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JA Clinical Reports Apr 2024Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and...
BACKGROUND
Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH.
CASE PRESENTATION
We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1.
CONCLUSIONS
Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH.
PubMed: 38647904
DOI: 10.1186/s40981-024-00710-7 -
Medicine Apr 2024Malignant hyperthermia (MH) is a rare yet serious medical complication that typically arises following general anesthesia or the administration of specific anesthetics....
Diagnosis and rescue of malignant hyperthermia induced by anesthesia during radical surgery in a cervical cancer patient using the National Remote Emergency System: A case report.
RATIONALE
Malignant hyperthermia (MH) is a rare yet serious medical complication that typically arises following general anesthesia or the administration of specific anesthetics. Due to the infrequency of MH, anesthesiologists often lack sufficient expertise in identifying and managing it, leading to misdiagnosis and inappropriate treatment. There is an urgent need to enhance the diagnosis and management of MH through the utilization of relevant tools.
PATIENT CONCERNS
In this case, a 52-year-old woman underwent radical cervical cancer surgery under general anesthesia, with no family or significant medical history. She experienced a gradual increase in end-tidal carbon dioxide (ETCO2) to a maximum of 75 mm Hg and a rise in body temperature from 36.5 to 37.5 °C in a very short period, as well as a blood gas analysis showing a pH of 7.217.
DIAGNOSIS
The anesthesiologist immediately used The WeChat applet-based National Remote Emergency System for Malignant Hyperthermia (MH-NRES), and the score was 40, which indicated that the patient was very likely to have MH.
INTERVENTIONS
We immediately discontinued sevoflurane and switched total intravenous anesthesia to maintain general anesthesia, with a rapid intravenous infusion of dantrolene sodium.
OUTCOMES
The ETCO2 and the temperature quickly dropped to normal, followed by successful completion of the surgery, and the patient was discharged 8 days after surgery.
LESSONS
The experience can provide a basis use of MH-NRES and improve the ability of anesthesiologists to deal with intraoperative MH as well as increase the survival probability of patients.
Topics: Female; Humans; Middle Aged; Malignant Hyperthermia; Uterine Cervical Neoplasms; Dantrolene; Sevoflurane; Anesthesia, General
PubMed: 38640306
DOI: 10.1097/MD.0000000000037699 -
Cureus Apr 2024As a result of the widespread prevalence of anesthetic usage, anesthesia-related complications are well studied, ranging from benign postoperative nausea and vomiting to... (Review)
Review
As a result of the widespread prevalence of anesthetic usage, anesthesia-related complications are well studied, ranging from benign postoperative nausea and vomiting to potentially fatal complications, such as paralysis, malignant hyperthermia, and death. However, one intersection that still needs further analysis is the relationship between vector-borne illnesses (VBIs) and anesthetic complications. With the advent of climate change and global warming, what were previously endemic vectors have spread far beyond their typical regions, resulting in the spread of VBI. As the incidence of VBIs rapidly increases in the United States, operations for diagnostic testing, and thus the identification and treatments of these VBIs, have significantly diminished. A literature review was conducted to analyze case reports of patients with VBIs and anesthetic concerns with sources from PubMed and Google Scholar databases, and a wide range of complications were found.
PubMed: 38586230
DOI: 10.7759/cureus.57517 -
Stem Cell Research Jun 2024RYR1 variants are the most common genetic cause of congenital myopathies, and typically cause central core disease (CCD) and/or malignant hyperthermia (MH). Here, we...
Generation of two iPSC lines from patients with inherited central core disease and concurrent malignant hyperthermia caused by dominant missense variants in the RYR1 gene.
RYR1 variants are the most common genetic cause of congenital myopathies, and typically cause central core disease (CCD) and/or malignant hyperthermia (MH). Here, we generated iPSC lines from two patients with CCD and MH caused by dominant RYR1 variants within the central region of the protein (p.Val2168Met and p.Arg2508Cys). Both lines displayed typical iPSC morphology, uniform expression of pluripotency markers, trilineage differentiation potential, and had normal karyotypes. These are the first RYR1 iPSC lines from patients with both CCD and MH. As these are common CCD/MH variants, these lines should be useful to study these conditions and test therapeutics.
Topics: Humans; Ryanodine Receptor Calcium Release Channel; Malignant Hyperthermia; Induced Pluripotent Stem Cells; Mutation, Missense; Myopathy, Central Core; Male; Female; Cell Line; Cell Differentiation
PubMed: 38583293
DOI: 10.1016/j.scr.2024.103410 -
Risk Management and Healthcare Policy 2024Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for...
BACKGROUND
Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists' understanding of MH in China.
METHODS
A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants' perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study.
RESULTS
Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (=0.003), academic degree (<0.001), hospital classification (<0.001), and urban hierarchy (<0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH.
CONCLUSION
Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.
