Hipertermia maligna / Malignant huperthermia

Carriers of malignant hyperthermia (MH), a subclinical metabolic myopathy, respond differently to the general population in response to triggering agents, such as volatile anesthetics and succinylcholine. Its incidence ranges from 1:10,000 to 1:250,000 anesthesias. Using etiological treatment, the current mortality rate is around 5%. The biochemical, metabolic, and physiological deterioration generally associated with MH is a direct result of a sudden and progressive increase in intracellular calcium in striated muscle cells. This generates a hypermetabolic state, with a rapid increase in body temperature that can lead to a fatal outcome if not diagnosed and treated in time. The genetic factors that determine susceptibility to MH are complex, with the participation of more than one gene. Its clinical symptoms are highly variable, from mild or moderate to fulminant attacks with severe muscle hypermetabolism and rhabdomyolysis. Capnography and pulse oximetry have great clinical diagnostic value. Other early symptoms of an MH attack may include sinus tachycardia, supraventricular or ventricular arrhythmia, and isolated masterean spasm or generalized muscle stiffness. The rise in temperature is a late sign. After an attack, or in possibly susceptible patients, the laboratory diagnosis is made with the in vitro contracture test, in which the contraction of muscle fibers, obtained through a skeletal muscle biopsy, is studied in the presence of halothane or caffeine. In patients known to be susceptible to MH, neuraxial and regional techniques should be preferred if surgery allows it; otherwise, trigger-free anesthetic methods (TIVA) should be available. Management of the MH crisis is based on three main actions: 1) stopping the administration of halogenates; 2) hyperventilation with 100% oxygen, and 3) administration of intravenous dantrolene.

La hipertermia maligna (HM) es una miopatía metabólica subclínica, cuyos portadores tienen una respuesta diferente a la población general ante la presencia de un agente desencadenante: anestésicos volátiles y succinilcolina. Su incidencia tiene rangos entre 1:10.000 a 1:250.000 anestesias. Su mortalidad actual usando tratamiento etiológico es de 5%. El deterioro bioquímico, metabólico y fisiológico asociado clásicamente al cuadro de HM es el resultado directo de un aumento súbito y progresivo del calcio intracelular de las células musculares estriadas, que genera un estado hipermetabólico, calor y un rápido aumento de la temperatura corporal, que puede llevar a un desenlace fatal si no se diagnostica y se trata a tiempo. Su herencia es complicada: se trata de una transmisión multigénica, en que la susceptibilidad a la HM depende de más de un gen. Los síntomas clínicos son muy variables, desde leves o moderados hasta crisis fulminantes con hipermetabolismo muscular severo y rabdomiólisis. La capnografía y la oximetría tiene un gran valor diagnóstico clínico. Otros síntomas tempranos de una crisis de HM pueden incluir taquicardia sinusal, arritmia supraventricular o ventricular y espasmo de maséteros aislado o rigidez muscular generalizada; el aumento de la temperatura es un signo tardío. Después de la crisis o en los pacientes posiblemente susceptibles, el diagnóstico de laboratorio se hace con el test de contractura , basado en la contracción de fibras musculares tomadas a partir de una biopsia de músculo estriado en presencia de halotano o cafeína. En los pacientes conocidamente susceptibles a HM se debe preferir las técnicas neuroaxiales y regionales si la cirugía lo permite; en caso contrario, debe disponerse de métodos anestésicos libres de agentes desencadenantes (TIVA). El manejo de la crisis de HM está basado en tres medidas principales: 1) la detención de la administración de halogenados; 2) la hiperventilación con oxígeno al 100% y 3) la administración de dantrolene endovenoso.

A propósito de un caso de elevación no explicada de la creatincinasa en un varón sano de 20 años de edad / A case report of unexplained elevation of creatin kinase in a 20 year old healthy male

Se expone el caso de un varón de 20 años de edad, sin antecedentes patológicos de interés, al que de forma incidental se le realiza un control analítico obteniéndose una creatincinasa (CK) en suero elevada que en un principio se achaca al ejercicio que estaba realizando en un gimnasio; tras una monitorización de la CK mensual y tras descartar patologías que pudiesen justificar dicha elevación y pactando con el paciente ejercicios en una pauta moderada, descartado el consumo de tóxicos y realizada una revisión bibliográfica, se filió el caso de una elevación no explicada de la CK en suero, que es un factor predisponente a la hipertermia maligna durante la anestesia con diversos fármacos

A case of a 20 year old male without any disease background of interest is presented. A laboratory analysis control was done by chance, obtaining an elevated creatin-kinase in serum which was first attributed to the exercise he was doing in a gymnasium. After monitoring the monthly CK and ruling out diseases that could justify this elevation and agreeing on exercises with the patient in a moderate regime, ruling out the consumption of toxics and performing a bibliographic review, the case was diagnosed as an unexplained elevation of CK in serum. This is a predisposing factor to malignant hyperthermia in patients during anesthesia with different drugs

Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients.

