Early clinical signs, triggering agents, time to onset of reaction, mortality and methods of treatment were identified in 123 suspected malignant hyperthermia reactions. In vitro contracture test results were compared with clinical signs and the Malignant Hyperthermia Clinical Grading Scale. Increased end-tidal carbon dioxide is the earliest sign when not preceded by masseter spasm. Earlier diagnosis reduces the incidence of rigidity and severe metabolic acidosis. The combination of suxamethonium and a potent volatile anaesthetic agent triggers an earlier reaction compared with a volatile agent alone. There has been zero mortality since 1981, essentially due to a combination of advanced monitoring capability, increased anaesthetist awareness of malignant hyperthermia, and dantrolene availability. DNA analysis has identified nine New Zealand families with ryanodine receptor gene mutations. A positive DNA test indicates malignant hyperthermia susceptibility with "causative" mutations but discordance requires that negative DNA tests are confirmed with in vitro contracture test. This test also demonstrated the shortcomings of the Malignant Hyperthermia Clinical Grading Scale.

Testing for malignant hyperthermia in New Zealand involves two tests-in vitro contracture testing of excised lateral quadriceps muscle and DNA analysis. In vitro contracture testing is regarded as the gold standard in malignant hyperthermia diagnosis but several publications have questioned the reliability of a normal result. Analysis of 479 anaesthetic records in 280 patients or their descendants throughout New Zealand who had tested negative for malignant hyperthermia, demonstrated there was no evidence of malignant hyperthermia episodes in this group who had been administered anaesthetic triggering agents. A wide range of anaesthetics were used over the study period. Analysis of each anaesthetic record was undertaken using the malignant hyperthermia grading scale which determines the likelihood that an anaesthetic event represents a malignant hyperthermia episode. Confirmation of the negative results was further supported by normal DNA analysis of patients in 48% of anaesthetics. There are advantages to using inhalational agents in certain situations and although demonstrating a zero risk of a malignant hyperthermia episode is not statistically possible, evidence in this large series suggests that the risk of an episode in these patients is extremely low and may be negligible. We suggest that anaesthetic triggering agents can be used safely in patients with normal in vitro contracture tests, and in their descendants.

As the reliability of malignant hyperthermia normal in vitro contracture test results has been questioned, this study set out to determine the reliability of malignant hyperthermia normal results in New Zealand. Three hundred and twenty-nine anaesthetics were administered to malignant hyperthermia normal patients, identified through the Palmerston North Hospital malignant hyperthermia database. Anaesthetic records were retrieved and scrutinised for a malignant hyperthermia reaction using the Malignant Hyperthermia Clinical Grading Scale. Patients were exposed to one or more of eight triggering agents and multiple anaesthetic agents were administered in 41% of cases. Six variables were analysed, and although a minority of variables were abnormal in a small number of patients, none of the findings supported a malignant hyperthermia reaction. While the analysis was limited by the adequacy of the anaesthesia records, it was supported by negative DNA analysis in 55% of patients. This study supports several previous studies in demonstrating that patients in New Zealand tested non-susceptible to malignant hyperthermia can safely be given triggering agents.

Patients who are malignant hyperthermia susceptible are often admitted overnight for observation, even after minor surgery. They may be declined care in a stand-alone day stay unit. This prospective audit set out to investigate whether patients susceptible to malignant hyperthermia can be safely treated as day stay patients. The audit was conducted for four years from late 2000. All patients who were known to be susceptible to malignant hyperthermia, and their untested relatives, who received day stay anaesthesia were included in the audit. Malignant hyperthermia status, age, duration of anaesthesia, anaesthetic technique, type of procedure, intraoperative and postanaesthesia care unit observations and complications were recorded. All patients received a trigger-free anaesthetic technique. Detailed postanaesthesia care unit monitoring was undertaken and patients were observed for two and a half hours postoperatively. Seventy-two patients were included in the audit. General anaesthesia was administered to 85% and regional to 15%. Only minor complications arose in the postoperative period, and none suggested a malignant hyperthermia reaction. Postanaesthesia care unit nursing staff contacted 49 (68%) of the patients the following day, and there was no evidence of malignant hyperthermia reactions. This audit suggests that malignant hyperthermia susceptible patients can be safely managed as day stay patients in appropriate facilities, with appropriate postoperative care.

