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Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study

John W Devlin12*, Yoanna Skrobik3, Richard R Riker4, Eric Hinderleider1, Russel J Roberts5, Jeffrey J Fong6, Robin Ruthazer7, Nicholas S Hill2 and Erik Garpestad2

Author Affiliations

1 Northeastern University School of Pharmacy, 360 Huntington Avenue, Mugar 206, Boston, MA 02115, USA

2 Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA

3 Department of Critical Care Medicine, Maisoneuve-Rosemont Hospital, 5415 de l'Assomption, Montreal, QC H1T 2M4, Canada

4 Department of Critical Care Medicine, Maine Medical Center, 22 Bramhall Street, Portland, ME, 04102, USA

5 Department of Pharmacy, Tufts Medical Center, 800 Washington Street, mailstop #420, Boston, MA 02111, USA

6 Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, 19 Foster Street, Worcester, MA 01608, USA

7 Institute for Clinical Research and Health Policy Studies, Biostatics Research Center Tufts Medical Center, 35 Kneeland Street, Boston, MA 02111, USA

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Critical Care 2011, 15:R215  doi:10.1186/cc10450

Published: 17 September 2011

Abstract

Introduction

We hypothesized that delirium symptoms may respond differently to antipsychotic therapy. The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the database of a randomized, double-blind, placebo-controlled study comparing quetiapine (Q) or placebo (P), both with haloperidol rescue, for critically ill patients with delirium.

Methods

Data for 10 delirium symptoms from the eight-domain, intensive care delirium screening checklist (ICDSC) previously collected every 12 hours were extracted for 29 study patients. Data between the Q and P groups were compared using a cut-off P-value of ≤0.10 for this exploratory study.

Results

Baseline ICDSC scores (5 (4 to 7) (Q) vs 5 (4 to 6)) (median, interquartile range (IQR)) and % of patients with each ICDSC symptom were similar in the two groups (all P > 0.10). Among patients with the delirium symptom at baseline, use of Q may lead to a shorter time (days) to first resolution of symptom fluctuation (4 (Q) vs. 14, P = 0.004), inattention (3 vs. 8, P = .10) and disorientation (2 vs. 10, P = 0.10) but a longer time to first resolution of agitation (3 vs. 1, P = 0.04) and hyperactivity (5 vs. 1, P = 0.07). Among all patients, Q-treated patients tended to spend a smaller percent of time with inattention (47 (0 to 67) vs. 78 (43 to 100), P = 0.025), hallucinations (0 (0 to 17) vs. 28 (0 to 43), P = 0.10) and symptom fluctuation (47 (19 to 67) vs. 89 (33 to 00), P = 0.04] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness (26% (13 to 63%) vs. 14% (0 to 33%), P = 0.17].

Conclusions

Our exploratory analysis suggests that quetiapine may resolve several intensive care unit (ICU) delirium symptoms faster than the placebo. Individual symptom resolution appears to differ in association with the pharmacologic intervention (that is, P vs Q, both with as needed haloperidol). Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes.