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Contact in Context 2023Dantrolene sodium is a direct-acting skeletal muscle relaxant. Dantrolene sodium for injection is indicated, along with suitable supportive measures, for the management...
Dantrolene sodium is a direct-acting skeletal muscle relaxant. Dantrolene sodium for injection is indicated, along with suitable supportive measures, for the management of sudden, severe hypermetabolism of skeletal muscle typical of malignant hyperthermia crises in patients of any age. The formulation scanned in this work was designed to be injected intravenously. Intra-lot and inter-lot variability in the spectra of REVONTO (dantrolene sodium) was measured in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Spectra of 69 vials from lot 20REV01A contained two groups (n=56 vials, n=13 vials) when scanned with an FTNIR. The two groups of spectra in lot 20REV01A were found to be 66.7 SDs apart using a subcluster detection test, suggesting that the two groups were manufactured differently. As a result, all available samples of dantrolene were examined. A library of spectra of 141 vials of dantrolene from 4 lots were found to contain 3 separate groups, also suggesting that different vials contain different materials.
PubMed: 37424832
DOI: 10.6084/m9.figshare.23317136 -
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 -
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 -
Biomedicines Jul 2022Glioblastoma (GBM) is the most commonly diagnosed and most lethal primary malignant brain tumor in adults. Standard treatments are ineffective, and despite promising... (Review)
Review
Glioblastoma (GBM) is the most commonly diagnosed and most lethal primary malignant brain tumor in adults. Standard treatments are ineffective, and despite promising results obtained in early phases of experimental clinical trials, the prognosis of GBM remains unfavorable. Therefore, there is need for exploration and development of innovative methods that aim to establish new therapies or increase the effectiveness of existing therapies. One of the most exciting new strategies enabling combinatory treatment is the usage of nanocarriers loaded with chemotherapeutics and/or other anticancer compounds. Nanocarriers exhibit unique properties in antitumor therapy, as they allow highly efficient drug transport into cells and sustained intracellular accumulation of the delivered cargo. They can be infused into and are retained by GBM tumors, and potentially can bypass the blood-brain barrier. One of the most promising and extensively studied groups of nanostructured therapeutics are metal-based nanoparticles. These theranostic nanocarriers demonstrate relatively low toxicity, thus they might be applied for both diagnosis and therapy. In this article, we provide an update on metal-based nanostructured constructs in the treatment of GBM. We focus on the interaction of metal nanoparticles with various forms of electromagnetic radiation for use in photothermal, photodynamic, magnetic hyperthermia and ionizing radiation sensitization applications.
PubMed: 35884903
DOI: 10.3390/biomedicines10071598 -
BMC Anesthesiology Apr 2021Malignant hyperthermia is a rare but life-threatening pharmacogenetic muscle disorder characterized by abnormal hypermetabolic reactions and commonly triggered in...
BACKGROUND
Malignant hyperthermia is a rare but life-threatening pharmacogenetic muscle disorder characterized by abnormal hypermetabolic reactions and commonly triggered in susceptible individuals by volatile anesthetics or succinylcholine, or both. Unfortunately, the specific medicine dantrolene is not readily available in many countries including China. The aim of this study was to find the characteristics of malignant hyperthermia under the situation that dantrolene is not readily available.
METHODS
The cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. The inclusion criteria were the MH episodes only related to anesthesia. The exclusion criteria were dubious MH episodes only caused by Ketamine administration or MH episodes irrelevant to anesthesia. Independent samples t-test and Pearson's chi-squared test were applied to assess the difference between the survived and death cases.
RESULTS
Ninety-two cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. Median (IQR [range]) age was 18.5 (11.8-37.0 [0-70.0]) years. Compared with the survived cases, the death cases had higher maximum end-tidal partial pressure of CO (P = 0.033), the maximum arterial partial pressure of CO2 (P = 0.006), temperature first measured when the patient was first discovered abnormal (P = 0.012), and maximum temperature (P < 0.001). Besides, the death cases had less minimum pH (P < 0.001) and higher potassium (P < 0.001) and were more likely to have coagulation disorders (p = 0.018). Concerning treatment, cases used furosemide (P = 0.024), mannitol (P = 0.029), blood purification treatment (P = 0.017) had the advantage on the outcome. Creatine phosphokinase, myoglobin, and MB isoenzyme of creatine phosphokinase differed greatly among cases during the first week. 43 (46.7%) cases had congenital diseases. 12 (13.0%) cases were reported with abnormal laboratory test results or abnormal signs that are possibly relevant before anesthesia.
