title: General anesthesia alters time perception by phase shifting the circadian clock.
abstract: Following general anesthesia, people are often confused about the time of day and experience sleep disruption and fatigue. It has been hypothesized that these symptoms may be caused by general anesthesia affecting the circadian clock. The circadian clock is fundamental to our well-being because it regulates almost all aspects of our daily biochemistry, physiology, and behavior. Here, we investigated the effects of the most common general anesthetic, isoflurane, on time perception and the circadian clock using the honeybee (Apis mellifera) as a model. A 6-h daytime anesthetic systematically altered the time-compensated sun compass orientation of the bees, with a mean anticlockwise shift in vanishing bearing of 87° in the Southern Hemisphere and a clockwise shift in flight direction of 58° in the Northern Hemisphere. Using the same 6-h anesthetic treatment, time-trained bees showed a delay in the start of foraging of 3.3 h, and whole-hive locomotor-activity rhythms were delayed by an average of 4.3 h. We show that these effects are all attributable to a phase delay in the core molecular clockwork. mRNA oscillations of the central clock genes cryptochrome-m and period were delayed by 4.9 and 4.3 h, respectively. However, this effect is dependent on the time of day of administration, as is common for clock effects, and nighttime anesthesia did not shift the clock. Taken together, our results suggest that general anesthesia during the day causes a persistent and marked shift of the clock effectively inducing "jet lag" and causing impaired time perception. Managing this effect in humans is likely to help expedite postoperative recovery.
authors.affiliation: Department of Anaesthesiology, School of Medicine, University of Auckland, Auckland 1142, New Zealand.
authors.forename: James F
authors.initials: JF
authors.lastname: Cheeseman
authors.forename: Eva C
authors.initials: EC
authors.lastname: Winnebeck
authors.forename: Craig D
authors.initials: CD
authors.lastname: Millar
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Kirkland
authors.forename: James
authors.initials: J
authors.lastname: Sleigh
authors.forename: Mark
authors.initials: M
authors.lastname: Goodwin
authors.forename: Matt D M
authors.initials: MD
authors.lastname: Pawley
authors.forename: Guy
authors.initials: G
authors.lastname: Bloch
authors.forename: Konstantin
authors.initials: K
authors.lastname: Lehmann
authors.forename: Randolf
authors.initials: R
authors.lastname: Menzel
authors.forename: Guy R
authors.initials: GR
authors.lastname: Warman
mesh_terms: D000204:Activity Cycles / Q000187:drug effects / Q000502:physiology; D000768:Anesthesia, General / Q000009:adverse effects*; D018681:Anesthetics, General / Q000009:adverse effects; D000818:Animals; D001483:Base Sequence; D001516:Bees / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D057906:Circadian Clocks / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005426:Flight, Animal / Q000187:drug effects / Q000502:physiology; D017344:Genes, Insect; D006801:Humans; D007530:Isoflurane / Q000009:adverse effects; D023421:Models, Animal; D017440:Photoperiod; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013998:Time Perception / Q000187:drug effects / Q000502:physiology*
chemical_list: D018681:Anesthetics, General; D012333:RNA, Messenger; D007530:Isoflurane