Zusammenfassung
Die maligne Hyperthermie (MH) ist eine seltene hereditäre, meist subklinische Myopathie. Triggersubstanzen wie volatile Anästhetika und das depolarisierende Muskelrelaxans Succinylcholin können bei prädisponierten Patienten eine potenziell letale Stoffwechselsteigerung auslösen. Ursächlich hierfür ist eine Dysregulation des myoplasmatischen Kalzium(Ca)-Haushalts. Mutationen im Dihydropyridin-Ryanodin-Rezeptorkomplex im Zusammenspiel mit den Triggersubstanzen sind für eine unkontrollierte Ca-Freisetzung aus dem sarkoplasmatischen Retikulum verantwortlich. Diese führt zur Aktivierung des kontraktilen Apparats und einer massiven Steigerung des zellulären Energieumsatzes. Das Erschöpfen der zellulären Energiereserven endet im lokalen Muskelzelluntergang mit konsekutivem Herz-Kreislauf-Versagen. Das klinische Bild einer MH-Episode ist sehr variabel. Hypoxie, Hyperkapnie und Herzrhythmusstörungen sind frühe Symptome, während der namensgebende Temperaturanstieg oft erst später auftritt. Entscheidend für den Verlauf einer MH-Episode ist die frühzeitige gezielte Therapie. Nach Einführung des Hydantoinderivats Dantrolen konnte die vormals hohe Letalität fulminanter MH-Verläufe auf weit unter 10 % gesenkt werden. Eine MH-Veranlagung kann mithilfe des invasiven In-vitro-Kontrakturtests (IVCT) oder der Mutationsanalyse nachgewiesen werden. Weniger aufwendige Diagnoseverfahren befinden sich in Entwicklung.
Abstract
Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage.
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Interessenkonflikt. T. Metterlein, F. Schuster, B.M. Graf und M. Anetseder geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag enthält keine Studien an Menschen oder Tieren.
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Metterlein, T., Schuster, F., Graf, B. et al. Maligne Hyperthermie. Anaesthesist 63, 908–918 (2014). https://doi.org/10.1007/s00101-014-2392-x
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DOI: https://doi.org/10.1007/s00101-014-2392-x