Clinical Chronobiology: A Timely Consideration in Critical Care Medicine

Helen McKenna; Gijsbertus T. J. van der Horst; Irwin Reiss; Daniel Martin


Crit Care. 2018;22(124) 

In This Article

Current Challenges and Future Perspectives on the Monitoring of Circadian Rhythms in the ICU

The volume of literature devoted to understanding the impact of circadian disruption on critically ill patients is small. In a setting in which heterogeneity of disease and treatments is sizable, linking cause with effect is challenging. Unless a patient's circadian rhythm is accurately determined, it is impossible to determine how it may influence clinical outcomes. Currently, this is not possible outside the setting of complex research projects. Improving chronofitness in critically ill patients will require the ability to monitor circadian rhythms in the clinical setting. Measuring circadian rhythms, in real time and in different tissues, will be essential for identification of circadian dysrhythmias and for assessing the effect of interventions to improve clock alignment. As every physiological function has a circadian oscillation, each proffers a potential biomarker for tracking rhythmicity. In healthy volunteers and ambulatory patients, circadian rhythms can be mapped using activity monitors.[87] However, this has been shown to overestimate sleep time compared to polysomnography in the critically ill,[88] presumably as actigraphy is unable to distinguish between true sleep and motionless wakefulness. It is usual to collect hourly physiological information from critically ill patients and the use of electronic data systems allows greater recording frequency of measurement variables providing a rich dataset of biorhythms. Although clinicians appreciate the importance of trends over time, we lack the terminology for describing or quantifying biological rhythms, or changes in their characteristics. Clinicians need to become more familiar with normal patterns of circadian oscillation in key physiological functions (e.g. the nadir of temperature, blood pressure and heart rate in the early hours of the morning), and to develop pattern recognition strategies to identify critical circadian disruption, similar to the manner in which we identify a rhythm disturbance in an electrocardiogram. A more sophisticated approach would require quantitative analysis of rhythms, perhaps via software able to process real-time physiological data, to identify: timing of peaks (or troughs) enabling phase shift determination; amplitude of variation, from peak to trough; and the consistency of the rhythm over days. Techniques to achieve this are commonly used in the experimental setting,[89] but have yet to transfer across to clinical practice. Medical education in the future may need to provide clinicians with the mathematical competence to handle more complex data relating to biological rhythms, or to use algorithms for their interpretation. Attempts have been made to plot circadian rhythms using biomarkers including serum melatonin[90] and cortisol levels,[91] urinary melatonin metabolites,[36,81] sleep–wake cycles using polysomnography[41] and hourly temperature and urine outputs.[92] A multitude of hormones related to metabolism levels are under circadian control such as insulin, ghrelin, leptin and growth hormone;[93,94] these too could be used to help determine circadian profiles in the critically ill in a study setting.[95] Finding the optimum tool to monitor critically ill patients therefore remains a key to research progress in this area.