Circadian rhythm in critically ill patients: Insights from the eICU Database

Abstract

Objective: To investigate the circadian variation among critically ill patients and its association with clinical characteristics and survival to hospital discharge in a large population of patients in the intensive care unit (ICU). Methods: Circadian variation was analyzed by fitting cosinor models to hourly blood pressure (BP) measurements in patients of the eICU Collaborative Research Database with an ICU length of stay of at least 3 days. We calculated the amplitude of the 24-hour circadian rhythm and time of the day when BP peaked. We determined the association between amplitude and time of peak BP and severity of illness, medications, mechanical intubation, and survival to hospital discharge. Results: Among 23,355 patients (mean age 65 years, 55% male), the mean amplitude of the 24-hour rhythm was 4.5 ± 3.1 mm Hg. Higher APACHE-IV scores, sepsis, organ dysfunction, and mechanical ventilation were associated with a lower amplitude and a shifted circadian rhythm (P < .05 for all). The timing of the BP peak was associated with in-hospital mortality (P < .001). Higher BP amplitude was associated with shorter ICU (2 mm Hg amplitude: 7.0 days, 8 mm Hg amplitude: 6.7 days) and hospital (2 mm Hg amplitude: 11.8 days, 8 mm Hg amplitude: 11.3 days) lengths of stay and lower in-hospital mortality (2 mm Hg amplitude: 18.2%, 8 mm Hg amplitude: 15.2%) (P < .001 for all). Conclusion: The 24-hour rhythm is dampened and phase-shifted in sicker patients and those on mechanical ventilation, vasopressors, or inotropes. Dampening and phase shifting are associated with a longer length of stay and higher in-hospital mortality.

Keywords

• Circadian variation
• Circadian rhythm
• Chronobiology
• Critical illness
• Cosinor analysis