A 23-year-old man is evaluated for prolonged paralysis following general anesthesia for an elective surgical procedure. Anesthesia was induced with propofol, succinylcholine was used for intubation, and anesthesia was maintained via propofol and fentanyl infusions. The patient has not had a return of neuromuscular function after several hours. His mother then discloses that she has also been "slow to wake up" from anesthesia. Which of the following is the most likely reason for this patient's prolonged paralysis?

Question

A 23-year-old man is evaluated for prolonged paralysis following general anesthesia for an elective surgical procedure.  Anesthesia was induced with propofol, succinylcholine was used for intubation, and anesthesia was maintained via propofol and fentanyl infusions.  The patient has not had a return of neuromuscular function after several hours.  His mother then discloses that she has also been "slow to wake up" from anesthesia.  Which of the following is the most likely reason for this patient's prolonged paralysis?

Quizplus · Accepted Answer

This patient who developed prolonged muscle weakness (eg, failure of spontaneous respiration, voluntary muscle activity) after receiving succinylcholine most likely has pseudocholinesterase deficiency, an autosomal recessive disorder caused by a genetic polymorphism in the BCHE gene. Succinylcholine is a depolarizing neuromuscular blocking agent used to induce skeletal muscle relaxation during intubation and surgery. It acts as a competitive agonist of nicotinic acetylcholine receptors of the motor endplate, where it induces persistent depolarization, leading to desensitization and skeletal muscle paralysis. Succinylcholine is rapidly hydrolyzed by plasma pseudocholinesterase; only around 10% of the administered dose reaches the neuromuscular junction, where it typically has a duration of action of <10 minutes. Patients with pseudocholinesterase deficiency are unable to metabolize succinylcholine, which leads to a large amount of the drug reaching the neuromuscular junction. Heterozygotes may experience double the normal duration of paralysis; homozygotes can have persistent paralysis for several hours. (Choice A) Decreased first-pass metabolism often occurs when drugs are administered via a nonoral route, allowing them to reach the systemic circulation without passing through the portal circulation and liver. Although succinylcholine is given intravenously, it is primarily inactivated in the plasma by pseudocholinesterase rather than the liver. (Choice C) The pharmacologic effects of drugs are typically enacted by the unbound (free) form of the drug. Therefore, increased binding to plasma proteins would likely decrease (rather than increase) the effect of the medication. (Choice D) Propofol is highly lipid soluble and has a very short duration of action (seconds) because of rapid redistribution from the brain (where it activates the GABA-A receptor) to other tissues (predominantly fat). However, propofol is a hypnotic agent; it does not cause muscle paralysis. (Choice E) Upregulation of target receptors would increase sensitivity to acetylcholine, which is one possible mechanism of spasticity in cerebral palsy. However, receptor upregulation occurs over many hours or days, not with a first dose. Educational objective: Succinylcholine, a depolarizing neuromuscular blocking agent, is rapidly hydrolyzed by plasma pseudocholinesterase. Patients with pseudocholinesterase deficiency have prolonged neuromuscular paralysis after drug administration.

A 23-Year-Old Man Is Evaluated for Prolonged Paralysis Following General