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Harefuah Jun 2020In this article we describe the treatment of a patient who developed suspicious symptoms of malignant hyperthermia syndrome during anesthesia for elective cerebral...
In this article we describe the treatment of a patient who developed suspicious symptoms of malignant hyperthermia syndrome during anesthesia for elective cerebral catheterization. We also described an up-to-date review of malignant hyperthermia, diagnosis and treatment. Details regarding the case: this is a case of a 57 year old male patient who was admitted for an elective catheterization under general anesthesia. Four hours following anesthesia induction, the patient presented with the following symptoms: a gradual increase in end tidal carbon dioxide measurements, an elevated core temperature, tachycardia, decreased oxygen saturation and excessive sweating. Arterial blood gases indicated respiratory acidosis. With a clinical diagnosis of malignant hyperthermia, the catheterization procedure was stopped. The patient was disconnected from the anesthesia machine and was ventilated with a clean ventilator with 100% oxygen. Additionally, active patient cooling was initiated along with supportive pharmacologic treatment. The patient was then moved, anesthetized and ventilated into the post anaesthesia care unit. Following a clinical and laboratory improvement the patient was extubated.
Topics: Anesthesia, General; Anesthesiology; Fever; Humans; Male; Malignant Hyperthermia; Middle Aged; Oxygen
PubMed: 32583646
DOI: No ID Found -
Human Molecular Genetics Nov 2022The ClinGen malignant hyperthermia susceptibility (MHS) variant curation expert panel specified the American College of Medical Genetics and Genomics/Association of...
The ClinGen malignant hyperthermia susceptibility (MHS) variant curation expert panel specified the American College of Medical Genetics and Genomics/Association of Molecular Pathologists (ACMG/AMP) criteria for RYR1-related MHS and a pilot analysis of 84 variants was published. We have now classified an additional 251 variants for RYR1-related MHS according to current ClinGen standards and updated the criteria where necessary. Criterion PS4 was modified such that individuals with multiple RYR1 variants classified as pathogenic (P), likely pathogenic (LP), or variant of uncertain significance (VUS) were not considered as providing evidence for pathogenicity. Criteria PS1 and PM5 were revised to consider LP variants at the same amino-acid residue as providing evidence for pathogenicity at reduced strength. Finally, PM1 was revised such that if PS1 or PM5 are used PM1, if applicable, should be downgraded to supporting. Of the 251 RYR1 variants, 42 were classified as P/LP, 16 as B/LB, and 193 as VUS. The primary driver of 175 VUS classifications was insufficient evidence supporting pathogenicity, rather than evidence against pathogenicity. Functional data supporting PS3/BS3 was identified for only 13 variants. Based on the posterior probabilities of pathogenicity and variant frequencies in gnomAD, we estimated the prevalence of individuals with RYR1-related MHS pathogenic variants to be between 1/300 and 1/1075, considerably higher than current estimates. We have updated ACMG/AMP criteria for RYR1-related MHS and classified 251 variants. We suggest that prioritization of functional studies is needed to resolve the large number of VUS classifications and allow for appropriate risk assessment. RYR1-related MHS pathogenic variants are likely to be more common than currently appreciated.
Topics: Humans; Genetic Testing; Genetic Variation; Malignant Hyperthermia; Ryanodine Receptor Calcium Release Channel; United States; Virulence
PubMed: 35849058
DOI: 10.1093/hmg/ddac145 -
Pflugers Archiv : European Journal of... Jul 2020Ca1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its... (Review)
Review
Ca1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its functions as L-type calcium channel. Consequently, all known Ca1.1-related diseases are muscle diseases and the molecular and cellular disease mechanisms relate to the dual functions of Ca1.1 in this tissue. To date, four types of muscle diseases are known that can be linked to mutations in the CACNA1S gene or to splicing defects. These are hypo- and normokalemic periodic paralysis, malignant hyperthermia susceptibility, Ca1.1-related myopathies, and myotonic dystrophy type 1. In addition, the Ca1.1 function in EC coupling is perturbed in Native American myopathy, arising from mutations in the Ca1.1-associated protein STAC3. Here, we first address general considerations concerning the possible roles of Ca1.1 in disease and then discuss the state of the art regarding the pathophysiology of the Ca1.1-related skeletal muscle diseases with an emphasis on molecular disease mechanisms.
