Abstract
This chapter provides a review of malignant hyperthermia. The author discusses the considerations related to intraoperative hyperthermia. The differential diagnosis of severe perioperative hyperthermia is considered including thyroid storm and neuroleptic malignant syndrome. The incidence, genetics, diagnostic testing and treatment of malignant hyperthermia is presented.
A three-year-old, 18 kg male presents for tonsillectomy and adenoidectomy. No other pertinent past medical history or family history was reported. Inhalational induction and intubation without muscle relaxation was safely performed. Fifteen minutes after intubation and initiation of adequate controlled ventilation, generalized muscle rigidity is noted. Vital signs at that time include: EtCO2 110 mmHg, BP 140/80, HR 160 bpm, and T 38ºC.
How Will You Approach This Constellation of Clinical Findings?
The most likely diagnosis for increased end tidal carbon dioxide, fever, and muscle rigidity in this age group is malignant hyperthermia (MH). Other possible diagnoses that are usually considered include serotonin syndrome, sepsis, pheochromocytoma, neuroleptic malignant syndrome, thyroid storm, and adverse drug reactions, but none of these alternatives have been reported in this type of patient and should not be considered.
MH is a hypermetabolic response to inhalational anesthetics or succinylcholine. Acute signs include hypercarbia, tachycardia, master muscle or generalized muscle rigidity, arrhythmia resulting from hyperkalemia, or hyperthermia as an early or later sign. A rapid elevation of temperature is associated with increased severity of disease. Arterial blood gas sampling demonstrates a respiratory acidosis and possibly metabolic acidosis. Complications from MH include disseminated intravascular coagulation (DIC) from prolonged severe hyperthermia, rhabdomyolysis and myoglobinuria, end-stage organ failure, cardiopulmonary collapse, and death.
How Is MH Diagnosed?
Acute MH is diagnosed only by clinical characteristics and index of suspicion. After the event, a diagnosis of MH susceptibility can be confirmed by a positive result of a caffeine-halothane contracture test (CHCT) from a skeletal muscle biopsy, or finding a known MH-causative mutation on genetic screening. However, only a negative CHCT can rule out MH susceptibility; a negative mutation analysis is not sufficient to rule out MH susceptibility. Most MH-causative mutations are located on the gene that encodes for the skeletal muscle ryanodine receptor (RYR1), and rarely on the CACNA1S gene that encodes for the dihydropyridine receptor. In very rare cases, MH has been associated with a mutation in the STAC3 gene, which also contributes to the excitation-contraction complex in skeletal muscle.
What Is the Incidence of MH?
The approximate incidence of acute MH during general anesthesia with triggering agents has been estimated to be between 1/10,000 and 1/25,000 cases. The estimated prevalence of MH susceptibility is thought to be between 1/3,000 and 1/8,500 people. Historically, half of the diagnosed cases of MH have been found in the pediatric population. However, in recent years, studies have found that only 17–18% of patients diagnosed with MH in the United States are under the age of 18. This may be due to better detection of MH susceptibility and anesthetic preparation for MH susceptible patients by anesthesiologists. Male sex is also predominant in pediatric patients diagnosed with MH.
What Diseases Are Associated with MH Susceptibility?
Diseases that are associated with or caused by mutations in RYR1, CACNA1S, or STAC3 should be presumed to be associated with MH susceptibility. They are summarized in Table 12.1.
