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25.06.2018 | Original Article

Myotoxicity of local anesthetics is equivalent in individuals with and without predisposition to malignant hyperthermia

verfasst von: Sachiko Otsuki, Toshimichi Yasuda, Keiko Mukaida, Yuko Noda, Rieko Kanzaki, Hirotsugu Miyoshi, Takashi Kondo, Hiroshi Hamada, Masashi Kawamoto

Erschienen in: Journal of Anesthesia | Ausgabe 4/2018

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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.

Halsall PJ, Ellis FR. Malignant hyperthermia. Anaesth Intensive Care. 2005;14:192–4.CrossRef

Schneiderbanger D, Johannsen S, Roewer N, Schuster F. Management of malignant hyperthermia: diagnosis and treatment. Ther Clin Risk Manag. 2014;10:355–62.PubMedPubMedCentral

Zink W, Bohl JRE, Hacke N, Sinner B, Martin E, Graf BM. The long term myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blocks. Anesth Analg. 2005;101:548–54.CrossRefPubMed

Neal JM, Salinas FV, Choi DS. Local anesthetic-induced myotoxicity after continuous adductor canal block. Reg Anesth Pain Med. 2016;41:723–7.CrossRefPubMed

Benoit PW, Yagiela A, Fort NF. Pharmacologic correlation between local anesthetic-induced myotoxicity and disturbances of intracellular calcium distribution. Toxicol Appl Pharmacol. 1980;52:187–98.CrossRefPubMed

Plank C, Hofmann P, Gruber M, Bollwein G, Graf BM, Zink W, et al. Modification of bupivacaine-induced myotoxicity with dantrolene and caffeine in vitro. Anesth Analg. 2016;122:418–23.CrossRefPubMed

Harrison GG, Morrell DF. Response of mhs swine to i.v. infusion of lignocaine and bupivacaine. Br J Anaesth. 1980;52:385–7.CrossRefPubMed

Wingard DW, Bobko S. Failure of lidocaine to trigger porcine malignant hyperthermia. Anesth Analg. 1979;58:99–103.CrossRefPubMed

Ibarra MCA, Ichihara Y, Hikita M, Yoshida K, Junji S, Maehara Y, et al. Effect of bupivacaine enantiomers on Ca²⁺ release from sarcoplasmic reticulum in skeletal muscle. Eur J Pharmacol. 2005;512:77–83.CrossRef

10.

Maemura Y. Effect of ropivacaine on Ca function of skinned skeletal muscle. Masui. 2002;51:19–24.PubMed

11.

Endo M, Iino M. Measurement of Ca2 + release in skinned fibers from skeletal muscle. Methods Enzymol. 1988;157:12–26.CrossRefPubMed

12.

Ohta T, Endo M, Nakano T, Morohoshi Y, Wanikawa K, Ohga A. Ca-induced Ca release in malignant hyperthermia-susceptible pig skeletal muscle. Am J Physiol. 1989;256:C358–67.CrossRefPubMed

13.

Oku S, Mukaida K, Nosaka S, Sai Y, Maehara Y, Yuge O. Comparison of the in vitro caffeine-halothane contracture test with the Ca-induced Ca release rate test in patients suspected of having malignant hyperthermia susceptibility. J Anesth. 2000;14:6–13.CrossRefPubMed

14.

Kobayashi M, Mukaida K, Migita T, Hamada H, Kawamoto M, Yuge O. Analysis of human cultured myotubes responses mediated by ryanodine receptor 1. Anaesth Intensive Care. 2011;39:252–61.PubMed

15.

Hofmann P, Metterlein T, Bollwein G, Gruber M, Plank C, Graf BM, et al. The myotoxic effect of bupivacaine and ropivacaine on myotubes in primary mouse cell culture and an immortalized cell line. Anesth Analg. 2013;117:634–40.CrossRefPubMed

16.

Zink W, Seif C, Bohl JRE, Hacke N, Braun PM, Sinner B, et al. The acute myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blockades. Anesth Analg. 2003;97:1173–9 (table of contents).CrossRefPubMed

17.

