Critical care research and practice · 2026
Potential Drug-Drug Interactions in Critically Ill Neonates: Association With Clinical Outcomes in a Prospective Cohort.
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Marques Daniel Paiva, da Silva Andreza Kelly Fernandes, de Medeiros Iris Ucella, Leopoldino Ramon Weyler Duarte, Oliveira Antonio Gouveia, Lima Waldenice de Alencar Morais, Martins Rand Randall
Аннотация
BACKGROUND AND AIMS: Neonates admitted to neonatal intensive care units (NICUs) are frequently exposed to multiple medications, increasing the risk of potential drug-drug interactions (pDDIs). However, the clinical impact of these interactions remains poorly understood in this population. This study aimed to evaluate the occurrence of pDDIs in critically ill neonates and their association with clinical outcomes and laboratory parameters.
METHODS: This prospective cohort study included 365 neonates admitted to a NICU in Brazil between March 2023 and March 2024. Pharmacotherapy was monitored daily for the identification of pDDIs using the UpToDate database. Interactions were grouped according to their potential clinical outcomes and analyzed for their association with clinical and laboratory parameters. The evaluated parameters included heart rate, respiratory rate, blood pressure, creatinine clearance, urine output, and blood urea nitrogen.
RESULTS: A total of 255 neonates (69.9%) experienced at least one pDDI, most of which were classified as risk category C (88.0%). The most frequent mechanisms of pDDIs were associated with heart rate changes (27.4%), nephrotoxicity (18.3%), central nervous system (CNS) depression (14.8%), and hypotension (14.8%). Neonates with pDDIs associated with heart rate changes had higher heart rates (158.1 ± 16.7 vs. 148.7 ± 17.0 bpm; p < 0.001). Nephrotoxic pDDIs were associated with reduced creatinine clearance (14.4 ± 13.5 vs. 25.8 ± 18.2 mL/min/1.73 m2; p < 0.001) and higher blood urea nitrogen levels (52.9 ± 36.2 vs. 27.6 ± 24.4 mg/dL; p < 0.001). pDDIs associated with hypotension significantly reduced mean arterial pressure (51.1 ± 11.5 vs. 58.3 ± 11.8 mmHg; p < 0.001).
CONCLUSION: pDDIs are frequent in NICUs and are associated with clinically relevant changes, particularly those involving an increased risk of higher heart rates, renal impairment, and hypotension.
METHODS: This prospective cohort study included 365 neonates admitted to a NICU in Brazil between March 2023 and March 2024. Pharmacotherapy was monitored daily for the identification of pDDIs using the UpToDate database. Interactions were grouped according to their potential clinical outcomes and analyzed for their association with clinical and laboratory parameters. The evaluated parameters included heart rate, respiratory rate, blood pressure, creatinine clearance, urine output, and blood urea nitrogen.
RESULTS: A total of 255 neonates (69.9%) experienced at least one pDDI, most of which were classified as risk category C (88.0%). The most frequent mechanisms of pDDIs were associated with heart rate changes (27.4%), nephrotoxicity (18.3%), central nervous system (CNS) depression (14.8%), and hypotension (14.8%). Neonates with pDDIs associated with heart rate changes had higher heart rates (158.1 ± 16.7 vs. 148.7 ± 17.0 bpm; p < 0.001). Nephrotoxic pDDIs were associated with reduced creatinine clearance (14.4 ± 13.5 vs. 25.8 ± 18.2 mL/min/1.73 m2; p < 0.001) and higher blood urea nitrogen levels (52.9 ± 36.2 vs. 27.6 ± 24.4 mg/dL; p < 0.001). pDDIs associated with hypotension significantly reduced mean arterial pressure (51.1 ± 11.5 vs. 58.3 ± 11.8 mmHg; p < 0.001).
CONCLUSION: pDDIs are frequent in NICUs and are associated with clinically relevant changes, particularly those involving an increased risk of higher heart rates, renal impairment, and hypotension.