Anaesthetic management of a known or suspected malignant hyperthermia susceptible patient

Abstract

Learning objectivesBy reading this article you should be able to:•Identify patients who are at increased risk of developing malignant hyperthermia (MH).•Describe the preoperative preparations required before anaesthetising a patient susceptible to MH.•Develop a plan for safe anaesthesia for specific operations in patients susceptible to MH.Key points•Enquiry about a family history of problems with anaesthesia is a mandatory part of the anaesthetic history.•Wherever possible, a patient suspected of being at risk of MH should have their status verified with confirmatory tests.•Conditions associated with variants in the RYR1 gene may also carry a risk of malignant hyperthermia.•Suxamethonium and potent inhalational anaesthetics are contraindicated in patients susceptible to MH.•Activated charcoal filters enable rapid preparation of the anaesthesia workstation for patients susceptible to MH. By reading this article you should be able to:•Identify patients who are at increased risk of developing malignant hyperthermia (MH).•Describe the preoperative preparations required before anaesthetising a patient susceptible to MH.•Develop a plan for safe anaesthesia for specific operations in patients susceptible to MH. •Enquiry about a family history of problems with anaesthesia is a mandatory part of the anaesthetic history.•Wherever possible, a patient suspected of being at risk of MH should have their status verified with confirmatory tests.•Conditions associated with variants in the RYR1 gene may also carry a risk of malignant hyperthermia.•Suxamethonium and potent inhalational anaesthetics are contraindicated in patients susceptible to MH.•Activated charcoal filters enable rapid preparation of the anaesthesia workstation for patients susceptible to MH. Malignant hyperthermia (MH) is a potentially lethal reaction to drugs used during general anaesthesia that occurs in genetically predisposed individuals. Deaths from MH still occur in modern UK anaesthetic practice and the mortality rate in developed countries is estimated to be 4–10%.1Forrest K.M. Foulds N. Millar J.S. et al.RYR1-related malignant hyperthermia with marked cerebellar involvement - a paradigm of heat-induced CNS injury?.Neuromuscul Disord. 2015; 25: 138-140Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar,2Biesecker L.G. Dirksen R.T. Girard T. et al.Genomic screening for malignant hyperthermia susceptibility.Anesthesiology. 2020; 133: 1277-1282Crossref PubMed Scopus (5) Google Scholar In a previous article in this journal we described the diagnosis and management of a suspected MH crisis.3Gupta P.K. Hopkins P.M. Diagnosis and management of malignant hyperthermia.BJA Educ. 2017; 17: 249-254Abstract Full Text Full Text PDF Scopus (18) Google Scholar Another key element in reducing mortality and morbidity from MH is the identification of individuals who are genetically predisposed to develop MH (MH-susceptible) before anaesthesia so that they are not exposed to MH-triggering drugs. The prevalence of MH susceptibility is not known. Estimates based on clinical epidemiological data suggest a prevalence of up to 1:10,000, but those based on the prevalence in large genomic databases of genetic variants known to be associated with MH suggest that 1:1500 people may be MH-susceptible.2Biesecker L.G. Dirksen R.T. Girard T. et al.Genomic screening for malignant hyperthermia susceptibility.Anesthesiology. 2020; 133: 1277-1282Crossref PubMed Scopus (5) Google Scholar The discrepancy between these estimates is likely to be multifactorial but a non-Mendelian genetic model of MH susceptibility seems to play a major part.4Shaw M.A. Hopkins P.M. Mission impossible or mission futile? Estimating penetrance for malignant hyperthermia.Anesthesiology. 2019; 131: 957-959Crossref PubMed Scopus (7) Google Scholar In this article we discuss the perioperative management of patients who have been found susceptible to MH or those suspected to be susceptible. As with any other patient requiring anaesthesia, perioperative care should be optimised for the patient who is, or who may be, at risk of developing MH within the constraints of time imparted by their surgical pathology. On this basis, when time permits, all reasonable efforts should be made to confirm or refute the patient's increased risk of developing MH under anaesthesia unless their anaesthetist would normally use a technique that does not involve drugs that trigger an MH reaction, including avoiding using suxamethonium for airway rescue. Usually, a patient is identified as being at risk of MH susceptibility from the history they give at the preoperative assessment clinic or to the anaesthetist during their preoperative consultation. MH-susceptible patients