Which of the following sedative agents is associated with the highest risk of propofol infusion syndrome (PRIS) when used for prolonged sedation in the ICU?

Explanation

## Propofol Infusion Syndrome (PRIS) **Key Point:** Propofol infusion syndrome is a rare but life-threatening complication characterized by metabolic acidosis, rhabdomyolysis, hyperkalemia, cardiac arrhythmias, and acute renal failure, typically occurring with prolonged high-dose infusions (>4 mg/kg/hr for >48 hours). ### Pathophysiology Propofol is metabolized by hepatic conjugation and extrahepatic tissues. At high infusion rates or prolonged durations, mitochondrial oxidative phosphorylation is impaired, leading to: 1. Uncoupling of oxidative phosphorylation 2. Accumulation of lactate and organic acids 3. Myocardial depression and dysrhythmias 4. Acute kidney injury ### Risk Factors - Infusion rate >4 mg/kg/hr - Duration >48 hours - Young age (children particularly vulnerable) - Critical illness with sepsis or severe trauma - Concurrent catecholamine use ### Clinical Presentation - Unexplained metabolic acidosis with elevated lactate - Bradycardia refractory to atropine - Green discoloration of urine (propofol metabolites) - Rhabdomyolysis (elevated CK) - Hyperkalemia - Acute renal failure **High-Yield:** PRIS is a diagnosis of exclusion and requires immediate cessation of propofol and supportive care including aggressive fluid resuscitation, dialysis, and treatment of hyperkalemia. **Clinical Pearl:** Modern ICU practice limits propofol infusion to <4 mg/kg/hr and duration <48 hours; alternative agents (dexmedetomidine, midazolam) are preferred for prolonged sedation.