• Tinka Bakker, Joanna E Klopotowska, Dave A Dongelmans, Saeid Eslami, Wytze J Vermeijden, Stefaan Hendriks, Julia Ten Cate, Attila Karakus, Ilse M Purmer, van BreeSjoerd H WSHWDepartment of Intensive Care, Ziekenhuis Gelderse Vallei, Ede, Netherlands., Peter E Spronk, Martijn Hoeksema, Evert de Jonge, Nicolette F de Keizer, Ameen Abu-Hanna, and SIMPLIFY study group.
• Department of Medical Informatics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Methodology, Amsterdam Public Health, Amsterdam, Netherlands. Electronic address: t.bakker1@amsterdamumc.nl.
• Lancet. 2024 Feb 3; 403 (10425): 439449439-449.

BackgroundDrug-drug interactions (DDIs) can harm patients admitted to the intensive care unit (ICU). Yet, clinical decision support systems (CDSSs) aimed at helping physicians prevent DDIs are plagued by low-yield alerts, causing alert fatigue and compromising patient safety. The aim of this multicentre study was to evaluate the effect of tailoring potential DDI alerts to the ICU setting on the frequency of administered high-risk drug combinations.MethodsWe implemented a cluster randomised stepped-wedge trial in nine ICUs in the Netherlands. Five ICUs already used potential DDI alerts. Patients aged 18 years or older admitted to the ICU with at least two drugs administered were included. Our intervention was an adapted CDSS, only providing alerts for potential DDIs considered as high risk. The intervention was delivered at the ICU level and targeted physicians. We hypothesised that showing only relevant alerts would improve CDSS effectiveness and lead to a decreased number of administered high-risk drug combinations. The order in which the intervention was implemented in the ICUs was randomised by an independent researcher. The primary outcome was the number of administered high-risk drug combinations per 1000 drug administrations per patient and was assessed in all included patients. This trial was registered in the Netherlands Trial Register (identifier NL6762) on Nov 26, 2018, and is now closed.FindingsIn total, 10 423 patients admitted to the ICU between Sept 1, 2018, and Sept 1, 2019, were assessed and 9887 patients were included. The mean number of administered high-risk drug combinations per 1000 drug administrations per patient was 26·2 (SD 53·4) in the intervention group (n=5534), compared with 35·6 (65·0) in the control group (n=4353). Tailoring potential DDI alerts to the ICU led to a 12% decrease (95% CI 5-18%; p=0·0008) in the number of administered high-risk drug combinations per 1000 drug administrations per patient, after adjusting for clustering and prognostic factors.InterpretationThis cluster randomised stepped-wedge trial showed that tailoring potential DDI alerts to the ICU setting significantly reduced the number of administered high-risk drug combinations. Our list of high-risk drug combinations can be used in other ICUs, and our strategy of tailoring alerts based on clinical relevance could be applied to other clinical settings.FundingZonMw.Copyright © 2024 Elsevier Ltd. All rights reserved.

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