Pharmacokinetics of vancomycin in adults receiving extracorporeal membrane oxygenation

Wu, Chih‐Yu; Shen, Li‐Jiuan; Hsu, Li-Feng; Ko, Wen‐Je; Wu, Fe-Lin Lin

doi:10.1016/j.jfma.2015.05.017

Cited by 42 publications

(30 citation statements)

References 28 publications

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“…Therefore, a one‐compartment model may appear to fit the data without much sampling in the distribution phase. Our study also reports similar results to other PK studies in adults receiving vancomycin and ECMO therapy . These studies generally report either no or limited differences in patients receiving ECMO compared to non‐ECMO patients.…”

Section: Discussionsupporting

confidence: 89%

A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy

Healy

Thoma

et al. 2016

CPT Pharmacom & Syst Pharma

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The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration–time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log‐likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach. The pharmacokinetics of vancomycin was adequately described with a two‐compartment model. Parameters included clearance of 2.83 L/hr, limited central volume of distribution 24.2 L, and low residual variability 0.67%. Findings from the analysis suggest that standard dosing recommendations for vancomycin in non‐ECMO patients are adequate to achieve therapeutic trough concentrations in ECMO patients. This further shows that ECMO minimally affects the PK of vancomycin in adults including in higher‐weight patients.

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Section: Discussionsupporting

confidence: 89%

A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy

Healy

Thoma

et al. 2016

CPT Pharmacom & Syst Pharma

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“…Data in adults is limited. Clvan in patients receiving ECMO with a roller pump was significantly lower than that in the matched cohort . As a result of drug sequestration and increased Vd, the ECMO procedure might lead to a decrease in drug concentrations.…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 81%

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Monteiro

Hahn

Gonçalves

et al. 2018

Pharmacology Res & Perspec

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Vancomycin is a fundamental antibiotic in the management of severe Gram‐positive infections. Inappropriate vancomycin dosing is associated with therapeutic failure, bacterial resistance and toxicity. Therapeutic drug monitoring (TDM) is acknowledged as an important part of the vancomycin therapy management, at least in specific patient subpopulations, but implementation in clinical practice has been difficult because there are no consensus and agglutinator documents. The aims of the present work are to present an overview of the current knowledge on vancomycin TDM and population pharmacokinetic (PPK) models relevant to specific patient subpopulations. Based on three published international guidelines (American, Japanese and Chinese) on vancomycin TDM and a bibliographic review on available PPK models for vancomycin in distinct subpopulations, an analysis of evidence was carried out and the current knowledge on this topic was summarized. The results of this work can be useful to redirect research efforts to address the detected knowledge gaps. Currently, TDM of vancomycin presents a moderate level of evidence and practical recommendations with great robustness in neonates, pediatric and patients with renal impairment. However, it is important to investigate in other subpopulations known to present altered vancomycin pharmacokinetics (eg neurosurgical, oncological and cystic fibrosis patients), where evidence is still unsufficient.

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“…Despite a lack of significant differences in PK in adults, there were noteworthy findings. First, the ECMO circuit loss of vancomycin was not significant because concomitant use of albumin decreased binding within the ECMO circuit . Second, the mean time to reach target trough concentrations of vancomycin was significantly longer in the ECMO group than in the non‐ECMO group .…”

Section: Resultsmentioning

confidence: 97%

“…However, the results of 3 studies of the PK of vancomycin in adult patients differed from those of the paediatric studies. These studies uniformly demonstrated that there were no statistically significant differences in the Vd, CL or elimination rate constant ( Ke ) between ECMO patients and intensive care unit patients not receiving ECMO . This difference in results may be explained by the difference in the contribution of priming fluid to the extracellular fluid in the body between neonates and adults (36% for a 4‐kg neonate vs 15% for a 70‐kg adult) …”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic changes of antibiotic, antiviral, antituberculosis and antifungal agents during extracorporeal membrane oxygenation in critically ill adult patients

2017

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SummaryWhat is known and objective: Extracorporeal membrane oxygenation (ECMO) is a life-saving system used for critically ill patients with cardiac and/or respiratory failure.The pharmacokinetics (PK) of drugs can change in patients undergoing ECMO, which can result in therapeutic failure or drug toxicity requiring further management of drug complications. In this review, we discussed changes in the PK of antibiotic, antiviral, antituberculosis and antifungal agents administered to adult patients on ECMO. These drugs are crucial for managing infections, which commonly occur during ECMO. Methods:A literature search was conducted using the PubMed and EMBASE databases with the following keywords: "extracorporeal membrane oxygenation OR extracorporeal membrane oxygenations OR ECMO" and "PK OR pharmacokinetics OR pharmacokinetic*" and "anti infective* OR antibiotic* OR antiviral* OR antituberculosis OR antifungal*."Results and discussion: Generally, the volume of distribution (Vd) increases and drug clearance (CL) and elimination decrease during ECMO. Highly significant changes in drug PK can occur by interactions with the ECMO device itself, drug characteristics, pathological changes and patient characteristics. This may affect the blood concentrations of drugs, which influence the success of therapy. The PK of vancomycin, piperacillin-tazobactam, meropenem, azithromycin, amikacin and caspofungin did not change significantly in adult patients receiving ECMO. However, there were significant changes in the PK of imipenem, oseltamivir, rifampicin and voriconazole. The trough concentrations of imipenem were highly variable; oseltamivir had a decreased CL and increased Vd, and rifampicin concentrations were below therapeutic levels, even when a higher-than-standard dose was used in patients treated with ECMO.Additionally, voriconazole exhibited high mean peak concentrations during ECMO. What is new and conclusion:The impact of ECMO on PK varies among drugs in adult patients, and there is no consistent correlation between the effects observed in adult and infant studies. This review suggested that doses of imipenem, oseltamivir, rifampicin and voriconazole should be adjusted and therapeutic drug monitoring is needed when ECMO is used in adult patients. In the future, large PK trials in adults on ECMO are needed to provide optimal dosing guidelines. A PK/PD modelling approach will be useful for determining the precise impact of ECMO and other factors that *[Correction added on 23 October 2017, after first online publication: Author Contributors section has been added].

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Pharmacokinetics of vancomycin in adults receiving extracorporeal membrane oxygenation

Abstract: Vancomycin clearance in patients receiving ECMO with a roller pump was significantly lower than that in the matched cohort. Vancomycin PK parameters in patients on ECMO with a centrifugal pump were comparable to those in the matched control group.

Cited by 42 publications

References 28 publications

A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy

A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Pharmacokinetic changes of antibiotic, antiviral, antituberculosis and antifungal agents during extracorporeal membrane oxygenation in critically ill adult patients

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