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Pharmacokinetic Changes During Extracorporeal Membrane Oxygenation: Implications for Drug Therapy of Neonates
Abstract
Extracorporeal membrane oxygenation (ECMO) is a prolonged form of cardiopulmonary bypass used to support patients with life-threatening respiratory or cardiac failure. In neonates, ECMO is used for a variety of indications, including sepsis and pulmonary diseases such as meconium aspiration syndrome, persistent pulmonary hypertension or congenital diaphragmatic hernia. In recent years, ECMO has been increasingly used after surgery to correct congenital cardiac defects. Despite the need for numerous drugs to maintain the ECMO circuit and treat the patient's underlying illness, relatively little is known of the disposition of drugs in this patient population. To date, the largest number of pharmacokinetic studies have been conducted with gentamicin and vancomycin. Both drugs have been found to have an increased volume of distribution, probably as a result of the addition of a large exogenous blood volume for circuit priming. Elimination half-lives for both drugs are prolonged during ECMO, with several studies demonstrating a return to expected values after decannulation. The reason for this prolonged elimination is probably multifactorial, with a reduction in renal function as the primary determinant. This same pattern of an increased volume of distribution and prolonged elimination has been found for several other drugs, including tobramycin, bumetanide and ranitidine. Other factors that affect drug disposition during ECMO include loss of the drug from adhesion to the circuit components and loss in the circulating blood volume during changes in the equipment. The benzodiazepines and propofol are largely sequestered within the circuit. Serum concentrations of heparin, morphine, fentanyl, furosemide, phenytoin and phenobarbital are also reduced by these mechanisms. The addition of haemofiltration or dialysis in up to a quarter of ECMO patients further complicates the determination of population pharmacokinetic parameters. The literature published to date on the pharmacokinetic changes associated with ECMO provide preliminary support for dosage adjustment; however, more research is needed to identify optimal administration strategies for this patient population.
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“Although dosing regimens have been well established in this population, there are limited data regarding changes in dosing imposed by the use of ECLS devices.”
From Phenobarbital use in an infant requiring extracorporeal membrane life support (2013) · cites this paper as [7]
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Metadata
- Authors
- Buck, M. L.
- Affiliations
- University of Virginia Health System (US)
- Corresponding author
- Buck, Marcia L
- ORCID
- Buck, Marcia L
- Venue
- Clinical Pharmacokinetics
- Published
- 2003
- Volume
- 42
- Issue
- 5
- Pages
- 403-417
- ISSN
- 0312-5963 (ISSN-L)
- OpenAlex
- W145838624
- Cited by
- 179
- References
- 47
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 19 · 2016: 14 · 2015: 3 · 2014: 9 · 2013: 7 · 2012: 18
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacokinetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Mechanical Circulatory Support Devices
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- extracorporeal membrane oxygenation, pharmacokinetics, drug disposition, neonates, gentamicin, vancomycin, volume of distribution, elimination half-life, renal function, hemofiltration, dialysis, dose adjustment, congenital heart disease, sepsis, meconium aspiration syndrome, persistent pulmonary hypertension, congenital diaphragmatic hernia
- MeSH terms
- Animals, Pharmaceutical Preparations, Humans, Infant, Newborn, Pharmacokinetics, Extracorporeal Membrane Oxygenation, Models, Animal
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