may have had several uneventful anaesthetics, which is why a family history of anaesthetic problems is a mandatory part of the anaesthetic history. The resources available to the anaesthetist when trying to establish a patient's MH risk depend on the provision of MH services through the relevant healthcare system. Some countries, or regions within larger countries, have a national or regional MH unit that carries out diagnostic testing. Diagnosis of MH susceptibility can be confirmed either through genetic testing or a muscle biopsy with in vitro contracture tests (IVCT) of the excised muscle.3Gupta P.K. Hopkins P.M. Diagnosis and management of malignant hyperthermia.BJA Educ. 2017; 17: 249-254Abstract Full Text Full Text PDF Scopus (18) Google Scholar Diagnostic MH units invariably maintain a database of all patients they have tested since the unit was founded (1970 in the case of the UK MH unit in Leeds) enabling the MH status of patients tested there to be confirmed. Diagnostic MH units affiliated with the European MH Group are established in Australia, Brazil, Israel, New Zealand, and South Africa, and European countries.5European MH Group: contact details of MH units. Available from: https://www.emhg.org/mh-units-map (accessed 14 December 2020).Google Scholar Diagnostic testing is available in Canada but access in the USA is poor: information about North American diagnostic MH units and other sources of advice is available through the Malignant Hyperthermia Association of the United States (MHAUS).6Malignant Hyperthermia Association of the United States. Available from: https://www.mhaus.org/(accessed 14 December 2020).Google Scholar The European Malignant Hyperthermia Group and MHAUS both provide advice about MH to anaesthetists working in parts of the world where there is no healthcare provision for MH. We have categorised patients according to the different features of the history that implicate, or may implicate, MH susceptibility. If confirmation of the diagnosis is not in the patient's medical records, the patient may carry correspondence or warning cards/tags issued by the diagnostic service that provided their diagnosis. Otherwise, the relevant diagnostic MH unit can be contacted. Increasingly, patients may receive a diagnosis of confirmed or possible MH susceptibility through a genetics laboratory not affiliated with an MH unit. For these patients it may still be helpful to obtain expert advice as there are currently no standards for the reporting of genetic variants associated with a possibility of MH susceptibility. Some patients may give a history that members of their family have been tested and found susceptible to MH. We strongly recommend that the relevant diagnostic MH unit is contacted in order to verify the history. Details of the family member tested and a family tree will be required in order to ascertain the risk for the patient. Patients often do not know the extent to which their family has been investigated: if a relative between the family index case and the current patient has been shown not to be susceptible, the patient is not at risk. Unless the line of inheritance for the MH susceptibility trait between the diagnosed family member and the patient is known to be broken, the patient should be considered at risk of developing MH until proved otherwise. An attempt should be made to obtain the medical records relating to the suspected episode. This may not be possible in all cases for a variety of reasons. If not, as much evidence as possible about the incident should be obtained from primary and secondary care records (all primary care records are retained in the UK until a year after the patient's death). Information from patients regarding the suspected episode may be useful, including the timing of the event (during surgery, in the postoperative recovery room, in the surgical ward); the clinical features of the episode; treatment given; whether unplanned treatment in intensive care was needed; and the cause of the event provided at the time. A referral should be made to a diagnostic MH unit for assistance in obtaining and interpreting such information. If the available information suggests the history is compatible with an MH reaction and it is not possible to exclude MH, the patient should be considered at risk of developing MH until proved otherwise. Patients are sometimes inappropriately labelled susceptible to MH without referral for definitive diagnosis even when such a service is available. All relevant information should be obtained from the patient and a referral should be made to a diagnostic MH unit where possible details of the family index case and a family tree will be required. If the family index case has not been previously referred to the MH unit, they will attempt to obtain the details of the index event. Again, if the available information suggests the history is compatible with an MH reaction and it is not possible to exclude MH, the patient should be considered at risk of developing MH until proved otherwise. RYR1 is the principal gene associated with MH susceptibility; variants in the gene are estimated to contribute to 75% of MH cases.7Miller D.M. Daly C. Aboelsaod E.M. et al.Genetic epidemiology of malignant hyperthermia in the United Kingdom.Br J Anaesth. 