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Nature Communications Jun 2022Exertional heat illness (EHI) and malignant hyperthermia (MH) are life threatening conditions associated with muscle breakdown in the setting of triggering factors...
Exertional heat illness (EHI) and malignant hyperthermia (MH) are life threatening conditions associated with muscle breakdown in the setting of triggering factors including volatile anesthetics, exercise, and high environmental temperature. To identify new genetic variants that predispose to EHI and/or MH, we performed genomic sequencing on a cohort with EHI/MH and/or abnormal caffeine-halothane contracture test. In five individuals, we identified rare, pathogenic heterozygous variants in ASPH, a gene encoding junctin, a regulator of excitation-contraction coupling. We validated the pathogenicity of these variants using orthogonal pre-clinical models, CRISPR-edited C2C12 myotubes and transgenic zebrafish. In total, we demonstrate that ASPH variants represent a new cause of EHI and MH susceptibility.
Topics: Animals; Caffeine; Calcium-Binding Proteins; Heat Stress Disorders; Humans; Malignant Hyperthermia; Membrane Proteins; Mixed Function Oxygenases; Muscle Contraction; Muscle Fibers, Skeletal; Muscle Proteins; Zebrafish
PubMed: 35697689
DOI: 10.1038/s41467-022-31088-8 -
Neuromuscular Disorders : NMD Aug 2022Malignant hyperthermia (MH) is a life-threatening reaction triggered by volatile anesthetics and succinylcholine. MH is caused by mutations in the skeletal muscle...
Malignant hyperthermia (MH) is a life-threatening reaction triggered by volatile anesthetics and succinylcholine. MH is caused by mutations in the skeletal muscle ryanodine receptor (RYR1) gene, as is rhabdomyolysis triggered by exertion and/or pyrexia. The discrepancy between the prevalence of risk genotypes and actual MH incidence remains unexplained. We investigated the role of pre-operative exercise and pyrexia as potential MH modifying factors. We included cases from 5 MH referral centers with 1) clinical features suggestive of MH, 2) confirmation of MH susceptibility on Contracture Testing (IVCT or CHCT) and/or RYR1 genetic testing, and a history of 3) strenuous exercise within 72 h and/or pyrexia >37.5 °C prior to the triggering anesthetic. Characteristics of MH-triggering agents, surgery and succinylcholine use were collected. We identified 41 cases with general anesthesias resulting in an MH event (GA+MH, n = 41) within 72 h of strenuous exercise and/or pyrexia. We also identified previous general anesthesias without MH events (GA-MH, n = 51) in the index cases and their MH susceptible relatives. Apart from pre-operative exercise and/or pyrexia, trauma and acute abdomen as surgery indications, emergency surgery and succinylcholine use were also more common with GA+MH events. These observations suggest a link between pre-operative exercise, pyrexia and MH.
Topics: Fever; Humans; Malignant Hyperthermia; Mutation; Preoperative Exercise; Ryanodine Receptor Calcium Release Channel; Succinylcholine
PubMed: 35738978
DOI: 10.1016/j.nmd.2022.06.003 -
Journal of Perianesthesia Nursing :... Aug 2022Malignant hypothermia (MH) is a potentially fatal hypermetabolic reaction of skeletal muscle. It is an autosomal dominant disorder that generally occurs in people with...
