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

Abstract

AimKnowledge 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 drug‐drug interactions (pDDIs) in the critical care setting: pDDIs with International Normalization Ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential.MethodsWe 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 pre‐select patients with potential DDI‐ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of pre‐selected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI‐ADEs using internationally prevailing standards.ResultsIn total 85,422 patients with ≥ one pDDI were included. Of these patients, 32,820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1,141 (3.5%) patients were pre‐selected 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).ConclusionThe 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 pre‐selection strategy.