A 45-year-old patient on propofol infusion at 6 mg/kg/hr for 72 hours in ICU develops metabolic acidosis, bradycardia refractory to atropine, lipaemic plasma, and elevated CK. The most likely diagnosis and the underlying mechanism involve:

• A Propofol-induced pancreatitis; lipase activation by propofol lipid vehicle
• B Serotonin syndrome; propofol's serotonergic partial agonism
• C Malignant hyperthermia; ryanodine receptor activation by propofol
• D Propofol infusion syndrome; uncoupling of mitochondrial oxidative phosphorylation ✓

Explanation

Propofol infusion syndrome (PRIS) is characterised by metabolic acidosis, rhabdomyolysis, lipid disturbances, cardiac dysrhythmias, and renal failure. The mechanism is impairment of mitochondrial electron transport chain (particularly Complex I and II) and uncoupling of oxidative phosphorylation, leading to cellular energy failure preferentially affecting cardiac and skeletal muscle. Risk factors include high doses (>4 mg/kg/hr), duration >48 hours, and critical illness. Malignant hyperthermia is triggered by volatile agents/succinylcholine, not propofol.

Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.

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Written and medically reviewed by the StethoPrep medical team.