Lorazepam as an adjuvant to haloperidol for agitated delirium at the end of life: A double-blind randomized controlled trial.

Abstract

10003 Background: Agitated delirium is a highly distressing neuropsychiatric syndrome common in the last days of life. The use of benzodiazepines for agitated delirium is highly controversial. We compared the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitated delirium. Methods: In this double-blind trial, we randomly assigned patients with advanced cancer admitted to an acute palliative care unit with agitated delirium despite scheduled haloperidol to either lorazepam 3 mg IV or placebo, in addition to haloperidol 2 mg IV upon the onset of agitation. The primary outcome was the Richmond Agitation Sedation Scale (RASS) over the first 8 hours, ranging from -5 (unarousable) to +4 (combative). Secondary endpoints were rescue neuroleptic use, perceived comfort, delirium-related distress, adverse effects and overall survival. 26 patients per arm provided 80% power to detect a between arm difference of 0.5 effect size in mean RASS with a=5%. We used the Wilcoxon Rank Sum test for primary comparison. Results: 52 of 58 (90%) patients who received the medications completed 8 h of observation. RASS decreased significantly within 30 min of treatment in both arms (Table). The lorazepam arm was associated with significantly greater reduction of RASS (Table), less rescue neuroleptics (mean haloperidol equivalent dose 1 mg v. 3 mg, P=0.02), and greater comfort as perceived by blinded caregivers (84% v. 37%, P=0.007) and nurses (77% v. 30%, P=0.005) compared to placebo. We found no significant between-group differences in delirium-related distress, adverse effects and overall survival (median 68 v. 73 h, P=0.56). Conclusions: The combination of lorazepam/haloperidol resulted in rapid and significant reduction of agitation compared to haloperidol alone. Our study supports the judicious use of single dose lorazepam/haloperidol for persistent agitated delirium. Clinical trial information: NCT01670097. [Table: see text]