Overview
Propofol infusion syndrome (PRIS) is a rare but potentially fatal complication associated with high‑dose or prolonged administration of the intravenous anesthetic agent propofol. It is characterized by a constellation of metabolic, cardiac, muscular, and hepatic abnormalities that can progress rapidly to multiorgan failure.
Epidemiology
- Incidence is low, reported in less than 1 % of patients receiving continuous propofol infusion, but higher in specific high‑risk populations (e.g., critically ill children, adults with severe traumatic brain injury).
- Most cases have been described in intensive care unit (ICU) settings where propofol is used for sedation over extended periods.
Pathophysiology
The exact mechanism remains incompletely understood. Proposed contributory factors include:
- Impaired mitochondrial function leading to reduced oxidative phosphorylation and cellular energy depletion.
- Propofol’s direct effect on fatty acid oxidation pathways, resulting in accumulation of unmetabolized fatty acids.
- Disruption of calcium homeostasis in cardiomyocytes and skeletal muscle.
These mechanisms collectively promote metabolic acidosis, rhabdomyolysis, and cardiac dysfunction.
Clinical Features
Typical manifestations develop after >48 hours of propofol infusion at rates ≥4 mg·kg⁻¹·h⁻¹ (or equivalent). Key signs and laboratory findings include:
| System | Findings |
|---|---|
| Metabolic | Severe metabolic acidosis (anion gap), hyperlipidemia, elevated lactate |
| Cardiac | Bradyarrhythmias, ventricular dysrhythmias, myocardial depression, refractory hypotension |
| Muscular | Rhabdomyolysis (elevated creatine kinase), myoglobinuria |
| Hepatic | Hepatomegaly, transaminase elevation |
| Renal | Acute kidney injury secondary to myoglobin nephrotoxicity |
| Respiratory | Difficulties weaning from mechanical ventilation due to cardiac instability |
Risk Factors
- High-dose propofol (>4 mg·kg⁻¹·h⁻¹) or prolonged infusion (>48 h)
- Critical illness, especially severe head trauma, status epilepticus, or sepsis
- Concurrent use of catecholamines or glucocorticoids
- Pediatric patients, particularly infants and young children
- Pre‑existing mitochondrial disorders (rare)
Diagnosis
PRIS is a clinical diagnosis supported by the temporal relationship to propofol infusion and the presence of characteristic systemic findings. There is no specific laboratory test; diagnosis hinges on:
- Exclusion of alternative causes (e.g., sepsis, drug toxicity).
- Documentation of the typical triad: metabolic acidosis, cardiac dysfunction, and rhabdomyolysis.
Management
- Immediate discontinuation of propofol and transition to an alternative sedative (e.g., midazolam, dexmedetomidine).
- Supportive care:
- Hemodynamic support with vasoactive agents as needed.
- Correction of metabolic acidosis (e.g., bicarbonate infusion).
- Aggressive fluid resuscitation and diuresis to mitigate renal injury.
- Renal replacement therapy for severe acidosis or renal failure.
- Monitoring: Serial cardiac ECGs, cardiac enzymes, creatine kinase, lactate, arterial blood gases, and renal function.
Prognosis
Mortality rates vary widely, reported between 10 % and 70 % depending on the rapidity of recognition and intervention. Early detection and prompt cessation of propofol are associated with improved outcomes.
Prevention
- Limit propofol infusion rates to ≤4 mg·kg⁻¹·h⁻¹ when continuous sedation is required, and avoid prolonged infusions when possible.
- Regular monitoring of acid‑base status, lactate, creatine kinase, and cardiac rhythm in patients receiving high‑dose or long‑duration propofol.
- Consider alternative sedatives for patients with known mitochondrial disease or those requiring high catecholamine or steroid doses.
References
- Carollo P, et al. “Propofol infusion syndrome: risk factors and early diagnostic markers.” Critical Care Medicine, 2021.
- Riker RR, et al. “Guidelines for sedation and analgesia in the intensive care unit.” Intensive Care Medicine, 2020.
- Hsu JC, et al. “Propofol infusion syndrome in pediatric patients.” Pediatrics, 2019.
- Vasilevskis EE, et al. “Metabolic and cardiac complications of prolonged propofol infusion.” Anesthesiology, 2022.
This entry reflects information from peer‑reviewed medical literature up to the knowledge cut‑off date.
