Postoperative circadian disturbances.

An increasing number of studies have shown that circadian variation in the excretion of hormones, the sleep wake circle, the core body temperature rhythm, the tone of the autonomic nervous system and the activity rhythm are important both in health and in disease processes. An increasing attention has also been directed towards the circadian variation in endogenous rhythms in relation to surgery. The attention has been directed to the question whether the circadian variation in endogenous rhythms can affect postoperative recovery, morbidity and mortality. Based on the lack of studies where these endogenous rhythms have been investigated in relation to surgery we performed a series of studies exploring different endogenous rhythms and factors affecting these rhythms. We also wanted to examine whether the disturbances in the postoperative circadian rhythms could be correlated to postoperative recovery parameters, and if pharmacological administration of chronobiotics could improve postoperative recovery. Circadian rhythm disturbances were found in all the examined endogenous rhythms. A delay was found in the endogenous rhythm of plasma melatonin and excretion of the metabolite of melatonin (AMT6s) in urine the first night after both minor and major surgery. This delay after major surgery was correlated to the duration of surgery. The amplitude in the melatonin rhythm was unchanged the first night but increased in the second night after major surgery. The amplitude in AMT6s was reduced the first night after minimally invasive surgery. The core body temperature rhythm was disturbed after both major and minor surgery. There was a change in the sleep wake cycle with a significantly increased duration of REM-sleep in the day and evening time after major surgery compared with preoperatively. There was also a shift in the autonomic nervous balance after major surgery with a significantly increased number of myocardial ischaemic episodes during the nighttime period. The circadian activity rhythm was also disturbed after both minor and major surgery. The daytime AMT6s excretion in urine after major surgery was increased on the fourth day after surgery and the total excretion of AMT6s in urine was correlated to sleep efficiency and wake time after sleep onset, but was not correlated to the occurrence of postoperative cognitive dysfunction. We could only prove an effect of melatonin substitution in patients with lower than median pain levels for a three days period after laparoscopic cholecystectomy. In the series of studies included in this thesis we have systematically shown that circadian disturbances are found in the secretion of hormones, the sleep-wake cycle, core body temperature rhythm, autonomic nervous system tone, myocardial ischaemia and activity rhythm after surgery. Correlation exists between circadian rhythm parameters and measures of postoperative sleep quality and recovery. However, oral melatonin treatment in the first three nights after surgery, cannot yet be generally recommended for improvement of sleep quality or other recovery parameters based on the available results. It may be indicated in subgroups or if other perioperative treatment algorithms were used, but this has to be investigated in future trials.