Sachiko Otsuki1, Toshimichi Yasuda2, Keiko Mukaida3, Yuko Noda4, Rieko Kanzaki4, Hirotsugu Miyoshi4, Takashi Kondo4, Hiroshi Hamada2, Masashi Kawamoto2. 1. Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. sachi85@hiroshima-u.ac.jp. 2. Department of Anesthesiology and Critical Care, Graduate School of Biomedical Sciences, Hirohima University, Hiroshima, Japan. 3. Department of Anesthesiology, Hiroshima Prefectural Rehabilitation Center, Higashi-hiroshima, Japan. 4. Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Abstract
PURPOSE: Malignant hyperthermia (MH) is an inherited muscle disorder caused by abnormal elevations of intracellular calcium (Ca2+) in skeletal muscle. There are several reports of myotoxicity caused by local anesthetics, and the increased intracellular Ca2+ is considered to be an important cause. However, there is insufficient evidence regarding myotoxicity in MH-susceptible individuals when large doses of local anesthetics are administered. This study investigated the effect of MH predisposition on myotoxicity. METHODS: Human skeletal muscle samples were obtained from 22 individuals to determine susceptibility to MH, and were evaluated according to whether their Ca2+-induced Ca2+ release (CICR) rates were accelerated or not. This study was performed using surplus muscle that remained after the CICR rate test. We calculated the 50% effective concentration (EC50) values of three local anesthetics, namely lidocaine, levobupivacaine, and ropivacaine using the ratiometric dye Fura-2 AM. Significance was tested using the unpaired t test. RESULTS: In the accelerated and unaccelerated groups, respectively, the mean ± SD of the EC50 values were 1.52 ± 0.72 and 1.75 ± 0.37 mM for lidocaine (p = 0.42), 0.72 ± 0.36 and 0.79 ± 0.46 mM for levobupivacaine (p = 0.68), and 1.21 ± 0.35 and 1.62 ± 0.57 mM for ropivacaine (p = 0.06). These values were similar in individuals with and without MH predisposition. CONCLUSION: The myotoxicity of local anesthetics was equivalent in individuals with and without predisposition to MH.
PURPOSE:Malignant hyperthermia (MH) is an inherited muscle disorder caused by abnormal elevations of intracellular calcium (Ca2+) in skeletal muscle. There are several reports of myotoxicity caused by local anesthetics, and the increased intracellular Ca2+ is considered to be an important cause. However, there is insufficient evidence regarding myotoxicity in MH-susceptible individuals when large doses of local anesthetics are administered. This study investigated the effect of MH predisposition on myotoxicity. METHODS:Human skeletal muscle samples were obtained from 22 individuals to determine susceptibility to MH, and were evaluated according to whether their Ca2+-induced Ca2+ release (CICR) rates were accelerated or not. This study was performed using surplus muscle that remained after the CICR rate test. We calculated the 50% effective concentration (EC50) values of three local anesthetics, namely lidocaine, levobupivacaine, and ropivacaine using the ratiometric dye Fura-2 AM. Significance was tested using the unpaired t test. RESULTS: In the accelerated and unaccelerated groups, respectively, the mean ± SD of the EC50 values were 1.52 ± 0.72 and 1.75 ± 0.37 mM for lidocaine (p = 0.42), 0.72 ± 0.36 and 0.79 ± 0.46 mM for levobupivacaine (p = 0.68), and 1.21 ± 0.35 and 1.62 ± 0.57 mM for ropivacaine (p = 0.06). These values were similar in individuals with and without MH predisposition. CONCLUSION: The myotoxicity of local anesthetics was equivalent in individuals with and without predisposition to MH.
Entities:
Keywords:
Local anesthetics; Malignant hyperthermia; Myotoxicity
Authors: Wolfgang Zink; Christoph Seif; Jürgen R E Bohl; Nicola Hacke; Peter M Braun; Barbara Sinner; Eike Martin; Rainer H A Fink; Bernhard M Graf Journal: Anesth Analg Date: 2003-10 Impact factor: 5.108
Authors: Petra Hofmann; Thomas Metterlein; Gabriele Bollwein; Michael Gruber; Christoph Plank; Bernhard M Graf; Wolfgang Zink Journal: Anesth Analg Date: 2013-07-18 Impact factor: 5.108