2018; 121: 944-952Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar However, variants in the RYR1 gene are associated with other phenotypes, the most established of which are various forms of congenital myopathy, notably the core myopathies (so named because of lack of oxidative enzyme staining producing clear ‘cores’ within the muscle fibres on histochemical analysis).8Klingler W. Rueffert H. Lehmann-Horn F. Girard T. Hopkins P.M. Core myopathies and risk of malignant hyperthermia.Anesth Analg. 2009; 109: 1167-1173Crossref PubMed Scopus (73) Google Scholar Previously, it was thought that all patients with the commonest type of core myopathy, autosomal dominant central core disease, were MH-susceptible. We now know that RYR1 variants associated with central core disease can cause either a loss of function or gain of function of the Ca2+ release channel (RyR1) encoded by RYR1. However, it is only those variants that cause a gain of function (increased sensitivity to RyR1 agonists) that also predispose to MH. It is likely that there is a similar situation with other core myopathies. Furthermore, locus heterogeneity (involvement of other genes) is now established for all of the core myopathies and it is only those patients with a RYR1 aetiology for their myopathy who may be at risk of MH susceptibility.Table 1Conditions that may be associated with an increased risk of MH. CPT2, carnitine palmitoyl transferase type 2ConditionCommentsCongenital myopathyOnly myopathies with an RYR1 or STAC3 genetic aetiology are implicatedExertional rhabdomyolysisSome causes of rhabdomyolysis are known not to be associated with MH (e.g. CPT2 deficiency, McArdle disease)Exertional heat illnessExclude extrinsic factors (e.g. drugs, concurrent illness, extreme environments)Idiopathic hyperCKaemiaPossible association with MH is a diagnosis of exclusion of other causesCarrier of RYR1 variant of unknown significanceNonsense variants leading to a loss of function in the protein are not implicated in MH Open table in a new tab Genetic research has revealed extensive overlap in the clinical and histological phenotypes between muscle disorders to the extent that genetic diagnosis has become the first line for the diagnosis of myopathies. For the same reason, genetic characterisation should be part of the preoperative evaluation of any patient with a congenital myopathy who has not previously received a genetic diagnosis in order to exclude an RYR1 aetiology. Other myopathies that have been associated with an RYR1 aetiology are congenital fibre type disproportion, nemaline rod myopathy, core-rod myopathy, benign Samaritan congenital myopathy and King-Denborough syndrome. The only other gene implicated in a congenital myopathy that is associated with MH susceptibility is the STAC3 gene. In this case, homozygous inheritance of a single variant is required for the myopathy and MH susceptibility. The variant is most prevalent in African and Middle Eastern populations. Loss of sarcolemmal integrity and even frank muscle damage can be a normal response to physical activity, especially intense resistance or eccentric exercise. There is a great deal of interindividual variability but creatine kinase (CK) concentrations greater than five times the upper limit of normal (the traditional diagnostic threshold for rhabdomyolysis) are not unusual. Factors that may contribute to a larger increase in CK include sex, ethnicity, physical fitness, underlying viral infection, intake of protein supplements, anabolic steroids, statins, non-prescription drugs and genetic factors. Some genetic disorders, such as McArdle disease and carnitine palmitoyltransferase type 2 deficiency are characterised by recurrent rhabdomyolysis. Variants in the RYR1 gene, some of which are implicated in MH susceptibility, have also been associated with exertional rhabdomyolysis and myalgia.9Dlamini N. Voermans N.C. Lillis S. et al.Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis.Neuromuscul Disord. 2013; 23: 540-548Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Patients with a history of exertional rhabdomyolysis may have abnormal IVCT responses: some of these have RYR1 variants but others do not.10Gardner L. Miller D.M. Daly C. et al.Investigating the genetic susceptibility to exertional heat illness.J Med Genet. 