Haloperidol for the Treatment of Delirium in ICU Patients

Nina C. Andersen-Ranberg*, Lone M. Poulsen, Anders Perner, Jørn Wetterslev, Stine Estrup, Johanna Hästbacka, Matt Morgan, Giuseppe Citerio, Jesus Caballero, Theis Lange, Maj Brit N. Kjær, Bjørn H. Ebdrup, Janus Engstrøm, Markus H. Olsen, Marie Oxenbøll Collet, Camilla B. Mortensen, Sven Olaf Weber, A. Sofie Andreasen, Morten H. Bestle, Bülent UsluHelle Scharling Pedersen, Louise Gramstrup Nielsen, Hans C. Toft Boesen, Jacob V. Jensen, Lars Nebrich, Kirstine La Cour, Jens Laigaard, Cecilie Haurum, Marie W. Olesen, Christian Overgaard-Steensen, Bo Westergaard, Björn Brand, Gitte Kingo Vesterlund, Pernille Thornberg Kyhnauv, Vibe S. Mikkelsen, Simon Hyttel-Sørensen, Inge de Haas, Søren R. Aagaard, Line O. Nielsen, Anne S. Eriksen, Bodil S. Rasmussen, Helene Brix, Thomas Hildebrandt, Martin Schønemann-Lund, Hans Fjeldsøe-Nielsen, Anna Maria Kuivalainen, Ole Mathiesen, AID-ICU Trial Group

*Corresponding author for this work

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BACKGROUND: Haloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited. METHODS: In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization. RESULTS: A total of 1000 patients underwent randomization; 510 were assigned to the haloperidol group and 490 to the placebo group. Among these patients, 987 (98.7%) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.6%). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval [CI], 32.9 to 38.6) in the haloperidol group and 32.9 (95% CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, -1.2 to 7.0) (P = 0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points [95% CI, -13.0 to -0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group. CONCLUSIONS: 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. (Funded by Innovation Fund Denmark and others; AID-ICU ClinicalTrials.gov number, NCT03392376; EudraCT number, 2017-003829-15.).

Original languageEnglish
JournalThe New England Journal of Medicine
Issue number26
Pages (from-to)2425-2435
Publication statusPublished - 29. Dec 2022

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