Implications of Circadian Biology for Anaesthesia

Abstract

Biological clocks pervade human physiology and behaviour. They control the daily timing of sleep and dictate changes in body temperature, heart rate, the perception of pain and variable responses to drugs. Anaesthetists have taken a conservative approach to adopting the principles of chronobiology. Patients are often treated rigidly as homeostatic organisms without regard to when drugs might have greater effect or when toxicity might better be tolerated. Anaesthetists working rotating shifts around the clock battle against the effects of circadian disruption and fatigue which may lead to performance deterioration and an increase in the instance of drug error. In this thesis the implications of circadian biology for anaesthesia are examined both with respect to the patient and the anaesthetist. Anaesthetists self-report an overall sleep debt (45 min/night) which may contribute to drug error. Objective measures of sleep and performance were measured using actigraphy, a validated psychomotor vigilance task (PVT), and a novel drug recognition performance test (DRPT) developed here. The quantity and quality of sleep was significantly worse (p = 0.019) on night shifts (mean 5.51 h (SE 27 min)) vs. day shifts (mean 6.90 h (SE 26 min)). Sleep deprivation was reflected in all measures of performance. DRPT performance was significantly worse (p = 0.001) during night shifts (mean speed 8.07 (SE 0.23)) than during days (mean speed 8.48 (SE 0.23). Anaesthetists made twice as many drug errors (n=12) at the conclusion of night shifts than at any other time of the day. A clinical trial was undertaken to examine the circadian variation in the action of the neuromuscular blocker rocuronium. Patients remained paralysed for up to 15 to 20 minutes longer in the morning than in the afternoon. The maximum duration (50 mins (SE 5 mins)) fell between 08:00 and 11:00 and the minimum duration (29 mins (SE 3 mins)) between 14:00 and 17:00 (p = 0.005). A pilot study tested the effects of anaesthesia, surgery and hospitalisation on the quality and quantity of sleep patients obtained. Sleep patterns were measured for a week pre and postoperatively and up to a week in hospital. Increasing sleep disruption was associated with longer hospital stay and low light exposure. In isolation the effects of circadian biology on the system of anaesthesia are significant and when considered together they have profound implications for the conduct of anaesthesia, and for the well-being of patients and anaesthetists.