Abstract

Circadian disruption is common in critically ill patients admitted to the intensive care unit (ICU). Understanding and treating circadian disruption in critical illness has significant potential to improve critical illness outcomes through improved cognitive, immune, cardiovascular, and metabolic function. Measurement of circadian alignment (i.e., circadian phase) can be resource-intensive as it requires frequent blood or urine sampling over 24 or more hours. Less cumbersome methods of assessing circadian alignment would advance investigations in this field. Thus, the objective of this study is to examine the feasibility of using continuous telemetry to assess diurnal variation in heart rate (HR) among medical ICU patients as a proxy for circadian alignment. In exploratory analyses, we tested for associations between misalignment of diurnal variation in HR and death during hospital admission. This was a prospective observational cohort study embedded within a prospective medical ICU biorepository. HR data were continuously collected (every 5 s) via telemetry systems for the duration of the medical ICU admission; the first 24 h of this data was analyzed. Patients were extensively characterized via medical record chart abstraction and patient interviews. Of the 56 patients with complete HR data, 48 (86%) had a detectable diurnal variation. Of these patients with diurnal variation, 39 (81%) were characterized as having the nadir of their HR outside of the normal range of 02:00–06:00 (“misalignment”). Interestingly, no deaths occurred in the patients with normally aligned diurnal variation; in contrast, there were seven deaths (out of 39 patients) in patients who had misaligned diurnal variation in HR. In an exploratory analysis, we found that the odds ratio of death for misaligned vs. aligned patients was increased at 4.38; however, this difference was not statistically significant (95% confidence interval 0.20–97.63). We conclude that diurnal variation in HR can be detected via continuous telemetric monitoring of critically ill patients. A majority of these patients with diurnal variation exhibited misalignment in their first 24 h of medical ICU admission. Exploratory analyses suggest possible associations between misalignment and death.

Highlights

  • Circadian rhythms are one of nature’s most pervasive adaptations allowing coordination between an organism and the earth’s daynight environmental changes

  • The objective of this study is to examine the feasibility of using continuous telemetry to assess diurnal variation in heart rate (HR) among medical intensive care unit (ICU) patients as a proxy for circadian alignment

  • 56 patients were included in the initial cosinor test for diurnal variation of HR; 48 (86%) out of 56 had diurnal variation in HR (Figure 1)

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Summary

Introduction

Circadian rhythms are one of nature’s most pervasive adaptations allowing coordination between an organism and the earth’s daynight environmental changes. Human circadian rhythms are self-sustaining oscillating processes driven by a central “master clock.”. Adjustment of this master clock into alignment with daynight occurs via external cues. Circadian misalignment in the intensive care unit (ICU) is likely caused by multifactorial insults of acute critical illness with or without associated brain dysfunction, abnormal light exposure, continuous nutritional intake, immobility, and pleiotropic medication effects [13, 14]. Circadian rhythm disruption overlaps and potentiates ICU sleep disruption forming a vicious cycle for critically ill patients. Sleep and circadian rhythm disruption are implicated in the development of ICU delirium [15,16,17]. Direct evidence in support of associations between circadian rhythm and outcomes relevant to critical illness outcomes is limited

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