A 28-year-old man is undergoing a laparoscopic appendectomy for acute appendicitis. Shortly after induction of anesthesia, the surgeon reports difficulty maintaining abdominal insufflation due to severe muscle rigidity. Pulse is 130/min and the ECG tracing shows sinus tachycardia. Physical examination reveals diffuse muscle stiffness. Inhibition of which of the following is most likely to improve this patient's condition?
Malignant hyperthermia | |
Pathophysiology |
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Clinical manifestations |
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Treatment |
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During laparoscopic procedures, small incisions are created to insert instruments into the abdominal cavity. Gas is insufflated to allow better visualization and easier access to organs while operating. Difficulty maintaining abdominal insufflation due to muscle contraction is often caused by insufficient doses of paralytic agents. However, if the patient has been appropriately medicated, sustained muscle contraction, especially when widespread, may be due to malignant hyperthermia (MH).
MH is often due to abnormal ryanodine receptors (RYR1) in the skeletal muscle. On exposure to certain anesthetic agents (typically succinylcholine and inhalational gases), these abnormal receptors allow the unregulated passage of calcium from the sarcoplasmic reticulum into the intracellular space. As a result of excessive calcium accumulation, patients develop sudden-onset, widespread muscle rigidity. Sustained muscle contraction produces excessive CO2, leading to hypercarbia and acidosis; depletes cellular oxygen, leading to lactic acid production; and causes muscle breakdown, leading to rhabdomyolysis. Hyperthermia is often a later clinical sign that develops as the increased cellular metabolism overwhelms the body's ability to dissipate heat.
Many pharmacologic muscle relaxants work upstream from the pathologic process of excessive calcium release and are therefore ineffective during an acute MH crisis. Dantrolene is used to treat MH because it directly inhibits intracellular calcium release from the abnormal ryanodine receptor (RYR1).
(Choice A) Neostigmine is an acetylcholinesterase inhibitor that prevents the degradation of acetylcholine in the neuromuscular junction. Therefore, it could increase, rather than decrease, the strength of muscle contractions.
(Choice B) Alpha-adrenergic antagonists (eg, phentolamine, phenoxybenzamine) inhibit alpha-receptor–mediated sympathetic activity. They are used primarily to lower blood pressure by decreasing vascular tone; they have minimal effect on skeletal muscle.
(Choices C and D) Baclofen is a GABA-B agonist that increases neuron hyperpolarization in the CNS to relax muscles. Nondepolarizing neuromuscular blocking agents (eg, rocuronium) are nicotinic receptor antagonists that inhibit the action of acetylcholine at the motor endplate. Both agents work upstream from intracellular calcium release and therefore have minimal impact on muscle contraction during an MH crisis.
Educational objective:
Malignant hyperthermia presents with widespread muscle rigidity after administration of inhalation anesthetics and/or succinylcholine to genetically susceptible individuals. It is treated with dantrolene, which blocks ryanodine receptors to prevent the release of calcium from the sarcoplasmic reticulum into the cytoplasm of skeletal muscle fibers.