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Anaesthesiology Intensive Therapy 2019
Review
Topics: Anesthetics, Inhalation; Humans; Malignant Hyperthermia; Neuromuscular Depolarizing Agents
PubMed: 31493330
DOI: 10.5114/ait.2019.87646 -
British Journal of Anaesthesia Feb 1988
Review
Topics: Calcium; Child; Dantrolene; Drug Interactions; Female; Humans; Malignant Hyperthermia; Muscles
PubMed: 3279988
DOI: 10.1093/bja/60.3.279 -
Anaesthesia Jan 2019
Topics: Anesthesia, Inhalation; Anesthetics, Inhalation; Charcoal; Emergency Medical Services; Filtration; Humans; Malignant Hyperthermia
PubMed: 30088269
DOI: 10.1111/anae.14407 -
Medicine Mar 2023Malignant hyperthermia (MH) is a life-threatening syndrome caused by sudden, uncontrolled skeletal muscle hypermetabolism in response to inhalation anesthetics and...
Malignant hyperthermia (MH) is a life-threatening syndrome caused by sudden, uncontrolled skeletal muscle hypermetabolism in response to inhalation anesthetics and depolarizing relaxants. The estimated incidence of MH is between 1:10,000 and 1:250,000 anesthetic procedures. In Poland, due to lack of reporting, the incidence of MH is unknown. Dantrolene is imported as a life-saving drug (target import) and temporally authorized for sale. The aim of the study was to evaluate the prevalence of malignant hyperthermia in Poland and to assess the accessibility to dantrolene in Poland. A questionnaire was conducted among the chiefs of anesthesia and intensive care units in Poland. During the years 2014 to 2019, 10 episodes of MH have been reported in 238 surveyed polish anesthesia departments. The estimated prevalence is 1:350,000. Eight patients survived the MH crisis. Dantrolene is stocked in 48 (20%) anesthesiology departments. Among the surveyed hospitals, only in 38 (16%) it is possible to administer dantrolene within 5 minutes of suspecting a MH reaction. Less than half units (44%) have an algorithm for the management of MH episode in the operating theaters. The results of the study revealed, that the prevalence of MH in Poland is lower than the prevalence reported in other countries. Access to dantrolene in Poland is limited.
Topics: Humans; Malignant Hyperthermia; Dantrolene; Poland; Surveys and Questionnaires; Anesthetics, Inhalation
PubMed: 36897682
DOI: 10.1097/MD.0000000000033238 -
The Journal of Biological Chemistry Aug 2023Malignant hyperthermia susceptibility (MHS) is an autosomal dominant pharmacogenetic disorder that manifests as a hypermetabolic state when carriers are exposed to...
Malignant hyperthermia susceptibility (MHS) is an autosomal dominant pharmacogenetic disorder that manifests as a hypermetabolic state when carriers are exposed to halogenated volatile anesthetics or depolarizing muscle relaxants. In animals, heat stress intolerance is also observed. MHS is linked to over 40 variants in RYR1 that are classified as pathogenic for diagnostic purposes. More recently, a few rare variants linked to the MHS phenotype have been reported in CACNA1S, which encodes the voltage-activated Ca channel Ca1.1 that conformationally couples to RyR1 in skeletal muscle. Here, we describe a knock-in mouse line that expresses one of these putative variants, Ca1.1-R174W. Heterozygous (HET) and homozygous (HOM) Ca1.1-R174W mice survive to adulthood without overt phenotype but fail to trigger with fulminant malignant hyperthermia when exposed to halothane or moderate heat stress. All three genotypes (WT, HET, and HOM) express similar levels of Ca1.1 by quantitative PCR, Western blot, [H]PN200-110 receptor binding and immobilization-resistant charge movement densities in flexor digitorum brevis fibers. Although HOM fibers have negligible Ca1.1 current amplitudes, HET fibers have similar amplitudes to WT, suggesting a preferential accumulation of the Ca1.1-WT protein at triad junctions in HET animals. Never-the-less both HET and HOM have slightly elevated resting free Ca and Na measured with double barreled microelectrode in vastus lateralis that is disproportional to upregulation of transient receptor potential canonical (TRPC) 3 and TRPC6 in skeletal muscle. Ca1.1-R174W and upregulation of TRPC3/6 alone are insufficient to trigger fulminant malignant hyperthermia response to halothane and/or heat stress in HET and HOM mice.
Topics: Animals; Mice; Calcium; Halothane; Heat-Shock Response; Malignant Hyperthermia; Muscle, Skeletal; Mutation; Ryanodine Receptor Calcium Release Channel; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
PubMed: 37392848
DOI: 10.1016/j.jbc.2023.104992 -
Journal of Neuromuscular Diseases 2023Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been...