CONCLUSIONS
In countries that dantrolene is not readily available, early warning, diagnosis, and prompt effective therapies are crucial for MH patients to survive.
Topics: Adolescent; Adult; Aged; Arterial Pressure; Blood Coagulation Disorders; Carbon Dioxide; Child; Child, Preschool; China; Creatine Kinase; Creatine Kinase, MB Form; Dantrolene; Databases, Factual; Female; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; Male; Malignant Hyperthermia; Middle Aged; Muscle Relaxants, Central; Myoglobin; Potassium; Tidal Volume; Young Adult
PubMed: 33863282
DOI: 10.1186/s12871-021-01328-3 -
International Journal of Hyperthermia :... 2023Cellular metabolic reprogramming is an important feature of malignant tumors. Metabolic reprogramming causes changes in the levels or types of specific metabolites... (Review)
Review
Cellular metabolic reprogramming is an important feature of malignant tumors. Metabolic reprogramming causes changes in the levels or types of specific metabolites inside and outside the cell, which affects tumorigenesis and progression by influencing gene expression, the cellular state, and the tumor microenvironment. During tumorigenesis, a series of changes in the glucose metabolism, fatty acid metabolism, amino acid metabolism, and cholesterol metabolism of tumor cells occur, which are involved in the process of cellular carcinogenesis and constitute part of the underlying mechanisms of tumor formation. Hyperthermia, as one of the main therapeutic tools for malignant tumors, has obvious effects on tumor cell metabolism. In this paper, we will combine the latest research progress in the field of cellular metabolic reprogramming and focus on the current experimental research and clinical treatment of hyperthermia in cellular metabolic reprogramming to discuss the feasibility of cellular metabolic reprogramming-related mechanisms guiding hyperthermia in malignant tumor treatment, so as to provide more ideas for hyperthermia to treat malignant tumors through the direction of cellular metabolic reprogramming.
Topics: Humans; Neoplasms; Carcinogenesis; Cell Transformation, Neoplastic; Glycolysis; Hyperthermia; Hyperthermia, Induced; Tumor Microenvironment
PubMed: 37871910
DOI: 10.1080/02656736.2023.2270654 -
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 -
Clinical Practice and Cases in... May 2023Malignant hyperthermia (MH) is a rare but deadly condition that may be encountered in the emergency department (ED). This report highlights a case of a patient who...
INTRODUCTION
Malignant hyperthermia (MH) is a rare but deadly condition that may be encountered in the emergency department (ED). This report highlights a case of a patient who initially presented for acute agitation with hypertension and tachycardia and provides explanation for how to manage MH.
CASE REPORT
A 44-year-old male presented to the ED with altered mental status, eventually requiring intubation with etomidate and succinylcholine. Despite being afebrile initially, the patient developed a rectal temperature of 105.3° Fahrenheit (F) with significantly elevated arterial carbon dioxide levels after intubation. The treating team initiated cooling measures and dantrolene, leading to a positive outcome.
CONCLUSION
Clinicians should strive for expeditious recognition of MH and treatment with an updated institutional protocol.
PubMed: 37285489
DOI: 10.5811/cpcem.1402 -
Frontiers in Immunology 2022According to the difference in temperature, thermotherapy can be divided into thermal ablation and mild hyperthermia. The main advantage of thermal ablation is that it... (Review)
Review
According to the difference in temperature, thermotherapy can be divided into thermal ablation and mild hyperthermia. The main advantage of thermal ablation is that it can efficiently target tumors in situ, while mild hyperthermia has a good inhibitory effect on distant metastasis. There are some similarities and differences between the two therapies with respect to inducing anti-tumor immune responses, but neither of them results in sustained systemic immunity. Malignant tumors (such as breast cancer, pancreatic cancer, nasopharyngeal carcinoma, and brain cancer) are recurrent, highly metastatic, and highly invasive even after treatment, hence a single therapy rarely resolves the clinical issues. A more effective and comprehensive treatment strategy using a combination of hyperthermia and immune checkpoint inhibitor (ICI) therapies has gained attention. This paper summarizes the relevant preclinical and clinical studies on hyperthermia combined with ICI therapies and compares the efficacy of two types of hyperthermia combined with ICIs, in order to provide a better treatment for the recurrence and metastasis of clinically malignant tumors.
Topics: Breast Neoplasms; Female; Humans; Hyperthermia, Induced; Immune Checkpoint Inhibitors; Immunotherapy; Radioimmunotherapy
PubMed: 36032103
DOI: 10.3389/fimmu.2022.969447 -
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