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The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome
Beatrice Vasile1, Frank Rasulo, Andrea Candiani
1Institute of Anesthesiology-Intensive Care, University of Brescia, Piazzale Ospedali Civili 1, 25125 Brescia, Italy.
Insights
Propofol infusion syndrome (PRIS) is a rare but fatal condition in critically ill patients. High-dose, long-term propofol use, especially with catecholamines or steroids, can trigger PRIS, leading to organ failure.
Area of Science:
- Critical Care Medicine
- Neuroscience
- Pharmacology
Background:
- Propofol infusion syndrome (PRIS) is a rare, potentially fatal condition.
- PRIS is characterized by cardiac failure, rhabdomyolysis, metabolic acidosis, and renal failure.
- Cases are reported in critically ill children and adults, particularly those with neurological or inflammatory conditions.
Purpose of the Study:
- To describe the clinical features, risk factors, and pathogenetic mechanisms of Propofol Infusion Syndrome (PRIS).
- To provide recommendations for the safe use of propofol in critically ill patients.
Main Methods:
- Review of reported pediatric and adult cases of PRIS.
- Analysis of contributing factors including propofol dosage, duration, and concomitant medications (catecholamines, steroids).
- Examination of subcellular mechanisms involving fatty acid utilization and mitochondrial function.
Main Results:
- PRIS involves cardiac and muscle dysfunction, metabolic derangements, and organ failure.
- Risk factors include prolonged (>48h) high-dose propofol (>5mg/kg/h), catecholamine/steroid co-administration, critical illness, and underlying neurological/inflammatory conditions.
- Pathogenesis involves impaired energy metabolism and mitochondrial dysfunction, exacerbated by inflammation and catecholamine/steroid effects.
Conclusions:
- PRIS is multifactorial, with propofol acting as a trigger, especially when combined with catecholamines and/or steroids.
- Caution is advised for prolonged (>48h) high-dose propofol sedation (>5mg/kg/h).
- Consider alternative sedatives or strict monitoring for myocytolysis signs in high-risk patients.
Abstract:
Propofol infusion syndrome (PRIS) is a rare and often fatal syndrome described in critically ill children undergoing long-term propofol infusion at high doses. Recently several cases have been reported in adults, too. The main features of the syndrome consist of cardiac failure, rhabdomyolysis, severe metabolic acidosis and renal failure. To date 21 paediatric cases and 14 adult cases have been described. These latter were mostly patients with acute neurological illnesses or acute inflammatory diseases complicated by severe infections or even sepsis, and receiving catecholamines and/or steroids in addition to propofol. Central nervous system activation with production of catecholamines and glucocorticoids, and systemic inflammation with cytokine production are priming factors for cardiac and peripheral muscle dysfunction. High-dose propofol, but also supportive treatments with catecholamines and corticosteroids, act as triggering factors. At the subcellular level, propofol impairs free fatty acid utilisation and mitochondrial activity. Imbalance between energy demand and utilisation is a key pathogenetic mechanism, which may lead to cardiac and peripheral muscle necrosis. Propofol infusion syndrome is multifactorial, and propofol, particularly when combined with catecholamines and/or steroids, acts as a triggering factor. The syndrome can be lethal and we suggest caution when using prolonged (>48 h) propofol sedation at doses higher than 5 mg/kg per h, particularly in patients with acute neurological or inflammatory illnesses. In these cases, alternative sedative agents should be considered. If unsuitable, strict monitoring of signs of myocytolysis is advisable.