• Dexmedetomidine offers minimal respiratory depression and avoids PRIS risk entirely 1
• Loading dose of 1 μg/kg over 10 minutes (avoid in hemodynamically unstable patients) 7
• Maintenance infusion can be increased to 1.5 μg/kg/hr as tolerated 7
• Monitor for bradycardia and hypotension 7

Benzodiazepine Options

• Midazolam: 0.02-0.1 mg/kg/hr after loading 0.01-0.05 mg/kg 7
• Lorazepam: 0.01-0.1 mg/kg/hr (≤10 mg/hr) after loading 0.02-0.04 mg/kg 7
• Critical caveat: Monitor for propylene glycol toxicity with lorazepam (metabolic acidosis, nephrotoxicity) 7, 1

Analgesic-First Approach

• Use low-dose fentanyl infusion with minimal sedative added as an alternative strategy for long-term sedation 1
• Remember that propofol has no analgesic properties and must be combined with opioids for painful procedures 9

Management of Established PRIS

Immediate Actions

1. Discontinue propofol immediately upon any suspicion of PRIS 1, 2, 6
2. Do not abruptly discontinue without alternative sedation as this causes rapid awakening with anxiety, agitation, and ventilator dyssynchrony 2
3. Transition to alternative sedation (dexmedetomidine or benzodiazepines) while maintaining light sedation 1, 2

Supportive Care

• Aggressive treatment of metabolic acidosis with sodium bicarbonate 1
• Renal replacement therapy (hemodialysis or continuous renal replacement therapy) for acute kidney injury and severe acidosis 1, 6
• Hemodynamic support with vasopressors and inotropes as needed 6
• Extracorporeal membrane oxygenation (ECMO) for refractory cardiac failure 6
• Fluid resuscitation and electrolyte management (particularly hyperkalemia) 8

Monitoring During Treatment

• Continuous cardiac monitoring for arrhythmias and cardiac arrest 2
• Serial arterial blood gases every 4-6 hours until acidosis resolves 8
• Daily creatine kinase and myoglobin levels 8
• Maintain patent airway and prepare for cardiovascular resuscitation 2

Critical Clinical Pitfalls

Warning sign escalation: If propofol dose requirements are increasing to maintain constant sedation levels, or if unexplained metabolic acidosis develops, immediately consider PRIS and switch sedation strategies. 2 Do not wait for full syndrome manifestation, as mortality is extremely high once multiorgan failure develops. 1, 3

ECG surveillance: T-wave inversions or Brugada-like patterns may precede circulatory collapse by 24-48 hours, providing a narrow window for intervention. 5 Meticulous ECG analysis during propofol sedation is essential. 5

Dose misconception: PRIS can occur at doses commonly used for surgical anesthesia and at durations shorter than 48 hours, so vigilance is required even with "standard" dosing. 3, 4