Malignant hypothermia (MH) is a potentially fatal hypermetabolic reaction of skeletal muscle. It is an autosomal dominant disorder that generally occurs in people with RYR1, CACNA1S, or STAC3 mutations. And these genetic abnormalities often cause the imperfection of calcium release channels of skeletal muscle. The incidence of MH among different racial groups across the world ranges from approximately 1:5,000-1:250,000, but there is no national statistic MH incidence in China. It is not clear whether there are racial or regional differences in the incidence, but patients under 18 years old may be more affected. MH can be triggered by anesthetics, or other stimuli, such as strenuous exercise, heat-stroke, and emotional stress. While viral infection, statins, hyperglycemia, and muscle metabolic dysfunctions might accelerate the onset of MH. The onset of MH is insidious and rapid, with the preclinical stage characterized by rigidity of the masseter muscle, a high level of end-tidal carbon dioxide, and a sharp and persistent increase in body temperature. Medical history, family history, clinical presentation, in vitro caffeine-halothane contracture testing (IVCT/CHCT) and genetic testing are commonly diagnostic methods of MH. As soon as the onset of MH is suspected, immediate cessation of exposure to stimuli, call for professional support, and access to dantrolene are the highest priorities. For symptomatic treatment, "5C principles" were summarized as an algorithm to guide clinicians.
Topics: Adolescent; Caffeine; China; Halothane; Humans; Malignant Hyperthermia; Mutation
PubMed: 35414440
DOI: 10.1016/j.jopan.2021.08.018 -
American Journal of Therapeutics Jul 2022
Topics: Atracurium; COVID-19; Humans; Malignant Hyperthermia; SARS-CoV-2
PubMed: 35802921
DOI: 10.1097/MJT.0000000000001453 -
Journal of Perianesthesia Nursing :... Feb 2022The purpose of this project was to prepare perioperative staff at a military ambulatory surgical center to respond to a malignant hyperthermia crisis effectively with...
PURPOSE
The purpose of this project was to prepare perioperative staff at a military ambulatory surgical center to respond to a malignant hyperthermia crisis effectively with the assistance the Stanford emergency manual cognitive aid.
DESIGN
This is an evidence-based practice improvement project.
METHODS
Multidisciplinary perioperative staff at a military ambulatory surgical center participated in an in-service about the Stanford emergency manual cognitive aid tool, and a simulation exercise was conducted to practice using the tool during a malignant hyperthermia crisis. Preproject and postproject implementation surveys were to used to measure staff perceptions of and willingness to use cognitive aids/emergency checklists during perioperative emergencies.
FINDINGS
Staff positive perception of and willingness to use the Stanford emergency manual cognitive aid improved after implementation of an education session and simulation exercise with the checklist tool.
CONCLUSIONS
Introduction of the Stanford emergency manual cognitive aid to multidisciplinary perioperative staff with an in-service and simulated malignant hyperthermia scenario improved staff perception of cognitive aid use during emergencies. Use of cognitive aid checklists during simulated perioperative emergencies was shown to reduce missed critical treatment steps.
Topics: Checklist; Cognition; Computer Simulation; Humans; Malignant Hyperthermia
PubMed: 34736836
DOI: 10.1016/j.jopan.2020.09.020 -
Canadian Journal of Anaesthesia =... Dec 2017HyperCKemia is a persistent rise in serum creatine kinase (CK) levels of at least 1.5 times the normal value, as evidenced by a minimum of two measurements at 30-day...
PURPOSE
HyperCKemia is a persistent rise in serum creatine kinase (CK) levels of at least 1.5 times the normal value, as evidenced by a minimum of two measurements at 30-day intervals. One of the neuromuscular diseases associated with hyperCKemia is malignant hyperthermia (MH). This study investigated the susceptibility to MH in patients with hyperCKemia via in vitro contracture testing (IVCT) and a search of mutations in the RYR1 gene.
METHODS
Patients in an MH centre were followed from 1997-2012, and their epidemiologic, clinical, and laboratory data were analyzed, including IVCT, muscle histochemical analysis, and next-generation sequencing molecular analysis.
RESULTS
There were nine patients (eight male) in our study with a mean (SD) age of 33 (12) yr. Four patients were Caucasian and five were African Brazilian. Most complained about myalgia or cramps, but all had a normal neurological examination. They persistently presented with hyperCKemia from three months to ten years, with a mean (SD) CK value of 788 (507) IU·L ranging from 210-1,667 IU·L. These values corresponded to a 1.5- to nine-fold increase in the normal value (mean increase, 3.7-fold). Six patients were MH susceptible (MHS) after a positive IVCT. Histopathological muscular analysis disclosed unspecified changes in four of the MHS patients. Mitochondrial proliferation was observed in the other two MHS patients and in three MH negative patients. No pathogenic mutations were identified in the RYR1 gene in the five patients evaluated.
