A 24-year-old man comes to the emergency department after injuring his shoulder. He was standing on a ladder hanging pictures in his living room when he lost his balance and fell, impacting his left shoulder on the hardwood floor. Radiographs show an anterior dislocation of the humerus. Reduction of the patient's dislocated joint is performed under procedural sedation with intravenous propofol. A single bolus of propofol provides adequate sedation for the procedure, and he becomes clinically alert several minutes after administration. Which of the following mechanisms most likely explains this patient's rapid recovery from anesthesia?
Show Explanatory Sources
Propofol is a highly lipophilic anesthetic drug used for both induction and maintenance of general anesthesia as well as procedural sedation. When administered as an intravenous bolus, its onset of action is approximately 30 seconds with a duration of action typically lasting <10 minutes. Administration causes a rapid decrease in the level of consciousness as well as a global amnestic effect.
Following bolus infusion, propofol is rapidly cleared from the plasma and preferentially distributed to organs receiving high blood flow (eg, brain). This initial distribution accounts for the rapid onset of sedation seen with its administration. Over time, propofol is redistributed to organs receiving less blood flow (eg, fat, muscle tissue). Because the site of action for propofol is the brain, redistribution accounts for the rapid termination of drug action.
(Choice A) Although propofol is metabolized in the liver through hepatic conjugation, its half-life is 4 hours to 1 day; therefore, hepatic metabolism does not occur fast enough to account for such a short duration of action.
(Choice B) Volatile, inhaled anesthetics such as halothane are predominately eliminated by the lungs.
(Choice C) Renal tubular secretion and glomerular filtration are the predominate mechanisms through which water-soluble drugs are eliminated.
(Choice D) Atracurium is a non-depolarizing neuromuscular blocking agent that spontaneously degrades in plasma and organ tissue, a type of metabolism known as Hofmann elimination.
Educational objective
Propofol and other highly lipophilic drugs readily diffuse across membranes, quickly accumulating in tissues receiving high blood flow; this accounts for their rapid onset of action. These compounds are subsequently redistributed to organs receiving less blood flow, which explains their short duration of action.