24461612
BACKGROUND	Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes .
BACKGROUND	Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness .
BACKGROUND	The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma .
METHODS	We did this double-blind , placebo-controlled randomised trial in a general adult intensive care unit ( ICU ) .
METHODS	Critically ill patients ( 18 years ) needing mechanical ventilation within 72 h of admission were enrolled .
METHODS	Patients were randomised ( by an independent nurse , in 1:1 ratio , with permuted block size of four and six , using a centralised , secure web-based randomisation service ) to receive haloperidol 2.5 mg or 0.9 % saline placebo intravenously every 8 h , irrespective of coma or delirium status .
METHODS	Study drug was discontinued on ICU discharge , once delirium-free and coma-free for 2 consecutive days , or after a maximum of 14 days of treatment , whichever came first .
METHODS	Delirium was assessed using the confusion assessment method for the ICU ( CAM-ICU ) .
METHODS	The primary outcome was delirium-free and coma-free days , defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause .
METHODS	Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma .
METHODS	ICU clinical and research staff and patients were masked to treatment throughout the study .
METHODS	Analyses were by intention to treat .
METHODS	This trial is registered with the International Standard Randomised Controlled Trial Registry , number ISRCTN83567338 .
RESULTS	142 patients were randomised , 141 were included in the final analysis ( 71 haloperidol , 70 placebo ) .
RESULTS	Patients in the haloperidol group spent about the same number of days alive , without delirium , and without coma as did patients in the placebo group ( median 5 days [ IQR 0-10 ] vs 6 days [ 0-11 ] days ; p = 0.53 ) .
RESULTS	The most common adverse events were oversedation ( 11 patients in the haloperidol group vs six in the placebo group ) and QTc prolongation ( seven patients in the haloperidol group vs six in the placebo group ) .
RESULTS	No patient had a serious adverse event related to the study drug .
CONCLUSIONS	These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients .
CONCLUSIONS	Although haloperidol can be used safely in this population of patients , pending the results of trials in progress , the use of intravenous haloperidol should be reserved for short-term management of acute agitation .
BACKGROUND	National Institute for Health Research .

