Exploring the effect of general anaesthesia on patients post-operative sleep and circadian rhythms
Our research focusses on how general anaesthesia (GA) causes sleep and circadian disruption in patients, and what might be done to minimise this disruption and improve post-operate recovery. The overarching goal of this work is to: (1) understand how GA affects the circadian clock and sleep post-operatively using animal models and (2) develop ways to combat post-operative sleep and circadian disruption in patients using the principles of chronobiology. In this talk I will discuss the findings from our animal studies and our clinical trials on donor nephrectomy patients, and will summarize our current understanding of the disruptive effect of GA on the clock and sleep and what might be done about it.
Using the honey bee we have previously shown that GA (2% isoflurane for six hours) can effectively cause ‘jet lag’, shifting the circadian clock to a different time zone by acting on the expression of the core genes (period and cryptochrome) that drive daily rhythms (1). Furthermore, we have shown that the shifting effects of GA can be ameliorated by the administration of bright light during anaesthesia (2). These findings led us to investigate the same effect in more mainstream model organisms: transgenic circadian clock-reporter flies and mice.
Initial clinical studies on the extent of post-operative circadian and sleep disruption were hindered by the fact that disease itself causes sleep and clock disruption. We have recently completed a trial with a unique patient population—40 donor nephrectomy patients—to examine the “real world” effects of anaesthesia and surgery on the clock and sleep. In this patient population we have shown that anaesthesia and surgery cause substantial sleep and clock disruption to patients, and that “clock shifting” (blue) light, administered intraoperatively can reduce post-operative clock disruption (as measured by core body temperature rhythms). Patients receiving blue light show a delay in core temperature rhythms of 1.5h post-operatively compared to 3.4 h in the placebo group. Furthermore, patients receiving “clock shifting light” also show a reduced post-operative hospital stay (on average 3.55 days) compared to those receiving placebo light (3.95 days).
Our immediate aims are to conduct a larger multicentre trial to investigate this effect in larger and more diverse patient population and to further investigate the mechanisms underlying this effect in our laboratory studies.
References:
(1) Cheeseman, J.F., Winnebeck, E.C., Millar, C.D., Kirkland, L.S., Sleigh, J., Goodwin, M., Pawley, M.D.M., Bloch G., Lehmann, K., Menzel, R., and Warman, G.R. (2016). General anaesthesia alters time perception by phase shifting the circadian clock. Proc Natl Acad Sci U S A. 109 (18): 7061-6.
(2) Ludin, N.M., Cheeseman, J.F., Merry, A.F., Millar C.D., Warman, G.R. (2016). The effects of the general anaesthetic isoflurane on the honey bee (Apis mellifera) circadian clock Chronobiology International 33 (1): 128-133