Pharmacotherapy in Neonatal and Pediatric Extracorporeal Membrane Oxygenation (ECMO)

Abstract

ECMO support is an established life saving therapy for potentially reversible respiratory and/or cardiac failure. Improvement of outcome depends on effective treatment of the primary diagnosis and complications. Adequate drug therapy is important in reaching these goals. Pharmacokinetic and pharmacodynamic data in neonates and older children on ECMO are sparse. Most studies show altered volume of distribution and clearance for the drugs studied. This article gives an overview of the available PK and PD studies in neonates and children on ECMO, suggests possible mechanisms of altered PK and PD and identifies areas of interest for further research.

Children in clinical trials: towards evidence-based pediatric pharmacotherapy using pharmacokinetic-pharmacodynamic modeling

“…For children younger than 2 years of age, gestational age, postmenstrual age, postconceptual age and postnatal age may be relevant covariates as well (65). Many other covariates which can influence the PK and /or PD of the drug studied, can be collected, such as disease state, comedications or the treatment with artificial devices such as extracorporeal membrane oxygenation (ECMO), ventricular assist devices or renal replacement (66,67). In general, correlations between potential covariates should be avoided whenever possible, as the combination of two correlated covariates in a population model may result in bias in parameter estimates (68).…”

Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review

“…The three main mechanisms by which ECMO alters PK through these interactions are with drug sequestration into the circuit, increasing the volume of distribution (Vd), and altering drug clearance and elimination [11][12][13][14].…”

“…Rosen et al also described differences in drug loss between polypropylene-based and silicone-based membrane CPB oxygenators with fentanyl binding being highest for the silicone-based oxygenators [15]. Finally, the circuit component that shows the most sequestration for some drugs may be the PVC tubing [8,14,16,17,20]. That being said, a recent evaluation of modified surface coatings showed no significant effects on the sequestration of morphine or fentanyl [21].…”

“…Second, there is a dilution effect of the additional fluid required to prime and maintain the ECMO circulating volume and hemostasis [12][13][14]. These first two issues mainly affect hydrophilic drugs while drug sequestration into the circuit will mainly affect the Vd of lipophilic drugs.…”

“…Studies investigating gentamicin PK in neonates and infants describe increased Vd as well as decreased CL during ECMO[72][73][74][75][76]. The increased Vd may have some component of circuit sequestration[14], however, this has yet to be tested in newer circuit components. TDM continues to be recommended to guide dosing.an empirically increased dosing regimen with the third child likely not achieving goal plasma levels likely due to inadequate enteral absorption.…”