Disruption of Rapid Eye Movement Sleep Homeostasis in Adolescent Rats after Neonatal Anesthesia

Anesthesiology. 2019 Jun;130(6):981-994. doi: 10.1097/ALN.0000000000002660.

Abstract

Background: Previous studies suggest that rapid eye movement sleep rebound and disruption of rapid eye movement sleep architecture occur during the first 24 h after general anesthesia with volatile anesthetics in adult rats. However, it is unknown whether rapid eye movement sleep alterations persist beyond the anesthetic recovery phase in neonatal rats. This study tested the hypothesis that rapid eye movement sleep disturbances would be present in adolescent rats treated with anesthesia on postnatal day 7.

Methods: Forty-four neonatal rats were randomly allocated to treatment with anesthesia consisting of midazolam, nitrous oxide, and isoflurane or control conditions for 2 h or 6 h. Electroencephalographic and electromyographic electrodes were implanted and recordings obtained between postnatal days 26 and 34. The primary outcome was time spent in rapid eye movement sleep. Data were analyzed using two-tailed unpaired t tests and two-way repeated measures analysis of variance.

Results: Rats treated with midazolam, nitrous oxide, and isoflurane exhibited a significant increase in rapid eye movement sleep three weeks later when compared with control rats, regardless of whether they were treated for 2 h (174.0 ± 7.2 min in anesthetized, 108.6 ± 5.3 in controls, P < 0.0001) or 6 h (151.6 ± 9.9 min in anesthetized, 108.8 ± 7.1 in controls, P = 0.002).

Conclusions: Treatment with midazolam, nitrous oxide, and isoflurane on postnatal day 7 increases rapid eye movement sleep three weeks later in rats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia, General / adverse effects
  • Anesthesia, General / trends*
  • Anesthetics, Inhalation / administration & dosage*
  • Anesthetics, Inhalation / adverse effects
  • Anesthetics, Intravenous / administration & dosage*
  • Anesthetics, Intravenous / adverse effects
  • Animals
  • Animals, Newborn
  • Electroencephalography / drug effects
  • Electroencephalography / methods
  • Female
  • Homeostasis / drug effects*
  • Homeostasis / physiology
  • Isoflurane / administration & dosage
  • Isoflurane / adverse effects
  • Male
  • Midazolam / administration & dosage
  • Midazolam / adverse effects
  • Nitrous Oxide / administration & dosage
  • Nitrous Oxide / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Sleep, REM / drug effects*
  • Sleep, REM / physiology

Substances

  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Isoflurane
  • Nitrous Oxide
  • Midazolam