Supratherapeutic drug concentration triggers: A novel data-driven approach to assess their value for medication safety surveillance in intensive care

Item Type: Journal Article

Authors: Langermans, Anne Paulien;Yasrebi-de Kom, Izak,A.R.;de Lange, Dylan Wayne;de Keizer, Nicolette Fransisca;Klopotowska, Joanna E. and RESCUE, Study group

Publication Date: 2026

Journal: British Journal of Clinical Pharmacology 92(9), pp. 3191–3201

Abstract: 

Aims Electronic triggers (e-triggers) are used as screening signals to detect potential adverse drug events (ADEs) and offer an effective system level approach for medication safety surveillance. Their clinical utility is typically evaluated through time-consuming manual chart review by experts, limiting implementation. Estimating associations between e-triggers and relevant ICU patient outcomes may provide a rapid, data-driven alternative. In this study, electronic supratherapeutic drug concentration triggers (eSDCT) were used as a use case. 

Methods Pseudonymized Electronic Health Record (EHR) data from adults admitted to 14 Dutch ICUs (2010-2020) were analysed. Patients with ≥1 therapeutic drug monitoring measurements were included. eSDCTs were selected based on literature, data availability and expert input. Associations with ICU Length of Stay (LOS), ICU mortality and hospital mortality were assessed using adjusted linear and logistic mixed-effects models. 

Results Among 6006 ICU admissions, 49.5% (n = 2973) had ≥1 of the five selected group-level eSDCTs. Exposed admissions showed higher hospital mortality (38.2% vs. 27.9%), ICU mortality (30.6% vs. 20.3%) and longer ICU LOS (median 13.8 IQR 5.6-28.1] vs. 7.5 3.2-15.7] days) compared with unexposed admissions. After adjustment, antibiotic and immunosuppressive eSDCTs remained associated with increased ICU mortality (OR 1.47 1.26-1.70] and 2.86 1.56-5.24]), hospital mortality (OR 1.46 1.27-1.68] and 1.81 1.07-3.10]) and prolonged ICU LOS (expB 1.82 1.71-1.94] and 2.99 2.46-3.62]). Conclusion Our data-driven approach shows that antibiotic and immunosuppressive eSDCTs are associated with worse ICU patient outcomes, supporting their implementation for ICU-level medication safety surveillance.

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