Malignant Hyperthermia

A narrative expert review aiming to summarize the clinical epidemiology and management of critically ill patients with malignant hyperthermia (MH). Medline searches were conducted to identify relevant articles describing the epidemiology, pathophysiology, and management of MH. Guidelines from key MH organizations were also incorporated into this review. Relevant studies regarding MH in both ICU and perioperative settings were reviewed. Data from relevant studies were summarized and qualitatively assessed. MH is a severe reaction triggered by inhalational volatile anesthetics and succinylcholine in genetically susceptible patients. The condition is characterized by an early onset (min to hr) rise in temperature, hypercarbia, and muscular rigidity following exposure to triggering medications with potential complications of coagulopathy, rhabdomyolysis, and acute kidney injury. Acute management necessitates a coordinated multidisciplinary team approach with specific management using dantrolene, active cooling, and hyperventilation. A suspected MH reaction has important implications for future anesthetic exposure for both the patient and their family. All suspected reactions should be followed up at a specialized MH testing center using muscle contracture and genetic testing. Increasing use of inhalational anesthetics in the ICU underscores the need for enhanced education on the diagnosis and management of MH to ensure optimal patient sedation care and safety.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants. It manifests as a hypermetabolic response resulting in tachycardia, tachypnea, hyperthermia, hypercapnia, acidosis, muscle rigidity and rhabdomyolysis. An increase in the end-tidal carbon dioxide is one of the earliest diagnostic signs. Dantrolene sodium is effective in the management of MH, and should be available whenever general anesthesia is administered. This review also aims to highlight the genetics and pathology of MH, along with its association with various inherited myopathy syndromes like central core disease, multi-mini core disease, Native-American myopathy, and King-Denborough syndrome.

Malignant hyperthermia is a potentially fatal complication of general anesthesia that may occur with greater frequency in some patients with ptosis or strabismus. The history of our knowledge of this recently described condition is outlined. The clinical features, pathophysiology, and differential diagnosis are reviewed in detail. A protocol for the treatment of the acute malignant hyperthermia crisis and guidelines for the management of susceptible patients are suggested. The medicolegal implications of the occurrence of such a crisis are discussed.

Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.

Malignant hyperthermia (MH) is a rare, life-threatening inherited disorder triggered by volatile inhalational anesthetics and/or the depolarizing muscle relaxant suxamethonium. In susceptible individuals, calcium release from the sarcoplasmic reticulum in the skeletal muscle becomes abnormally accelerated, leading to a hypermetabolic state. Early signs of MH include unexplained hypercarbia (end-tidal carbon dioxide > 55 mm Hg), tachycardia, and muscle rigidity, particularly in the masseter. Rapid increases in core temperature (> 0.5 °C/15 min, with temperatures often exceeding 40 °C) are typical. With progression, respiratory and metabolic acidosis, arrhythmias, cola-colored urine (myoglobinuria), elevated serum potassium, and tented T-waves may develop, potentially leading to cardiac arrest or multiorgan failure. The Japanese Society of Anesthesiologists' guidelines for the management of MH in 2025 (Japanese version) emphasize the importance of early recognition and immediate intervention. The essential steps include discontinuing triggering agents, administering intravenous dantrolene (initially 1-2 mg/kg), aggressive cooling of the body, and managing complications, such as hyperkalemia and acidosis. On the basis of international standards, a higher initial dose of dantrolene is recommended. Preoperative assessment of MH risk should include history taking for anesthetic complications, a family history suggestive of MH susceptibility, signs of congenital myopathies, and careful anesthetic planning using non-triggering agents. Genetic testing and muscle biopsy may aid in the diagnosis but are not definitive in all cases. The Japanese translation of these guidelines has been posted on the following website: https://anesth.or.jp/files/pdf/guideline_akuseikounetsu . pdf.

