TY - JOUR
T1 - Adverse drug events caused by three high-risk drug–drug interactions in patients admitted to intensive care units
T2 - A multicentre retrospective observational study
AU - Klopotowska, Joanna E.
AU - Leopold, Jan-Hendrik
AU - Bakker, Tinka
AU - Yasrebi-de Kom, Izak
AU - Engelaer, Frouke M.
AU - de Jonge, Evert
AU - Haspels-Hogervorst, Esther K.
AU - van den Bergh, Walter M.
AU - Renes, Maurits H.
AU - Jong, Bas T.
AU - Kieft, Hans
AU - Wieringa, Andre
AU - Hendriks, Stefaan
AU - Lau, Cedric
AU - van Bree, Sjoerd H. W.
AU - Lammers, Hendrick J. W.
AU - Wierenga, Peter C.
AU - Bosman, Rob J.
AU - de Jong, Vincent M.
AU - Slijkhuis, Mirjam
AU - Franssen, Eric J. F.
AU - Vermeijden, Wytze J.
AU - Masselink, Joost
AU - Purmer, Ilse M.
AU - Bosma, Liesbeth E.
AU - Hoeksema, Martin
AU - Wesselink, Elsbeth
AU - de Lange, Dylan W.
AU - de Keizer, Nicolette F.
AU - Dongelmans, Dave A.
AU - Abu-Hanna, Ameen
N1 - Funding Information: We thank all participating ICUs, their patients, and The Netherlands Organisation for Health Research and Development (ZonMw) for making this study possible. Especially we would like to acknowledge assistance of Johan Vogelaar from Itémedical with data extractions, staff of NICE research and support with linking EHR data with NICE data, and help of EHR specialists at the participating ICUs in identifying EHR records for review and their availability for questions from our research team regarding the data. Furthermore, we would like to thank Alden van Putten from Clinical Research Unit of Amsterdam UMC, for his help in developing the eCRFs in CASTOR EDC. Funding Information: This study was funded by The Netherlands Organisation for Health Research and Development (ZonMw project number: 836041019). The funder had no role in the design of the study or writing the manuscript. Funding information Publisher Copyright: © 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - adverse drug events
KW - drug–drug interactions
KW - intensive care
KW - patient safety
KW - triggers
UR - http://www.scopus.com/inward/record.url?scp=85169689287&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bcp.15882
DO - https://doi.org/10.1111/bcp.15882
M3 - Article
C2 - 37567767
SN - 0306-5251
VL - 90
SP - 164
EP - 175
JO - British journal of clinical pharmacology
JF - British journal of clinical pharmacology
IS - 1
ER -