Propofol infusion syndrome

Overview

Propofol infusion syndrome (PRIS) is a rare but potentially fatal complication associated with prolonged or high-dose administration of propofol, an intravenous anesthetic agent commonly used for sedation and anesthesia. PRIS is characterized by metabolic acidosis, cardiac dysfunction, rhabdomyolysis, hyperlipidemia, and renal failure. Although initially described in critically ill pediatric patients, PRIS has since been recognized in adults, particularly those in intensive care units receiving high doses of propofol for sedation over extended periods. Early recognition and immediate discontinuation of propofol are essential to improve survival outcomes.

Causes

Propofol infusion syndrome is believed to result from mitochondrial dysfunction and impaired fatty acid oxidation triggered by propofol. The precise pathophysiology is not fully understood but involves a disruption of cellular energy production. Known contributing factors and risks include:

• High-dose propofol: Typically more than 4 mg/kg/hr (or >67 mcg/kg/min) for over 48 hours

• Prolonged infusion: Extended sedation periods increase risk

• Catecholamine use: Concurrent administration of vasopressors may exacerbate mitochondrial stress

• Glucocorticoid therapy: May further impair cellular metabolism

• Critical illness: Especially in patients with traumatic brain injury, sepsis, or severe respiratory conditions

• Children: Pediatric patients are at increased risk, though adults can also develop PRIS

Symptoms

Symptoms of propofol infusion syndrome often develop insidiously and can progress rapidly to multiorgan failure. Clinical features include:

Metabolic and Cardiovascular

• Severe metabolic acidosis (lactic acidosis)

• Bradycardia progressing to asystole or other arrhythmias

• Cardiovascular collapse or heart failure

Musculoskeletal and Renal

• Rhabdomyolysis (muscle breakdown), with elevated creatine kinase (CK) levels

• Myoglobinuria leading to acute kidney injury

• Hyperkalemia from muscle breakdown

Hepatic and Other Findings

• Hepatomegaly or liver dysfunction

• Hyperlipidemia (elevated triglycerides)

• Elevated lactate levels

• Electrolyte imbalances

Symptoms often emerge after 48 hours of high-dose infusion but can occur sooner in susceptible individuals. Sudden deterioration in a critically ill patient receiving propofol should raise suspicion for PRIS.

Diagnosis

Diagnosis of propofol infusion syndrome is primarily clinical, supported by laboratory findings and a history of propofol administration. There is no single definitive test, so a high index of suspicion is necessary. Diagnostic steps include:

• History: High-dose or prolonged propofol infusion, particularly in the presence of other risk factors

• Laboratory tests:

  • Arterial blood gas: Reveals metabolic (lactic) acidosis

  • Serum creatine kinase: Elevated levels indicating rhabdomyolysis

  • Serum lactate: Elevated due to mitochondrial dysfunction

  • Serum triglycerides: Often markedly elevated

  • Renal function tests: Elevated creatinine indicating kidney injury

  • Electrolytes: Hyperkalemia, hypophosphatemia, and others

• Cardiac monitoring: ECG abnormalities such as bradycardia or arrhythmias

• Urinalysis: May reveal myoglobinuria, a sign of muscle breakdown

Diagnosis is made by recognizing the constellation of signs in the context of propofol exposure and ruling out other causes of metabolic derangements and organ dysfunction.

Treatment

Treatment of propofol infusion syndrome requires immediate cessation of propofol and supportive management to address the life-threatening consequences of the syndrome. Key treatment approaches include:

Immediate Actions

• Stop propofol infusion immediately upon suspicion of PRIS

• Switch to alternative sedative agents (e.g., midazolam, dexmedetomidine)

Supportive Care

• Cardiovascular support: Use of inotropes, anti-arrhythmic drugs, or mechanical support (e.g., ECMO) if necessary

• Management of metabolic acidosis: Intravenous bicarbonate therapy as indicated

• Renal support: Hemodialysis or continuous renal replacement therapy (CRRT) in cases of acute kidney injury

• Correction of electrolyte imbalances: Monitor and manage potassium, calcium, and phosphate levels

• Treatment of rhabdomyolysis: Aggressive IV fluids, alkalinization of urine, and monitoring for renal complications

Monitoring

• Close monitoring in an intensive care setting

• Frequent assessment of acid-base status, cardiac function, renal output, and muscle enzymes

Prognosis

The prognosis for patients with propofol infusion syndrome depends on the timing of recognition and the severity of organ involvement. Mortality rates can be as high as 30% to 60%, particularly in cases with delayed diagnosis or multisystem failure. Early cessation of propofol and prompt initiation of supportive measures are critical to improving survival outcomes.

Survivors of PRIS may fully recover or may experience long-term complications, including renal impairment or residual cardiac dysfunction. Prevention through cautious use of propofol—particularly avoiding high doses over extended periods—is key. Awareness of risk factors and close monitoring in high-risk populations are essential to minimize the occurrence of this potentially fatal syndrome.