Hyperthermia, malignant treatment

Denboroug, M.A., Phil, D. (1985). Current concepts of the etiology and treatment of malignant hyperthermia susceptible patients (letter). Anesthesiology 62,99. 

Which of the following agents is useful in the treatment of malignant hyperthermia ... 

The answer is e. (Kat ung, pp 428-429J Although a rare occurrence, halothane and other inhaled gas anesthetics may cause malignant hyperthermia Apparently, this occurs in genetically susceptible individuals Its onset may be accelerated by the concomitant use of succinylcholine. Immediate treatment includes administration of dantrolene. 

Succinylcholine-induced hyperkalemia may lead to cardiac arrhythmia and arrest when plasma reaches 7 and 10 mM, respectively. The drug also may precipitate a fulminant attack of malignant hyperthermia in susceptible individuals (not to be confused with neuroleptic malignant hyperpyrexia, which involves dopamine and the CNS). Treatment in either case consists of cooling the body and administering oxygen and dantrolene sodium (discussed later). 

Note Many drugs and toxins block neuromuscular transmission by other mechanisms, such as interference with the synthesis or release of acetylcholine, but most of these agents are not employed clinically for this purpose. One exception is botulinus toxin, which has been administered locally into muscles of the orbit in the management of blepharospasm and strabismus. This treatment produces a long-lasting interruption of neuromuscular transmission and reduction of spasmodic ocular movements. Another exception is dantrolene, which blocks release of Ca2+ from the sarcoplasmic reticulum and is used in the treatment of malignant hyperthermia. 

Dantrolene, a hydantoin derivative, reduces the contraction of skeletal muscle, acting directly on the muscle and not at the neuromuscular junction. It is thought to reduce the amount of calcium released and hence prevent excitation-contraction coupling (Figure 26.4). Its usefulness in the treatment of anesthetic-induced malignant hyperthermia may be due to its calcium-related uncoupling actions. 

Schroeder SA, McPhee SJ. 1990. Malignant hyperthermia. In Schroeder SA, Krupp MA, Tierney LM, et al., eds. Current medical diagnosis and treatments. Norwalk, CT Appleton and Lange, 172. 

Anaesthesia in MH-susceptible patients is achieved safely with total intravenous anaesthesia using propofol and opioids. Dantrolene for intravenous use must be available in every surgical theatre. The relation of malignant hyperthermia syndrome with neuroleptic malignant syndrome (for which dantrolene may be used as adjunctive treatment, see p. 388) is uncertain. 

Dantrolene (1,2) is the agent of choice for treatment of malignant hyperthermia and greatly reduces the mortality to under 10% if given in time (3) together with general supportive measures. 

Management of fulminant hypermetabolism of skeletal muscle because of malignant hyperthermia crisis. Treatment of neuroleptic malignant syndrome, relief induced pain in patients with muscular of exercise-dystrophy, treatment of flexor spasms... 

Treatment entails intravenous administration of dantrolene (dantrium), which blocks Ca release and its sequelae in skeletal muscle. Rapid cooling, inhalation of 100% oxygen, and control of acidosis should be considered adjunct therapy in malignant hyperthermia. 

In addition to its use in managing an acute attack of malignant hyperthermia see above), dantrolene has been used in the treatment of spasticity and hyperreflexia. Dantrolene causes a generalized weakness thus, its use should be restricted to nonambulatory patients with severe spasticity. Hepatotoxicity has been reported with continued use, requiring hver function tests. 

Prompt treatment is essential in malignant hyperthermia to control body temperature, correct acidosis, and prevent calcium release. Dantrolene blocks the release of activator calcium from its stores in the sarcoplasmic reticulum, preventing the tension-generating interaction of actin with myosin. The answer is (B). 

Muscle relaxant blocks Ca " release from sarcoplasmic reticulum of skeletal muscle. Used in muscle spasm (cerebral palsy, multiple sclerosis, cord injury) and in emergency treatment of malignant hyperthermia. 

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