A96-01 Subtypes of Acute Brain Dysfunction Severity Trajectories During the First 7 Days in the Intensive Care Unit

Rationale Longer duration and severity of acute brain dysfunction (ABD), including delirium and coma, have been associated with worse clinical outcomes in critically ill adults. Examining ABD trajectories over time may offer deeper insights into understanding its heterogeneity. This study aimed to characterize ABD trajectories and examine its relationship with clinical characteristics and 30-day mortality. Methods We analyzed data from the multicenter BRAIN-ICU and MIND-ICU prospective cohort study, which included adults with acute respiratory failure and/or shock. Delirium presence and severity were determined twice daily for 7 days using the CAM-ICU-7. A score of 0 indicates no delirium, 1-2 indicates subsyndromal delirium, 3-5 indicates mild-to-moderate delirium, and 6-7 indicates severe delirium. Patients with a RASS of -4 or -5, indicating coma, were assigned a CAM-ICU-7 score of 7. We applied group-based trajectory modeling of CAM-ICU-7 to identify ABD severity trajectory patterns and compared demographics, clinical characteristics, and 30-day mortality among trajectory groups. Results The 1035 patients analyzed had a median age of 62 [IQR, 53-72] years, 61% were male, and 91% were White. Overall, patients had a median Charlson Comorbidity Index of 2 (1-4) and SOFA score at enrollment of 6 (4-9). 731 patients (70.6%) had delirium at some point during the study. Five ABD severity trajectories were identified as the optimal model fit based on global fit indices and clinical interpretability: T1 was associated with mild and persistent ABD, while T2-T5 were characterized by severe ABD early during critical illness with different resolution patterns (Figure). Trajectory membership varied by patient clinical characteristics. T1 had lighter levels of sedation (median RASS score: -2) in the 24 hours surrounding ICU admission than T2-T5 (median RASS scores: -3, -3, -4, and -3, respectively) (p<.001). At enrollment, T1 and T2 had lower modified SOFA scores (median scores: 6) compared to T5 (median score: 7) (p<.001). Trajectory membership independently predicted 30-day mortality, with T5 having the highest 30-day mortality and T2, which had the fastest resolution of ABD, the lowest (p<.001). Conclusions We identified five trajectories of ABD severity over the first week of a patient’s ICU stay. These trajectories were differentially associated with mortality and clinical characteristics, suggesting trajectory-based approaches may enable more nuanced risk stratification and support the tailoring of interventions and clinical trial designs to specific ABD trajectory patterns. Future work should validate these trajectories in independent cohorts, explore whether they modify treatment effects, and determine if they represent distinct mechanistic pathways. This abstract is funded by: NIH/NIA