Abstract
Case history
DC, a 23-year-old female student, came to see me one busy Monday morning mid-surgery. She had been invited for testing for malignant hyperthermia (MH) as her brother had recently suffered a reaction while undergoing a general anaesthetic that had been diagnosed as MH. As the testing centre was in Leeds, more than 200 miles away, and DC had already had several general anaesthetics herself without problems, she wanted to know whether it was really necessary for her to go for testing.
Discussion
MH was first recognized in a family in Australia in 1962 (Denborough et al., 1962). It is a rare life-threatening condition that occurs as a result of 1 in 4500 to 1 in 60 000 general anaesthetic episodes, depending on the anaesthetic agent used. Drugs used in general anaesthesia may trigger a rapid and uncontrolled increase in skeletal muscle oxidative metabolism known as an MH crisis. Such crises result in generalized skeletal muscle rigidity, especially of the masseter muscle, acidosis, hypoxia and significantly increased body temperature. The condition can be fatal if not recognized early and treated.
Halothane was originally linked to a large proportion of cases, but it is now rarely used in anaesthesia. However, any halogenated anaesthetic agent is a potential trigger of MH, as is suxamethonium, a neuromuscular blocking agent. As MH does not occur with every exposure to triggering agents, DC's previous history of uneventful general anaesthesia was not a reason for her not to be tested for MH.
Susceptibility to MH is often inherited in an autosomal dominant pattern. Therefore, if DC's brother had inherited his tendency to MH, DC had a one in two chance of having the condition herself. Several genes have been implicated with the most common being a mutation of the ryanodine receptor gene (RYR1). Seventy percent of patients with MH have an RYR1 mutation, and currently 27 different mutations have been identified that may cause MH.
At present, around 50% of affected UK families can be tested for MH with genetic screening for RYR1 mutations (Leeds Clinical Molecular Genetics Laboratory, 2010). However, DC was told that she was not suitable for genetic testing and instead had been invited for an in vitro contracture test (IVCT) using a muscle biopsy taken from her vastus medialis muscle (part of the quadriceps) on the inner thigh under local anaesthetic.
The fresh muscle biopsy is exposed to solutions containing halothane and caffeine according to a set protocol. Normal muscle will relax when exposed to halothane, whereas MH muscle will contract. MH muscle is also more sensitive to caffeine and will contract at much lower concentrations than normal muscle.
Currently, the Leeds test centre is the only test centre for MH in the UK, so DC was advised to attend there for her IVCT. Her IVCT was negative and she was reassured that she would be unlikely to develop MH. Further information about MH for both patients and professionals can be obtained from the British Malignant Hyperthermia Association website (www.bmha.co.uk).