ASSOCIATION WITH OTHER DISORDERS

The King-Denborough syndrome, characterized by short stature, musculoskeletal abnormalities, and mental retardation, is associated with susceptibility to MH, as is CCD. CCD was present in the family of Denborough's original patient ^[5] and discovered during later evaluations. Duchenne dystrophy is an X-linked myopathy; the associated deterioration of muscle membranes can result in a clinical MH episode on exposure to membrane perturbors such as MH triggers despite normal contracture testing results.^[84] Patients with Duchenne dystrophy can respond to anesthesia with sudden, acute, difficult-to-resuscitate cardiac arrest or sudden, acute rhabdomyolysis, even without the use of succinylcholine. ^{[84] [90] [91] [92]} Patients with any occult myopathy, even without exposure to succinylcholine, may experience these potentially and rapidly disastrous anesthetic events.^{[90] [91] [92]}

Neuroleptic malignant syndrome^[116] (NMS) is an uncommon condition caused by central effects of drugs with dopamine antagonist properties, including antipsychotics (e.g., haloperidol), and by drugs used for sedation or as antiemetics (e.g., Compazine, metoclopramide, droperidol). In affected patients, these drugs may cause a reaction involving a range of symptoms culminating in fulminant MH-like hypermetabolism. The onset ranges from hours to days after beginning drug treatment. There are three key clinical components of NMS. First, the patient usually experiences an impairment of motor function with generalized rigidity, akinesia, or extrapyramidal disturbances, or some combination of these conditions. Second, deterioration in mental status occurs, producing coma, stupor, or delirium. Third, hyperpyrexia develops, with deterioration and lability of other "vegetative" functions, resulting in diaphoresis, dehydration, fluctuations in blood pressure and heart rate, and tachypnea. Duration averages 7 to 10 days, with gradual recovery that parallels the slow metabolism of the triggering drugs.

NMS patients may experience predictable complications of hypermetabolism, including rhabdomyolysis, renal failure, disseminated intravascular coagulation, thromboembolism, and sudden cardiac arrest. Treatment involves discontinuation of the drugs and symptomatic control of temperature, acid-base balance, intravenous fluid balance, and muscle tone. Specific pharmacotherapy is empirical. Clinical reports support consideration of benzodiazepines, dopamine agonists, and dantrolene. Dantrolene aids in therapy because it lowers muscle heat production and therefore body temperature, and it eases rigidity without the need for tracheal intubation. In refractory cases and patients with prominent catatonic features, electroconvulsive therapy has helped. Succinylcholine, usually part of such therapy, may risk hyperkalemia in patients with muscle necrosis. Although often similar in presentation, NMS and MH result from different pathophysiology. Unlike MH, dopamine antagonists trigger NMS in the brain; it may respond to centrally acting agents, electroconvulsive therapy, and neuromuscular blockers. MH triggers appear safe in NMS patients and their families. Some NMS patients have had positive MH muscle biopsy results, but their significance is unclear.

The relationship of isolated CK elevations and MH susceptibility remains unclear. Some have had positive contracture testing, and others with a long-standing benign course have received triggers uneventfully.^[117] Less convincing is a direct association of MH with other disorders: crib death, or sudden infant death syndrome; Smith-Lemli-Opitz syndrome^[118] ; and Charcot-Marie-Tooth syndrome.^[119] Exercise and heat stroke are discussed under "Awake Triggering: Exercise and Heat Stroke." Succinylcholine induces contractures in myotonic muscle,

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