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ANESTHETIC PHARMACOLOGY

Characterization of the Interactions Between Volatile Anesthetics and Neuromuscular Blockers at the Muscle Nicotinic Acetylcholine Receptor

Matthias Paul, MD DEAA^*, Ralf M. Fokt^*, Christoph H. Kindler, MD DEAA, Natalie C. J. Dipp, and C. Spencer Yost, MD^*

*Department of Anesthesia and Perioperative Care, University of California, San Francisco; Department of Anesthesia, Kantonsspital, Basel, Switzerland; and University of Cologne, Germany

Address correspondence and reprint requests to C. Spencer Yost, MD, Department of Anesthesia and Perioperative Care, University of California, 513 Parnassus Ave., Box 0542, San Francisco, CA 94143-0542. Address e-mail to spyost{at}itsa.ucsf.edu

Volatile anesthetics enhance the neuromuscular blockade produced by nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a postulated site of this interaction. We tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptor. The adult mouse muscle nicotinic acetylcholine receptor (₂, ß, , ) was heterologously expressed in Xenopus laevis oocytes. Concentration-effect curves for the inhibition of acetylcholine-induced currents were established for vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the volatile anesthetics at a concentration equivalent to half the concentration producing a 50% inhibition alone. All individually tested compounds produced rapid and readily reversible concentration-dependent inhibition. The calculated 50% inhibitory concentration values were 9.9 nM (95% confidence interval [CI], 8.4–11.4 nM), 43.4 nM (95% CI, 33.6–53.3 nM), 897 µM (95% CI, 699–1150 µM), and 818 µM (95% CI, 685–1001 µM) for vecuronium, d-tubocurarine, isoflurane, and sevoflurane, respectively. Coapplication of either isoflurane or sevoflurane significantly enhanced the inhibitory effects of vecuronium and d-tubocurarine, especially so at small concentrations of NDMRs. Volatile anesthetics increase the potency of NDMRs, possibly by enhancing antagonist affinity at the receptor site. This effect may contribute to the clinically observable enhancement of neuromuscular blockade by volatile anesthetics.

IMPLICATIONS: Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors.

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