What is propofol infusion syndrome (PRIS)?

Propofol Infusion Syndrome (PRIS): A Life-Threatening Complication

Propofol infusion syndrome (PRIS) is a rare but potentially fatal constellation of metabolic derangements and multi-organ system failures that occurs with propofol administration, characterized by severe metabolic acidosis, cardiac dysfunction, rhabdomyolysis, hyperkalemia, and acute renal failure, with mortality rates reaching 33%. 1, 2

Clinical Presentation

PRIS manifests with variable but recognizable features:

Core Features:

• Metabolic acidosis (worsening, often severe)
• Cardiac dysfunction: Hypotension requiring escalating vasopressor support, arrhythmias (including Brugada-like ECG changes with coved ST elevation), bradycardia progressing to asystole, and impaired myocardial contractility 1, 2, 3
• Rhabdomyolysis with elevated creatine kinase
• Hyperkalemia
• Acute kidney injury

Additional Features:

• Hypertriglyceridemia/lipemia
• Hepatomegaly and liver dysfunction
• Lactic acidosis
• Myoglobinuria
• Fever (more common in children) 1, 3, 4

Important caveat: The classic triad of hypertriglyceridemia, fever, and hepatomegaly is frequently absent (>95% of cases), making diagnosis challenging 4. Cardiac failure and metabolic acidosis appear early and are dose-dependent, while arrhythmias and ECG changes occur later after prolonged infusions 4.

Risk Factors and Dosing Thresholds

High-Risk Scenarios:

• Prolonged propofol infusions >48 hours at doses >5 mg/kg/hr (>70 μg/kg/min) 1, 2
• Decreased oxygen delivery to tissues
• Serious neurological injury (particularly traumatic brain injury) 3, 4
• Sepsis
• High-dose vasoconstrictors, steroids, or inotropes
• Young age (especially <3 years)
• Critical illness with depleted carbohydrate stores 5

Critical warning: PRIS can occur at lower doses (<4 mg/kg/hr) and with shorter durations, even during surgical anesthesia with large-dose, short-term infusions 1, 2, 4, 6. Recent case reports document PRIS in older patients at lower propofol doses than historically recognized 4.

Pathophysiology

The underlying mechanism involves mitochondrial dysfunction with:

• Inhibition of the mitochondrial respiratory chain
• Impaired fatty acid oxidation
• Disrupted ATP synthesis leading to cellular hypoxia
• Diversion of carbohydrate metabolism to fat substrates
• Accumulation of propofol metabolites and free fatty acids that cannot undergo adequate beta-oxidation 1, 5

Diagnosis and Monitoring

Monitor these parameters in all patients receiving propofol sedation:

• Continuous ECG (watch for Brugada-like changes, arrhythmias)
• Serial creatine kinase (CK), CK-MB, troponin
• Lactate levels
• Arterial blood gases (metabolic acidosis)
• Potassium
• Triglycerides
• Liver enzymes (AST, ALT)
• Renal function
• Urine myoglobin 1, 5

Red flags requiring immediate action:

• Unexplained metabolic acidosis
• Increasing propofol requirements to maintain constant sedation level
• New-onset ECG changes or arrhythmias
• Rising CK levels
• Hemodynamic instability with escalating vasopressor needs 1, 2

Management Algorithm

1. Immediate Discontinuation:

• Stop propofol infusion immediately upon suspicion of PRIS—this is the single most critical intervention 1, 2
• Switch to alternative sedation (dexmedetomidine or benzodiazepines)

2. Supportive Care:

• Aggressive hemodynamic support with vasopressors/inotropes
• Correct metabolic acidosis
• Manage hyperkalemia
• Treat arrhythmias
• Provide renal replacement therapy as needed 1, 3

3. Consider Early Continuous Hemofiltration:

• Recommended for management of severe PRIS 3

4. Avoid Abrupt Discontinuation During Weaning:

• When stopping propofol for other reasons, taper gradually to prevent rapid awakening with anxiety, agitation, and ventilator dyssynchrony 2

Prevention Strategies

Dose Limitations:

• Avoid propofol infusions >5 mg/kg/hr (>70 μg/kg/min) for >48 hours 1, 2
• Use lowest effective dose for sedation goals
• Consider alternative sedatives (dexmedetomidine) for prolonged sedation needs

High-Risk Populations:

• Exercise extreme caution in patients with traumatic brain injury, sepsis, or requiring high-dose vasopressors
• Propofol is not recommended for long-term sedation in pediatric ICU patients due to PRIS risk 2
• In children, use only when benefits clearly outweigh risks and monitor intensively

Clinical Vigilance:

• Maintain high index of suspicion in any patient on prolonged propofol
• The variable presentation and lack of diagnostic specificity make early recognition difficult but critically important 1
• Even after discontinuation, mortality can occur, requiring continued intensive monitoring 1

Incidence and Mortality

PRIS occurs in approximately 1% of patients receiving propofol infusions 1. Mortality is high, reaching up to 33%, and can occur even after propofol discontinuation 1. Independent predictors of mortality include fever and hepatomegaly in children, and ECG changes, hypotension, hyperkalemia, traumatic brain injury, and mean infusion rates >5 mg/kg/hr in adults 3.