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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 -
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 -
Anesthesiology Jan 2019
Topics: Anesthesia; Dantrolene; Humans; Malignant Hyperthermia; Succinylcholine
PubMed: 30550424
DOI: 10.1097/ALN.0000000000002507 -
Postgraduate Medical Journal Jan 1998Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents... (Review)
Review
Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents (such as potent volatile anaesthetics and succinylcholine). A sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a nonspecific muscle relaxant. Certain precautions should be taken before anaesthesia of patients known to be susceptible to malignant hyperthermia. These include the prohibition of the use of triggering agents, monitoring of central body temperature and expired CO2, and immediate availability of dantrolene. In addition, careful cleansing of the anaesthesia machine of vapours of halogenated agents is recommended. If these measures are taken, the chances of an MH episode are greatly reduced. When malignant hyperthermia-does occur in the operating room, prompt recognition and treatment usually prevent a potentially fatal outcome. The most reliable test to establish susceptibility to malignant hyperthermia is currently the in vitro caffeine-halothane contracture test. It is hoped that in the future a genetic test will be available.
Topics: Anesthesia; Anesthetics, Inhalation; Caffeine; Central Nervous System Stimulants; Dantrolene; Halothane; Humans; Malignant Hyperthermia; Muscle Relaxants, Central
PubMed: 9538480
DOI: 10.1136/pgmj.74.867.11 -
Philosophical Transactions of the Royal... Jun 2023Skeletal and cardiac muscle excitation-contraction coupling commences with Na1.4/Na1.5-mediated, surface and transverse (T-) tubular, action potential generation. This... (Review)
Review
Skeletal and cardiac muscle excitation-contraction coupling commences with Na1.4/Na1.5-mediated, surface and transverse (T-) tubular, action potential generation. This initiates , allosteric or Ca-mediated, T-sarcoplasmic reticular (SR) junctional, voltage sensor-Cav1.1/Cav1.2 and ryanodine receptor-RyR1/RyR2 interaction. We review recent structural, physiological and translational studies on possible actions of the resulting SR Ca release on Na1.4/Na1.5 function in native muscle. Finite-element modelling predicted potentially regulatory T-SR junctional [Ca] domains. Na1.4/Na1.5, III-IV linker and C-terminal domain structures included Ca and/or calmodulin-binding sites whose mutations corresponded to specific clinical conditions. Loose-patch-clamped native murine skeletal muscle fibres and cardiomyocytes showed reduced Na currents () following SR Ca release induced by the Epac and direct RyR1/RyR2 activators, 8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphate and caffeine, abrogated by the RyR inhibitor dantrolene. Conversely, dantrolene and the Ca-ATPase inhibitor cyclopiazonic acid increased . Experimental, catecholaminergic polymorphic ventricular tachycardic and metabolically deficient cardiomyocytes also showed reduced accompanying [Ca] abnormalities rescued by dantrolene- and flecainide-mediated RyR block. Finally, hydroxychloroquine challenge implicated action potential (AP) prolongation in slowing AP conduction through modifying Ca transients. The corresponding tissue/organ preparations each showed pro-arrhythmic, slowed AP upstrokes and conduction velocities. We finally extend discussion of possible Ca-mediated effects to further, Ca, K and Cl, channel types. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.
Topics: Animals; Mice; Ryanodine Receptor Calcium Release Channel; Dantrolene; Feedback; Muscle, Skeletal; Action Potentials; Calcium
PubMed: 37122213
DOI: 10.1098/rstb.2022.0162 -
Korean Journal of Anesthesiology Feb 2019
Topics: Dantrolene; Humans; Malignant Hyperthermia
PubMed: 29921086
DOI: 10.4097/kja.d.18.00139 -
European Review For Medical and... Apr 2021Disruption of intracellular Ca2+ homeostasis via excessive and pathological Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR) through... (Review)
Review
Disruption of intracellular Ca2+ homeostasis via excessive and pathological Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR) through ryanodine receptor (RyRs) Ca2+ channels play a critical role in the pathology of systemic inflammatory response syndrome (SIRS) and associated multiple organ dysfunction syndrome (MODS) in sepsis or septic shock. Dantrolene, a potent inhibitor of RyRs, is expected to ameliorate SIRS and MODS and decrease mortality in sepsis or septic shock patients. This review summarized the potential mechanisms of therapeutic effects of dantrolene in sepsis or septic shock at molecular, cell, and organ levels and provided suggestions and strategies for future clinical studies.
Topics: COVID-19; Calcium; Calcium Channel Blockers; Dantrolene; Drug Repositioning; Endoplasmic Reticulum; Humans; Mortality; Multiple Organ Failure; Ryanodine Receptor Calcium Release Channel; SARS-CoV-2; Sarcoplasmic Reticulum; Sepsis; Shock, Septic; COVID-19 Drug Treatment
PubMed: 33877683
DOI: 10.26355/eurrev_202104_25569 -
Alzheimer Disease and Associated... 2015Alzheimer disease (AD) is a fatal progressive disease and the most common form of dementia without effective treatments. Previous studies support that the disruption of... (Review)
Review
Alzheimer disease (AD) is a fatal progressive disease and the most common form of dementia without effective treatments. Previous studies support that the disruption of endoplasmic reticulum Ca through overactivation of ryanodine receptors plays an important role in the pathogenesis of AD. Normalization of intracellular Ca homeostasis could be an effective strategy for AD therapies. Dantrolene, an antagonist of ryanodine receptors and an FDA-approved drug for clinical treatment of malignant hyperthermia and muscle spasms, exhibits neuroprotective effects in multiple models of neurodegenerative disorders. Recent preclinical studies consistently support the therapeutic effects of dantrolene in various types of AD animal models and were summarized in the current review.
Topics: Alzheimer Disease; Animals; Calcium Signaling; Dantrolene; Humans; Neuroprotective Agents; Ryanodine Receptor Calcium Release Channel; Treatment Outcome
PubMed: 25551862
DOI: 10.1097/WAD.0000000000000076