Epidemiology of Polypharmacy and Potential Drug-Drug Interactions Among Pediatric Patients in ICUs of U.S. Children's Hospitals

Abstract

Objectives: Polypharmacy is common in hospitalized children in the United States and has been identified as a major risk factor for exposure to potential drug-drug interactions. Little is known about the characteristics and prevalence of exposure of pediatric patients to polypharmacy and potential drug-drug interactions in PICUs.

Design: Retrospective cohort study using the Pediatric Health Information System database.

Setting: Forty-two freestanding children's hospitals throughout the United States.

Patients: A total of 54,549 patients less than 18 years old cared for in PICUs in 2011. Patients in neonatal ICUs were not included.

Measurements and main results: PICU patients were on average exposed to 10 distinct drugs each hospital day and to 20 drugs cumulatively during their hospitalization. Seventy-five percent of patients were exposed to greater than or equal to one potential drug-drug interaction regardless of severity level, 6% to greater than or equal to one contraindicated potential drug-drug interaction, 69% to greater than or equal to one major potential drug-drug interaction, 57% to greater than or equal to one moderate potential drug-drug interaction, 19% to greater than or equal to one minor potential drug-drug interaction. Potential drug-drug interaction exposures were significantly associated with specific diagnoses (p < 0.001), presence of complex chronic conditions (p < 0.001), increasing number of total distinct drugs used (p < 0.001), increasing length of stay in PICU (p < 0.001), and white race (p < 0.001).

Conclusions: Many PICU patients are exposed to substantial polypharmacy and potential drug-drug interactions. Future research should identify the risk of adverse drug events following specific potential drug-drug interaction exposures, especially the risk of adverse drug events due to multiple potential drug-drug interaction exposures, and determine the probability and magnitude of the actual harm (if any) for each specific potential drug-drug interaction, especially for multiple potential drug-drug interaction exposures.

Figure 1

Number of daily and cumulative distinct drug and therapeutic agent exposures in PICU patients by age group. Shown are the levels of exposure to distinct drugs and therapeutic agents for each hospital day, from day 1 up to day 30 of hospitalization in ICU, for patients who remained in ICU for those lengths of stay. For each hospital day, we determined the level of exposure for patients at various percentiles of exposure; the plotted solid lines display the median, the plotted short dash lines display 10^th and the 90^th percentiles, and the shaded zone the interquartile range (IQR). Number of daily drug exposures is defined as the number of distinct drug and therapeutic agent that patients at each percentile were exposed to on that hospital day in ICU. Number of cumulative drug exposures is defined as the number of distinct drug and therapeutic agent that patients at each percentile were exposed to up to and including that hospital day in ICU.

Figure 2

Number of daily and cumulative distinct PDDI exposures in PICU patients by age group. Shown are the levels of exposure to distinct PDDI for each hospital day, from day 1 up to day 30 of hospitalization in ICU, for patients who remained in ICU for those lengths of stay. For each hospital day, we determined the level of exposure for patients at various percentiles of exposure; the plotted solid lines display the median, the plotted short dash lines display 10^th and the plotted 90^th percentiles, and the shaded zone the interquartile range (IQR). Number of daily PDDI exposures is defined as the number of distinct PDDI that patients at each percentile were exposed to on that hospital day in ICU. Number of cumulative PDDI exposures is defined as the number of distinct PDDI that patients at each percentile were exposed to up to and including that hospital day in ICU.