A narrative expert review aiming to summarize the clinical epidemiology and management of critically ill patients with malignant hyperthermia (MH). Medline searches were conducted to identify relevant articles describing the epidemiology, pathophysiology, and management of MH. Guidelines from key MH organizations were also incorporated into this review. Relevant studies regarding MH in both ICU and perioperative settings were reviewed. Data from relevant studies were summarized and qualitatively assessed. MH is a severe reaction triggered by inhalational volatile anesthetics and succinylcholine in genetically susceptible patients. The condition is characterized by an early onset (min to hr) rise in temperature, hypercarbia, and muscular rigidity following exposure to triggering medications with potential complications of coagulopathy, rhabdomyolysis, and acute kidney injury. Acute management necessitates a coordinated multidisciplinary team approach with specific management using dantrolene, active cooling, and hyperventilation. A suspected MH reaction has important implications for future anesthetic exposure for both the patient and their family. All suspected reactions should be followed up at a specialized MH testing center using muscle contracture and genetic testing. Increasing use of inhalational anesthetics in the ICU underscores the need for enhanced education on the diagnosis and management of MH to ensure optimal patient sedation care and safety.

Since malignant hyperthermia (MH) was first described in 1960, the number of cases of this potentially life-threatening reaction to anaesthesia with fatal or serious outcomes has been markedly reduced thanks to continuous advances in knowledge about triggering, clinical course, and treatment. Another essential and evolving pillar of patient safety remains diagnostics, which serve to confirm or rule out suspected cases of MH and to identify other individuals at risk of MH for prevention. For more than 40 yr, the British Journal of Anaesthesia has published the updated consensus diagnostic protocols of the European Malignant Hyperthermia Group at regular intervals. The presented diagnostic guidelines have been comprehensively revised 10 yr after the last update after substantial advances in DNA-based testing methods. In addition to the previous classification of MH susceptibility by the in vitro halothane/caffeine contracture test, a new diagnostic designation, the MH genotype, has been introduced. The latter is reflected in the revised diagnostic pathways, which also include the adapted European Malignant Hyperthermia Group curation system for the classification of genetic variants with regard to their relevance to MH. In addition to minor changes in the in vitro halothane/caffeine contracture test protocol, the guidelines address updated patient referral criteria and clinical interpretation of diagnostic results. And for the first time, the guidelines provide a consensus definition of a clinical MH event.

Two potentially fatal syndromes, malignant hyperthermia (MH), an adverse reaction to general anesthesia, and exertional rhabdomyolysis (ER) share some clinical features, including hyperthermia, muscle rigidity, tachycardia, and elevated serum creatine kinase. Some patients with ER have experienced an MH event and/or have been diagnosed as MH susceptible (MHS). In order to assess the relationship between ER and MH further, we conducted a retrospective cohort study summarizing clinical and genetic information on Canadian patients with ER who were diagnosed as MHS. In addition, a systematic literature review was performed to compile further evidence on MH susceptibility and RYR1 and CACNA1S variants associated with rhabdomyolysis. Demographic, clinical, and genetic information was collected on Canadian MHS patients who presented with rhabdomyolysis. In addition, we performed a systematic review of the literature published during 1995-2016 on genetic screening of the RYR1 and CACNA1S genes in patients with ER. Retrospective data on Canadian MHS patients with ER showed that ten out of 17 patients carried RYR1 or CACNA1S variants that were either known MH-causative mutations or potentially pathogenic variants. The systematic review revealed 39 different rare RYR1 variants, including 13 MH-causative/associated mutations and five rare potentially deleterious CACNA1S variants in 78% of patients with ER. Findings from the Canadian patient cohort and the systematic review all signal a potential association between MH susceptibility and ER. The presence of MH-causative mutations and putative deleterious RYR1 variants in ER patients without a history of adverse anesthetic reactions suggests their possible increased risk for MH.

Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

Malignant hyperthermia (MH) is a rare, life-threatening inherited disorder triggered by volatile inhalational anesthetics and/or the depolarizing muscle relaxant suxamethonium. In susceptible individuals, calcium release from the sarcoplasmic reticulum in the skeletal muscle becomes abnormally accelerated, leading to a hypermetabolic state. Early signs of MH include unexplained hypercarbia (end-tidal carbon dioxide > 55 mm Hg), tachycardia, and muscle rigidity, particularly in the masseter. Rapid increases in core temperature (> 0.5 °C/15 min, with temperatures often exceeding 40 °C) are typical. With progression, respiratory and metabolic acidosis, arrhythmias, cola-colored urine (myoglobinuria), elevated serum potassium, and tented T-waves may develop, potentially leading to cardiac arrest or multiorgan failure. The Japanese Society of Anesthesiologists' guidelines for the management of MH in 2025 (Japanese version) emphasize the importance of early recognition and immediate intervention. The essential steps include discontinuing triggering agents, administering intravenous dantrolene (initially 1-2 mg/kg), aggressive cooling of the body, and managing complications, such as hyperkalemia and acidosis. On the basis of international standards, a higher initial dose of dantrolene is recommended. Preoperative assessment of MH risk should include history taking for anesthetic complications, a family history suggestive of MH susceptibility, signs of congenital myopathies, and careful anesthetic planning using non-triggering agents. Genetic testing and muscle biopsy may aid in the diagnosis but are not definitive in all cases. The Japanese translation of these guidelines has been posted on the following website: https://anesth.or.jp/files/pdf/guideline_akuseikounetsu . pdf.

Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.

Since malignant hyperthermia (MH) was first described in 1960, the number of cases of this potentially life-threatening reaction to anaesthesia with fatal or serious outcomes has been markedly reduced thanks to continuous advances in knowledge about triggering, clinical course, and treatment. Another essential and evolving pillar of patient safety remains diagnostics, which serve to confirm or rule out suspected cases of MH and to identify other individuals at risk of MH for prevention. For more than 40 yr, the British Journal of Anaesthesia has published the updated consensus diagnostic protocols of the European Malignant Hyperthermia Group at regular intervals. The presented diagnostic guidelines have been comprehensively revised 10 yr after the last update after substantial advances in DNA-based testing methods. In addition to the previous classification of MH susceptibility by the in vitro halothane/caffeine contracture test, a new diagnostic designation, the MH genotype, has been introduced. The latter is reflected in the revised diagnostic pathways, which also include the adapted European Malignant Hyperthermia Group curation system for the classification of genetic variants with regard to their relevance to MH. In addition to minor changes in the in vitro halothane/caffeine contracture test protocol, the guidelines address updated patient referral criteria and clinical interpretation of diagnostic results. And for the first time, the guidelines provide a consensus definition of a clinical MH event.

Two potentially fatal syndromes, malignant hyperthermia (MH), an adverse reaction to general anesthesia, and exertional rhabdomyolysis (ER) share some clinical features, including hyperthermia, muscle rigidity, tachycardia, and elevated serum creatine kinase. Some patients with ER have experienced an MH event and/or have been diagnosed as MH susceptible (MHS). In order to assess the relationship between ER and MH further, we conducted a retrospective cohort study summarizing clinical and genetic information on Canadian patients with ER who were diagnosed as MHS. In addition, a systematic literature review was performed to compile further evidence on MH susceptibility and RYR1 and CACNA1S variants associated with rhabdomyolysis. Demographic, clinical, and genetic information was collected on Canadian MHS patients who presented with rhabdomyolysis. In addition, we performed a systematic review of the literature published during 1995-2016 on genetic screening of the RYR1 and CACNA1S genes in patients with ER. Retrospective data on Canadian MHS patients with ER showed that ten out of 17 patients carried RYR1 or CACNA1S variants that were either known MH-causative mutations or potentially pathogenic variants. The systematic review revealed 39 different rare RYR1 variants, including 13 MH-causative/associated mutations and five rare potentially deleterious CACNA1S variants in 78% of patients with ER. Findings from the Canadian patient cohort and the systematic review all signal a potential association between MH susceptibility and ER. The presence of MH-causative mutations and putative deleterious RYR1 variants in ER patients without a history of adverse anesthetic reactions suggests their possible increased risk for MH.

Malignant hyperthermia (MH) is a rare, life-threatening inherited disorder triggered by volatile inhalational anesthetics and/or the depolarizing muscle relaxant suxamethonium. In susceptible individuals, calcium release from the sarcoplasmic reticulum in the skeletal muscle becomes abnormally accelerated, leading to a hypermetabolic state. Early signs of MH include unexplained hypercarbia (end-tidal carbon dioxide > 55 mm Hg), tachycardia, and muscle rigidity, particularly in the masseter. Rapid increases in core temperature (> 0.5 °C/15 min, with temperatures often exceeding 40 °C) are typical. With progression, respiratory and metabolic acidosis, arrhythmias, cola-colored urine (myoglobinuria), elevated serum potassium, and tented T-waves may develop, potentially leading to cardiac arrest or multiorgan failure. The Japanese Society of Anesthesiologists' guidelines for the management of MH in 2025 (Japanese version) emphasize the importance of early recognition and immediate intervention. The essential steps include discontinuing triggering agents, administering intravenous dantrolene (initially 1-2 mg/kg), aggressive cooling of the body, and managing complications, such as hyperkalemia and acidosis. On the basis of international standards, a higher initial dose of dantrolene is recommended. Preoperative assessment of MH risk should include history taking for anesthetic complications, a family history suggestive of MH susceptibility, signs of congenital myopathies, and careful anesthetic planning using non-triggering agents. Genetic testing and muscle biopsy may aid in the diagnosis but are not definitive in all cases. The Japanese translation of these guidelines has been posted on the following website: https://anesth.or.jp/files/pdf/guideline_akuseikounetsu . pdf.