The postoperative care of malignant hyperthermia (MH) patients is subject to international variation, with a paucity of data in the literature to guide management. Over a series of three studies, our aim was to evaluate whether MH-susceptible patients (and relatives who had not yet been investigated), who had received a non-triggering anaesthetic, could be managed in the same way as the standard surgical population. Following a retrospective study, 206 anaesthetics were administered in a prospective second study to MH-susceptible/related individuals who were monitored for a minimum of one hour in the post anaesthesia care unit and a further 90 minutes in a step-down facility. No problems relating to MH were encountered. The postoperative monitoring time was subsequently changed and, in a third study, patients were managed no differently from standard surgical patients. One hundred and twenty-five anaesthetics were administered with no evidence of problems. This data shows that standard postoperative monitoring times are safe and appropriate in MH-susceptible patients.

Background: Central core disease and malignant hyperthermia are human disorders of skeletal muscle resulting from aberrant Ca2+ handling. Most malignant hyperthermia and central core disease cases are associated with amino acid changes in the type 1 ryanodine receptor (RyR1), the skeletal muscle Ca2+-release channel. Malignant hyperthermia exhibits a gain-of-function phenotype, and central core disease results from loss of channel function. For a variant to be classified as pathogenic, functional studies must demonstrate a correlation with the pathophysiology of malignant hyperthermia or central core disease.Objective: We assessed the pathogenicity of four C-terminal variants of the ryanodine receptor using functional analysis. The variants were identified in families affected by either malignant hyperthermia or central core disease.Methods: Four variants were introduced separately into human cDNA encoding the skeletal muscle ryanodine receptor. Following transient expression in HEK-293T cells, functional studies were carried out using calcium release assays in response to an agonist. Two previously characterized variants and wild-type skeletal muscle ryanodine receptor were used as controls.Results: The p.Met4640Ile variant associated with central core disease showed no difference in calcium release compared to wild-type. The p.Val4849Ile variant associated with malignant hyperthermia was more sensitive to agonist than wild-type but did not reach statistical significance and two variants (p.Phe4857Ser and p.Asp4918Asn) associated with central core disease were completely inactive.Conclusions: The p.Val4849Ile variant should be considered a risk factor for malignant hyperthermia, while the p.Phe4857Ser and p.Asp4918Asn variants should be classified as pathogenic for central core disease.

Malignant hyperthermia (MH) is a hypermetabolic disorder of skeletal muscle triggered almost exclusively by potent inhalational agents and suxamethonium. Signs of an MH reaction are non-specific and may be confused with the presentation of other problems such as sepsis and overheating of a patient. A high index of suspicion is needed to be aware of an early presentation of MH. Nine patients are presented who showed abnormal signs with an earlier anaesthetic where the possible diagnosis of an MH reaction was missed. These patients either presented later with an MH reaction, confirmed by DNA analysis and in some cases in vitro contracture testing, or were diagnosed by the identification of a causative mutation confirming MH susceptibility. The MH clinical grading scale is helpful in determining the likelihood that clinical indicators indicate a possible MH reaction. Masseter muscle rigidity is a known sign of MH, confirmed in this report by positive in vitro contracture testing and DNA analysis. Several uncommon muscle disorders have a high association with MH, and postoperative myalgia unrelated to suxamethonium can be a sign which is associated with MH. These reports emphasise the importance of a thorough family history (as the MH status was known by the family in four patients), a high index of suspicion for MH, and documentation of the possibility of MH susceptibility in the anaesthesia record.

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