Critically ill patients with a reverse blood pressure dipping phenotype at increased risk for delirium and death

The ICU environment is disruptive to a patient's biological rhythms where sleep-wake cycles are often desynchronized from the environmental day-night changes. This puts patients at increased risk to develop delirium with consequent fiscal pressure for the health care system. An underappreciated dimension is how time-specific patient phenotypes in the critical care environment relate to clinical outcomes. We set out to analyze how rhythmic components (or the lack thereof) in physiological data streams sampled at high resolution in the ICU were associated with the future incidence of delirium and death. To offer cues for further interrogation into mechanism and risk prognosis, we examined differences in 24-hour fluctuations of clinical labs in ICU patient populations at risk. Rhythmic components using dipping ratios and JTK_CYCLE statistics were derived from 24-hour blood pressure and heart rate measurements available from ICU patient admissions recorded in the MIMIC IV database. Logistic adjusted regression models assessed the association between disrupted vital sign rhythms and the future incidence of delirium during the same hospital admission and death. Aggregation of numeric clinical lab measurements across the first 24 h from all patient admissions allowed modeling of rhythmic patterns and subsequent association studies to link potential biochemical mechanisms to perturbed vital sign rhythms and adverse ICU outcomes. Patients with reverse blood pressure dipping were at a 40% higher risk to have a diagnosis of delirium (Odds Ratio: 1.38, 95% CI 1.13-1.71) and a 13% increased risk of death (Odds Ratio: 1.13, 95% CI 1.02-1.26). Compared to the patient population with nocturnal blood pressure dip, reverse dippers showed 24-hour biochemistry profiles suggestive of altered circadian programs specifically in clinical parameters of renal, metabolic, and hemostatic function. Reverse blood pressure dipping can be an early sign for the future development of delirium in the ICU and is accompanied by disrupted biorhythms across multiple organ systems. Dampened and reversed heart rate and blood pressure rhythms are associated with a higher risk for death in ICU patients. Considering the inclusion of these risk factors in preventive care may improve patient outcomes and reduce burden on the health care system.