Melatonin ameliorates the sleep disorder induced by surgery under sevoflurane anaesthesia in aged mice

Basic Clin Pharmacol Toxicol. 2021 Feb;128(2):256-267. doi: 10.1111/bcpt.13498. Epub 2020 Oct 16.

Abstract

Post-operative sleep disorders induce adverse effects on patients, especially the elderly, which may be associated with surgery and inhalational anaesthetics. Melatonin is a neuroendocrine regulator of the sleep-wake cycle. In this study, we analysed the alterations of post-operative sleep in aged melatonin-deficient (C57BL/6J) mice, and investigated if exogenous melatonin could facilitate entrainment of circadian rhythm after laparotomy under sevoflurane anaesthesia. The results showed that laparotomy under sevoflurane anaesthesia had a greater influence on post-operative sleep than sevoflurane alone. Laparotomy under anaesthesia led to circadian rhythm shifting forward, altered EEG power density and delta power of NREM sleep, and lengthened REM and NREM sleep latencies. In the light phase, the number of waking episodes tended to decline, and wake episode duration elevated. However, these indicators presented the opposite tendency during the dark phase. Melatonin showed significant efficacy for ameliorating the sleep disorder and restoring physiological sleep, and most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist.

Keywords: circadian rhythm; laparotomy; melatonin; sevoflurane; sleep.

MeSH terms

  • Activity Cycles / drug effects
  • Age Factors
  • Anesthetics, Inhalation / toxicity*
  • Animals
  • Circadian Rhythm / drug effects*
  • Electroencephalography
  • Electromyography
  • Female
  • Laparotomy / adverse effects*
  • Melatonin / deficiency
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Photoperiod
  • Postoperative Complications / etiology
  • Postoperative Complications / metabolism
  • Postoperative Complications / physiopathology
  • Postoperative Complications / prevention & control*
  • Sevoflurane / toxicity*
  • Sleep Aids, Pharmaceutical / pharmacology*
  • Sleep Stages / drug effects*
  • Sleep Wake Disorders / etiology
  • Sleep Wake Disorders / metabolism
  • Sleep Wake Disorders / physiopathology
  • Sleep Wake Disorders / prevention & control*
  • Sleep, REM / drug effects
  • Time Factors

Substances

  • Anesthetics, Inhalation
  • Sleep Aids, Pharmaceutical
  • Sevoflurane
  • Melatonin