Mitochondrial Disease and Anesthesia

Hsieh, Vincent C.; Krane, Elliot J.; Morgan, Philip G.

doi:10.1177/2326409817707770

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Brasil

Journal of Inborn Errors of Metabolism and Screening

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Brasil

Español English

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Sumário

Review • J. inborn errors metab. screen. 5 • 2017 • https://doi.org/10.1177/2326409817707770 copy

Mitochondrial Disease and Anesthesia

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

It is increasingly common for children with mitochondrial disease to undergo surgery and anesthesia. Although many different anesthetics have been used successfully for these patients, serious, unexpected complications have occurred during and following anesthetic exposure. This has led to the widespread opinion among anesthesiologists that mitochondrial patients are at increased risk from the stress of surgery and anesthesia. Defects in function of the mitochondrial electron transport chain can lead to striking hypersensitivity to volatile anesthetics in children. Despite this striking finding, the connection between mitochondrial function and response to anesthetics is unknown. We review here the anesthetic considerations for patients with mitochondrial defects. In addition, we present an approach to anesthetic care of these patients at our institutions.

Keywords
anesthetics; genetics; biochemistry; mitochondria; perioperative

Medication		Mitochondrial Effects	References
Barbiturates		Complex I inhibition	³³33 Chance, B, Williams, GR, Hollunger, G. Inhibition of electron and energy transfer in mitochondria. I. Effects of Amytal, thiopental, rotenone, progesterone, and methylene glycol. J Biol Chem. 1963;238:418–431.
Etomidate		Complex I inhibition, mild inhibition complex III	³²32 Devin, A, Nogueira, V, Averet, N, Leverve, X, Rigoulet, M. Profound effects of the general anesthetic etomidate on oxidative phosphorylation without effects on their yield. J Bioenerg Biomembr. 2006;38(2):137–142.
Propofol		Acylcarnitine transferase, complexes I/II/IV inhibition	²⁵25 Wolf, A, Weir, P, Segar, P, Stone, J, Shield, J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet. 2001;357(9256):606–607.,³⁷37 Bergamini, C, Moruzzi, N, Volta, F. Role of mitochondrial complex I and protective effect of CoQ10 supplementation in propofol induced cytotoxicity. J Bioenerg Biomembr. 2016;48(4):413–423.,³⁸38 Wu, GJ, Tai, YT, Chen, TL, Lin, LL, Ueng, YF, Chen, RM. Propofol specifically inhibits mitochondrial membrane potential but not complex I NADH dehydrogenase activity, thus reducing cellular ATP biosynthesis and migration of macrophages. Ann N Y Acad Sci. 2005;1042:168–176.
Benzodiazepines		Complex I/M/IM inhibition	³⁴34 Colleoni, M, Costa, B, Gori, E, Santagostino, A. Biochemical characterization of the effects of the benzodiazepine, midazolam, on mitochondrial electron transfer. Pharmacol Toxicol. 1996;78(2):69–76.
Ketamine		Increase energy consumption +/− reports of complex I	³⁵35 Ito, H, Uchida, T, Makita, K. Ketamine causes mitochondrial dysfunction in human induced pluripotent stem cell-derived neurons. PLoS One. 2015;10(5):e0128445.,³⁶36 Venancio, C, Felix, L, Almeida, V. Acute ketamine impairs mitochondrial function and promotes superoxide dismutase activity in the rat brain. Anesth Analg. 2015;120(2):320–328.
Dexmedetomidine		None reported	None
Fentanyl/remifentanil		Minimal	³⁹39 Mastronicola, D, Arcuri, E, Arese, M. Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells. Cell Mol Life Sci. 2004;61(23):2991–2997.
Morphine		Mild complex I inhibition	³⁹39 Mastronicola, D, Arcuri, E, Arese, M. Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells. Cell Mol Life Sci. 2004;61(23):2991–2997.,⁴⁰40 Cunha-Oliveira, T, Silva, L, Silva, AM, Moreno, AJ, Oliveira, CR, Santos, MS. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria. Toxicol Lett. 2013;219(3):298–306.
Volatile Anesthetics		Complex I inhibition	²⁰20 Harris, RA., Munroe, J., Farmer, B., Kim, KC., Jenkins, P. Action of halothane upon mitochondrial respiration. Arch Biochem Biophys. 1971;142(2):435–444.,²¹21 Cohen, PJ . Effect of anesthetics on mitochondrial function. Anesthesiology. 1973;39(2):153–164.,²⁷27 Kayser, EB, Sedensky, MM, Morgan, PG, Hoppel, CL. Mitochondrial oxidative phosphorylation is defective in the long-lived mutant clk-1. J Biol Chem. 2004;279(52):54479–54486.
Bupivacaine		Acylcarnitine translocase	²⁴24 Weinberg, GL, Palmer, JW, VadeBoncouer, TR, Zuechner, MB, Edelman, G, Hoppel, CL. Bupivacaine inhibits acylcarnitine exchange in cardiac mitochondria. Anesthesiology. 2000;92(2):523–528.
	(Etidocaine)	Mild complex I

Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) Rua Ramiro Barcelos, 2350, CEP: 90035-903, Porto Alegre, RS - Brasil, Tel.: 55-51-3359-6338, Fax: 55-51-3359-8010 - Porto Alegre - RS - Brazil
E-mail: rgiugliani@hcpa.edu.br

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[1] Corresponding Author: Philip G. Morgan, Department of Anesthesiology and Perioperative Medicine, University of Washington, Seattle, WA, USA. Email: pgm4@uw.edu