Lisa D Burry1, David R Williamson2, Sangeeta Mehta3, Marc M Perreault4, Ioanna Mantas5, Ranjeeta Mallick6, Dean A Fergusson7, Orla Smith8, Eddy Fan9, Sebastien Dupuis10, Margaret Herridge11, Louise Rose12. 1. Department of Pharmacy, Sinai Health System, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. Electronic address: lisa.burry@sinaihealthsystem.ca. 2. Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, 5400 Boulevard Gouin Ouest, Montreal, Quebec H4J 1C5, Canada. Electronic address: david.williamson@umontreal.ca. 3. Department of Medicine, Sinai Health System, 600 University Ave, Toronto, Ontario M5G 1X5, Canada. Electronic address: geeta.mehta@utoronto.ca. 4. Department of Pharmacy, The Montreal General Hospital, McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada. Electronic address: marc.perreault@umontreal.ca. 5. Department of Pharmacy, Sinai Health System, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. Electronic address: ioanna.mantas@sinaihealthsystem.ca. 6. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Centre for Practice-Changing Research, 501 Smyth Road, Box 201B, Ottawa, Ontario K1H 8L6, Canada. Electronic address: rmallick@ohri.ca. 7. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Centre for Practice-Changing Research, 501 Smyth Road, Box 201B, Ottawa, Ontario K1H 8L6, Canada. Electronic address: dafergusson@ohri.ca. 8. Critical Care Department, St. Michael's Hospital Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada. Electronic address: smitho@smh.ca. 9. Interdepartmental Division of Critical Care Medicine and Institute for Health Policy, Management and Evaluation, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2, Canada. Electronic address: eddy.fan@uhn.ca. 10. Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, 5400 Boulevard Gouin Ouest, Montreal, Quebec H4J 1C5, Canada. Electronic address: sebastien.dupuis.1@umontreal.ca. 11. Interdepartmental Division of Critical Care Medicine and Institute of Medical Science, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2, Canada. Electronic address: dr.margaret.herridge@uhn.ca. 12. Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Electronic address: louise.rose@utoronto.ca.
Abstract
PURPOSE: Investigate the relationship between psychoactive drugs and delirium. MATERIALS AND METHODS: Prospective observational study of 520 critically ill adult patients admitted ≥24h to 6 intensive care units (ICUs). Data were collected on psychoactive drug exposure, use of sedation administration strategies, and incident delirium (Intensive Care Delirium Screening Checklist score≥4). RESULTS: Delirium was detected in 260 (50%) patients, median (IQR) duration 2 (1-5) days, and time to onset 3 (2-5) days. Delirious patients received more low-potency anticholinergic (P<0.0001), antipsychotic (P<0.0001), benzodiazepine (P<0.0001) and non-benzodiazepine sedative (P<0.0001), and opioid (P=0.0008) drugs. Primary regression (24-hours preceding drug exposure) revealed no association between any psychoactive drug and delirium. Post-hoc analysis (extended 48-hour exposure) revealed an association between delirium and high-potency anticholinergic (HR 2.45, 95% CI 1.08-5.54) and benzodiazepine (HR 1.08 per 5mg midazolam-equivalent increment, 95% CI 1.04-1.12) drugs. Delirious patients had longer ICU (P<0.0001) and hospital (P<0.0001) length of stay, and higher ICU and hospital mortality (P=0.003 and P=0.007, respectively). CONCLUSIONS: The identification of psychoactive drugs as modifiable delirium risk factors plays an important role in the management of critically ill patients. This is particularly important given the burden of exposure and combinations of drugs used in this vulnerable patient population.
PURPOSE: Investigate the relationship between psychoactive drugs and delirium. MATERIALS AND METHODS: Prospective observational study of 520 critically ill adult patients admitted ≥24h to 6 intensive care units (ICUs). Data were collected on psychoactive drug exposure, use of sedation administration strategies, and incident delirium (Intensive Care Delirium Screening Checklist score≥4). RESULTS:Delirium was detected in 260 (50%) patients, median (IQR) duration 2 (1-5) days, and time to onset 3 (2-5) days. Delirious patients received more low-potency anticholinergic (P<0.0001), antipsychotic (P<0.0001), benzodiazepine (P<0.0001) and non-benzodiazepine sedative (P<0.0001), and opioid (P=0.0008) drugs. Primary regression (24-hours preceding drug exposure) revealed no association between any psychoactive drug and delirium. Post-hoc analysis (extended 48-hour exposure) revealed an association between delirium and high-potency anticholinergic (HR 2.45, 95% CI 1.08-5.54) and benzodiazepine (HR 1.08 per 5mg midazolam-equivalent increment, 95% CI 1.04-1.12) drugs. Delirious patients had longer ICU (P<0.0001) and hospital (P<0.0001) length of stay, and higher ICU and hospital mortality (P=0.003 and P=0.007, respectively). CONCLUSIONS: The identification of psychoactive drugs as modifiable delirium risk factors plays an important role in the management of critically ill patients. This is particularly important given the burden of exposure and combinations of drugs used in this vulnerable patient population.
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