Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study

SIMPLIFY Study Group, Tinka Bakker*, Ameen Abu-Hanna, Dave A Dongelmans, Wytze J Vermeijden, Rob J Bosman, Dylan W de Lange, Joanna E Klopotowska, Nicolette F de Keizer, S Hendriks, J Ten Cate, P F Schutte, D van Balen, M Duyvendak, A Karakus, M Sigtermans, E M Kuck, N G M Hunfeld, H van der Sijs, P W de FeiterE-J Wils, P E Spronk, H J M van Kan, M S van der Steen, I M Purmer, B E Bosma, H Kieft, R J van Marum, E de Jonge, A Beishuizen, K Movig, F Mulder, E J F Franssen, W M van den Bergh, W Bult, M Hoeksema, E Wesselink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting.

MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting.

RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs.

CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Original languageEnglish
Pages (from-to)124-130
Number of pages7
JournalJournal of Critical Care
Publication statusPublished - Apr-2021


  • Intensive care
  • Drug-drug interactions
  • Patient safety
  • Pharmacoepidemiology
  • Clinical decision support
  • Medication safety

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