Zhang C, Phamonvaechavan P, Rajan A, Poon DY, Topcu-Yilmaz P, Guyton DL. Concentration-dependent bupivacaine myotoxicity in rabbit extraocular muscle. J AAPOS. 2010;14:323–7.CrossRefPubMed

18.

Benoit PW, Belt WD. Destruction and regeneration of skeletal muscle after treatment with a local anaesthetic, bupivacaine (Marcaine). J Anat. 1970;107:547–56.PubMedPubMedCentral

19.

McLoon LK, Nguyen LT, Wirtschafter J. Time course of the regenerative response in bupivacaine injured orbicularis oculi muscle. Cell Tissue Res. 1998;294:439–47.CrossRefPubMed

20.

Zink W, Graf BM. Local anesthetic myotoxicity. Reg Anesth Pain Med.;29:333–40.

21.

Melzer W, Herrmann-Frank A, Lüttgau HC. The role of Ca²⁺ ions in excitation-contraction coupling of skeletal muscle fibres. Biochim Biophys Acta. 1995;1241:59–116.CrossRefPubMed

22.

Schiemann AH, Stowell KM. Comparison of pathogenicity prediction tools on missense variants in RYR1 and CACNA1S associated with malignant hyperthermia. Br J Anaesth. 2016;117:124–8.CrossRefPubMedPubMedCentral

23.

Shoshan-Barmatz V, Zchut S. The interaction of local anesthetics with the ryanodine receptor of the sarcoplasmic reticulum. J Membr Biol. 1993;133:171–81.CrossRefPubMed

24.

Hyvelin JM, Martin C, Roux E, Marthan R, Savineau JP. Human isolated bronchial smooth muscle contains functional ryanodine/caffeine-sensitive Ca-release channels. Am J Respir Crit Care Med. 2000;162:687–94.CrossRefPubMed

25.

Gordienko DV, Harhun MI, Kustov MV, Pucovský V, Bolton TB. Sub-plasmalemmal [Ca²⁺]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca²⁺ release induced by voltage-gated Ca²⁺ entry. Cell Calcium. 2008;43:122–41.CrossRefPubMedPubMedCentral

26.

Prakriya M, Lewis RS. Store-operated calcium channels. Physiol Rev. 2015;95:1383–436.CrossRefPubMedPubMedCentral

27.

Franco-Obregón A, Lansman JB. Changes in mechanosensitive channel gating following mechanical stimulation in skeletal muscle myotubes from the mdx mouse. J Physiol. 2002;539:391–407.CrossRefPubMedPubMedCentral

28.

Riazi S, Kraeva N, Muldoon SM, Dowling J, Ho C, Petre M-A, et al. Malignant hyperthermia and the clinical significance of type-1 ryanodine receptor gene (RYR1) variants: proceedings of the 2013 MHAUS Scientific Conference. Can J Anesth. 2014;61:1040–9.CrossRefPubMed

29.

Hopkins PM, Rüffert H, Snoeck MM, Girard T, Glahn KPE, Ellis FR, et al. European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility. Br J Anaesth. 2015;115:531–9.CrossRefPubMed

30.

Wehner M, Rueffert H, Koenig F, Meinecke CD, Olthoff D. The Ile2453Thr mutation in the ryanodine receptor gene 1 is associated with facilitated calcium release from sarcoplasmic reticulum by 4-chloro-m-cresol in human myotubes. Cell Calcium. 2003;34:163–8.CrossRefPubMed

Titel: Myotoxicity of local anesthetics is equivalent in individuals with and without predisposition to malignant hyperthermia
verfasst von: Sachiko Otsuki
Toshimichi Yasuda
Keiko Mukaida
Yuko Noda
Rieko Kanzaki
Hirotsugu Miyoshi
Takashi Kondo
Hiroshi Hamada
Masashi Kawamoto
Publikationsdatum: 25.06.2018
Verlag: Springer Japan
Erschienen in: Journal of Anesthesia / Ausgabe 4/2018
Print ISSN: 0913-8668
Elektronische ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-018-2526-4

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Myotoxicity of local anesthetics is equivalent in individuals with and without predisposition to malignant hyperthermia