General anesthesia alters time perception by phase shifting the circadian clock

Area of Science:

• Chronobiology
• Anesthesiology
• Animal Behavior

Background:

• General anesthesia can lead to postoperative confusion, fatigue, and sleep disruption.
• These symptoms are hypothesized to result from anesthesia's impact on the circadian clock, which regulates daily physiological and behavioral rhythms.

Purpose of the Study:

• To investigate the effects of isoflurane, a common general anesthetic, on time perception and the circadian clock.
• To use the honeybee (Apis mellifera) as a model organism to study these effects.

Main Methods:

• A 6-hour daytime administration of isoflurane was used on honeybees.
• Time-compensated sun compass orientation, time-trained foraging behavior, and whole-hive locomotor activity were measured.
• mRNA oscillations of core clock genes (cryptochrome-m and period) were analyzed.

Main Results:

• Daytime anesthesia caused significant shifts in sun compass orientation (87° anticlockwise in Southern Hemisphere, 58° clockwise in Northern Hemisphere).
• Anesthesia delayed the onset of foraging by 3.3 hours and locomotor activity rhythms by 4.3 hours.
• Molecular analysis revealed phase delays in cryptochrome-m (4.9 h) and period (4.3 h) gene expression, indicating a shift in the core molecular clockwork.

Conclusions:

• Daytime general anesthesia induces a persistent phase delay in the circadian clock, akin to jet lag, impairing time perception.
• The timing of anesthesia administration is critical; nighttime anesthesia did not produce similar clock-shifting effects.
• Understanding and managing anesthesia-induced circadian disruption may improve postoperative recovery in humans.