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Acta Anaesthesiologica Scandinavica Jul 2024Malignant hyperthermia (MH) is a rare pharmacogenetic disorder that can lead to a life-threatening reaction during general anaesthesia with triggering agents. Prompt...
BACKGROUND
Malignant hyperthermia (MH) is a rare pharmacogenetic disorder that can lead to a life-threatening reaction during general anaesthesia with triggering agents. Prompt life-saving treatment includes the immediate administration of the antidote dantrolene. This study investigated Swedish healthcare providers' awareness and adherence to guidelines and recommendations with respect to MH and whether adherence to safe MH-praxis varies with hospital care-complexity level and private versus public management form.
METHOD
Agreements and procurement specifications between all 21 Swedish County Councils and privately run surgical care providers were reviewed alongside with questionnaire-aided collection of information from 62 publicly funded health care providers (both privately and publicly run).
RESULTS
No procurement requirement specification or contract contained requirements on anaesthesia or aspects of MH. All publicly run hospitals stocked dantrolene and 28 out of 52 (54%) stocked the recommended amount. Seven out of nine (78%) of the privately run institutions stocked dantrolene, and one stocked the recommended amount. Publicly run hospitals adhered to recommendations to a greater extent than privately run institutions, both with respect to stocking of dantrolene (p = .02) and to stocking the recommended amount (p = .03).
CONCLUSIONS
Contracts between Swedish county councils and private surgical care subcontractors rarely outline expectations of standards for the safe practice of anaesthesia such as preparedness to handle a life-threatening MH reaction. Among Swedish publicly funded anaesthesia providers there is room for improvement in adherence to the EMHG guideline on dantrolene availability. Publicly run hospitals seem to have better compliance with these recommendations than privately run institutions. Raising awareness about current guidelines is important to improve safety for known and unknown MH-susceptible individuals.
Topics: Malignant Hyperthermia; Humans; Sweden; Dantrolene; Guideline Adherence; Surveys and Questionnaires; Muscle Relaxants, Central
PubMed: 38566397
DOI: 10.1111/aas.14417 -
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 Equine Veterinary Science May 2024Quarter horses (QH), a prominent athletic breed in Brazil, are affected by muscular genetic disorders such as myosin-heavy chain myopathy (MYHM), polysaccharide storage...
Quarter horses (QH), a prominent athletic breed in Brazil, are affected by muscular genetic disorders such as myosin-heavy chain myopathy (MYHM), polysaccharide storage myopathy (PSSM1), hyperkalemic periodic paralysis (HyPP), and malignant hyperthermia (MH). Bull-catching (vaquejada), primarily involving QH, is a significant equestrian sport in Brazil. Since the allele frequencies (AF) of MYHM, PSSM1, HyPP, and MH in vaquejada QH remain unknown, this study evaluated the AF in 129 QH vaquejada athletes, specifically from the Brazilian Northeast. These variants were exclusively observed in heterozygosity. The MYHM exhibited the highest AF (0.04 ±0.01), followed by PSSM1 (0.01 ±0.01) and the HyPP variant (0.004 ±0.01), while the MH variant was not identified in this study. This study represents the first identification of these variants in vaquejada QH, emphasizing the need to implement measures to prevent the transmission of pathogenic alleles and reduce the occurrence of clinical cases of these genetic diseases.
Topics: Gene Frequency; Muscular Diseases; Animals; Horses; Horse Diseases; Male; Female; Brazil; Paralysis, Hyperkalemic Periodic; Malignant Hyperthermia; Polysaccharides; Genetic Testing
PubMed: 38531516
DOI: 10.1016/j.jevs.2024.105052 -
Prenatal Diagnosis Apr 2024Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present...
Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.
Topics: Female; Humans; Pregnancy; Abnormalities, Multiple; Cleft Palate; Lymphangioma, Cystic; Malignant Hyperthermia; Muscular Diseases; Ryanodine Receptor Calcium Release Channel; Skin Abnormalities; Fetal Diseases
PubMed: 38520674
DOI: 10.1002/pd.6553 -
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 -
European Journal of Anaesthesiology May 2024Delays in treating anaesthesia-induced malignant hyperthermia increase risks of complications and death. NPJ5008 is a novel formulation of the indicated treatment,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Delays in treating anaesthesia-induced malignant hyperthermia increase risks of complications and death. NPJ5008 is a novel formulation of the indicated treatment, dantrolene sodium, developed to shorten preparation and administration times compared with the reference formulation Dantrium®. The two formulations have been compared preclinically.
OBJECTIVES
Assess bioequivalence of overall dantrolene (free acid) exposure of NPJ5008 versus Dantrium® and ascertain similarities in their pharmacokinetics and safety/tolerability profiles. Evaluate preparation/administration time savings for the new formulation.
DESIGN
Part 1 of this open-label trial in humans was a 1 : 1 randomised crossover study; part 2 was a single-arm study. Trial pharmacy data and laboratory simulations assessed preparation/administration step timings.
SETTING
Single clinical centre in the UK, April to July 2021.
PARTICIPANTS
Twenty-one healthy male and female individuals.
INTERVENTIONS
Part 1: single intravenous 60 mg dose of NPJ5008 or Dantrium®, sequentially. Part 2: single intravenous 120 mg dose of NPJ5008. Simulation: five vials per formulation using paediatric and adult cannulas.
MAIN OUTCOME MEASURES
Overall drug exposure to last measurable concentration (AUC 0 to last ) and extrapolated to infinity (AUC 0 to ∞ ) were primary endpoints. Other pharmacokinetic, clinical and muscle-function parameters, and adverse events, were monitored.
RESULTS
Adjusted geometric mean ratios of NPJ5008 versus Dantrium® were 90.24 and 90.44% for AUC 0 to last and AUC 0 to ∞ , respectively, with the 90% confidence intervals (CI) within the 80 to 125% acceptance interval, establishing bioequivalence. No new safety issues emerged: any adverse events were of a similar magnitude across treatments and related to pharmacological properties of dantrolene. Pharmacy and simulation data revealed that every step in preparation and administration was 26 to 69% faster for NPJ5008 than Dantrium®.
CONCLUSION
NPJ5008 showed comparable pharmacokinetic and safety profiles to Dantrium®, while reducing dantrolene dose preparation/administration times, potentially reducing patient complications/healthcare resourcing in malignant hyperthermia.
TRIAL REGISTRATION
EudraCT Number: 2020-005719-35, MHRA approval.
Topics: Adult; Humans; Male; Female; Child; Dantrolene; Biological Availability; Malignant Hyperthermia; Healthy Volunteers; Therapeutic Equivalency; Cross-Over Studies; Area Under Curve; Administration, Oral
PubMed: 38445365
DOI: 10.1097/EJA.0000000000001966