Abstract Title Assessing the Burden of Agitation in Hospitalized Traumatic Brain Injury Patients with Comorbid Substance Use Disorders

Background Traumatic brain injury (TBI) is a major cause of morbidity and prolonged hospitalization in the United States. While substance use disorders (SUD) frequently co-occur in this population, their role in shaping the incidence and severity of post-TBI agitation remains poorly understood. Prior research has seldom examined how premorbid SUD influences agitation-related outcomes or care needs. This study aims to fill this gap by characterizing the relationship between SUD, agitation, and clinical outcomes in hospitalized patients with acute TBI.

Methods This single-center retrospective cohort study reviewed 650 consecutive TBI admissions at an academic Level I trauma center from March 2024 to March 2025. Patients hospitalized for at least three days were included (n=467). Agitation was defined by documented clinical observations, use of physical restraints, or administration of agitation-targeted medications. SUD was determined based on documented diagnoses within the preceding year, patient or collateral reports, toxicology results (excluding substances administered emergently), and referrals to addiction services. TBI severity was classified by the best Glasgow Coma Scale (GCS) score within 24 hours of admission. Patients were categorized into three groups: no agitation, agitation without SUD, and agitation with SUD. Primary endpoints included ICU and hospital length of stay, agitation duration, restraint utilization, and addiction-related consults.

Results Among 467 patients meeting inclusion criteria, 52.2% demonstrated clinically significant agitation, exceeding previously reported estimates of 31.7%. SUD was identified in 40.7% of patients, most frequently involving alcohol (31.4%) and tobacco (12.2%), with 37.8% exhibiting polysubstance use. The mean ICU length of stay was significantly longer in patients with agitation compared to those without agitation (19.26 vs. 9.32 days; p<0.001). Although patients with both agitation and SUD experienced a longer mean duration of agitation (13.46 vs. 11.18 days; p=0.23) relative to those without SUD, this difference did not reach statistical significance. This interim analysis, representing 30% of planned enrollment, identified significant associations between agitation and increased ICU utilization, while differences in agitation duration by SUD status did not achieve significance.

Conclusion These findings demonstrate a high prevalence of agitation and SUD among hospitalized TBI patients, emphasizing the need for systematic screening and targeted management strategies. Although premorbid SUD was linked to numerically longer agitation duration, this association was not statistically significant. Significant relationships were observed between agitation and greater ICU resource use and restraint application. Ongoing data collection will help determine whether integrated approaches addressing SUD and withdrawal can improve outcomes after TBI.