Muscle Relaxants

Depolarizing Muscle Relaxants

Although decamethonium was the first depolarizing muscle relaxant introduced into clinical practice in the late 1940s, it is no longer used in patient care, so this discussion is limited to SCh. Because of its structural similarity to two acetylcholine molecules joined together, succinylcholine initially stimulates acetylcholine receptors at the neuromuscular junction. Subsequently, as occurs in the presence of excess acetylcholine, these receptors remain inactive until the drug diffuses away and is broken down by local pseudocholinesterase.

Arrhythmias, most commonly sinus bradycardia or junctional rhythm, frequently accompany the administration of SCh. Bradycardia is due to SCh’s similarity to acetylcholine’s parasympathetic action on the heart. Its occurrence is particularly relevant in pediatric practice because it can cause significant hypotension in infants and children whose cardiac output is largely heart-rate dependent or, in the case of junctional rhythm, dependent on properly timed atrial contractions to augment ventricular filling (e.g., hypertrophic, dilated, or restrictive cardiomyopathy or arrhythmogenic right ventricular dysplasia; see Chapter 39 ). Further, asystole has been reported in patients of all ages after SCh administration. Life-threatening ventricular arrhythmias heralding severe rhabdomyolysis, hyperkalemia, or malignant hyperthermia occur less frequently.

Succinylcholine can cause elevations in intragastric, intraocular, and intracranial pressure as a result of muscle fasciculations and elevations in cerebral blood flow and metabolism.

Rhabdomyolysis and myoglobinemia can be detected in a significant proportion of children following SCh administration. Although some patients may have detectable myoglobinuria, in the vast majority, rhabdomyolysis is a benign sequela of SCh. In high-risk populations, however, including patients with congenital muscle disease or malignant hyperthermia sensitivity, SCh-induced rhabdomyolysis can be life threatening due to associated electrolyte disturbances, renal failure, or disseminated intravascular coagulation.

Prolonged neuromuscular blockade can occur after administering SCh to patients with heterozygous or homozygous genetic abnormalities in the butyrylcholinesterase gene (pseudocholinesterase deficiency) (see Chapter 98 ). Because the short-acting, nondepolarizing muscle relaxant mivacurium (which is no longer marketed in the United States) is also metabolized by butyrylcholinesterase, its use may produce this response as well.

Masseter spasm (or trismus) is characterized by an exaggerated increase in the tension of the masseter muscle that prevents mouth opening after SCh administration. Careful investigations have shown that masseter muscle tone is commonly increased after SCh administration. Hence, trismus may represent an extreme in the normal dose-related increase in muscle tension after SCh. As a result, masseter rigidity alone is not considered diagnostic of malignant hyperthermia. Recognition and management of malignant hyperthermia are discussed in Chapter 195 .

Nondepolarizing Muscle Relaxants

Intraoperative anaphylaxis to neuromuscular blocking agents is a rare but serious complication. Although at times difficult to diagnose, clinical signs include flushing, hypotension, tachycardia, and bronchospasm following administration of the agent.

Histamine release occurs with some benzylisoquinoline relaxants, and is recognized by skin flushing, hypotension, and tachycardia. Alternatively, the increased heart rate and hypertension observed with pancuronium is thought to involve blockade of muscarinic M2 receptors with associated vagolytic effects, as well as blockade of neuronal reuptake of norepinephrine.

Life-threatening episodes of bronchospasm, characterized by profound difficulty in ventilation with absent end-tidal carbon dioxide, as well as some deaths due to irreversible bronchospasm, were reported after the introduction of the aminosteroid NDMR rapacuronium bromide to clinical practice in 1999. Subsequent laboratory studies suggested that clinically relevant concentrations of rapacuronium may provoke bronchospasm due to muscarinic airway effects, and the drug was withdrawn from the market in 2001, less than 2 years after Food and Drug Administration (FDA) approval.