PubMed: 38562250
DOI: 10.2147/RMHP.S454895 -
Toxicology Reports Jun 2024The Neuroleptic Malignant Syndrome (NMS), alternatively referred to as the Antipsychotic Malignant Syndrome, is a potentially fatal condition that is infrequently...
INTRODUCTION
The Neuroleptic Malignant Syndrome (NMS), alternatively referred to as the Antipsychotic Malignant Syndrome, is a potentially fatal condition that is infrequently observed and is linked to the administration of antipsychotic medications. This syndrome is characterized by a disturbance in consciousness, autonomic instability manifesting as hyperthermia, and muscular rigidity. The onset of this syndrome is typically within the initial month of treatment or following an escalation in the dosage of an antipsychotic medication. This case report delineates a case where NMS was precipitated by an excessive intake of haloperidol, a typical antipsychotic drug.
CASE DESCRIPTION
In the Emergency Department (ED), a 23-year-old male was admitted following an overdose of haloperidol, a typical antipsychotic drug. The patient exhibited symptoms of tachypnea and tachycardia, and initially presented with hypotension. His level of consciousness was variable, but maximal upon stimulation. Notably, there was a significant increase in muscle tension, characterized by cogwheel rigidity. His body temperature rose to 38.6 degrees Celsius. Laboratory findings revealed a substantial high anion gap metabolic acidosis, with a lactate level of 21.2 mmol/L. Additionally, his creatine kinase level was elevated, measuring 1347 U/L. The therapeutic approach encompassed the intravenous administration of midazolam (2.5 mg), lorazepam (2.5 mg), and biperiden (5 mg), in conjunction with resuscitation involving 2 liters of 0.9% NaCl. The patient demonstrated a positive response to this regimen, leading to his admission to the ward. Following a full recovery, he was discharged from the hospital the subsequent day.
DISCUSSION
The patient in our case fulfilled all the diagnostic criteria for NMS as stipulated in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). NMS is not contingent on the dosage, although an increased dosage does elevate the risk. A thorough review of existing literature did not yield any cases mirroring ours.
CONCLUSION
In conclusion, we present a case where NMS developed after an overdose of haloperidol.
PubMed: 38560509
DOI: 10.1016/j.toxrep.2024.03.003 -
Turk Psikiyatri Dergisi = Turkish... 2024Electroconvulsive therapy (ECT) is an effective and safe treatment method for many psychiatric disorders. In general medical practice, ECT may cause side effects as most...
Electroconvulsive therapy (ECT) is an effective and safe treatment method for many psychiatric disorders. In general medical practice, ECT may cause side effects as most other treatment methods do. Headache, myalgia, nausea, vomiting, confusion, anterograde amnesia are common side effects of electroconvulsive therapy. Fever; in addition to general medical conditions such as infection, malignancy, connective tissue diseases, drug treatments, malignant hyperthermia, convulsions, it can also occur due to conditions such as neuroleptic malignant syndrome (NMS), serotonin syndrome, catatonia, malignant catatonia, which are frequently encountered in psychiatry clinics. In the literature, transient fever response due to electroconvulsive therapy application have been described, albeit rarely. Although there are many proposed mechanisms for the emergence of a fever response, regardless of its cause, it is still not understood why some fever responses occur. In this article, we present the differential diagnosis of the fever response, possible causes, and the mechanisms that may reveal the secondary fever response to electroconvulsive therapy in a case with a diagnosis of catatonic schizophrenia, who developed a fever response during electroconvulsive therapy sessions and no fever response was observed at times other than electroconvulsive therapy sessions. In this case, postictal benign fever response associated with electroconvulsive therapy was considered after excluding other medical conditions that may cause a fever response after electroconvulsive therapy. Keywords: ECT, Fever, Catatonia, NMS.
Topics: Humans; Schizophrenia, Catatonic; Catatonia; Schizophrenia; Electroconvulsive Therapy; Neuroleptic Malignant Syndrome
PubMed: 38556940
DOI: 10.5080/u26972 -
International Journal of Molecular... Mar 2024Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This...
Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This condition is caused primarily by pathogenic variants in the calcium-release channel RYR1, which disrupts calcium signalling in skeletal muscle. However, our understanding of MH genetics is incomplete, with no variant identified in a significant number of cases and considerable phenotype diversity. In this study, we applied a transcriptomic approach to investigate the genome-wide gene expression in MH-susceptible cases using muscle biopsies taken for diagnostic testing. Baseline comparisons between muscle from MH-susceptible individuals (MHS, = 8) and non-susceptible controls (MHN, = 4) identified 822 differentially expressed genes (203 upregulated and 619 downregulated) with significant enrichment in genes associated with oxidative phosphorylation (OXPHOS) and fatty acid metabolism. Investigations of 10 OXPHOS target genes in a larger cohort (MHN: = 36; MHS: = 36) validated the reduced expression of and in MHS samples, but the remaining 8 selected were not statistically significant. Further analysis also identified evidence of a sex-linked effect in and expression, and a difference in expression across individuals with MH sub-phenotypes (trigger from in vitro halothane exposure only, MHS ( = 4); trigger to both in vitro halothane and caffeine exposure, MHS ( = 4)). Our data support a link between MH-susceptibility and dysregulated gene expression associated with mitochondrial bioenergetics, which we speculate plays a role in the phenotypic variability observed within MH.
