None listed
Conditions
Brief summary
Title: Malignant Hyperthermia - A new simple diagnostic test Malignant Hyperthermia is a life threatening uncommon complication associated with having an anaesthetic. It may be passed down through families from one generation to the next. Many people at risk of Malignant Hyperthermia may be confirmed by a simple genetic test. However all other patients require a sample of muscle (muscle biopsy) taken from the leg, to have special functional testing to confirm they are at risk of Malignant Hyperthermia – the in-vitro contracture test (IVCT). The muscle biopsy is taken from the leg, requiring a surgical operation and a general anaesthetic that is known to be safe with MH. Technical advancements have enabled the design of a new test on a very small component of the muscle obtained from a minor needle biopsy, under local anaesthetic. Through this project we will show this simple less invasive technique is a reliable test to determine a patient’s potential risk of malignant hyperthermia. On the east coast of Australia, we have two Malignant Hyperthermia testing units. The Malignant Hyperthermia Units at The Royal Melbourne Hospital (RMH), Victoria and The Children’s Hospital, Westmead, NSW have been established for more than 15 years, and offer assessment of malignant hyperthermia risk through consultation, the muscle biopsy test and genetic analysis. The Muscle Research Laboratory, The University of Queensland, has extensive experience and understanding of skeletal muscle functioning. We will combine the excellence of all departments to improve our understanding of malignant hyperthermia and develop this simple, cheaper less invasive testing for malignant hyperthermia risk. This study will have implications for providing a clear diagnosis for patients at risk of malignant hyperthermia, while being significantly less invasive than the current muscle biopsy test. A simple investigation acceptable to the general population will increase the number of patients agreeing to define their risk of malignant hyperthermia and thus contribute to safer anaesthesia for our community.
Interventions
Malignant Hyperthermia (MH) is a potentially life threatening event in response to anaesthetic triggering agents – volatile anaesthetics or depolarising muscle relaxants, resulting from alterations in intracellular calcium homeostasis of skeletal muscle cells.
Current diagnosis of MH involves a functional test on a large skeletal muscle biopsy from the leg, obtained under a non-triggering general anaesthetic - the in-vitro contracture test (IVCT). A diagnosis of MH susceptible is determined at
Malignant Hyperthermia (MH) is a potentially life threatening event in response to anaesthetic triggering agents – volatile anaesthetics or depolarising muscle relaxants, resulting from alterations in intracellular calcium homeostasis of skeletal muscle cells. Current diagnosis of MH involves a functional test on a large skeletal muscle biopsy from the leg, obtained under a non-triggering general anaesthetic - the in-vitro contracture test (IVCT). A diagnosis of MH susceptible is determined at a critical threshold of 0.2 g of force at 2 mM or less of caffeine and 2% or less of halothane in each test. This study will assess intracellular calcium movements in isolated skeletal muscle fibres, to diagnose MH. Force is not used as a measure of responsiveness to RYR1 agonists. In single muscle fibre testing, the Ca2+ waves induced by caffeine or halothane imaged by confocal microscopy are classified by their amplitude and frequency. The amplitude is typically an indicator of the amount of Ca2+ being released through the RyR1s; and the frequency of the waves is indicative of the susceptibility of the RyR1 to opening in the presence of agonist. Individual testing will occur over 3 hours. Results from the IVCT and the single muscle fibre assay will be collated. Direct comparison of the results will establish the reliability of the new technique, with reference to the current IVCT. We will calculate the proportion of these where the two methods give identical categorization as negative or susceptible using the Wilson method. If 200 out of 200 patients are categorized identically by the two methods then the 95% CI will be 0.981 to 1.00, meaning that the level of disagreement is no more than 1.2%. Recruitment of 200 samples will occur over a two year period.
Sponsors
Dr Margaret Perry
Eligibility
Sex/Gender
All
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
Patients who have experienced a MH clinical episode or their relatives have MH susceptibility, or they do not carry the diagnostic family genetic pathogenic variant. These patients display no clinical signs of neuromuscular disease.
Exclusion criteria
Children will be excluded
Outcome results
None listed