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CRITICAL CARE AND TRAUMA

Sepsis Stage Dependently and Differentially Attenuates the Effects of Nondepolarizing Neuromuscular Blockers on the Rat Diaphragm In Vitro

Eichi Narimatsu, MD, PhD^*, Tomohisa Niiya, MD^*, Mikito Kawamata, MD, PhD^*, and Akiyoshi Namiki, MD, PhD^*

Departments of *Anesthesiology and Critical Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

Address correspondence and reprint requests to Eichi Narimatsu, MD, PhD, Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. Address e-mail to enarimat{at}sapmed.ac.jp.

We investigated the effects of early and late sepsis on the actions of nondepolarizing neuromuscular blockers by using a rat sepsis model induced by cecal ligation and puncture. Isometric twitch tensions of nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Rocuronium, pancuronium, and d-tubocurarine dose-dependently decreased the twitch tensions of the nonseptic, early septic, and late septic diaphragms (P < 0.01 each by analysis of variance [ANOVA]). Late sepsis shifted the concentration-twitch tension curves rightward from those of nonsepsis to larger degrees than did early sepsis, as indicated by increases in 50% inhibitory concentration (IC₅₀) values (P < 0.01 each by ANOVA and P < 0.01 or 0.05 by the Scheffé F test). The standardized rightward shifts in early and late sepsis were largest for pancuronium, second largest for rocuronium, and smallest for d-tubocurarine (5.741, 2.979, and 1.660 times in late sepsis, respectively; P < 0.01 each by ANOVA and the Scheffé F test). Sepsis-induced increases in IC₅₀ values did not accompany the decreases in slopes. The results indicate that sepsis induces hyposensitivities to nondepolarizing neuromuscular blockers, the degree of which depends on the stage of sepsis and on the kind of neuromuscular blocker.