Also known as malignant hyperpyrexia, this is a hypermetabolic state that is known to be caused by anaesthetic agents such as suxamethonium and/or volatile halogenated anaesthetic agents. Local anaesthetics, benzodiazepines, narcotics, atracurium, pancuronium and vecuronium are safe.

Malignant hyperthermia is a medical emergency.

The incidence has been reported to be between 1:4,500 to 1:60,000 procedures involving a general anaesthetic. This disorder occurs worldwide and affects all racial groups. Most cases however occur in children and young adults. There is a strong family association for this condition, which is inherited in an autosomal dominant pattern.

Pathophysiology
Animal models have shown that the underlying problem is a defect in skeletal muscle cells that causes increased calcium ion uptake on exposure to these anaesthetic agents. The calcium ion uptake provokes muscle contraction, leading to muscle rigidity. The muscle literally cannot relax. Tachycardia, cyanosis (hypoxaemia), generalised muscle rigidity, and cardiac arrhythmias are common clinical signs. Lactic acidosis followed by cyanosis and hypercarbia precede the rise in temperature. There may also be hyperkalaemia, hyperphosphataemia, and hypocalcaemia from muscle-cell breakdown. Myoglobinaemia and myoglobinuria are common and renal failure may result from the rhabdomyolysis.


Treatment
The first thing to do is to discontinue suxamethonium and inhalational agents and ventilate with 100% O2. Sodium bicarbonate is given to neutralize the metabolic acidosis present.

Dantrolene is the only drug that works when this syndrome is recognized. Originally looked into as a possible antibiotic, Dantrolene acts by inhibiting the excitation-contraction coupling in skeletal muscle without affecting neuromuscular transmission or the electrical properties of muscle. 2.5mg/kg is given ASAP and doses may be pumped up to 10mg/kg if necessary. Mortality without administration of this drug approaches 70%.

Cooling measures including cold IV solutions and cold packs should be used. Severe hyperkalaemia should be treated with Dextrose and soluble insulin. Arrhythmias should be treated with anti-arrhythmics.

Frusemide may be given for a short period to induce diuresis to reduce the risk of renal damage secondary to myoglobinuria.


Diagnosis
Testing for MH susceptibility is recommended for any patient who has a previous episode of MH and for anybody who has a family history of MH. Testing is done using a muscle biopsy specimen from the thigh (quadriceps) which is tested with to measure the response to halothane and caffeine. Patients with a contracture of 0.5 g or more to 3% halothane and a contracture of 0.2 g or more to 2 mmol/L caffeine are considered to be susceptible to MH.


Prevention
Anyone diagnosed with a susceptibility to MH should be kept off suxamethonium and all volatile anaesthetic agents. Spinal and epidural anaesthetics should be considered if possible. Genetic counselling should be offered to other members of the family of anyone diagnosed with MH.


The trouble with this condition is that it is rare and that Dantrolene is expensive and has a shelf life of 2 years. The hospital I am in (which is reasonably big) has not seen a case of malignant hyperthermia for 10 years but still keeps ordering it faithfully, just in case.


Having said all that, MH also manifests in conditions such as heatstroke, rhabdomyolysis, neuroleptic malignant syndrome and SIDS (sudden infant death syndrome) in that many patients with these have been found to have the exact same susceptibility to MH as those undergoing an anaesthetic.


A quote from a review of Malignant Hyperthermia in the Lancet, illustrating how it became known (emphases mine):

The story of malignant hyperthermia (hyperpyrexia, MH) begins on April 14, 1960, when a 21-year-old student was run over by a car and sustained compound fractures of his right tibia and fibula. In the casualty department of the Royal Melbourne Hospital, Australia, he was less concerned about his leg than by the prospect of a general anaesthetic; he said that 10 close relatives had died during or after anaesthesia, usually for minor procedures. Because ether had been incriminated in all the previous cases, it was decided to proceed cautiously with halothane, which had recently become available. Unfortunately after 10 min of anaesthesia the patient became acutely ill; his blood pressure was falling, pulse rate rising, and he was cyanosed and felt very hot. The soda-lime canister was also hot, and it was changed. The anaesthetic was stopped and the patient was rubbed down with ice-cold packs. He recovered and his subsequent course was uneventful. Detailed clinical examination and routine pathological and biochemical tests revealed no abnormality but inquiry into the deaths in the family indicated a previously undescribed inborn error of metabolism inherited as a dominant characteristic. In the hope that others might have noted similar clinical events, this patient's anaesthetic complication was described in The Lancet, but with no response.

A year later the man needed another anaesthetic, this time for a stone impacted in his left ureter. After considerable discussion the patient was connected to every possible monitor and given a spinal anaesthetic, which he tolerated uneventfully. The knowledge that local anaesthesia could be used safely was a great help because the patient came from a very large family, one very prone to accidents and operations. 2 years later I learned of three anaesthetic deaths in a family in Wisconsin, USA, and further cases were published. One such child had died in Toronto, Canada. Beverley Britt, the anaesthetist, with Werner Kalow (a pharmacologist who had been interested in MH since it was first described) and the professor of anaesthesia, R A Gordon, organised inquiries throughout Canada, which led to 13 cases of MH being presented at a symposium in Toronto in 1966. One interesting observation to come out of this meeting was that during the MH reaction some patients developed muscular rigidity. The syndrome became known as malignant hyperthermia or MH-hyperthermia, because a steep and rapid rise in body temperature was a common accompaniment, and malignant, because in those days the case-fatality rate was 70%.

Denborough, Michael, Malignant hyperthermia Seminar, The Lancet, Volume 352(9134) pp 1131-1136(1998)

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