Isoflurane anesthesia does not satisfy the homeostatic need for rapid eye movement sleep

Abstract

Background: Sleep and general anesthesia are distinct states of consciousness that share many traits. Prior studies suggest that propofol anesthesia facilitates recovery from rapid eye movement (REM) and non-REM (NREM) sleep deprivation, but the effects of inhaled anesthetics have not yet been studied. We tested the hypothesis that isoflurane anesthesia would also facilitate recovery from REM sleep deprivation.

Methods: Six rats were implanted with superficial cortical, deep hippocampal, and nuchal muscle electrodes. Animals were deprived of REM sleep for 24 hours and then (1) allowed to sleep ad libitum for 8 hours or (2) were immediately anesthetized with isoflurane for a 4-hour period followed by ad libitum sleep for 4 hours. The percentage of REM and NREM sleep after the protocols was compared with similar conditions without sleep deprivation. Hippocampal activity during isoflurane anesthesia was also compared with activity during REM sleep and active waking.

Results: Recovery after deprivation was associated with a 5.7-fold increase (P = 0.0005) in REM sleep in the first 2 hours and a 2.6-fold increase (P = 0.004) in the following 2 hours. Animals that underwent isoflurane anesthesia after deprivation demonstrated a 3.6-fold increase (P = 0.001) in REM sleep in the first 2 hours of recovery and a 2.2-fold increase (P = 0.003) in the second 2 hours. There were no significant differences in REM sleep rebound between the first 4 hours after deprivation and the first 4 hours after both deprivation and isoflurane anesthesia. Hippocampal activity during isoflurane anesthesia was not affected by REM sleep deprivation, and the probability distribution of events during anesthesia was more similar to that of waking than to REM sleep.

Conclusion: Unlike propofol, isoflurane does not satisfy the homeostatic need for REM sleep. Furthermore, the regulation and organization of hippocampal events during anesthesia are unlike sleep. We conclude that different anesthetics have distinct interfaces with sleep.

Figure 1

Schematic of rapid eye movement (REM) deprivation experiments.

Figure 2

Confirmation of electrode placement in the hippocampus and θ activity during rapid eye movement (REM) sleep. A, Electrode in the left dorsal hippocampus. B, Top row of signals, electromyography; lower row, hippocampal electroencephalography.

Figure 3

Rapid eye movement (REM) sleep rebound in the first 4 hours of natural recovery and in the first 4 hours postisoflurane. If isoflurane anesthesia satisfied the homeostatic need for sleep, we would expect no sleep rebound phenomenon in hours 4 to 8. Instead (bottom panel), the observed REM sleep rebound after isoflurane suggests that recovery from deprivation had not occurred during the anesthetic. Mean ± SE shown; * P < 0.05

Figure 4

Behavior of hippocampal θ activity during rapid eye movement (REM) sleep, active waking, and isoflurane anesthesia. A, The percentage of hippocampal θ-dominant epochs during isoflurane anesthesia was not changed by REM sleep deprivation. B, Spectral analysis of active waking, REM sleep, and θ-dominant isoflurane (iso) anesthesia: a 1-way analysis of variance indicates that θ frequency during the anesthetized state is significantly lower, which is consistent with previous studies of isoflurane. C, The cumulative probability distributions of the normalized hippocampal θ duration data are presented in semilogarithmic and double logarithmic (inset) scales. The power law fitting for the data of the waking state (square) and anesthesia (circle), as well as the exponential fitting for the sleep data (triangle), are denoted with dotted lines.