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Missouri Medicine 2019Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants.... (Review)
Review
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.
Topics: Anesthetics; Dantrolene; Humans; Malignant Hyperthermia; Muscle Relaxants, Central; Neuromuscular Depolarizing Agents
PubMed: 31040503
DOI: No ID Found -
Orphanet Journal of Rare Diseases Aug 2015Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as... (Review)
Review
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006.
Topics: Genetic Counseling; Humans; Malignant Hyperthermia
PubMed: 26238698
DOI: 10.1186/s13023-015-0310-1 -
Advanced Emergency Nursing JournalMalignant hyperthermia (MH) is caused by a genetic disorder of the skeletal muscle that induces a hypermetabolic response when patients are exposed to a triggering agent... (Review)
Review
Malignant hyperthermia (MH) is caused by a genetic disorder of the skeletal muscle that induces a hypermetabolic response when patients are exposed to a triggering agent such as volatile inhaled anesthetics or depolarizing neuromuscular blockers. Symptoms of MH include increased carbon dioxide production, hyperthermia, muscle rigidity, tachypnea, tachycardia, acidosis, hyperkalemia, and rhabdomyolysis. Common scenarios for triggering agents are those used are during surgery and rapid sequence intubation. Hypermetabolic symptoms have a rapid onset; hence, prompt recognition and treatment are vital to prevent morbidity and mortality. The first-line treatment agent for an MH response is dantrolene. Further treatment includes managing complications related to a hypermetabolic response such as hyperkalemia and arrhythmias. This review is focused on the recognition and treatment considerations of MH in the emergency department to optimize therapy and improve patient morbidity and mortality.
Topics: Dantrolene; Diagnosis, Differential; Emergency Service, Hospital; Humans; Malignant Hyperthermia; Muscle Relaxants, Central; Risk Factors
PubMed: 33915557
DOI: 10.1097/TME.0000000000000344 -
Anaesthesia May 2021Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general...
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.
Topics: Acidosis; Body Temperature; Calcium; Carbon Dioxide; Compartment Syndromes; Dantrolene; Disseminated Intravascular Coagulation; Heart Rate; Humans; Hyperkalemia; Malignant Hyperthermia; Muscle Relaxants, Central; Myoglobinuria; Pulmonary Ventilation; Risk Factors; Sodium Bicarbonate
PubMed: 33399225
DOI: 10.1111/anae.15317 -
Lancet (London, England) Jun 2016Core body temperature is normally tightly regulated to within a few tenths of a degree. The major thermoregulatory defences in humans are sweating, arteriovenous shunt... (Review)
Review
Core body temperature is normally tightly regulated to within a few tenths of a degree. The major thermoregulatory defences in humans are sweating, arteriovenous shunt vasoconstriction, and shivering. The core temperature triggering each response defines its activation threshold. General anaesthetics greatly impair thermoregulation, synchronously reducing the thresholds for vasoconstriction and shivering. Neuraxial anaesthesia also impairs central thermoregulatory control, and prevents vasoconstriction and shivering in blocked areas. Consequently, unwarmed anaesthetised patients become hypothermic, typically by 1-2°C. Hypothermia results initially from an internal redistribution of body heat from the core to the periphery, followed by heat loss exceeding metabolic heat production. Complications of perioperative hypothermia include coagulopathy and increased transfusion requirement, surgical site infection, delayed drug metabolism, prolonged recovery, shivering, and thermal discomfort. Body temperature can be reliably measured in the oesophagus, nasopharynx, mouth, and bladder. The standard-of-care is to monitor core temperature and to maintain normothermia during general and neuraxial anaesthesia.
Topics: Anesthesia; Body Temperature Regulation; Humans; Hypothermia; Malignant Hyperthermia; Perioperative Care
PubMed: 26775126
DOI: 10.1016/S0140-6736(15)00981-2 -
AORN Journal Oct 2022
Topics: Humans; Malignant Hyperthermia
PubMed: 36165669
DOI: 10.1002/aorn.13802 -
British Journal of Anaesthesia Oct 2018Gaps in our understanding of genetic susceptibility to malignant hyperthermia (MH) limit the application and interpretation of genetic diagnosis of the condition. Our...
