The patient was a 7-year-old boy with kyphoscoliosis and strabismus and a history of an anesthetic-related death in the family in Wisconsin. Therefore, in addition to the respiratory problems associated with kyphoscoliosis, he presented a likelihood of susceptibility to MH syndrome. The supporting factors for strong suspicion were the family history, kyphoscoliosis, and geographic location. There is a high density of MH-susceptible families in the state of Wisconsin.

MH, first described by Denborough and Lovell in 1960, is an inherited clinical syndrome characterized by elevated core temperature, tachycardia, tachypnea, hypercarbia, muscle rigidity and rhabdomyolysis, acidosis, and hyperkalemia. The underlying abnormality relates to an uncontrolled elevation of intracellular calcium in skeletal muscle cells leading to activation of muscle contractile elements and hypermetabolism. These changes are reversed with the administration of dantrolene, but in the absence of timely treatment, death is likely. In almost every instance, the clinical syndrome occurs in a susceptible patient when a “triggering” anesthetic agent is employed. There are several documented instances where an apparent MH crisis has occurred in humans in the absence of anesthetic drugs.

A family history, if present, particularly in a first-degree relative, is a strong indicator of MH susceptibility. Epidemiologic studies have demonstrated that certain comorbidities such as scoliosis and muscle disorders are more frequent in MH-susceptible individuals. However, only a few diseases involving skeletal muscle are known to be associated with MH susceptibility. They include central core disease, King-Denborough syndrome, multiminicore
disease, centronuclear myopathy, congenital fiber-type disproportion, and Native American myopathy (Table 54.1). Nevertheless, many patients susceptible to MH do not have obvious musculoskeletal disorders or a positive family history.

Confusion often exists among some anesthesia providers regarding Duchenne or Becker muscular dystrophy and whether such patients need a nontriggering anesthetics. The concern about Duchenne or Becker dystrophy is related to the use of volatile anesthetics resulting in rhabdomyolysis and hyperkalemia due to the direct damage to the muscle cells. However, the pathophysiology of this adverse reaction is apparently not similar to that of MH. MH triggers, especially succinylcholine, should be avoided.

No, it does not. Cases may occur during a second or subsequent anesthetic course. A notable case is one described in the case report, of an 8-month-old infant born at 24 weeks of gestation who died unexpectedly 12 hours after his ninth uneventful general anesthetic. The authors have personal experience with similar cases where uneventful anesthetics with triggering agents preceded fulminant episode of MH at a later anesthetic exposure.

The clinical features of MH are the result of an uncontrolled, exaggerated, hypermetabolic state triggered by the use of potent inhalation anesthetic agents and/or succinylcholine. In humans, MH-like events have occurred in association with heat and exercise. Some of those patients harbor MH causative mutations in the ryanodine receptor 1 (RYR1) gene. Common manifestations of MH include the following:

The laboratory values reflect changes of a hypermetabolic state and muscle tissue damage (Table 54.2). Hence, hypercarbia, respiratory and metabolic acidosis, hyperkalemia, elevated creatine kinase, myoglobinemia, and coagulopathy are common findings. Disseminated intravascular coagulation syndrome may result in cases of extreme (>105°F) hyperthermia.

The incidence of clinical MH is difficult to measure because many clinical syndromes resemble MH, and often, the anesthetic management is altered when initial signs suggesting MH are detected. The incidence also depends on the prevalence in a population of genetic mutations causal for MH as well as the prevalence of use of MH trigger agents.

One of the earliest epidemiologic studies of MH was conducted in Denmark, where an estimate of the incidence of fulminant MH was noted to be 1 in 260,000 general anesthetics and 1 in 60,000 anesthetics where succinylcholine was used. The incidence was even higher, that is, 1 in 5,000 anesthetics, when such signs as masseter muscle rigidity, unexplained tachycardia, and unexplained fever were included.

Genetic studies as well as studies of discharge diagnoses after surgery have suggested that the prevalence as opposed to incidence of MH is much higher. Mutations causal for MH have
been found in 1 in 3,000 people in France and in Japan. A recent study in the United States documented a prevalence of genetic changes associated with MH close to 1 in 500 people.

It is generally acknowledged that MH is more common in children than adults. In addition, the incidence in males is higher than in females. Two recent studies of coded hospital discharge data showed that the prevalence of MH is 1 in 100,000 hospital discharges for adults and 4 per 100,000 discharges for children.

MH is inherited in humans in an autosomal dominant fashion with reduced penetrance and variable expressivity. It is heterogenetic with up to seven gene loci implicated, but only three are confirmed to be causal for MH.

More than 70% of MH cases are linked to the RYR1 located on chromosome 19. Less than 2% are related to mutations in the gene coding for dihydropyridine receptor (DHPR) known as CACNA1s. Over 300 mutations have been found in the RYR1 gene with at least 35 mutations documented to be causal for the syndrome by the European Malignant Hyperthermia Group (EMHG.org).

Because MH is inherited in an autosomal dominant manner, the susceptibility to it does not “skip” generations. Nevertheless, because of the low penetrance, not all of those with MH mutations display the syndrome on exposure to trigger agents.