A narrative expert review aiming to summarize the clinical epidemiology and management of critically ill patients with malignant hyperthermia (MH). Medline searches were conducted to identify relevant articles describing the epidemiology, pathophysiology, and management of MH. Guidelines from key MH organizations were also incorporated into this review. Relevant studies regarding MH in both ICU and perioperative settings were reviewed. Data from relevant studies were summarized and qualitatively assessed. MH is a severe reaction triggered by inhalational volatile anesthetics and succinylcholine in genetically susceptible patients. The condition is characterized by an early onset (min to hr) rise in temperature, hypercarbia, and muscular rigidity following exposure to triggering medications with potential complications of coagulopathy, rhabdomyolysis, and acute kidney injury. Acute management necessitates a coordinated multidisciplinary team approach with specific management using dantrolene, active cooling, and hyperventilation. A suspected MH reaction has important implications for future anesthetic exposure for both the patient and their family. All suspected reactions should be followed up at a specialized MH testing center using muscle contracture and genetic testing. Increasing use of inhalational anesthetics in the ICU underscores the need for enhanced education on the diagnosis and management of MH to ensure optimal patient sedation care and safety.

Since malignant hyperthermia (MH) was first described in 1960, the number of cases of this potentially life-threatening reaction to anaesthesia with fatal or serious outcomes has been markedly reduced thanks to continuous advances in knowledge about triggering, clinical course, and treatment. Another essential and evolving pillar of patient safety remains diagnostics, which serve to confirm or rule out suspected cases of MH and to identify other individuals at risk of MH for prevention. For more than 40 yr, the British Journal of Anaesthesia has published the updated consensus diagnostic protocols of the European Malignant Hyperthermia Group at regular intervals. The presented diagnostic guidelines have been comprehensively revised 10 yr after the last update after substantial advances in DNA-based testing methods. In addition to the previous classification of MH susceptibility by the in vitro halothane/caffeine contracture test, a new diagnostic designation, the MH genotype, has been introduced. The latter is reflected in the revised diagnostic pathways, which also include the adapted European Malignant Hyperthermia Group curation system for the classification of genetic variants with regard to their relevance to MH. In addition to minor changes in the in vitro halothane/caffeine contracture test protocol, the guidelines address updated patient referral criteria and clinical interpretation of diagnostic results. And for the first time, the guidelines provide a consensus definition of a clinical MH event.

Two potentially fatal syndromes, malignant hyperthermia (MH), an adverse reaction to general anesthesia, and exertional rhabdomyolysis (ER) share some clinical features, including hyperthermia, muscle rigidity, tachycardia, and elevated serum creatine kinase. Some patients with ER have experienced an MH event and/or have been diagnosed as MH susceptible (MHS). In order to assess the relationship between ER and MH further, we conducted a retrospective cohort study summarizing clinical and genetic information on Canadian patients with ER who were diagnosed as MHS. In addition, a systematic literature review was performed to compile further evidence on MH susceptibility and RYR1 and CACNA1S variants associated with rhabdomyolysis. Demographic, clinical, and genetic information was collected on Canadian MHS patients who presented with rhabdomyolysis. In addition, we performed a systematic review of the literature published during 1995-2016 on genetic screening of the RYR1 and CACNA1S genes in patients with ER. Retrospective data on Canadian MHS patients with ER showed that ten out of 17 patients carried RYR1 or CACNA1S variants that were either known MH-causative mutations or potentially pathogenic variants. The systematic review revealed 39 different rare RYR1 variants, including 13 MH-causative/associated mutations and five rare potentially deleterious CACNA1S variants in 78% of patients with ER. Findings from the Canadian patient cohort and the systematic review all signal a potential association between MH susceptibility and ER. The presence of MH-causative mutations and putative deleterious RYR1 variants in ER patients without a history of adverse anesthetic reactions suggests their possible increased risk for MH.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