2020; 57: 531-541Crossref PubMed Scopus (15) Google Scholar Patients with recurrent or severe rhabdomyolysis should be offered genetic screening through sequencing of a rhabdomyolysis gene panel and, depending on the results, referred to a diagnostic MH unit for further assessment where possible. A patient carrying an RYR1 variant of unknown significance that is associated with exertional rhabdomyolysis should be considered at risk of developing MH until proved otherwise. Basal CK concentrations may be persistently increased in patients with muscle disorders (including sex-linked dystrophy carriers); denervation syndromes; malignancy (BB isoform of CK); haemolytic syndromes; hypothyroidism; and those taking statins or using anabolic steroids or other recreational drugs. Persistently increased CK concentrations greater than twice the upper limit of normal for more than 3 months in the absence of a discernible cause is termed ‘idiopathic hyperCKaemia’. MH susceptibility is a cause of idiopathic hyperCKaemia and these patients should be referred to an MH unit for advice and further assessment where possible.11Weglinski M.R. Wedel D.J. Engel A.G. Malignant hyperthermia testing in patients with persistently increased serum creatine kinase levels.Anesth Analg. 1997; 84: 1038-1041Crossref PubMed Scopus (72) Google Scholar As with exertional rhabdomyolysis, anyone can develop exertional heat illness and many of the same factors predisposing to exertional rhabdomyolysis also predispose to heat illness. An inherited contribution and link to MH susceptibility were demonstrated 30 yrs ago but it is only very recently that a role for the RYR1 and CACNA1S (involved in 1–2% of MH cases) genes has been confirmed.10Gardner L. Miller D.M. Daly C. et al.Investigating the genetic susceptibility to exertional heat illness.J Med Genet. 2020; 57: 531-541Crossref PubMed Scopus (15) Google Scholar Patients who give a history of exertional heat illness requiring hospitalisation, especially if non-genetic factors are excluded or with recurrent episodes should be referred for evaluation by an MH unit where possible. A patient carrying an RYR1 variant of unknown significance that is associated with exertional heat illness should be considered at risk of developing MH until proved otherwise. The RYR1 gene has a coding sequence of ∼15,000 bases and there are a possible ∼30,000 missense changes in these bases that could lead to a substitution in one of the 5000 amino acids that make up the RyR1 protein sequence (missense variants are the type most frequently implicated in MH susceptibility). Determining if a missense variant in RYR1 leads to a gain of function change in the protein (and is therefore pathogenically implicated in MH susceptibility) is technically challenging. Currently, only 50 RYR1 variants have been demonstrated to be pathogenic for MH after functional characterisation (www.emhg.org/diagnostic-mutations). Further criteria have been devised to evaluate other RYR1 variants for likely pathogenicity (https://www.emhg.org/genetic-scoring-matrix) but the majority remain variants of unknown significance. RYR1 sequencing is included in gene panels for the investigation of suspected congenital myopathies, metabolic myopathies, arthrogryposis and when whole exome or genome sequencing is done. There is an estimated 6% chance that a rare RYR1 missense variant of unknown significance will be found in a DNA sample of a healthy member of the population selected at random. A patient with an incidental finding of an RYR1 variant of unknown significance should be considered potentially at risk of MH susceptibility and they should be referred for an MH opinion. If diagnosis established—proceed with trigger-free anaesthesia. If diagnosis not established—consider the risk of proceeding with trigger-free anaesthesia or postponing the procedure until a diagnosis may be established. The European Malignant Hyperthermia Group has recently published guideline recommendations for management of anaesthesia for a patient who is MH-susceptible.12Rueffert H. Bastian B. Bendixen D. et al.Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group.Br J Anaesth. 