BACKGROUND
Gaps in our understanding of genetic susceptibility to malignant hyperthermia (MH) limit the application and interpretation of genetic diagnosis of the condition. Our aim was to define the prevalence and role of variants in the three genes implicated in MH susceptibility in the largest comprehensively phenotyped MH cohort worldwide.
METHODS
We initially included one individual from each positive family tested in the UK MH Unit since 1971 to detect variants in RYR1, CACNA1S, or STAC3. Screening for genetic variants has been ongoing since 1991 and has involved a range of techniques, most recently next generation sequencing. We assessed the pathogenicity of variants using standard guidelines, including family segregation studies. The prevalence of recurrent variants of unknown significance was compared with the prevalence reported in a large database of sequence variants in low-risk populations.
RESULTS
We have confirmed MH susceptibility in 795 independent families, for 722 of which we have a DNA sample. Potentially pathogenic variants were found in 555 families, with 25 RYR1 and one CACNA1S variants previously unclassified recurrent variants significantly over-represented (P<1×10) in our cohort compared with the Exome Aggregation Consortium database. There was genotype-phenotype discordance in 86 of 328 families suitable for segregation analysis. We estimate non-RYR1/CACNA1S/STAC3 susceptibility occurs in 14-23% of MH families.
CONCLUSIONS
Our data provide current estimates of the role of variants in RYR1, CACNA1S, and STAC3 in susceptibility to MH in a predominantly white European population.
Topics: Adaptor Proteins, Signal Transducing; Calcium Channels; Calcium Channels, L-Type; Cohort Studies; Computer Simulation; Exome; Family; Genetic Predisposition to Disease; Genetic Testing; Genetic Variation; Humans; Malignant Hyperthermia; Ryanodine Receptor Calcium Release Channel; United Kingdom
PubMed: 30236257
DOI: 10.1016/j.bja.2018.06.028 -
British Journal of Anaesthesia Jul 2023The molecular mechanisms of susceptibility to malignant hyperthermia are complex. The malignant hyperthermia susceptibility phenotype should be reserved for patients who...
The molecular mechanisms of susceptibility to malignant hyperthermia are complex. The malignant hyperthermia susceptibility phenotype should be reserved for patients who have a personal or family history consistent with malignant hyperthermia under anaesthesia and are subsequently demonstrated through diagnostic testing to be at risk.
Topics: Humans; Malignant Hyperthermia; Halothane; Caffeine; Anesthesia; Biopsy
PubMed: 37198032
DOI: 10.1016/j.bja.2023.04.014 -
Handbook of Clinical Neurology 2018Malignant hyperthermia (MH) is a form of heat illness caused by increased heat generation exceeding the body's capacity for heat loss. It is classified separately from... (Review)
Review
Malignant hyperthermia (MH) is a form of heat illness caused by increased heat generation exceeding the body's capacity for heat loss. It is classified separately from other forms of heat illness as the latter require assessment of mental function for differential diagnosis. This is not possible with MH which occurs during general anesthesia when mental function cannot be assessed. MH occurs in genetically predisposed individuals exposed to inhalation anesthetics or succinylcholine. The genetic defects identified so far cause perturbation of skeletal muscle excitation-contraction coupling resulting in myoplasmic calcium dysregulation. The most commonly involved gene is RYR1. Increased myoplasmic calcium leads to hypermetabolism and sustained muscle contractile activity with consequent increased oxygen consumption, carbon dioxide production, sympathetic stimulation, muscle rigidity, heat production, rhabdomyolysis, and disseminated intravascular coagulation. Untreated reactions are fatal. In this chapter we summarize clinical features and management and review current understanding of the pathophysiology and molecular genetics of MH.
Topics: Animals; Humans; Malignant Hyperthermia; Muscle, Skeletal; Ryanodine Receptor Calcium Release Channel
PubMed: 30459030
DOI: 10.1016/B978-0-444-64074-1.00038-0 -
AORN Journal Sep 2020
Topics: Humans; Hyperthermia; Malignant Hyperthermia
PubMed: 32857404
DOI: 10.1002/aorn.13167