Patterns of Medication Exposure in Children on Extracorporeal Membrane Oxygenation: A Step in Prioritizing Future Pharmacologic Studies

Abstract

To identify medications administered to pediatric patients on extracorporeal membrane oxygenation and to review the available pharmacokinetics and pharmacodynamics literature for the most commonly administered medications.

Design: Retrospective single-center study.

Setting: ICUs at Children's Hospital of Philadelphia.

Patients: Pediatric patients supported by extracorporeal membrane oxygenation between October 1, 2014, and September 30, 2018.

Interventions: None.

Measurements and main results: Drug exposure was described according to age group (< 1 mo, 1 mo to < 2 yr, 2 to < 12 yr, and > 12 yr) and ICU (cardiac, neonatal, pediatric). The association of drug exposure with patient's characteristics was examined using one-way analysis of variance for categorical variables and linear regression for continuous variables. All pharmacokinetics and pharmacodynamics literature for the 50 most commonly administered medications on extracorporeal membrane oxygenation was reviewed, with inclusion of studies that reported dosing regimens in conjunction with pharmacokinetics or pharmacodynamics data. A total of 179 different medications were administered to 254 children. Cumulative drug exposure increased with the duration of extracorporeal membrane oxygenation from a median (interquartile) of 10 drugs (6-14) at 1 week to 31 drugs (21-45) at 5 weeks following cannulation. There were significant differences in total drug exposure between age groups and ICUs. With exclusion of in vitro studies, published literature was available to support the use of 40% (20/50) of the most commonly administered medications. Dosing guidance was available for 20% (10/50) of medications and was primarily based on simulations and retrospective studies focusing on neonates and infants.

Conclusions: This study highlights specific needs for future pharmacokinetics and pharmacodynamics studies. Dosing guidelines are essential to optimize the care of critically ill children supported by extracorporeal membrane oxygenation.

Keywords: critical care; drug utilization; extracorporeal life support; pediatrics; pharmacokinetics; review literature.

Figure 1.

Median cumulative drug exposure versus days on extracorporeal membrane oxygenation (ECMO) stratified by hospitalization units (A) and age groups (B). CICU = cardiac ICU, NICU = neonatal ICU.

Figure 2.

Proportion of children supported on extracorporeal membrane oxygenation exposed to different drug classes stratified by age groups (*p < 0.05).