Humans maintain core body temperature via a complicated system of physiologic mechanisms that counteract heat/cold fluctuations from metabolism, exertion, and the environment. Overextension of these mechanisms or disruption of body temperature homeostasis leads to bodily dysfunction, culminating in a syndrome analogous to exertional heat stroke (EHS). The inability of this thermoregulatory process to maintain the body temperature is caused by either thermal stress or certain drugs. EHS is a syndrome characterized by hyperthermia and the activation of systemic inflammation. Several drug-induced hyperthermic syndromes may resemble EHS and share common mechanisms. The purpose of this article is to review the current literature and compare exertional heat stroke (EHS) to three of the most widely studied drug-induced hyperthermic syndromes: malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), and serotonin syndrome (SS). Drugs and drug classes that have been implicated in these conditions include amphetamines, diuretics, cocaine, antipsychotics, metoclopramide, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and many more. Observations suggest that severe or fulminant cases of drug-induced hyperthermia may evolve into an inflammatory syndrome best described as heat stroke. Their underlying mechanisms, symptoms, and treatment approaches will be reviewed to assist in accurate diagnosis, which will impact the management of potentially life-threatening complications.

Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.

A narrative expert review aiming to summarize the clinical epidemiology and management of critically ill patients with malignant hyperthermia (MH). Medline searches were conducted to identify relevant articles describing the epidemiology, pathophysiology, and management of MH. Guidelines from key MH organizations were also incorporated into this review. Relevant studies regarding MH in both ICU and perioperative settings were reviewed. Data from relevant studies were summarized and qualitatively assessed. MH is a severe reaction triggered by inhalational volatile anesthetics and succinylcholine in genetically susceptible patients. The condition is characterized by an early onset (min to hr) rise in temperature, hypercarbia, and muscular rigidity following exposure to triggering medications with potential complications of coagulopathy, rhabdomyolysis, and acute kidney injury. Acute management necessitates a coordinated multidisciplinary team approach with specific management using dantrolene, active cooling, and hyperventilation. A suspected MH reaction has important implications for future anesthetic exposure for both the patient and their family. All suspected reactions should be followed up at a specialized MH testing center using muscle contracture and genetic testing. Increasing use of inhalational anesthetics in the ICU underscores the need for enhanced education on the diagnosis and management of MH to ensure optimal patient sedation care and safety.

Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.

Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.

Malignant hyperthermia susceptibility is an important risk factor during general anesthesia. Affected patients have an asymptomatic but potentially lethal hypermetabolic reaction after contact with volatile anesthetics or succinylcholine. Classic symptoms include hemodynamic instability, combined with acidosis, rigor, and hyperthermia. During cardiopulmonary bypass, these signs may be obscured, delaying correct diagnosis and lifesaving treatment. Malignant hyperthermia-susceptible individuals are more sensitive to heat and stress, so rewarming and catecholamine administration may trigger an episode, necessitating prophylactic measures. This systematic review identified typical malignant hyperthermia symptoms during cardiopulmonary bypass and investigated other factors in cardiac surgery that might trigger an episode in susceptible individuals. Approaches used to treat and prevent malignant hyperthermia during cardiopulmonary bypass were systematically analyzed. We conducted a systematic search for reports about malignant hyperthermia and cardiopulmonary bypass. Search terms included malignant hyperthermia and cardiopulmonary bypass, extracorporeal circulation, or cardiac surgery. We found 24 case reports and case series including details of 26 patients. In 14 cases, malignant hyperthermia crises during or shortly after cardiopulmonary bypass were described. Fourteen reports discussed prevention of an episode. Early symptoms of a malignant hyperthermia episode include excessive carbon dioxide production and metabolic acidosis. Massively increased creatine kinase levels are a strong indicator of a malignant hyperthermia reaction. Rewarming is associated with development of clinical signs of malignant hyperthermia. In potentially susceptible patients, apart from avoiding classic trigger substances, aggressive rewarming should not be applied. Hemodynamic instability in conjunction with the described symptoms should result in a diagnostic algorithm.