Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study
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We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality.
All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use.
We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23–27)] of whom 145 received haloperidol [46% (41–52)]. Other interventions for delirium were benzodiazepines in 36% (31–42), dexmedetomidine in 21% (17–26), quetiapine in 19% (14–23) and olanzapine in 9% (6–12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9–74.5); mixed 10.0 (5.0–20.2); hypoactive 3.0 (1.2–6.7)] and circulatory support 2.7 (1.7–4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1–6.9). Haloperidol use within 0–24 h and within 0–72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5–2.5); p = 0.66] and [aOR 1.9 (1.0–3.9); p = 0.07], respectively.
In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.
KeywordsDelirium ICU Haloperidol Cohort Critical care
The AID-ICU cohort study investigators are listed in the ESM.
The AID-ICU study is funded by the Innovation Foundation Denmark.
Compliance with ethical standards
Conflicts of Interest
The ICU at Rigshospitalet has received support for research from Fresenius Kabi, CSL Behring and Ferring Pharmaceuticals. The ICU at Bern University Hospital has received support from Orion Corporation, Abbott Nutrition International, B. Braun Medical AG, CSEM SA, Edwards Lifesciences Services GmbH/SA, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical research AG and Nestlé. Same ICU department received educational grants from Fresenius Kabi, GSK, MSD, Lilly, Baxter, Astellas, AstraZeneca, B. Braun Medical AG, CSL Behring, Maquet, Novartis, Covidien, Nycomed, Pierre Fabre Pharma (Robe Pharma), Pfizer, and Orion Pharma. Author Jesus Caballero has received funds from Astellas, Medtronic, Sedana Medical, Orion Pharma, Pfizer and Brinda Healthcare.
- 2.Slooter AJC, Van De Leur RR, Zaal IJ (2017) Delirium in critically ill patients. Handb Clin Neurol 141:449–466. https://doi.org/10.1016/B978-0-444-63599-0.00025-9 CrossRefPubMedGoogle Scholar
- 8.Han HJ, Shintani A, Eden S, Morandi A, Solberg LM, Schnelle J, Dittus RS, Storrow AB, Ely EW (2010) Delirium in the emergency department: an independent predictor of death within 6 months. Ann Emerg Med 56:244–252. https://doi.org/10.1016/j.annemergmed.2010.03.003 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Lat I, McMillian W, Taylor S, Janzen JM, Papadopoulos S, Korth L, Ehtisham A, Nold J, Aqarwai S, Azocar R, Burke P (2009) The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med 37:1898–1905. https://doi.org/10.1097/CCM.0b013e31819ffe38 CrossRefPubMedGoogle Scholar
- 12.Zhang Z, Pan L, Ni H (2013) Impact of delirium on clinical outcome in critically ill patients: a meta-analysis. Gen Hosp Psychiatry 35:105–111. https://doi.org/10.1016/j.genhosppsych.2012.11.003 CrossRefPubMedGoogle Scholar
- 14.Sakusic A, O’Horo JC, Dziadzko M, Volha D, Ali R, Singh TD, Kashyap R, Farrell AM, Fryer JD, Petersen R, Gajic O, Rabinstein AA (2018) Potentially modifiable risk factors for long-term cognitive impairment after critical illness: a systematic review. Mayo Clin Proc 93:68–82. https://doi.org/10.1016/j.mayocp.2017.11.005 CrossRefPubMedGoogle Scholar
- 17.von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP (2008) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61:344–349. https://doi.org/10.1016/j.ijsu.2014.07.013 CrossRefGoogle Scholar
- 26.Devlin JW, Boleske G, Mlynarek M, Nerenze DR, Peterson E, Jankowski M, Horst HM, Zarowitz BJ (1999) Motor activity assessment scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit. Crit Care Med 27:1271–1275CrossRefPubMedGoogle Scholar
- 28.Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, McArthur C, Cook D, Nielsen N, Pelosi P, Keus F, Guttormsen AB, Moller AD, Møller MH (2015) Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acultely ill adult intensive care patients. Intensive Care Med 41:833–845. https://doi.org/10.1007/s00134-015-3725-1 CrossRefPubMedGoogle Scholar
- 29.Granholm A, Perner A, Krag M, Hjortrup PB, Haase N, Holst LB, Marker S, Collet MO, Jensen AKG, Møller MH (2018) Development and internal validation of the simplified mortality score for the intensive care unit (SMS-ICU). Acta Anaesthesiol Scand 62:3. https://doi.org/10.1111/aas.13048 CrossRefGoogle Scholar
- 31.Burry LD, Williamson DR, Metha S, Perreault MM, Mantas I, Mallick R, Fergusson DA, Smith O, Fan E, Dupuis S, Herridge M, Rose L (2017) Delirium and exposure to psychoactive medications in critally ill adults: a multi-centre observational study. J Crit Care 42:268–274. https://doi.org/10.1016/j.jcrc.2017.08.003 CrossRefPubMedGoogle Scholar
- 32.Ely EW, shintani A, Truman B, Speroff T, Gordon SM, Harrell FR Jr, Inouye SK, Bernard GR, Dittus RS (2004) Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. J Am Med Assoc 14:1753–1762. https://doi.org/10.1001/jama.291.14.1753 CrossRefGoogle Scholar
- 37.Duprey MS, Al-Qadheeb N, Roberts R, Skrobik Y, Schumaker G, Devlin JW (2016) The use of low-dose IV haloperidol is not associated with QTc prolongation: post hoc analysis of a randomized, placebo-controlled trial. Intensive Care Med 42:1818–1819. https://doi.org/10.1007/s00134-016-4512-3 CrossRefPubMedGoogle Scholar