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Microinjection of a wide range of sedative agents, including triazolam, pentobarbital, ethanol and adenosine, into the medial preoptic area has been shown to increase sleep, suggesting that it is an important (though not necessarily the only) anatomic site mediating hypnotic effects of these compounds. The mechanism by which adenosine increases sleep at this site is not clear, but one possibility is that this is related to its effects on the GABA(A)-benzodiazepine receptor complex. In order to assess this possibility, this paper describes the administration of adenosine, alone and in combination with the benzodiazepine receptor blocker flumazenil, into the MPA. It was found that 12.5 and 25 nM of adenosine significantly reduced sleep latency and increased total sleep time. The sleep-inducing effect was blocked by flumazenil. Flumazenil caused a modest increase in total sleep, and prevented the increase in total sleep induced by the higher dose of adenosine. These data suggest that at least one aspect of the hypnotic properties of adenosine is mediated by a direct or indirect action on the GABA(A)-benzodiazepine receptor complex.

A 15-year-old female presented to the emergency department with complaints of vaginal bleeding. She was pale, anxious, cool and clammy with tachycardic, thready peripheral pulses and hemoglobin of 2.4g/dL. Her abdomen was gravid appearing, approximately early to mid-second trimester in size. Pelvic examination revealed 2 cm open cervical os with spontaneous discharge of blood, clots and a copious amount of champagne-colored grapelike spongy material. After 2L boluses of normal saline and two units of crossmatched blood, patient was transported to the operating room. Surgical pathology confirmed a complete hydatidiform mole.

Background Sleep and anesthesia differ physiologically but produce a similar loss of responsiveness to environmental stimuli. Recent data suggest that neuronal networks active in naturally occurring sleep also play a role in the anesthetized state. Changes in the propensity to sleep may then modify the response to anesthetic agents. The authors tested the hypothesis that sleep-deprived rats would require less anesthetic than rested rats to achieve a similar loss of responsiveness. Methods Rats were subjected to a 24-h period of either sleep deprivation or ad libitum activity. Sleep deprivation was produced by placing rats on a disk that rotated when sleep was detected by electroencephalographic and electromyographic (EEG, EMG) monitoring. A fixed dose of anesthetic agent was then administered, and the time required to induce loss of righting reflex was measured. Anesthetic administration was then stopped, and the time to recovery measured. All rats received both treatments separated by 7 days. Results Sleep deprivation reduced the time to loss of righting reflex by 40% for propofol (P < 0.025) and 55% for isoflurane (P < 0.025) and prolonged the time to recovery. In a separate control experiment, exposure to the deprivation environment but with disk rotation modified to allow adequate sleep did not affect the response to anesthetic administration. Conclusions Sleep deprivation significantly potentiated the ability of inhaled and intravenous anesthetic agents to induce a loss of righting reflex. These results support the hypothesis that neuronal networks active in sleep are also involved in the anesthetized state and suggest that sleep deprivation may partly explain the variability in patient response to anesthesia.

Recent introduction of the intravenous anesthetic propofol as an ICU sedative has allowed a deeply sedated state to be maintained for extended periods in the ICU without delays in emergence. Although such sedation has been advocated to promote physiologic sleep, little evidence exists to support such a strategy. To explore propofol's effect on sleep regulation, we administered propofol directly into the medial preoptic area (MPA) of the rat, an anatomic site where administration of other sedatives (triazolam and phenobarbital) also induce sleep. We performed three two-hour sleep studies in the daytime with the lights on following the administration of propofol (8 ng or 40 ng) or vehicle (intralipid). The higher dose of propofol significantly reduced sleep latency and increased nonREM and total sleep times when compared to vehicle. REM sleep times, intermittent waking times and number of transitions were not altered. Mean nonREM sleep bout length was increased significantly at the higher dose. These findings suggest that propofol may enhance sleep by acting at a hypothalamic site.

The intravenous anesthetic, propofol, has been shown to increase sleep when microinjected into the medial preoptic area (MPA) of the rat. Similar increases in sleep have also been observed with triazolam, pentobarbital and ethanol microinjection. Together, these findings implicate the MPA as an important anatomic site mediating the effects of sedatives on naturally occurring sleep. Although the molecular mechanism by which propofol in the MPA acts to induce sleep is unclear, potentiating effects on the GABA(A) receptor complex may play a role. To assess this possibility, we microinjected propofol alone, and in combination with the benzodiazepine receptor antagonist flumazenil, into the MPA. At a dose of 0.76 microg, flumazenil had no effect on sleep when given alone, and completely blocked the increase in sleep caused by a 40-ng dose of propofol although it did not affect the increase in sleep caused by an 80-ng dose of propofol. These data suggest that the sleep inducing property of propofol is in part mediated by direct or indirect actions on the GABA(A)-benzodiazepine receptor complex.