BACKGROUND
Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility.
OBJECTIVE
To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients.
METHODS
We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders.
RESULTS
A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy.
CONCLUSIONS
Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity.
Topics: Humans; Cross-Sectional Studies; Genetic Predisposition to Disease; Malignant Hyperthermia; Muscle, Skeletal; Mutation; Prospective Studies; Ryanodine Receptor Calcium Release Channel; Ultrasonography
PubMed: 37154182
DOI: 10.3233/JND-230018 -
Journal of Neurology Apr 2019The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to RYR1 mutations have only been reported...
OBJECTIVE
The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to RYR1 mutations have only been reported in a few cases.
METHODS
We performed a retrospective multi-centre cohort study focussing on the histopathological features of patients with MH or RM due to RYR1 mutations (1987-2017). All muscle biopsies were reviewed by a neuromuscular pathologist. Additional morphometric and electron microscopic analysis were performed where possible.
RESULTS
Through the six participating centres we identified 50 patients from 46 families, including patients with MH (n = 31) and RM (n = 19). Overall, the biopsy of 90% of patients showed one or more myopathic features including: increased fibre size variability (n = 44), increase in the number of fibres with internal nuclei (n = 30), and type I fibre predominance (n = 13). Abnormalities on oxidative staining, generally considered to be more specifically associated with RYR1-related congenital myopathies, were observed in 52%, and included unevenness (n = 24), central cores (n = 7) and multi-minicores (n = 3). Apart from oxidative staining abnormalities more frequently observed in MH patients, the histopathological spectrum was similar between the two groups. There was no correlation between the presence of cores and the occurrence of clinically detectable weakness or presence of (likely) pathogenic variants.
CONCLUSIONS
Patients with RYR1-related MH and RM exhibit a similar histopathological spectrum, ranging from mild myopathic changes to cores and other features typical of RYR1-related congenital myopathies. Suggestive histopathological features may support RYR1 involvement, also in cases where the in vitro contracture test is not informative.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Male; Malignant Hyperthermia; Middle Aged; Muscles; Mutation; Phenotype; Retrospective Studies; Rhabdomyolysis; Ryanodine Receptor Calcium Release Channel; Young Adult
PubMed: 30788618
DOI: 10.1007/s00415-019-09209-z -
Brazilian Journal of Anesthesiology... 2023Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during... (Observational Study)
Observational Study
BACKGROUND
Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional.
OBJECTIVE
The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression.
METHODS
A cross-sectional observational study was carried out with three groups ... 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity).
RESULTS
There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9.ß...ß1.9 vs. 3.9.ß...ß2, t-test unpaired, p.ß<.ß0.05).
CONCLUSION
We did not detect subjective fatigue in MH susceptible patients, although we reported protracted recovery after physical activity, which may alert us to further investigation requirements.
Topics: Humans; Malignant Hyperthermia; Halothane; Cross-Sectional Studies; Depression; Contracture; Exercise; Disease Susceptibility
PubMed: 34626754
DOI: 10.1016/j.bjane.2021.07.038 -
The Journal of Thoracic and... Jun 2011Malignant hyperthermia susceptibility is an important risk factor during general anesthesia. Affected patients have an asymptomatic but potentially lethal hypermetabolic... (Review)
Review
OBJECTIVES
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anesthesia, General; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Hemodynamics; Humans; Malignant Hyperthermia; Middle Aged; Prognosis; Risk Assessment; Risk Factors
PubMed: 21376345
DOI: 10.1016/j.jtcvs.2011.01.034 -
Experimental Biology and Medicine... Apr 2022The isolated tissue bath research methodology was first developed in 1904. Since then, it has been recognized as an important tool in pharmacology and physiology... (Review)
Review
The isolated tissue bath research methodology was first developed in 1904. Since then, it has been recognized as an important tool in pharmacology and physiology research, including investigations into neuromuscular disorders. The tissue bath is still used routinely as the instrument for performing the "gold standard" test for clinical diagnosis of malignant hyperthermia susceptibility - the caffeine-halothane contracture test. Our research group has utilized this tool for several decades for a range of research studies, and we are currently one of four North American diagnostic centers for determining susceptibility for malignant hyperthermia. This review provides a brief summary of some of the historical uses of the tissue bath. Important experimental considerations for the operation of the tissue bath are further described. Finally, we discuss the different studies our group has performed using isolated tissue baths to highlight the broad potential applications.
Topics: Baths; Caffeine; Humans; In Vitro Techniques; Laboratories; Malignant Hyperthermia; Muscle Contraction; Research Design; Translational Research, Biomedical
PubMed: 35068214
DOI: 10.1177/15353702211070535