In this episode, I’ll discuss haloperidol for the treatment of delirium in ICU patients.
Despite there not being strong literature support to justify use to improve outcomes, haloperidol is frequently used to treat ICU patients with delirium. A systematic review of the available evidence published in 2020 identified only 1 placebo controlled trial that evaluated haloperidol for ICU delirium and the authors of this review judged the evidence to be “sparse, of low quality and inconclusive.”
A group of authors recently published a placebo-controlled randomized blinded trial of 1000 patients with ICU delirium that were split between treatment with haloperidol or placebo. The IV haloperidol group received 2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg. There was no limit set on the duration of treatment. The authors decided to use as the primary outcome the number of days alive and out of the hospital at 90 days after randomization. Mortality was evaluated as a secondary outcome.
At 90 days there was no difference between groups in the primary outcome of days alive and out of the hospital. However the mortality rate at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group, and this difference was statistically significant. Serious adverse event rates were similar between groups at 11 for haloperidol and 9 for placebo.
QTc prolongation was responsible for study drug discontinuation in 12 haloperidol patients and 7 placebo patients.
The authors concluded:
Among patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo.
While I agree this study does not provide sufficient evidence to routinely prescribe haloperidol for ICU delirium for the purpose of improving outcomes, it seems to me that there is a slight bias against haloperidol in the interpretation of the results, specifically the secondary outcome showing less mortality in the haloperidol group. Regarding this outcome, the authors state that “Although our results suggest that mortality may have been lower with haloperidol than with placebo, no conclusions may be drawn.” and they also state one of the reasons their study may have showed improved mortality where a smaller one did not was the larger sample size (yet this is also listed as a strength of the study).
Regardless of whether an improved mortality benefit should be attributed to haloperidol based on this study, the authors do not seem to address the practical reason why clinicians in a modern ICU choose to give IV haloperidol. From my experience, clinicians don’t use haloperidol to hasten delirium resolution or to improve mortality; they use it because the delirious patient has agitation that is putting them at risk of self-harm from pulling out lines and tubes, or because staff members are at risk of being injured by the patient. Taken from this point of view, the study could support the opinion that if haloperidol has to be used for agitated delirium to keep patients and staff safe, compared to placebo it has at worse no difference in days alive and out of the hospital and at best a slight chance of also reducing 90-day mortality.
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