Personalized Sedation Goals for Agitated End-of-Life Delirium: Secondary Analysis of RECORD Trial.

Abstract

End-of-life delirium causes substantial distress for patients and families. Personalized sedation goals (PSGs) offer a patient-centered approach to delirium management by defining treatment targets based on caregiver preferences. We compared haloperidol, lorazepam, haloperidol plus lorazepam, and placebo in achieving caregiver-defined PSGs for agitated end-of-life delirium. This preplanned secondary analysis used data from a multicenter, double-blind, double-dummy, parallel-group randomized clinical trial conducted from July 16, 2019, to June 8, 2023, with 30-day follow-up. Patients with advanced cancer and persistent agitation despite nonpharmacologic measures and standard-dose haloperidol were enrolled from three acute palliative care units in the United States and Taiwan. Participants received haloperidol dose escalation, lorazepam rotation, combination therapy, or placebo. Caregivers defined PSGs at enrollment. A personalized response was defined as a Richmond Agitation-Sedation Scale score within ±1 category of the PSG. Of 245 eligible patients, 111 were enrolled and 72 included in the primary analysis. Caregiver-defined PSGs were available for 67 patients included in this secondary analysis. At 24 hours, PSG achievement differed significantly across groups (p = 0.02): lorazepam 10/13 (76.9%), combination therapy 8/13 (61.5%), placebo 7/13 (53.8%), and haloperidol 3/14 (21.4%). Compared with haloperidol, lorazepam (odds ratio = 12.2; 95% CI = 2.0-75.1; p = 0.01) and combination therapy (odds ratio = 5.9; 95% CI = 1.1-32.0; p = 0.04) were more likely to achieve caregiver-defined PSGs. Lorazepam-based regimens were more likely than haloperidol alone to achieve caregiver-defined sedation goals, supporting their role in goal-concordant care for agitated end-of-life delirium.