Association among rescue neuroleptic use, agitation, and perceived comfort: secondary analysis of a randomized clinical trial on agitated delirium

Background: Few studies have examined how the use of rescue medications could be used to inform on the efficacy of interventions in delirium clinical trials. The objective of this study was to determine the association among rescue medication use, Richmond Agitation-Sedation Scale (RASS), and perceived comfort by the nurses and caregivers. Methods: This was a pre-planned secondary analysis of a double-blind, randomized clinical trial comparing the use of a single dose of lorazepam plus haloperidol versus placebo plus haloperidol in patients with agitated delirium. Rescue medications were considered the gold standard for this analysis. The optimal cutoff for RASS analysis was calculated by using general linear regression models and determining the area of the curve and using the top left approach. We used 2 × 2 tables to examine the association between rescue medication use and perceived comfort. Results: Fifty-eight patients received the study medications and 52 (89%) completed the 8-h observation period. There were 26 (50%) patients in each arm. The lorazepam/haloperidol arm required fewer rescue doses (4/26 (15%)) vs. 16/26 (62%), p = 0.004). Patients with a greater initial RASS reduction required fewer rescue doses. The cutoff value for RASS improvement was 4 points, area under the curve (AUC) 0.64 (95% CI 0.49–0.79) for those who required no rescue doses, and 3 points, AUC 0.74 (95% CI 0.52–0.96) for those who required more than one rescue dose. Conclusions: Rescue medication use was responsive to change and associated with both RASS scores and perceived patient comfort by the nurse and caregiver.