Severe Potential Drug-Drug Interactions and the Increased Length of Stay of Children in Intensive Care Unit.

Elisangela Da Costa Lima,Raquel Belmino De Souza,Barbara Dias Camarinha,Luciane Cruz Lopes,Anderson Gonçalves Panisset,Marcus Tolentino Silva,Nathalia Cristina Ferreira Bezerra

doi:10.3389/fphar.2020.555407

Abstract

Children are exposed to drug-drug interactions (DDI) risks due to their organism’s complexity and the need for several medicines prescriptions in pediatric intensive care units (PICU). This study aimed to assess the prevalence of potential DDIs in a Brazilian PICU. We carried out a cross-sectional study at a pediatric teaching hospital from Rio de Janeiro (Brazil) over one year. Potential DDIs (pDDIs) between prescribed medicines for hospitalized children in PICU (n = 143) were analyzed according to severity using Micromedex®. Sex, age group, number of drugs prescribed, vasoactive amines use (a proxy of clinical complexity), and the PICU length of stay were summarized using descriptive statistics. Association between the PICU length stay, and variables sex, age, clinical condition complexity, number of drugs prescribed, and severity of pDDI were examined by univariate and multiple linear regression. Seventy percent of patients aged three days to 14 years old were exposed at least one potential DDIs during PICU stay. Two hundred eighty-four different types of pDDIs were identified, occurring 1,123 times. Nervous system drugs were implicated in 55% of the interactions, and fentanyl (10%) was most involving in pDDIs. Most pDDIs were classified as higher severity (56.2%), with reasonable documentation (64.6%) and unspecified onset time (63.8%). Worse clinical condition, ten or more drugs prescribed, and most severe pDDIs were associated with a longer PICU length of stay. Multiple linear regression analysis showed an increase of 9.83 days (95% confidence interval: 3.61–16.05; p = 0.002) in the PICU length of stay in children with major or contraindicated pDDIs. The results of this research may support the monitoring and prevention of pDDIs related to adverse events in children in intensive care and the design and conduction of new studies.

Highlights

Adverse drug events (ADE) are among the leading causes of increased morbidity, mortality, and health costs (Dai et al, 2016)
Potential Drug-drug interaction (DDI) refers to the possibility, in theory, of one drug physiologically altering the pharmacological effects of another drug, concomitantly prescribed (Brunton et al, 2010)
A cross-sectional study was conducted, and data were collected over one year (May 2014 and April 2015) at a pediatric teaching hospital located in Rio de Janeiro (Brazil) and integrated into the public health system

Summary

Introduction

Adverse drug events (ADE) are among the leading causes of increased morbidity, mortality, and health costs (Dai et al, 2016). The hepatic and urinary systems’ maturation is slow, which means less expression or even lack of cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, and CYP2D6 isoenzymes), decreased renal blood flow, glomerular filtration, and tubular function, until the age of three-years-old (Fernandez et al, 2011). These variations may affect the absorption, distribution, metabolism, and elimination of drugs in children, increasing the risk of toxicity (Fernandez et al, 2011). Potential DDI (pDDI) refers to the possibility, in theory, of one drug physiologically altering the pharmacological effects of another drug, concomitantly prescribed (Brunton et al, 2010)

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