What is Propofol (propofol) infusion syndrome?

Propofol Infusion Syndrome (PRIS)

Propofol infusion syndrome is a rare but potentially fatal complication characterized by metabolic acidosis, hypertriglyceridemia, hypotension with increasing vasopressor requirements, arrhythmias, rhabdomyolysis, and organ failure that occurs primarily with prolonged administration of high-dose propofol (>5 mg/kg/hr for >48 hours). 1

Definition and Clinical Features

Propofol infusion syndrome presents with a constellation of symptoms and laboratory abnormalities:

• Primary features:

  • Severe metabolic acidosis
  • Cardiac dysfunction (arrhythmias, ECG changes, heart failure)
  • Rhabdomyolysis
  • Hyperkalemia
  • Hypertriglyceridemia
  • Acute kidney injury
  • Hepatomegaly and liver dysfunction 1, 2

• ECG changes may include:

  • Coved ST segment elevation (similar to Brugada syndrome) 2
  • Various arrhythmias

Epidemiology and Risk Factors

The incidence of PRIS is approximately 1% in patients receiving propofol infusions 1. Mortality from PRIS is high, reported up to 33%, and can occur even after discontinuation of the infusion 1.

Major risk factors include:

• Dosage-related factors:

  • High-dose propofol infusions (>5 mg/kg/hr)
  • Prolonged administration (>48 hours) 1, 3, 4

• Patient-related factors:

  • Critical illness, particularly acute neurological or inflammatory conditions
  • Young age (particularly children)
  • Depleted carbohydrate stores
  • Concomitant administration of:
    • Catecholamines (vasopressors)
    • Corticosteroids 3, 4

Pathophysiology

The pathophysiological mechanisms of PRIS include:

1. Mitochondrial dysfunction: Propofol impairs mitochondrial function and free fatty acid utilization 3
2. Energy imbalance: Disruption of the electron transport chain leading to impaired ATP production 5
3. Fatty acid metabolism: Inhibition of beta-oxidation of fatty acids 4
4. Cardiac effects: Blockage of beta-adrenoreceptors and cardiac calcium channels 4

Diagnosis

Diagnosis is challenging as PRIS has variable presentation and lacks specific diagnostic criteria. Early warning signs include:

• Unexplained metabolic acidosis (often an early sign)
• Increasing vasopressor requirements
• Cardiac dysfunction
• Rising creatine kinase (indicating rhabdomyolysis)
• Lipemic serum 1, 6

Recent evidence suggests PRIS can develop at lower doses than previously thought, with some cases occurring at infusion rates <4 mg/kg/hr 6.

Management

Management of PRIS includes:

1. Immediate discontinuation of propofol upon suspicion of PRIS 1, 4
2. Supportive care:
   • Correction of metabolic acidosis
   • Management of cardiac dysfunction and arrhythmias
   • Hemodynamic support
   • Treatment of rhabdomyolysis and renal failure
3. Advanced interventions in severe cases:
   • Hemodialysis
   • Extracorporeal membrane oxygenation (ECMO) for refractory cardiac failure 4

Prevention

Prevention is critical given the high mortality associated with PRIS:

• Limit propofol dosage: Maintain doses below 5 mg/kg/hr whenever possible 1, 3
• Limit duration: Consider alternative sedatives for patients requiring prolonged sedation (>48 hours) 1, 4
• Monitor high-risk patients closely for early signs of PRIS, including:
  • Daily monitoring of arterial blood gases
  • Serum lactate, triglycerides, creatine kinase
  • Cardiac function
  • Renal and hepatic parameters 5
• Consider alternative sedatives in patients with risk factors for PRIS 4

Special Considerations

• PRIS was initially described in children but is now recognized in adults as well 3
• The presentation of PRIS appears to be evolving, with more recent cases describing older patients developing PRIS at lower propofol doses with different symptom patterns 6
• Early recognition is critical as PRIS can progress rapidly once established 1

Remember that while propofol is an excellent sedative with many advantageous properties for ICU sedation, vigilance for PRIS is essential, particularly in high-risk patients receiving prolonged infusions.