Abstract

Despite the high prevalence of potential drug–drug interactions in pediatric intensive care units, their clinical relevance and significance are unclear. We assessed the characteristics and risk factors of clinically relevant potential drug–drug interactions to facilitate their efficient monitoring in pediatric intensive care units. This retrospective cohort study reviewed the medical records of 159 patients aged <19 years who were hospitalized in the pediatric intensive care unit at Seoul National University Hospital (Seoul, Korea) for ≥3 days between August 2019 and February 2020. Potential drug–drug interactions were screened using the Micromedex Drug-Reax® system. Clinical relevance of each potential drug–drug interaction was reported with official terminology, magnitude of severity, and causality, and the association with the patient’s clinical characteristics was assessed. In total, 115 patients (72.3%) were exposed to 592 potential interactions of 258 drug pairs. In 16 patients (10.1%), 22 clinically relevant potential drug–drug interactions were identified for 19 drug pairs. Approximately 70% of the clinically relevant potential drug–drug interactions had a severity grade of ≥3. Exposure to potential drug–drug interactions was significantly associated with an increase in the number of administrated medications (6–7 medications, p = 0.006; ≥8, p<0.001) and prolonged hospital stays (1–2 weeks, p = 0.035; ≥2, p = 0.049). Moreover, clinically relevant potential drug–drug interactions were significantly associated with ≥8 prescribed drugs (p = 0.019), hospitalization for ≥2 weeks (p = 0.048), and ≥4 complex chronic conditions (p = 0.015). Most potential drug–drug interactions do not cause clinically relevant adverse outcomes in pediatric intensive care units. However, because the reactions that patients experience from clinically relevant potential drug–drug interactions are often very severe, there is a medical need to implement an appropriate monitoring system for potential drug–drug interactions according to the pediatric intensive care unit characteristics.

Highlights

  • Coadministration of two or more drugs is associated with a potential drug–drug interaction (PDDI), which is the possibility that the drugs alter each other’s effect [1]

  • Compared with patients who stayed in the pediatric intensive care units (PICUs) for 2 weeks had an eight-fold higher likelihood of PDDI exposure (p = 0.049)

  • We demonstrated that patients with multiple chronic conditions were at a higher risk of clinically relevant (CR)-PDDIs, and special attention is required

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Summary

Introduction

Coadministration of two or more drugs is associated with a potential drug–drug interaction (PDDI), which is the possibility that the drugs alter each other’s effect [1]. Ill patients are at a higher risk of drug-drug interactions (DDIs), due to multiple medications and because of disease complexity, accompanying organ dysfunction, and pharmacotherapy complexity [2]. With increasing concerns regarding medication safety in intensive care units (ICUs), numerous studies have reported PDDIs over the past decades. According to a recent meta-analysis, the proportion of adult patients in ICUs with exposure to at least one PDDI is 58%, which is higher than that in general wards [4]. In pediatric intensive care units (PICUs), the overall prevalence of PDDIs is 59.4%–75.2%, similar to that in adult ICUs [5,6]

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