Delirium affects up to 80% of sedated, mechanically ventilated critically ill patients and is associated with long-term cognitive impairment.1,2,3 The management of delirium has always involved intravenous haloperidol despite the scarcity of evidence with regards to its benefit on delirium duration and other outcomes.4 Recent Society of Critical Care guidelines for the management of pain, agitation, and delirium also note the absence of evidence for its use.5
The HOPE-ICU trial, published in The Lancet Respiratory Medicine6 is a randomized placebo controlled, double blind, clinical effectiveness trial. The study meant to evaluate the effect of the early administration of haloperidol on duration of delirium in 142 mechanically ventilated patients at high risk of delirium. Patients were randomized to receive either haloperidol (H) 2.5 mg intravenously every 8 h (n=71) or 0.9% saline placebo (P) (n=70) irrespective of delirium and coma status. Patients were randomized within a day of admission and were screened for delirium four times daily using the confusion assessment method (CAM) for the ICU.
There was no difference between the two groups with regards to the primary outcome of delirium free and coma-free days, defined as the proportion of patients alive and without coma and delirium until the 14th day of the study (median 5 days [IQR 0–10] in the H group vs. 6 days [0–11] in the P Group, p=0.53). Secondary outcomes such as delirium duration, coma, or mechanical ventilation time were also not different. The most common adverse events were over-sedation defined as a Richmond Agitation and Sedation Score (RASS) of a point or deeper than prescribed despite ceasing sedatives for more than 24 h (11 patients in the H group vs. six in the P group) and QTc prolongation (seven patients in the H group vs. six in the P group).
In terms of agitation, the study showed that patients receiving haloperidol were agitated much less frequently and received significantly less opiate and sedating drugs when compared to the group receiving placebo.
This study demonstrates that haloperidol shall be reserved to patients with agitated delirium but has no benefit in altering delirium duration and coma in critically ill mechanically ventilated patients. In addition, it is important to note that haloperidol in this study might have been administered to patients that already have delirium and therefore the treatment or preventive effect could not be differentiated.
1. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA.
2. Peterson J, Pun B, Dittus R, et al. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc.
3. Pisani M, Murphy T, Van Ness P, et al. Characteristics associated with delirium in older patients in a medical intensive care unit. Arch Intern Med. ...