Interações medicamentosas em Terapia Intensiva Neonatal e suas relações com desfechos clínicos

Abstract

Introduction: Neonates under intensive care are susceptible to adverse events due to physiological immaturity, severity of cases, and administration of multiple drugs, increasing the risk of drug interactions (DIs). Unlike adult ICUs, DIs in neonatology are not well characterized, especially regarding clinical relevance and outcomes. Many of these DIs are, in fact, unavoidable, and the lack of data makes it difficult to assess their risk-benefit ratio. Objective: To investigate the occurrence of drug interactions in neonates under intensive care and their relationships with clinical outcomes. Methodology: A prospective cohort study was conducted between March 2023 and March 2024, including 365 patients admitted to the Neonatal Intensive Care Unit (NICU) of Maternidade Escola Januário Cicco (MEJC) and using at least one drug, where neonates were evaluated daily for the occurrence of DIs. Clinical, laboratory, and pharmacotherapeutic parameters were evaluated. The influence of the occurrence of DIs in neonates was correlated with the main clinical outcomes (death, treatment time, and weight variation) through univariate and multivariate modeling (logistic and mixed-effects linear). Results: Approximately 69.9% (255 patients) presented 1 or more interactions during hospitalization, with greater emphasis on interactions involving therapeutic failure (58.6%), potential arrhythmogenic (27.4%), nephrotoxic (18.3%), and those that can cause Central Nervous System depression (16.8%), where the incidence of the group of interactions related to arrhythmia and CNS depression tends to decrease over time (respectively β= -0.106; p<0.01 and β= -0.088; p<0.01). On the other hand, DIs associated with nephrotoxicity increase during hospitalization (β= 0.097; p<0.01). Potential arrhythmia-related DIs increased heart rate by 5.9% (p<0.001), those associated with nephrotoxicity decreased glomerular filtration rate by 44% (p<0.001), and those associated with CNS depression decreased heart rate by 6% (p<0.001). Conclusion: DIs were significantly associated with arrhythmias, nephrotoxicity, and central nervous system depression, negatively impacting critical clinical parameters. Although the risk of arrhythmias and CNS depression decreases with length of stay, the risk of nephrotoxicity increases. These findings emphasize the importance of careful monitoring and management of DIs to improve clinical outcomes in neonates.