Pancuronium enhances isoflurane anesthesia in rats via inhibition of cerebral nicotinic acetylcholine receptors

Abstract

Purpose

This study was conducted to elucidate the mechanism of enhancement of volatile anesthetics by neuromuscular blocking agents in rats and to consider the relevance of this enhancement to clinical anesthesia.

Methods

Male Sprague–Dawley rats were used. After confirming a movement in response to tail clamping under 1.1 % isoflurane anesthesia, response was determined when the tail clamp was applied at several points after microinjection of pancuronium into the lateral ventricle. Arousal responses to microinjection of nicotine into the lateral ventricle were assessed with or without pretreatment with intraventricular pancuronium. The intravenous 50 % effective dose (ED50) and 95 % effective dose (ED95) for neuromuscular blockade with pancuronium administered in a cumulative fashion at 1.1 % isoflurane were calculated.

Results

Intraventricular pancuronium dose-dependently reduced the response to tail clamping, and the dose required to show immobilization of 50 % of rats (intraventricular ED50) was 1.62 µg/kg. Pretreatment with pancuronium at 6 µg/kg significantly reduced the effect of awakening by nicotine under isoflurane anesthesia (P = 0.044). The intravenous ED50 and ED95 for neuromuscular blockade were 63 µg/kg (90 % confidence interval [CI] 52–75 µg/kg) and 133 µg/kg (90 % CI 109–158 µg/kg), respectively. The ratio of intraventricular ED50 to intravenous ED50 was 0.026.

Conclusion

Pancuronium microinjection into the lateral ventricle dose-dependently enhances the depth of isoflurane anesthesia, which might be caused by inhibition of neuronal nicotinic acetylcholine receptor transmission in the cerebrum. Intravenous injection of pancuronium at high doses might increase the cerebrospinal concentration to a level at which an effect can be observed.

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Authors

Corresponding author

Correspondence to Hiroshi Sunaga.

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Conflict of interest

Yusuke Miyazaki, Hiroshi Sunaga, Shotaro Hobo, and Kazuko Miyano have no conflicts to disclose. Shoichi Uezono is a paid consultant of Edwards Lifesciences, Corp.

Funding

This work was funded by MEXT KAKENHI Grant No. 24592317 and the Department of Anesthesiology, Jikei University School of Medicine.

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Miyazaki, Y., Sunaga, H., Hobo, S. et al. Pancuronium enhances isoflurane anesthesia in rats via inhibition of cerebral nicotinic acetylcholine receptors. J Anesth 30, 671–676 (2016). https://doi.org/10.1007/s00540-016-2178-1

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Keywords

  • Pancuronium
  • Central nervous system
  • Isoflurane
  • Rat
  • Acetylcholine receptor