Malignant hyperthermia

From Felipedia

Malignant hyperthermia (MH), which has only been reportedly sporadically in cats, is a life-threatening hypermetabolic and contractile condition that is triggered in cats by certain anaesthetic agents (e.g., halothane, isoflourane).

The underlying defect in calcium (Ca²⁺) homeostasis occurs at the level of the skeletal muscle sarcoplasmic reticulum where there is hypersensitive and heightened ligand-gating of the Ca-release channel. The Ca²⁺ channel is readily opened by certain drugs, such as caffeine and halothane. Caffeine- or halothane-induced muscle contracture develops as a result of sustained increase in cytoplasmic Ca²⁺ levels and subsequent activation of the actin-myosin contractile proteins. In addition, calcium uptake is reduced. The continuous contraction results in depletion of glycogen stores, hypoxemia, and accumulation of heat, hyperkalemia, lactic acid, and metabolic and respiratory acidosis.

In people, as a consequence of severe muscle necrosis, CK levels may rise 100-fold and myoglobinuria and disseminated intravascular coagulation may occasionally occur, which may lead to renal failure. Recent reports indicate that canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1), similar to that found in pigs and humans but not yet in cats[1].

Clinical signs

Reports of MH in cats are most often associated with halothane anaesthesia. It should be noted that this disorder does not always occur during the first exposure to halothane anaesthesia. Clinical signs can include hyperthermia, tachycardia, tachypnea, severe limb rigidity, and trismus, followed by respiratory and cardiac arrest. In some animals, extreme trismus and generalized muscle rigidity occur immediately after death. Succinylcholine and enflurane, but not methoxyflurane, have also been implicated as triggers of MH[2].

Histopathologic features in skeletal muscle tend to be fairly non-specific and include fibre size variation, fibre hypertrophy, and increased numbers of internal nuclei in muscle cells. Occasional perivascular infiltrates of lymphocytes with infrequent perimysial and epimysial neutrophils have also been noted [209]. In some patients, muscle biopsies are normal. Ultrastructurally, there may be loss of mitochondria, presence of moth-eaten fibers, cores, and Z-line streaming. Diagnosis of fulminating MH can be suggested by historical data and by development of characteristic clinical signs while under anaesthesia or accidental caffeine ingestion. Signs may occur after 30 to 300 minutes of halothane exposure.

Treatment

Prognosis is guarded. Removal of triggering agents and symptomatic treatment (total body cooling, corticosteroids, sodium bicarbonate, intravenous fluids) usually are ineffectual in reversing MH episodes, although hyperventilation with 100% oxygen, stomach lavage with iced water, body surface cooling, and IV administration of cold isotonic saline solution was successful in one report[3]. Dantrolene is the drug of choice for treating affected animals. It can prevent a malignant hyperthermia crisis or reverse aesthetic-induced MH if given early in the development of the syndrome. A recommended intravenous dosage is 3 to 5 mg/kg. Injectable dantrolene may also be prepared from an oral preparation[4].

In instances where MH is suspected, susceptible animals can safely undergo anaesthesia if triggering agents are avoided. Screening tests for animals susceptible to MH include caffeine/halothane-contracture tests (CCT), erythrocyte osmotic fragility test (EOFT), lymphocyte Ca test, and biochemical tests for defective Ca-transport in sarcoplasmic reticulum isolated from skeletal muscle. Several reports have noted that the initial sign of a MH episode was a rapid increase in end tidal partial pressure of carbon dioxide before any increase in rectal temperature or muscle tone[5].

It is now established that the Ca channel may also be triggered by stressors such as excitement, fighting for dominance, and by exercise. Absence of myoglobinuria rules out a diagnosis of exertional rhabdomyolysis. Hypercontracted myofibers have been observed in muscle biopsies. Recovery can be relatively rapid (e.g., within 30 minutes of rest) and this condition may represent "mild aborted malignant hyperthermia". A suggested diagnostic protocol for animals with canine-stress syndrome includes exercise/challenge testing, EOFT, and serum CK levels. In susceptible animals, CCT and EOFT are not always positive. The halothane-challenge test is likely risk prohibitive. Note that in dogs with exercise-induced hyperthermia, administration of dantrolene prior to exercise may not prevent the stress syndrome occurring[6].