Isoflurane Anesthesia Does Not Satisfy the Homeostatic Need for Rapid Eye Movement Sleep

Mashour, George A.; Lipinski, William J.; Matlen, Lisa; Walker, Amanda J.; Turner, Ashley M.; Schoen, Walter; Lee, UnCheol; Poe, Gina R.

doi:10.1213/ane.0b013e3181d3e861

Cited by 52 publications

(61 citation statements)

References 24 publications

(39 reference statements)

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“…21–24 This has led to the speculation that the brains of anesthetized subjects may be locked into a NREM-like state while being mutually excluded from accessing rapid eye movement (REM) sleep and wakefulness. 13,25 If true, then time spent in anesthesia might fulfill NREM sleep requirements, but one might expect a REM rebound upon termination of the anesthetic exposure as the homeostatic drive for REM sleep accrues. 26 …”

Section: Introductionmentioning

confidence: 99%

Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

et al. 2011

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Background General anesthesia has been likened to a state in which anesthetized subjects are locked out of access to both rapid eye movement (REM) sleep and wakefulness. Were this true for all anesthetics, one might expect a significant REM rebound following anesthetic exposure. However, for the intravenous anesthetic propofol, studies demonstrate that no sleep debt accrues. Moreover, pre-existing sleep debts dissipate during propofol anesthesia. To determine whether these effects are specific to propofol or are typical of volatile anesthetics we tested the hypothesis that REM sleep debt would accrue in rodents anesthetized with volatile anesthetics. Methods Electroencephalographic and electromyographic electrodes were implanted in 10 mice. After 9–11 days of recovery and habituation to a 12h:12h light:dark cycle, baseline states of wakefulness, non-rapid eye movement sleep, and REM sleep were recorded in mice exposed to 6 hours of an oxygen control and on separate days to 6 hours of isoflurane, sevoflurane, or halothane in oxygen. All exposures were conducted at the onset of light. Results Mice in all three anesthetized groups exhibited a significant doubling of REM sleep during the first six-hours of the dark phase of the circadian schedule while only mice exposed to halothane displayed a significant increase in non-rapid eye movement sleep that peaked at 152% of baseline. Conclusion REM sleep rebound following exposure to volatile anesthetics suggests that these volatile anesthetics do not fully substitute for natural sleep. This result contrasts with the published actions of propofol for which no REM sleep rebound occurred.

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Section: Introductionmentioning

confidence: 99%

Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

et al. 2011

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“…Indeed, as observed by Mashour and collaborators, 4h of isoflurane anaesthesia does not affect the REM sleep rebound after selective REM sleep deprivation for 24h [42]. Specifically, REM sleep was significantly increased in both groups subjected to SD interventions (SD.IS and SD_Sham groups,) suggesting, that the increases in the intensity of REM sleep, as well as the number of short REM sleep bouts, are related to the extent of sleep deprivation and represent a homeostatic recovery response [43].…”

Section: Discussionmentioning

confidence: 88%

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

et al. 2017

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Study ObjectivesSleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke.MethodsSprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.ResultsA reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.ConclusionsOur data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

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“…In contrast, saline-treated animals exhibited a significant increase in sleep (total sleep time, NREM and REM) in the day following cessation of anesthesia. Whereas propofol anesthesia appears to satisfy some sleep need 47 , accrual of sleep debt (specifically REM) is known to occur with the administration of isoflurane in rodents 48,49 . Although sleep deprivation was not a part of our study, the animals that received a single administration of flumazenil prior to emergence did not demonstrate the change in sleep patterns as the saline-treated animals.…”

Section: Discussionmentioning

confidence: 99%

Effects of γ-Aminobutyric Acid Type A Receptor Modulation by Flumazenil on Emergence from General Anesthesia

et al. 2016

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Background Transitions into conscious states are partially mediated by inactivation of sleep networks and activation of arousal networks. Pharmacologic hastening of emergence from general anesthesia has largely focused on activating subcortical monoaminergic networks, with little attention on antagonizing the γ-aminobutyric acid type A receptor (GABAAR). As the GABAAR mediates the clinical effects of many common general anesthetics, the authors hypothesized that negative GABAAR modulators would hasten emergence, possibly via cortical networks involved in sleep. Methods The authors investigated the capacity of the benzodiazepine rescue agent, flumazenil, which had been recently shown to promote wakefulness in hypersomnia patients, to alter emergence. Using an in vivo rodent model and an in vitro GABAAR heterologous expression system, they measured flumazenil’s effects on behavioral, neurophysiologic, and electrophysiologic correlates of emergence from isoflurane anesthesia. Results Animals administered intravenous flumazenil (0.4 mg/kg, n = 8) exhibited hastened emergence compared to saline-treated animals (n = 8) at cessation of isoflurane anesthesia. Wake-like electroencephalographic patterns occurred sooner and exhibited more high-frequency electroencephalography power after flumazenil administration (median latency ± median absolute deviation: 290 ± 34 s) compared to saline administration (473 ± 186 s; P = 0.042). Moreover, in flumazenil-treated animals, there was a decreased impact on postanesthesia sleep. In vitro experiments in human embryonic kidney-293T cells demonstrated that flumazenil inhibited isoflurane-mediated GABA current enhancement (n = 34 cells, 88.7 ± 2.42% potentiation at 3 μM). Moreover, flumazenil exhibited weak agonist activity on the GABAAR (n = 10 cells, 10.3 ± 3.96% peak GABA EC20 current at 1 μM). Conclusions Flumazenil can modulate emergence from isoflurane anesthesia. The authors highlight the complex role GABAARs play in mediating consciousness and provide mechanistic links between emergence from anesthesia and arousal.

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Isoflurane Anesthesia Does Not Satisfy the Homeostatic Need for Rapid Eye Movement Sleep

Cited by 52 publications

References 24 publications

Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

Effects of γ-Aminobutyric Acid Type A Receptor Modulation by Flumazenil on Emergence from General Anesthesia

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