Half of the family members of critically ill patients experience excessive daytime sleepiness.

BACKGROUND: Sleepiness and fatigue are commonly reported by family members of intensive care unit (ICU) patients. Sleep deprivation may result in cognitive deficits. Sleep deprivation and cognitive blunting have not been quantitatively assessed in this population. We sought to determine the proportion of family members of ICU patients that experience excessive daytime sleepiness, sleep-associated functional impairment, and cognitive blunting. METHODS: Multicenter, cross-sectional survey of family members of patients admitted to ICUs at the University of Maryland Medical Center, Johns Hopkins University Hospital, and Christiana Hospital. Family members of ICU patients were evaluated using the Epworth Sleepiness Scale, a validated survey assessing sleepiness in everyday situations (normal, less than 10); the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), a questionnaire quantifying the impact of sleepiness on daily activities (normal, at least 17.9); and psychomotor vigilance testing, a test of cognitive function, in relation to sleep deprivation (normal mean reaction time less than 500 ms). RESULTS: A total of 225 family members were assessed. Of these, 50.2 % (113/225) had Epworth scores consistent with excessive daytime sleepiness. Those with sleepiness experienced greater impairment in performing daily activities by FOSQ-10 (15.6 ± 3.0 vs 17.4 ± 2.2, p < 0.001). Cognitive blunting was found in 13.3 % (30/225) of family members and 15.1 % (14/93) of surrogate decision-makers. Similar rates of cognitive blunting as reported by mean reaction time of at least 500 ms were found among family members whether or not they reported sleepiness (15.0 % (17/113) vs. 11.6 % (13/112), p = 0.45). CONCLUSIONS: Half of the family members of ICU patients suffer from excessive daytime sleepiness. This sleepiness is associated with functional impairment, but not cognitive blunting.

Genetic and anatomical basis of the barrier separating wakefulness and anesthetic-induced unresponsiveness.

A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states.

Rapid eye movement sleep debt accrues in mice exposed to volatile anesthetics.

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, a significant REM rebound after anesthetic exposure might be expected. However, for the intravenous anesthetic propofol, studies demonstrate that no sleep debt accrues. Moreover, preexisting sleep debts dissipate during propofol anesthesia. To determine whether these effects are specific to propofol or are typical of volatile anesthetics, the authors 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 12 h:12 h light-dark cycle, baseline states of wakefulness, nonrapid eye movement sleep, and REM sleep were recorded in mice exposed to 6 h of an oxygen control and on separate days to 6 h 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 6 h of the dark phase of the circadian schedule, whereas only mice exposed to halothane displayed a significant increase in nonrapid eye movement sleep that peaked at 152% of baseline. CONCLUSION: REM sleep rebound after 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.

A conserved behavioral state barrier impedes transitions between anesthetic-induced unconsciousness and wakefulness: evidence for neural inertia.

One major unanswered question in neuroscience is how the brain transitions between conscious and unconscious states. General anesthetics offer a controllable means to study these transitions. Induction of anesthesia is commonly attributed to drug-induced global modulation of neuronal function, while emergence from anesthesia has been thought to occur passively, paralleling elimination of the anesthetic from its sites in the central nervous system (CNS). If this were true, then CNS anesthetic concentrations on induction and emergence would be indistinguishable. By generating anesthetic dose-response data in both insects and mammals, we demonstrate that the forward and reverse paths through which anesthetic-induced unconsciousness arises and dissipates are not identical. Instead they exhibit hysteresis that is not fully explained by pharmacokinetics as previously thought. Single gene mutations that affect sleep-wake states are shown to collapse or widen anesthetic hysteresis without obvious confounding effects on volatile anesthetic uptake, distribution, or metabolism. We propose a fundamental and biologically conserved concept of neural inertia, a tendency of the CNS to resist behavioral state transitions between conscious and unconscious states. We demonstrate that such a barrier separates wakeful and anesthetized states for multiple anesthetics in both flies and mice, and argue that it contributes to the hysteresis observed when the brain transitions between conscious and unconscious states.