[The action of ketamine on muscle contractile behavior. In vitro studies on the musculature of subjects susceptible to malignant hyperthermia].
Since ketamine has been incriminated as triggering malignant hyperthermia (MH) [3, 9, 13, 14, 18], but has still been used uneventfully in MH susceptible patients, we performed an in vitro study to examine the safety of ketamine for use in human MH. METHODS. Muscle specimens of 20 patients who had muscle biopsies to diagnose MH were investigated. In every patient diagnostic contracture tests (2 halothane (Hal) and 2 caffeine (Caf) were done according to the protocol established by the European MH group (EMHG). In addition, one test unit for investigating the effect of stepwise increased bath-concentrations of ketamine (5, 10, 20, 60, 120, 240 and 960 mumol/l) and a further one serving as control (no drugs added to the bath) were used. Combined Hal (2 vol%) and Ket (960 mumol/l) tests were performed in 9 patients (4 MHS, 4 MHN, 1 MHEh). Changes in baseline contractures and mechanical twitch tension were evaluated. RESULTS. The diagnostic test showed MHS in 8, MHN in 8 and MHEh in 4 patients. Ketamine did not induce baseline contractures in any of the tests performed. Contractures induced by 2 vol% of halothane in 4 MHS muscles did not change significantly when ketamine was added to the bath (concentration 960 mumol/l). A significant, dose-related decrease in mechanical twitch tension occurred, when ketamine was added to the test. At the highest concentration (960 mumol) twitch tension was reduced by 55%. Twitch tension remained stable in untreated muscles. No significant differences were found between the specimens from MHS, MHN and MHE patients. This reduction in twitch tension was more pronounced in specimens exposed to both halothane (2 vol%) and ketamine (960 mumol/l), resulting in an average decrease of 71%. CONCLUSION. In accordance with Fletcher et al., our results indicate that ketamine - at least in vitro - does not trigger MH. In MHS muscles, ketamine does not augment halothane-induced baseline contractures. The ketamine-induced reduction of mechanical twitch tension in directly stimulated human muscles has not been described before. Analogous findings in frog sartorius muscles can be found in the literature. Whereas the effect of ketamine on indirectly stimulated muscle has been investigated by several authors, the underlying mechanism of ketamine-induced twitch suppression in directly stimulated muscles is not known. Inhibition of calcium release from or accelerated uptake into the sarcoplasmatic reticulum have been reported.
Hackl
W
W
L. Boltzmann Institut für Experimentelle Anaesthesie und Intensivmedizinische Forschung, Universität Wien.
Winkler
M
M
Mauritz
W
W
Steinbereithner
K
K
D002110:Caffeine; D004198:Disease Susceptibility; D006221:Halothane; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*
D002110:Caffeine; D007649:Ketamine; D006221:Halothane
Die Wirkung von Ketamin auf das muskuläre Kontraktionsverhalten. In vitro Studien an der Muskulatur von Anlageträgern der Malignen Hyperthermie (MH).