Adverse drug events caused by three high-risk drug–drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study

Joanna E. Klopotowska*, Jan Hendrik Leopold, Tinka Bakker, Izak Yasrebi-de Kom, Frouke M. Engelaer, Evert de Jonge, Esther K. Haspels-Hogervorst, Walter M. van den Bergh, Maurits H. Renes, Bas T. Jong, Hans Kieft, Andre Wieringa, Stefaan Hendriks, Cedric Lau, Sjoerd H.W. van Bree, Hendrick J.W. Lammers, Peter C. Wierenga, Rob J. Bosman, Vincent M. de Jong, Mirjam SlijkhuisEric J.F. Franssen, Wytze J. Vermeijden, Joost Masselink, Ilse M. Purmer, Liesbeth E. Bosma, Martin Hoeksema, Elsbeth Wesselink, Dylan W. de Lange, Nicolette F. de Keizer, Dave A. Dongelmans, Ameen Abu-Hanna

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
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Abstract

Aims: Knowledge about adverse drug events caused by drug–drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. 

Methods: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. 

Results: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). 

Conclusion: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.

Original languageEnglish
Pages (from-to)164-175
Number of pages12
JournalBritish Journal of Clinical Pharmacology
Volume90
Issue number1
DOIs
Publication statusPublished - Jan-2024

Keywords

  • adverse drug events
  • drug–drug interactions
  • intensive care
  • patient safety
  • triggers

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