Delirium: Common Treatment No Better Than Placebo

Diedtra Henderson

August 26, 2013

The antipsychotic drug haloperidol was no more effective than saline solution at safeguarding critically ill patients from delirium in a randomized clinical trial. Patients in both trial groups survived a median of 5 to 6 days without delirium or coma.

Valerie J. Page, MBBCh, from the Intensive Care Unit, Watford General Hospital, and the Faculty of Medicine at Imperial College, London, United Kingdom, and coauthors report their findings in an article published online August 21 in the Lancet Respiratory Medicine.

Approximately 30% of critically ill patients suffer from delirium, but that figure soars to 60% to 80% among those who require sedation and ventilation. Moreover, critically ill patients who suffer from delirium are 3 times more likely to die within 6 months.

Despite scant evidence for its effectiveness, haloperidol is the most commonly prescribed medicine for delirium, according to Dr. Page and coauthors. They designed the randomized, double-blind, placebo-controlled trial to put conventional wisdom to the test.

Between November 9, 2010, and September 21, 2012, the researchers enrolled 142 patients who were being treated at a general adult intensive care unit who were older than 18 years and who required mechanical ventilation within 72 hours of admission. Of that group, 71 were randomly assigned to receive 2.5 mg haloperidol intravenously every 8 hours and 70 received a 0.9% saline solution at the same intervals.

"During the 14-day period from randomisation, 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 [(interquartile range [IQR],) 0–10] in the haloperidol group vs 6 days in the placebo group [0–11]; p=0.53)," Dr. Page and colleagues write. "The number of days assessed as spent in delirium (as opposed to coma or normal) did not differ between the two groups (median 5 days [IQR 2–8] in the haloperidol group vs 5 days [1–8] in the placebo group; p=0.99)."

Emergency physicians routinely use haloperidol in combination with benzodiazepines when critically ill patients are given short "sedation breaks" to reduce the incidence of ventilator-associated pneumonia, Dr. Howard Mell, a spokesman for the American College of Emergency Physicians, told Medscape Medical News. "We've done so because the data had always suggested, and the teaching had always been, that this is a good combination for delirium from all causes," said Dr. Mell, who practices in emergency rooms throughout Ohio.

"It may not be worth the routine use of [haloperidol] in an [intensive care unit] setting anymore," he said. "The reality is, this paper says we're not treating [delirium] effectively."

Although a subset of critically ill patients may experience a modest benefit from haloperidol, the authors note that a much larger study would be needed to demonstrate the benefit, and the magnitude of the benefit would likely be small, given the current results.

"Our results suggest a commonly used haloperidol dose regimen does not decrease delirium in an unselected population of critically ill patients requiring mechanical ventilation, when commenced early during [intensive care unit] stay," the researchers conclude. "Identification of a pharmacological intervention to prevent or reduce delirium and improve adverse outcomes, including in the [intensive care unit] setting, remains a high priority within delirium research."

Support for this study was provided by the National Institute for Health Research. One study author disclosed receiving funding from Orion. A second investigator disclosed receiving funding from the National Institutes of Health, Abbott, Hospira, and Orion. A third study author disclosed receiving funding from AstraZeneca, GlaxoSmithKline, and Orion. Neither the remaining study authors nor the commentator have disclosed relevant financial relationships.

Lancet Respir Med. Published online August 21, 2013. Abstract

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