A 42-year-old woman is hospitalized for surgical removal of a mediastinal mass. The patient has had intermittent episodes of double vision, difficulty chewing food, and weakness of the extremities for the past several months. During evaluation she was found to have a circumscribed anterior mediastinal mass. Preoperative nerve conduction studies revealed a decremental response to repetitive motor nerve stimulation. She has no other medical conditions and does not use tobacco, alcohol, or illicit drugs. The patient has no drug allergies. Compared to a healthy individual, which of the following anesthesia-related medications is most likely to have increased potency in this patient?

Question

A 42-year-old woman is hospitalized for surgical removal of a mediastinal mass.  The patient has had intermittent episodes of double vision, difficulty chewing food, and weakness of the extremities for the past several months.  During evaluation she was found to have a circumscribed anterior mediastinal mass.  Preoperative nerve conduction studies revealed a decremental response to repetitive motor nerve stimulation.  She has no other medical conditions and does not use tobacco, alcohol, or illicit drugs.  The patient has no drug allergies.  Compared to a healthy individual, which of the following anesthesia-related medications is most likely to have increased potency in this patient?

Quizplus · Accepted Answer

This patient has an anterior mediastinal mass and a nerve conduction study consistent with myasthenia gravis (MG), an autoimmune disease caused by autoantibodies against postsynaptic nicotinic acetylcholine receptors of the neuromuscular junction. Antibody-induced degradation leads to fewer functional receptors, which may be insufficient to generate muscle action potentials despite normal acetylcholine release. Weakness (most commonly of the extraocular, bulbar, and proximal muscles) worsens with repetitive nerve stimulation (fatigability) as acetylcholine stores in the presynaptic nerve terminal are depleted. Thymic abnormalities (eg, thymoma, thymic hyperplasia) are common and may appear as an anterior mediastinal mass on imaging. Neuromuscular blocking agents are used to induce skeletal muscle relaxation during surgery by competing with acetylcholine at the postsynaptic membrane. They can be subclassified by their effects: Nondepolarizing agents (eg, vecuronium, rocuronium) are competitive antagonists of nicotinic acetylcholine receptors. Due to the low number of functioning receptors, patients with MG are extremely sensitive to these agents; very small doses can induce paralysis with loss of airway patency. Depolarizing agents (eg, succinylcholine) are competitive agonists of nicotinic acetylcholine receptors; persistent depolarization leads to desensitization of the motor end plate. Due to the low number of functioning receptors, patients with MG are often resistant to these agents; extremely large doses are required to induce muscle relaxation. (Choices A and B) Isoflurane is a general anesthetic (acts centrally on multiple receptors) that can cause malignant hyperthermia in those with genetic predispositions. Midazolam is a benzodiazepine (acts on the GABA_A receptor) to produce sedation. These medications are not contraindicated in MG. (Choice C) The mainstay of symptomatic treatment for MG is acetylcholinesterase inhibitors (eg, pyridostigmine, neostigmine); these agents inhibit the degradation of acetylcholine in the synapse, thereby increasing the amount available to stimulate muscle contractions. (Choice D) Atropine is a muscarinic acetylcholine receptor antagonist often used as premedication before general anesthesia to decrease salivary and bronchial secretions (helps maintain airway patency) and prevent myocardial depression (minimizes risk of hypotension); it has no effect on nicotinic acetylcholine receptors in the neuromuscular junctions. Educational objective: Myasthenia gravis (MG) is caused by autoantibodies against postsynaptic nicotinic acetylcholine receptors, leading to fewer functional receptors and fatigable muscle weakness. Nondepolarizing neuromuscular blocking agents (eg, vecuronium) are competitive antagonists of nicotinic receptors; due to the depletion of receptors, patients with MG are extremely sensitive to these agents.

A 42-Year-Old Woman Is Hospitalized for Surgical Removal of a Mediastinal