1. Altered Circadian Rhythmicity in Patients in the ICU Joost A. C
Altered Circadian Rhythmicity in Patients in the ICU Joost A.C. Gazendam, MD, PhD; Hans P.A. Van Dongen, PhD; Devon A. Grant, MS; Neil S. Freedman, MD; Jan H. Zwaveling, MD, PhD; Richard J. Schwab, MD
Erin Dauchy, DO
January 28, 2016

2. Background and Study Objective
Patients in the ICU are thought to have an abnormal circadian rhythm, but quantitative data to support the hypothesis are lacking
The primary goal of this study was to identify abnormality and clinical correlation of the disruption in the 24-hour circadian rhythm of ICU patients

3. Introduction
Nearly all human physiologic processes exhibit a near-24-hr circadian rhythm
The SCN in the hypothalamus contain the biologic clock that regulates circadian rhythm
The circadian rhythm cannot be directly measured and so surrogates such as core body temperature (CBT) and plasma melatonin are considered reliable physiologic markers

4. Limited data from evaluation of circadian rhythms in ICU patients suggests considerable disruption of the rhythm
Alteration of the circadian rhythm can have a significant physiologic impact
Drug efficacy/half-life/toxicity
Can impair recovery from sepsis
May affect respiratory muscle performance

5. Methods 28 non-comatose ICU patients were selected
Patients had to afebrile, not on any anti-pyretic or sedative
If intubated, had to be on stable vent settings
The authors chose to use CBT as their marker of the circadian rhythm
Measured with temp-sensing Foley or temp-sensing rectal probe

6. APACHE III score was assessed on the first day of CBT measurements

7. Statistical Analysis
Hourly averages of CBT were calculated for each subject
Repeated measures ANOVA was used in a time by day design to evaluate the day-to-day variation
A harmonic regression model was fitted to each patient’s 48-h time series
Allowed for determination of clock time of CBT minimum and maximum

8. Correlation and stepwise linear regression was performed to evaluate for association of demographic and medical variables with the degree of circadian disruption
One-way ANOVA was used to detect differences in circadian disruption between mechanically ventilated and non-ventilated patients
Also compared disease categories
Renal insufficiency, myasthenia gravis, COPD exacerbation and ARDS

9. Results
Seven of the 28 patients enrolled in the study were excluded from analyses

13. Discussion
Although a circadian rhythm was detectable in these patients, the rhythm was disrupted
The finding that rhythm disruption correlates to increasing APACHE III score suggests that severity of illness may contribute to rhythm disruption

14. Study Strength/Weaknesses
Due to study requirements, most patients were studied while far along in their hospital stay
Average LOS at time of study was 20 days
Using two different methods of CBT measurement may have introduced some variability in CBT recording
Unlike previous studies, this study used patients who were non-comatose and not sedated

15. Conclusions
The authors demonstrate circadian rhythm disruption in critically ill patients in the ICU
Disruption more pronounced in those with higher APACHE III score
Although the circadian rhythm was disrupted, it remained relatively stable over the 48 hours of recording

16. The cause of circadian disruption was not determined in this study - more research is needed
However, the authors’ findings suggest that appropriately timed patient care and therapies may be beneficial for critically ill patients in their path toward recovery