Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study

Abstract

Objective: To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ≥ 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3).

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States.

Patients: Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation.

Interventions: Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge.

Measurements and main results: Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ≥ 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ≤ 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups.

Conclusions: Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium.

Figure 1

Patient screening, enrollment, and randomization. ICDSC, Intensive Care Delirium Checklist

Figure 2

Kaplan-Meier plot for time to first delirium occurrence between haloperidol and placebo groups

Figure 3

Presence of delirium on each study day between the haloperidol and placebo groups.