CONCLUSION
When investigating patients with idiopathic hyperCKemia, susceptibility to MH should be taken into account, and guidance should be offered to prevent anesthetic complications in the family.
Topics: Adolescent; Adult; Creatine Kinase; Disease Susceptibility; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Malignant Hyperthermia; Middle Aged; Mutation; Risk Factors; Ryanodine Receptor Calcium Release Channel; Time Factors; Young Adult
PubMed: 28952030
DOI: 10.1007/s12630-017-0978-x -
Current Opinion in Anaesthesiology Jun 2017The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing... (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients. The use of succinylcholine should be avoided in muscular dystrophies, motor neuron diseases, and intrinsic muscle disease due to a risk of malignant hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of quantitative neuromuscular monitoring should be strongly considered whenever nondepolarizing neuromuscular blocking agents are administered. A number of case series and reports have been recently published demonstrating that sugammadex can be safely used in patients with neuromuscular disease; the risk of residual neuromuscular is nearly eliminated when this agent is administered intraoperatively.
SUMMARY
Careful assessment and management of patients with underlying neuromuscular diseases is required to reduce postoperative complications. This article reviews the anesthetic implications of patients undergoing surgery with neuromuscular disorder.
Topics: Anesthesia; Anesthetics; Heart Arrest; Humans; Hyperkalemia; Intraoperative Complications; Malignant Hyperthermia; Neuromuscular Blocking Agents; Neuromuscular Diseases; Neuromuscular Monitoring; Perioperative Care; Postoperative Complications; Prevalence; Respiratory Insufficiency; Rhabdomyolysis; Risk Assessment; Succinylcholine; Sugammadex; Surgical Procedures, Operative; gamma-Cyclodextrins
PubMed: 28448298
DOI: 10.1097/ACO.0000000000000466 -
Anesthesiology Jan 2018
Topics: Disease Susceptibility; Humans; Malignant Hyperthermia
PubMed: 28926348
DOI: 10.1097/ALN.0000000000001879 -
Cold Spring Harbor Perspectives in... Feb 2015Signaling pathways regulate contraction of striated (skeletal and cardiac) and smooth muscle. Although these are similar, there are striking differences in the pathways... (Review)
Review
Signaling pathways regulate contraction of striated (skeletal and cardiac) and smooth muscle. Although these are similar, there are striking differences in the pathways that can be attributed to the distinct functional roles of the different muscle types. Muscles contract in response to depolarization, activation of G-protein-coupled receptors and other stimuli. The actomyosin fibers responsible for contraction require an increase in the cytosolic levels of calcium, which signaling pathways induce by promoting influx from extracellular sources or release from intracellular stores. Rises in cytosolic calcium stimulate numerous downstream calcium-dependent signaling pathways, which can also regulate contraction. Alterations to the signaling pathways that initiate and sustain contraction and relaxation occur as a consequence of exercise and pathophysiological conditions.
Topics: Calcium Signaling; Cardiomegaly; Heart Failure; Malignant Hyperthermia; Models, Biological; Muscle Contraction; Muscle, Skeletal; Muscle, Smooth; Muscle, Smooth, Vascular; Myocardium; Signal Transduction
PubMed: 25646377
DOI: 10.1101/cshperspect.a006023 -
A&A Practice Jan 2021
Topics: Hemodynamics; Humans; Hyperthermia; Malignant Hyperthermia; Muscular Diseases; Ryanodine Receptor Calcium Release Channel
PubMed: 33512901
DOI: 10.1213/XAA.0000000000001377