• Extrapyramidal & Movement Disorders
• Dementias
• Pulmonary Clinical Trials
• Nursing

• Extrapyramidal & Movement Disorders
• Dementias
• Pulmonary & Critical Care
• Pulmonary Clinical Trials
• Nursing

Treatment of ventilated patients in the intensive care unit (ICU) with haloperidol or intravenous saline resulted in similar rates of delirium- and coma-free days. Valerie Page, MB, BCh, Wirral University Teaching Hospital NHS Foundation Trust, Wirral, United Kingdom, presented data from the Randomised, Double-Blind, Placebo-Controlled Trial to Compare the Early Administration of Intravenous Haloperidol Versus Placebo in the Prevention and Treatment of Delirium in Critically Ill Ventilated Patients [HOPE-ICU; ISRCTN83567338].

Between 55% and 80% of ventilated ICU patients have delirium, with an estimated 65% unrecognized or untreated. Although limited evidence supports the use of haloperidol in delirium in critical patients, a survey of practitioners in the United Kingdom demonstrated that up to 95% and 80% of practitioners use haloperidol to treat hyperactive delirium and hypoactive delirium, respectively. The HOPE-ICU trial tested the hypothesis that early treatment of critically ill patients with haloperidol will increase the number of days alive without delirium or coma.

In the single-center, Phase 2, double-blind, placebo-controlled HOPE-ICU trial, 142 patients were randomized 1:1 to receive haloperidol 2.5 mg or intravenous saline every 8 hours for up to 14 days, at discharge, or until patient was delirium-free for 2 consecutive days. Patients were included if they required ventilation within 72 hours of ICU admission and were excluded for chronic antipsychotic use, Parkinson's disease, a QTC of greater than 500 msec, uncomplicated elective heart surgery, dementia, likelihood to leave or die within 48 hours, pregnancy, or readmission. Patients were assessed daily for delirium by the confusion assessment method-ICU.

The primary endpoint of the HOPE-ICU trial was the number of days alive free of delirium or coma at 14 days. The number of ventilator-free days at Day 14, delirium-free, coma-free, and mortality at 28 days, length of critical care, and length of hospital stay were considered secondary endpoints.

No significant difference was observed in delirium-free or coma-free days at Day 14 between patients that were treated with haloperidol or placebo. The trend of nonsignificance continued to Day 28. In addition, there was no significant difference between the haloperidol or placebo arms in the secondary endpoints of number of ventilator-free days at Day 14, delirium-free days and mortality at Day 28, length of ICU stay, and length of hospital stay.

The safety profiles were similar among the haloperidol and placebo arms. A QTC of >500 msec after electrolyte correction occurred in seven patients in the haloperidol arm and four patients in the placebo arm (p=0.29). Oversedation despite decreasing the dose by half occurred in eight patients in the haloperidol arm and five patients in the placebo arm (p=0.35). Extrapyramidal symptoms were not observed among patients in the haloperidol arm (after halving the dose) and in one patient in the placebo arm (p=0.57).

The data from HOPE-ICU indicates that treatment of ventilated ICU patients with haloperidol does not prevent or treat delirium. Prof. Page said that, in ICU patients with delirium, perhaps the target pathophysiology is actually neuroinflammation, rather than neurotransmitter imbalance.

• © 2013 MD Conference Express®