2021; 126: 120-130Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Other than establishing the risk of MH, there are no specific implications for preoperative assessment; a standard preoperative assessment should be performed for all patients who are MH-susceptible. A thorough drug history should be taken. Patients susceptible to MH are not at increased risk of developing serotonin syndrome but it is recommended that they are not prescribed combinations of serotonergic drugs, as a perioperative serotonin syndrome may be confused with an MH reaction. Antiparkinsonian medications should be continued in the perioperative period to avoid the possibility of neuroleptic malignant syndrome that may be caused by their withdrawal. Routine investigations should be undertaken in line with national guidelines, but no extra tests are required routinely. Measuring baseline CK concentrations purely on the grounds that a patient is MH-susceptible will not change clinical management. Patients susceptible to MH should not be exposed to any of the triggering drugs (isoflurane, sevoflurane, desflurane, enflurane, halothane, methoxyflurane, suxamethonium). There are no reports that indicate that MH can occur during anaesthesia when triggering drugs have been avoided. ‘Trigger-free’ anaesthesia can be provided using regional anaesthesia or TIVA. Regional anaesthesia or local anaesthesia using any available local anaesthetic is safe to use in MH-susceptible patients and is an excellent choice if the planned surgery is compatible. If general anaesthesia is indicated, the patient should be advised that there is a higher risk of awareness with TIVA when compared with volatile anaesthesia.13Pandit J.J. Andrade J. Bogod D.G. et al.5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors.Br J Anaesth. 2014; 113: 549-559Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar There are guidelines for using TIVA.14Nimmo A.F. Absalom A.R. Bagshaw O. et al.Guidelines for the safe practice of total intravenous anaesthesia (TIVA).Anaesthesia. 2019; 74: 211-224Crossref PubMed Scopus (77) Google Scholar However, if the anaesthetist is not experienced with TIVA, or does not perform TIVA on a regular basis, it is suggested that they seek assistance from a colleague who is. A plan is advised both to minimise the need for airway rescue should it occur, and to manage it without the use of inhalational anaesthetics or suxamethonium. Oral or i.v. dantrolene is not recommended for the prevention of MH in susceptible patients. Dantrolene is not needed if triggering anaesthetics are avoided, and it associated with a high incidence of muscle weakness and nausea.12Rueffert H. Bastian B. Bendixen D. et al.Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group.Br J Anaesth. 2021; 126: 120-130Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar During inhalational anaesthesia, volatile agents are adsorbed onto rubber and plastic components of the machine, ventilator bellows, the soda lime canister, and the breathing circuit. If adsorbed anaesthetic agent is not cleared before use of the workstation for an MH-susceptible patient, there is a theoretical risk that an MH reaction could be triggered. It is therefore a requirement for an anaesthesia workstation to be prepared so that it delivers <5 parts per million (ppm) of any potent inhalational anaesthetic before it is used for a patient susceptible to MH. The 5 ppm threshold is an arbitrary figure with no evidential basis for relevance to triggering of an MH reaction (see ‘Environmental exposure’ below) but it has become the standard target for preparing a ‘vapour-free machine’. Modern anaesthesia workstations can have complex internal circuitry and bench tests have shown that it may take from 5 min (Ohmeda modulus) to 104 min (Dräger Fabius)15Gunter J.B. Ball J. Than-Win S. Preparation of the Dräger Fabius anesthesia machine for the malignant-hyperthermia susceptible patient.Anesth Analg. 2008; 107: 1936-1945Crossref PubMed Scopus (32) Google Scholar to clear the volatile agents at a fresh gas flow rate of 10 L min−1 to achieve a concentration of <5 ppm (initial concentrations after prior use of 3% sevoflurane for 2 h can be as high as 5000 ppm). The recommended procedure for preparation of a trigger-free anaesthesia workstation is summarised in Figure 1. Details of the time required to flush specific workstations and any workstation-specific procedures have been collated by Rueffert and colleagues.12Rueffert H. Bastian B. Bendixen D. et al.Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group.Br J Anaesth. 2021; 126: 120-130Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar We suggest that the relevant preparation time is kept with each workstation, for example at the front of the machine-check logbook. It should be noted that the workstation should be prepared for MH-susceptible patients even if regional anaesthesia is planned in case conversion to general anaesthesia is required. Activated charcoal filters have been a significant recent introduction to anaesthesia practice in relation to MH. Bench testing has demonstrated that they can reduce the concentration of volatile agent delivered from a contaminated workstation to <5 ppm within 3 min. If they are kept in place, volatile agent concentration can be maintained <5 ppm with a fresh gas flow >1 L min−1 for at least 24 h, although recommendations are that the fresh gas flow is maintained at 3 L min−1 and the filters are changed after 12 h of use. Activated charcoal filters are especially useful when surgery for an MH-susceptible patient needs to proceed and there is insufficient time to flush the workstation (Fig. 1). Inhalational anaesthetics can be detected in the air at any location where they are administered (even where scavenging systems are used) and in a PACU where patients who have received inhalational anaesthesia are recovered. There are no reports of MH episodes in susceptible patients from environmental exposure or healthcare workers who work in operating theatres. There are anaesthetists, surgeons and operating theatre staff who have MH susceptibility and who work in the operating theatre without any adverse effects. This is likely to be because triggering of MH in a susceptible individual is a time- and dose-dependent response and the environmental concentrations do not reach the threshold for triggering.16Hopkins P.M. Malignant hyperthermia – pharmacology of triggering.Br J Anaesth. 2011; 107: 48-56Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar We do not know the minimum time-weighted concentration that could trigger an MH reaction, but ex vivo studies using muscle samples excised from susceptible individuals suggest that it is one to two orders of magnitude greater than the maximum occupational exposure limits for isoflurane (50 ppm) and sevoflurane (60 ppm) as defined by the Control of Substances Hazardous to Health regulations in the UK. In the USA, the maximum concentration of any halogenated anaesthetic permitted during occupational exposure is 2 ppm. Maximum environmental concentrations of sevoflurane during inhalational induction in children can approach 60 ppm.17Raj N. Henderson K.A. Hall J.E. et al.Evaluation of personal, environmental and biological exposure of paediatric anaesthetists to nitrous oxide and sevoflurane.Anaesthesia. 2003; 58: 630-636Crossref PubMed Scopus (22) Google Scholar Routine monitoring in line with national standards should be used for MH-susceptible patients. All patients can be recovered in a standard PACU. Environmental concentrations of sevoflurane measured in a PACU did not exceed 1 ppm.18Heiderich S. Thoben C. Dennhardt N. et al.Low anaesthetic waste gas concentrations in postanaesthesia care unit: a prospective observational study.Eur J Anaesthesiol. 2018; 35: 534-538Crossref PubMed Scopus (11) Google Scholar This provides a large safety margin between the concentration that an MH-susceptible patient might be exposed to and the concentration required to trigger an MH reaction. When a pregnant woman is anaesthetised, so is her fetus, and triggering agents should be avoided if either is at risk of developing MH. Potent inhalational anaesthetic agents readily cross the placenta and so there is a risk of triggering MH in a susceptible fetus even if the mother is not MH-susceptible, although we are not aware of any such cases that have been confirmed. Suxamethonium does not readily cross the placental barrier, but low concentrations of suxamethonium have been found in umbilical vein blood after administration of higher doses of suxamethonium (300–500 mg) to the mother.19Moya F. Kvisselgaard N. The placental transmission of succinylcholine.Anesthesiology. 1961; 22: 1-6Crossref PubMed Scopus (31) Google Scholar However, there is no evidence as to whether or not these concentrations of suxamethonium are safe in a susceptible fetus; we suggest that the risk of the fetus developing MH or significant rhabdomyolysis from the transfer of suxamethonium across the placenta is low after a standard maternal dose of 1 mg kg−1. When a pregnant woman who is, or may be, at risk of MH or whose fetus may be at risk is booked into maternity services, the obstetric anaesthesia service should be notified as soon as possible. There are several scenarios. A detailed delivery plan should be made that minimises the possible need for an emergency Caesarean section under general anaesthesia. This includes starting epidural analgesia early in labour so that it can be rapidly extended if Caesarean section is needed.20European Malignant Hyperthermia Group. Recommendations for the management of malignant hyperthermia patients during pregnancy. Available from: www.emhg.org/recommendations-1/mh-during-pregnancy (accessed 15 December 2020).Google Scholar There should also be a plan for emergency general anaesthesia if required for Caesarean section, postpartum haemorrhage or other obstetric emergency. The anaesthesia machine can be rapidly prepared using activated charcoal filters (Fig. 1). For rapid-sequence induction, neuromuscular block can be achieved with rocuronium but we recommend that sugammadex 16 mg kg−1 is drawn up and is ready to give in case early reversal is indicated. Maintenance of anaesthesia should be with