How does general anaesthesia affect the circadian clock?
Post-operative patients experience sleep disturbances. Animal studies demonstrate that general anaesthesia (GA) can disrupt circadian rhythms and cause changes in the molecular clock, indicating that anaesthesia contributes to post-operative circadian disruption. Here we review the effect of anaesthesia on the circadian clock and its rhythms in order to summarise current findings outline commonalities between studies and propose mechanisms by which effects may be mediated.



1) GA has strong effects on the main neurotransmitter systems linked with circadian control (Gamma aminobutyric acid/N-methyl-D-aspartate (GABA/NMDA)) and may act by interfering with light-entrainment of the clock. 2) Expression of the core clock gene per2 is inhibited by GA (possibly via a NMDA/glycogen synthase kinase 3β (GSK3β) pathway). 3) GA's effect on circadian rhythms appears greatest when administered during animals' active phases 4) GA may have different effects when administered under free-running and entrained conditions. 5) Anaesthesia may mimic the mechanism involved in adaptation of the clock to changes in daylength. There is agreement that GA can strongly affect the circadian clock. How anaesthesia-induced changes in the molecular clock lead to changes in behaviour remains unclear. The answer, and what it may mean for patients post-operatively, will rely on systematic studies at molecular, behavioural, and clinical levels using standardised protocols.
Dept of Medicine, University of Auckland, Auckland, New Zealand.
Raewyn C
RC
Poulsen
Dept of Anaesthesiology, University of Auckland, Auckland, New Zealand.
Guy R
GR
Warman
Dept of Anaesthesiology, University of Auckland, Hamilton, New Zealand.
Jamie
J
Sleigh
Dept of Anaesthesiology, University of Auckland, Auckland, New Zealand.
Nicola M
NM
Ludin
Dept of Anaesthesiology, University of Auckland, Auckland, New Zealand. Electronic address: j.cheeseman@auckland.ac.nz.
James F
JF
Cheeseman
D000768:Anesthesia, General / Q000009:adverse effects*; D000818:Animals; D057906:Circadian Clocks / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016202:N-Methylaspartate / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate
Brain and muscle ARNT-like 1; Clock genes; GABA; Hypnotic drugs; NMDA; Post-operative sleep disruption; Sleep/wake cycle; Suprachiasmatic nucleus; Zeitgeber