Propofol Infusion Syndrome : A rare but serious complication

Over the past year, I encountered two clinical cases strongly suspected to be instances of Propofol Infusion Syndrome (PRIS). This rare but severe complication, associated with prolonged and/or high-dose propofol use, captured my attention due to its potentially life-threatening implications. Motivated to deepen my understanding of its pathophysiology, risk factors and management strategies, I conducted a thorough review of the available scientific literature. With the aim of sharing this knowledge and raising awareness among my colleagues, I decided to synthesize my findings into a concise article, hoping to contribute to improved vigilance and better patient care practices.

Propofol, an intravenous anesthetic, is widely used for sedation and anesthesia due to its rapid onset, short duration of action and favorable pharmacokinetic profile. Despite its advantages, prolonged infusion at high doses can lead to PRIS, a syndrome characterized by metabolic acidosis, cardiac dysfunction, rhabdomyolysis, renal failure and hyperlipidemia. First described in children in the 1990s, PRIS remains a challenging condition to diagnose and manage due to its nonspecific symptoms and rapid progression.

Pathophysiology

The exact mechanisms underlying PRIS are not fully understood. Proposed theories suggest mitochondrial dysfunction and impaired fatty acid metabolism as central mechanisms. Propofol and its lipid exipients disrupt electron transport within mitochondria, leading to decreased ATP production, accumulation of toxic fatty acid intermediates and oxidative stress. This metabolic derangement affects multiple organ systems, particularly the heart and skeletal muscles, resulting in the hallmark features of PRIS.

Clinical and biological presentation

PRIS presents with a wide range of signs and symptoms that include :

• Metabolic acidosis : Elevated lactate levels and severe metabolic acidosis are common early markers.
• Cardiac dysfunction : Bradycardia, arrhythmias and refractory heart failure can develop, often culminating in cardiovascular collapse.
• Rhabdomyolysis : Muscle breakdown leads to elevated creatine phosphokinase (CPK) levels, myoglobinuria and renal impairment.
• Hyperlipidemia : Elevated triglycerides and lipemia may be observed, often accompanying worsening clinical signs.
• Renal failure : Secondary to rhabdomyolysis or direct toxic effects on renal tubules.

Risk factors

Several factors increase the risk of developing PRIS :

• High-dose propofol : Infusions exceeding 4 mg/kg/hour for more than 48 hours.
• Critical illness: Particularly in patients with sepsis, traumatic brain injury (the 2 cases in my department) or severe burns.
• Concurrent medications : Use of catecholamines or corticosteroids may exacerbate mitochondrial stress.
• Pediatric population : Children appear more susceptible, although PRIS also occurs in adults.

Diagnosis

PRIS is primarily a clinical diagnosis supported by laboratory and imaging findings. Key diagnostic tools include:

• Laboratory tests : Arterial blood gas analysis for metabolic acidosis, serum CPK levels for rhabdomyolysis and lipid panels for hyperlipidemia.
• Imaging : Echocardiography may reveal cardiac dysfunction, while muscle biopsies can confirm mitochondrial abnormalities.

Management

The management of PRIS is mainly symptomatic. It focuses on prompt recognition, discontinuation of propofol, and supportive care :

• Discontinuation of propofol and use of alternative sedation : Immediate cessation is essential to halt disease progression. Transition to other sedatives, such as benzodiazepines or dexmedetomidine is recommended but is not so simple in practice.
• Hemodynamic support : Vasopressors and inotropes may be required to stabilize cardiovascular function but can make the situation worse because of the role of cathecolamins in the pathophysiology of PRIS.
• Correction of metabolic derangements : Sodium bicarbonate for acidosis, lipid-lowering agents for hyperlipidemia, and renal replacement therapy for acute kidney injury.

In severe cases, extracorporeal membrane oxygenation (ECMO) has been used successfully to support cardiac and respiratory function.

Prevention

Preventive strategies include limiting propofol infusion rates and durations, closely monitoring high-risk patients and using alternative sedatives when prolonged sedation is anticipated. Regular monitoring of metabolic parameters, including lactate levels and CPK, is critical in patients receiving hight dose propofol infusions.

Conclusion

Propofol infusion syndrome (PRIS) is a rare but life-threatening condition associated with the use of propofol in critically ill patients. Its management remains challenging, as treatment is purely symptomatic, aiming to address metabolic derangements, cardiac dysfunction and renal failure once they occur. Prevention is equally difficult due to the widespread use of propofol as a primary sedative agent in intensive care units, where its rapid onset and favorable pharmacokinetic profile make it indispensable. Awareness of PRIS, lactate and CPK monitoring of at-risk patients are critical to minimizing the incidence and improving outcomes in affected individuals.

References

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