Risk Factors for Propofol Infusion Syndrome
The primary risk factors for propofol infusion syndrome (PRIS) include prolonged propofol administration (>48 hours), high infusion rates (>70 μg/kg/min or >4 mg/kg/hr), critical illness with decreased oxygen delivery, serious neurological injury, sepsis, and concomitant use of vasoconstrictors, steroids, or inotropes. 1, 2
Dose and Duration-Related Risk Factors
- High-dose propofol infusion >70 μg/kg/min (>4 mg/kg/hr) is the most critical modifiable risk factor, though PRIS has been reported at doses as low as 1.9-2.6 mg/kg/hr 1, 3
- Prolonged infusions exceeding 48 hours significantly increase risk, though cases have occurred with shorter durations 1, 4
- The FDA explicitly warns that "prolonged, high-dose infusions of propofol (greater than 5 mg/kg/h for greater than 48h)" represent major risk factors 2
- Recent evidence shows PRIS can develop even with propofol infusion <4 mg/kg per hour, challenging earlier assumptions about "safe" dosing thresholds 5
Patient-Specific Risk Factors
- Critical illness with decreased oxygen delivery to tissues is a major predisposing factor 2, 6
- Serious neurological injury (particularly traumatic brain injury) substantially increases risk, as these patients often require higher propofol doses for intracranial pressure control 2, 3
- Sepsis creates a high-risk metabolic environment for PRIS development 2
- Young age (particularly children under 3 years) represents increased vulnerability 6, 4
- Obesity may predispose to PRIS through altered lipid metabolism 6
Metabolic and Pharmacologic Risk Factors
- Depleted carbohydrate stores force reliance on lipid metabolism, increasing free fatty acid burden 6, 7, 4
- Elevated serum catecholamines (either endogenous from critical illness or exogenous from vasopressor administration) are major risk factors 2, 6
- Concomitant steroid therapy acts as a triggering factor 2, 4
- Concurrent vasopressor or inotrope use significantly increases risk, particularly when combined with high-dose propofol 2, 3
- Pre-existing hyperlipidemia may contribute to metabolic derangements 6
Clinical Context Risk Factors
- Traumatic brain injury patients are particularly vulnerable because they commonly receive both high-dose propofol (for ICP control) and vasopressors (for cerebral perfusion pressure maintenance) simultaneously 3
- Increasing propofol dose requirements to maintain constant sedation levels should raise suspicion for developing PRIS 2
- Onset of metabolic acidosis during propofol administration is an early warning sign requiring immediate evaluation 2
Important Clinical Pitfalls
- PRIS has been reported following "large-dose, short-term infusions during surgical anesthesia," meaning duration >48 hours is not an absolute requirement 2
- The syndrome's presentation is variable—typical features like hypertriglyceridemia, fever, and hepatomegaly are often missing (>95% of cases), making diagnosis challenging 5
- Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmias and rhabdomyolysis appear later after prolonged infusions 5
- Mortality is independently associated with higher propofol infusion rates, longer duration, presence of traumatic brain injury, and fever 5