Prophylactic haloperidol not linked to improved survival in ICU patients: The REDUCE trial

1. In ICU patients, prophylactic haloperidol did not improve 28-day or 90-day survival.

2. Prophylactic haloperidol also did no reduce delirium incidence, delirium-free days, duration of mechanical ventilation, nor ICU and hospital length of stay.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Delirium manifests as waxing and waning consciousness in ill patients and is a common phenomenon in the ICU, where it represents a poor prognosis. Though haloperidol is often given to reduce agitation in delirium, it is unknown if prophylactic haloperidol improves outcomes. This randomized controlled trial compared prophylactic haloperidol versus placebo in critically ill ICU patients and determined how these interventions affected outcomes. There were no differences in patient survival at 28 or 90 days after either intervention. In addition, there were no differences between delirium incidence, delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay.

Overall, this study suggests that prophylactic haloperidol is ineffective in improving outcomes o ICU patients with delirium. However, the median time that prophylactic therapy was given was 2 days, and this may be too short of prevent delirium. Additionally, only low doses of haloperidol were given and higher doses may be needed to achieve an effect on the measured endpoints. Finally, the study only included critically ill patients in the ICU whose neural function may have been too severely impacted for haloperidol to improve outcomes.

Click to read the study, published in JAMA

Relevant Reading: Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized clinical trial

In-Depth [randomized controlled trial]: This study randomized 1789 patients treated at 21 ICUs in the Netherlands without delirium who stayed in the ICU at least a day from 2013-2016. Patients were randomized to prophylactic treatment 3 times daily with 1 mg or 2 mg of intravenous haloperidol or intravenous 0.9% sodium chloride as placebo. The 28-day survival rates were 88.3% for the 2-mg haloperidol group and 82.7% for the placebo group (p < 0.05). The median 28-day survival was 28 days in the 2mg haloperidol group and 28 days in the placebo group (0 day difference; CI_95% 0-0, p = 0.93). The median 90-day survival was 90 days in the 2mg haloperidol group and 90 days in the placebo group (0 day difference; CI_95% 0-0). Secondary outcomes in the study were also not statistically different, including delirium incidence, delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay (p < 0.05). The rate of serious adverse events was not statistically different between groups.

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