a total i.v. technique. Nitrous oxide is safe to give, either during general anaesthesia or for analgesia in labour. This may be because the mother has had a suspected episode herself or there is a family history of proved or suspected MH. Early referral to an MH unit should be made where possible so that the history can be evaluated. If it is not possible to exclude the risk in the mother, she should be treated as being MH-susceptible. The IVCT (the only definitive test to establish low-risk status) has not been validated in pregnancy. In this case the unborn baby has a 50% risk of being susceptible to MH. Up until the time that the umbilical cord is clamped, the mother should be treated as MH-susceptible, but after this she may receive anaesthesia as normal. However, there may be situations where the anaesthetist considers the risks to the mother to be materially reduced by using suxamethonium for rapid-sequence induction. Here the safety of the mother is paramount and we recommend that suxamethonium is used so that the mother's safety is not compromised in favour of a small theoretical risk to the fetus. This differs from the situation where the history is on the mother's side as ultimately the father can have their status definitively confirmed by IVCT before delivery of the child if they have access to a diagnostic MH unit. This is greatly facilitated by early referral of the family to the relevant MH unit. Most dental operations in adults are performed in peripheral standalone dental surgeries using local anaesthetic injections with or without single-agent conscious sedation, most commonly midazolam. Previously, local anaesthetics were implicated as triggers for MH. This has now been disproved; both amide and ester local anaesthetics are safe to use in patients susceptible to MH. Some dental clinics use inhalational agents to provide sedation in children. Nitrous oxide (with oxygen) is safe for a child at risk of MH susceptibility, but sevoflurane (or any other potent inhalational anaesthetic agent) is not. If general anaesthesia is required for dental surgery the same considerations should be applied as for other elective surgery. Electroconvulsive therapy is usually performed at remote sites with limited access to extensive resources or experienced personnel. Patients usually receive an i.v. induction agent followed by a small dose of neuromuscular blocking agent to dampen or reduce the extent of muscle contractions during seizures. Suxamethonium is most commonly used for this as it has a rapid onset and short duration of action. In patients with a history of MH susceptibility, suxamethonium cannot be used; we recommend vecuronium or rocuronium, which can be rapidly antagonised using sugammadex. For emergency surgery there is rarely time to explore a personal or family history that is suspicious of MH. Patients in this category, along with patients with a definitive diagnosis of MH susceptibility, should be treated as at risk. In this situation, activated charcoal filters are likely to be of benefit (Fig. 1) in preparing a ‘vapour-free’ machine. If charcoal filters are not available and there is insufficient time to prepare a workstation, oxygenation and ventilation of the lungs may be maintained on a temporary basis using a transport ventilator or even manually with a self-inflating resuscitation bag. If general anaesthesia is required, we recommend direct supervision by a senior anaesthetist familiar with TIVA. The bronchodilator properties of potent inhalational anaesthetic agents have been known for many years and they are a recognised treatment for resistant status asthmaticus. More recently, clinicians are using sevoflurane for sedation in patients receiving artificial ventilation in ICU. Intensivists need to exclude MH susceptibility in their patients before using inhalational anaesthetic agents in ICU.21Kaura V. Hopkins P.M. Sevoflurane may not be a complete sigh of relief in COVID-19.Br J Anaesth. 2020; 125: e487-e488Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Approaching 10,000 patients globally have been definitively diagnosed with MH susceptibility but there are many more who are labelled as ‘MH-risk’ without definitive diagnosis. When these patients present for elective surgery, the principle of ‘personalised anaesthesia’ should be applied so that the safest anaesthetic technique is identified for the individual patient. This may require delaying elective surgery until the patient's MH status is clarified. The key to provision of safe anaesthesia in the patient at risk of MH is a management plan that avoids exposing the patient to MH-triggering drugs and includes contingencies for dealing with anaesthesia complications, especially airway emergencies, without recourse to inhalational anaesthetics or suxamethonium.