Effect of hypothermia on the action of sugammadex in a rat phrenic nerve-hemidiaphragm preparation

Abstract

Introduction: Anesthesiologists are often faced with the condition to use a neuromuscular blocking agent and the reversal agent in patients under hypothermia. It was shown that hypothermia affected the muscle contraction and response to neuromuscular blocking agents. However, little is known about the effect of hypothermia on the antagonism of muscle relaxation by sugammadex. Therefore, we aimed to evaluate the impact of hypothermia on the action of sugammadex.

Methods: Phrenic nerve-hemidiaphragm preparations of rats were randomly allocated into four groups; group 1, 36°C (normothermia); Group 2, 24°C (deep hypothermia); Group 3, 28°C (moderate hypothermia); and Group 4, 32°C (mild hypothermia) (according to the Swiss classification). Rocuronium was administered cumulatively until the complete blockade of first twitch (T1) of train-of-four (TOF). After 10 min, rocuronium-equimolar dose of sugammadex was administered. The recovery of T1 height and TOF ratio and recovery index were evaluated.

Results: A total of 40 phrenic nerve-hemidiaphragm preparations were included in the analysis. Dose-response curve of rocuronium showed significant difference among the four groups (p < 0.001). Rocuronium was potentiated in group 2 compared group 3 and group 4 (all p < 0.001). The recovery of T1 height demonstrated that there was delay in group 2 and group 3 compared with group 1 (all p < 0.001). Additionally, the recovery of TOF ratio also showed delay in group 2 and group 3 (all p < 0.001). Analysis of the recovery index identified significant delay of reversal effect of sugammadex in group 2 and group 3 compared to group 1 (p = 0.005 and 0.028, respectively).

Conclusion: In this in vitro study, muscle relaxation induced by rocuronium was potentiated in deep hypothermic condition. The reversal effect by sugammadex was reduced under moderate and deep hypothermia. However, mild hypothermia had no significant effect on the action of sugammadex.