STUDY OBJECTIVES: To study the in vitro effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible (MHS) and normal (MHN) patients. DESIGN: Prospective study. SETTING: Malignant hyperthermia (MH) laboratory at a university hospital. PATIENTS: 47 patients with clinical suspicion for MH undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility. INTERVENTIONS: Biopsies of M. quadriceps femoris were performed in adult patients with a 3-in-1 nerve block and in children with trigger-free general anesthesia. MEASUREMENTS AND MAIN RESULT: Patients were first classified as MHS or MHN by the IVCT according to the protocol of the European MH Group (EMHG). Patients with equivocal results (MHE) or with neuromuscular diseases were excluded from the study. Enoximone was added to the organ bath to surplus vital muscle specimens in single bolus concentrations of 0.4, 0.6, 0. 8, or 1.6 mmol/L. The in vitro effects of enoximone on muscle contractures and twitch were measured. Seventeen patients were classified as MHS and 30 as MHN by the EMHG criteria. Enoximone induced contractures in skeletal muscles in a dose-dependent manner. Contractures of MHS compared to MHN muscle specimens were significantly larger at all concentrations used in this study. No overlap in maximum contractures was seen between MHS and MHN muscles at a bath concentration of 0.6 mmol/L enoximone only. CONCLUSIONS: Diagnosis of MH by an IVCT test with a single bolus administration of enoximone seems to be possible using a concentration of 0.6 mmol/L. The findings of this study may indicate an involvement of the phosphodiesterase-III and cAMP system in pathogenesis of MH. Further in vivo investigation should determine the trigger potency of enoximone in MH susceptible individuals.

Classification of malignant hyperthermia-equivocal patients by 4-chloro-M-cresol.

To clarify the contracture response to 4-chloro-m-cresol (4-CmC) in malignant hyperthermia (MH) equivocal (MHE) muscle, we studied the effect of cumulative concentrations of 4-CmC. In vitro contracture test (IVCT) was performed in 35 probands according to the European MH test protocol. Surplus muscle bundles were exposed to 4-CmC (25-200 micromol/L), maintaining each concentration for 4 and 8 min. After 4 min exposure, the contracture increase of MH susceptible (MHS) (n = 7) muscle specimens was significantly (P = 0.05) greater at 50 micromol/L compared with either MHE halothane sensitive (MHEh) (n = 13) or MH normal (MHN) (n = 15) classified patients. Statistically significant differences (P < 0.05) were also found at 75 micromol/L. Exposure for 8 min yielded significant differences at 50 micromol/L only between MHS and MHEh. MHEh muscles revealed a dose-response curve similar to that found in MHN specimens. MHS muscles showed a significantly higher sensitivity to 4-CmC than either MHEh or MHN, and, in the probands tested so far, MHEh and MHN muscles seem to identically respond to 4-CmC, which seems to indicate a normal response in MHEh probands, implying no MH susceptibility. Therefore, 4-CmC might reduce the frequency of MHEh diagnosis based on standard halothane-caffeine IVCT. However, since MHE individuals may also represent an aberrant genetic status, with MH causing defects linked to unknown mutations, it is premature to consider 4-CmC as a solution to the diagnostic uncertainty of the true status of MHE probands. Presently, 4-CmC may provide supplementary information for a more precise phenotypic categorization of MHE individuals.

Clinical presentation of suspected malignant hyperthermia during anaesthesia in 402 probands.

As anaesthetists have become more aware of malignant hyperthermia the mortality rate has fallen, but concommitantly the number of dubious and aborted cases has increased. All probands who developed a suspected malignant hyperthermia reaction during anaesthesia and subsequently underwent muscle biopsy were classified according to the clinical presentation. A probability for malignant hyperthermia can be calculated, using the classification, for each type of clinical presentation; this varied from 0.96 to 0.07. Certain clinical features were found to be of more value as predictors than others; these included a high creative kinase and myoglobinuria. The accuracy of prediction depends on a clear contemporaneous description of the clinical events.

Malignant hyperthermia: the clinical syndrome.

Malignant hyperthermia (MH) reactions can be classified into four categories: the fulminant form, the abortive MH, the masseter spasm and atypical presentations. The latter group includes syndromes such as hyperthermia and heat strokes, sudden death and the neuroleptic malignant syndrome. The different signs and symptoms of each category are recalled thus offering criteria for the differential diagnosis with other clinical entities.

[Malignant hyperthermia in Austria. I. Epidemiology and clinical aspects]. / Maligne Hyperthermie in Osterreich. I. Epidemiologie und Klinik.

Investigation of malignant hyperthermia (MH) was started in 1975; by March 1986, 79 suspected cases had been reported. In vitro contracture tests were performed in 66 probands or their parents; in 61 of these (92%), MH was confirmed and 5 (8%) proved negative. In 4 lethal crises, the parents refused biopsy, but because of well-documented clinical histories these were also included as confirmed MH reactions. We were able to analyse 65 cases of documented MH, and 9 patients are still to be investigated. About 18% of all Austrian hospitals (29 of 158) had reported 1-14 MH reactions (mean 2.7/hospital); it must therefore be assumed that a high number of crises are either not detected or not reported, and the total incidence of MH cannot be estimated. In our hospital (the University Hospital of Vienna), the incidence was 1:23,600 (including children and adults), whereas in Bludenz (Vorarlberg), the incidence was as low as 1:1,300 (in children only). This might partly be explained by genetic factors (such as inbreeding); we identified 3 families, all from Vorarlberg (which is a small, secluded mountain area), in which both parents were carriers of the MH trait. Fulminant crises (of which three times as many were rigid as were non-rigid) accounted for 58%, and masseter spasm for 26%, of all MH reactions. There was a significant influence of sex (72% males) and age (71% less than 20 years) on incidence. Neuromuscular symptoms or other signs reported to be associated with MH were found in only 5 patients (8%). During crises, cardiac symptoms (81%) and cyanosis (71%) were frequently observed; rigidity (45%) and body temperature above 39 degrees C (27%) showed remarkably low incidences. The overall mortality was 17% (11 of 65); it was significantly increased if the maximum temperature exceeded 39 degrees C, after acute surgery or anaesthesia lasting greater than 60 min, and in patients aged over 20 y. Most crises required no specific therapy; dantrolene was administered to only 10 patients. In the future, earlier detection via better monitoring, improved documentation, and mandatory reporting of suspected MH reactions should allow a more detailed description of MH and could further decrease the mortality associated with this condition.