Topics: Humans; Malignant Hyperthermia; Halothane; Oxidative Phosphorylation; Calcium; Muscle, Skeletal; Disease Susceptibility; Biopsy; Gene Expression; Muscle Contraction; Ryanodine Receptor Calcium Release Channel; Carrier Proteins
PubMed: 38542460
DOI: 10.3390/ijms25063489 -
Journal of Nanobiotechnology Mar 2024Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis....
BACKGROUND
Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis. Timely diagnosis and precise treatment of TNBC are substantially challenging. Abnormal tumor vessels play a crucial role in TNBC progression and treatment. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis, while effective NO delivery can normalize the tumor vasculature. Accordingly, we have proposed here a tumor vascular microenvironment remodeling strategy based on NO-induced vessel normalization and extracellular matrix collagen degradation with multimodality imaging-guided nanoparticles against TNBC called DNMF/PLGA.
RESULTS
Nanoparticles were synthesized using a chemotherapeutic agent doxorubicin (DOX), a NO donor L-arginine (L-Arg), ultrasmall spinel ferrites (MnFeO), and a poly (lactic-co-glycolic acid) (PLGA) shell. Nanoparticle distribution in the tumor was accurately monitored in real-time through highly enhanced magnetic resonance imaging and photoacoustic imaging. Near-infrared irradiation of tumor cells revealed that MnFeO catalyzes the production of a large amount of reactive oxygen species (ROS) from HO, resulting in a cascade catalysis of L-Arg to trigger NO production in the presence of ROS. In addition, DOX activates niacinamide adenine dinucleotide phosphate oxidase to generate and supply HO. The generated NO improves the vascular endothelial cell integrity and pericellular contractility to promote vessel normalization and induces the activation of endogenous matrix metalloproteinases (mainly MMP-1 and MMP-2) so as to promote extravascular collagen degradation, thereby providing an auxiliary mechanism for efficient nanoparticle delivery and DOX penetration. Moreover, the chemotherapeutic effect of DOX and the photothermal effect of MnFeO served as a chemo-hyperthermia synergistic therapy against TNBC.
CONCLUSION
The two therapeutic mechanisms, along with an auxiliary mechanism, were perfectly combined to enhance the therapeutic effects. Briefly, multimodality image-guided nanoparticles provide a reliable strategy for the potential application in the fight against TNBC.
Topics: Humans; Nitric Oxide; Triple Negative Breast Neoplasms; Reactive Oxygen Species; Hydrogen Peroxide; Doxorubicin; Hyperthermia, Induced; Nanoparticles; Phototherapy; Collagen; Cell Line, Tumor; Tumor Microenvironment
PubMed: 38481281
DOI: 10.1186/s12951-024-02366-y -
Advanced Science (Weinheim,... May 2024Nanomedicine has reshaped the landscape of cancer treatment. However, its efficacy is still hampered by innate tumor defense systems that rely on adenosine triphosphate...
Nanomedicine has reshaped the landscape of cancer treatment. However, its efficacy is still hampered by innate tumor defense systems that rely on adenosine triphosphate (ATP) for fuel, including damage repair, apoptosis resistance, and immune evasion. Inspired by the naturally enzymatic reaction of glucose oxidase (GOx) with glucose, here a novel "two birds with one stone" technique for amplifying enzyme-mediated tumor apoptosis and enzyme-promoted metabolic clearance is proposed and achieved using GOx-functionalized rhenium nanoclusters-doped polypyrrole (Re@ReP-G). Re@ReP-G reduces ATP production while increasing HO concentrations in the tumor microenvironment through GOx-induced enzymatic oxidation, which in turn results in the downregulation of defense (HSP70 and HSP90) and anti-apoptotic Bcl-2 proteins, the upregulation of pro-apoptotic Bax, and the release of cytochrome c. These processes are further facilitated by laser-induced hyperthermia effect, ultimately leading to severe tumor apoptosis. As an enzymatic byproduct, HO catalyzes the conversion of rhenium nanoclusters in Re@ReP-G nanostructures into rhenate from the outside in, which accelerates their metabolic clearance in vivo. This Re@ReP-G-based "two birds with one stone" therapeutic strategy provides an effective tool for amplifying tumor apoptosis and safe metabolic mechanisms.
Topics: Animals; Apoptosis; Mice; Glucose Oxidase; Neoplasms; Humans; Disease Models, Animal; Cell Line, Tumor; Nanomedicine; Tumor Microenvironment; Hydrogen Peroxide; Polymers
PubMed: 38447152
DOI: 10.1002/advs.202308251