Delirium Severity Trajectories and Outcomes in ICU Patients Defining a Dynamic Symptom Phenotype

Rationale: Delirium severity and duration are independently associated with higher mortality and morbidity. No studies to date have described a delirium trajectory by integrating both severity and duration. Objectives: The primary aim was to develop delirium trajectories by integrating symptom severity and duration. The secondary aim was to investigate the association among trajectory membership, clinical characteristics, and 30-day mortality. Methods: A secondary analysis of the PMD (Pharmacologic Management of Delirium) randomized control trial (ClinicalTrials.gov Identifier: NCT00842608; N= 531) was conducted. The presence of delirium and symptom severity were measured at least daily for 7 days using the Confusion Assessment Method for the intensive care unit (CAM-ICU) and CAM-ICU-7 (on a scale of 0-7, with 7 being the most severe). Delirium trajectories were defined using an innovative, data-driven statistical method (group-based trajectory modeling [GBTM]) and SAS v9.4. Results: A total of 531 delirious participants (mean age 60 yr [standard deviation = 16], 55% female, and 46% African American) were analyzed. Five distinct delirium trajectories were described (CAM-ICU-7: mean [standard deviation]); mildbrief (CAM-ICU-7: 0.5 [0.5]), severe-rapid recovers (CAM-ICU-7: 2.1 [1.0]), mild-accelerating (CAM-ICU-7: 2.2 [0.9]), severe-slow recovers (CAM-ICU-7: 3.9 [0.9]), and severe-nonrecovers (CAM-ICU-7: 5.9 (1.0]). Baseline cognition and race were associated with trajectory membership. Trajectory membership independently predicted 30-day mortality while controlling for age, sex, race, cognition, illness severity, and comorbidities. Conclusions: This secondary analysis described five distinct delirium trajectories based on delirium symptom severity and duration using group-based trajectory modeling. Trajectory membership predicted 30-day mortality.