Topics: Adaptor Proteins, Signal Transducing; Animals; Calcium Channels, L-Type; Channelopathies; Humans; Muscle, Skeletal; Mutation
PubMed: 32222817
DOI: 10.1007/s00424-020-02368-3 -
CMAJ : Canadian Medical Association... Jun 2022
Topics: Humans; Malignant Hyperthermia; Rhabdomyolysis; Succinylcholine
PubMed: 35760427
DOI: 10.1503/cmaj.146480-l -
Clinical Genetics Mar 2024Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early... (Review)
Review
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.
Topics: Humans; Malignant Hyperthermia; Ryanodine Receptor Calcium Release Channel; Risk Factors; Risk Assessment
PubMed: 38148504
DOI: 10.1111/cge.14475 -
British Journal of Anaesthesia Aug 2022
Topics: Calcium Channels, L-Type; Czech Republic; Humans; Malignant Hyperthermia; Mutation; Ryanodine Receptor Calcium Release Channel; Slovakia
PubMed: 35718563
DOI: 10.1016/j.bja.2022.04.029 -
Journal of Biochemistry Jul 2023Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious... (Review)
Review
Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious consequences can arise due to the unwanted but unavoidable responses of biological systems to heat. This review aims to present a range of responses to heat in biological systems across various spatial scales. We begin by examining the impaired thermogenesis of malignant hyperthermia in model mice and skeletal muscle cells, demonstrating that the progression of this disease is caused by a positive feedback loop between thermally driven Ca2+ signaling and thermogenesis at the subcellular scale. After we explore thermally driven force generation in both muscle and non-muscle cells, we illustrate how in vitro assays using purified proteins can reveal the heat-responsive properties of proteins and protein assemblies. Building on these experimental findings, we propose the concept of 'trans-scale thermal signaling'.
Topics: Animals; Mice; Ryanodine Receptor Calcium Release Channel; Malignant Hyperthermia; Calcium; Muscle, Skeletal
PubMed: 37461189
DOI: 10.1093/jb/mvad053 -
Anesthesia and Analgesia Dec 2019
Topics: Ambulatory Surgical Procedures; Anesthesia; Anesthesiologists; Anesthesiology; Humans; Malignant Hyperthermia; United States
PubMed: 31743208
DOI: 10.1213/ANE.0000000000004449 -
Clinical Psychopharmacology and... Feb 2021Hyperthermia, or extreme elevations in body temperature, can be life-threatening and may be caused by prescription drugs or illegal substances acting at a number of... (Review)
Review
Hyperthermia, or extreme elevations in body temperature, can be life-threatening and may be caused by prescription drugs or illegal substances acting at a number of different levels of the neuraxis. Several psychotropic drug classes and combinations have been associated with a classic clinical syndrome of hyperthermia, skeletal muscle hyper-metabolism, rigidity or rhabdomyolysis, autonomic dysfunction and altered mental status ranging from catatonic stupor to coma. It is critical for clinicians to have a high index of suspicion for these relatively uncommon drug-induced adverse effects and to become familiar with their management to prevent serious morbidity and mortality. Although these syndromes look alike, they are triggered by quite different mechanisms, and apart from the need to withdraw or restore potential triggering drugs and provide intensive medical care, specific treatments may vary. Clinical similarities have led to theoretical speculations about common mechanisms and shared genetic predispositions underlying these syndromes, suggesting that there may be a common "thermic stress syndrome" triggered in humans and animal models by a variety of pharmacological or environmental challenges.
PubMed: 33508784
DOI: 10.9758/cpn.2021.19.1.1