Ex vivo models for research in extracorporeal membrane oxygenation: a systematic review of the literature

Malfertheiner, Maximilian; Broman, Lars Mikael; Vercaemst, Leen; Belliato, Mirko; Aliberti, Anna; Nardo, Matteo Di; Swol, Justyna; Barrett, Nicholas A; Pappalardo, Federico; Bělohlávek, Jan; Taccone, Fabio Silvio; Millar, Jonathan; Crawford, Lachlan; Lorusso, Roberto; Suen, Jacky Y.

doi:10.1177/0267659120907439

Cited by 5 publications

(9 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, this occurs only in the case of less susceptible strains to the selected antibiotic and if renal function is not impaired, in particular during the very early phase of therapy. The use of ECMO has been shown to further alter drug PK, especially in ex vivo studies, primarily due to sequestration of antibiotics in the ECMO circuit, increased Vd and decreased drug CL [17], although the extent of such changes remains poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

“…As such, 110 patients for a total of 222 TDMs (CEF, n = 41; TZP, n = 85; MEM, n = 96) were included in the final analysis. Characteristics of the study population are shown in Table 2; APACHE II score on admission was 24 [17][18][19][20][21][22][23][24][25][26][27][28][29] and VA ECMO was used in 33 (30%) patients. Respiratory infections were the most frequent; Pseudomonas aeruginosa was identified in 24 (21%) patients.…”

Section: Study Populationmentioning

confidence: 99%

“…Respiratory infections were the most frequent; Pseudomonas aeruginosa was identified in 24 (21%) patients. ICU length of stay was 19 [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] days and ICU mortality was reported in 61 (55%) patients.…”

Section: Study Populationmentioning

confidence: 99%

See 2 more Smart Citations

Prediction of Insufficient Beta-Lactam Concentrations in Extracorporeal Membranous Oxygenation Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background: The aim of this study was to identify predictors of insufficient beta-lactam concentrations in patients undergoing extracorporeal membrane oxygenation (ECMO). Methods: Retrospective analysis of all patients receiving ECMO support and treated with ceftazidime or cefepime (CEF), piperacillin/tazobactam (TZP), or meropenem (MEM). Trough drug concentrations (Cmin) were measured before the subsequent dose, according to the decision of the attending physician. Insufficient drug concentrations were identified if Cmin was below the clinical breakpoint of Pseudomonas aeruginosa. Results: A total of 222 Cmin (CEF, n = 41; TZP, n = 85; MEM, n = 96) from 110 patients were included; insufficient concentrations were observed in 26 (12%) antibiotic assessments; 21 (81%) of those occurred during MEM therapy. Insufficient Cmin were associated with a shorter time from initiation of antibiotics to measurement, a lower single dose of antibiotic, a higher creatinine clearance (CrCL), lower sequential organ failure assessment (SOFA) scores, and less use of continuous renal replacement therapy (CRRT) when compared to others. Conclusions: Insufficient broad-spectrum beta-lactam concentrations were observed in 12% of drug measurement during ECMO therapy. Higher than recommended drug regimens could be considered in the very early phase of therapy and in those patients with augmented renal clearance and with less severe organ dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

See 1 more Smart Citation

Prediction of Insufficient Beta-Lactam Concentrations in Extracorporeal Membranous Oxygenation Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, tubing was depleted of the BIOLINE coating layer after rigorous cleaning. Previous studies have also used similar doses of heparin for in vitro ECMO testing [ 18 , 38 ]. However, we were able to maintain the physiological range of RBC, hematocrit ( Figure 2 ), and hemodynamic ( Table 1 ) and blood gas parameters ( Table 2 ) among different testing conditions, consistently with our previous studies using brand new circuits [ 16 ].…”

Section: Limitationsmentioning

confidence: 99%

Extracorporeal Membrane Oxygenation-Induced Hemolysis: An In Vitro Study to Appraise Causative Factors

Chan

Zhang

et al. 2021

Membranes

View full text Add to dashboard Cite

In vitro hemolysis testing is commonly used to determine hemocompatibility of ExtraCorporeal Membrane Oxygenation (ECMO). However, poor reproducibility remains a challenging problem, due to several unidentified influencing factors. The present study investigated potential factors, such as flow rates, the use of anticoagulants, and gender of blood donors, which could play a role in hemolysis. Fresh human whole blood was anticoagulated with either citrate (n = 6) or heparin (n = 12; 6 female and 6 male blood donors). Blood was then circulated for 360 min at 4 L/min or 1.5 L/min. Regardless of flow rate conditions, hemolysis remained unchanged over time in citrated blood, but significantly increased after 240 min circulation in heparinized blood (p ≤ 0.01). The ratio of the normalized index of hemolysis (NIH) of heparinized blood to citrated blood was 11.7-fold higher at 4 L/min and 16.5–fold higher at 1.5 L/min. The difference in hemolysis between 1.5 L/min and 4 L/min concurred with findings of previous literature. In addition, the ratio of NIH of male heparinized blood to female was 1.7-fold higher at 4 L/min and 2.2-fold higher at 1.5 L/min. Our preliminary results suggested that the choice of anticoagulant and blood donor gender could be critical factors in hemolysis studies, and should be taken into account to improve testing reliability during ECMO.

show abstract

“…6 Conducting clinical trials in intensive care populations, especially with pediatric patients, are often difficult to perform due to recruitment related issues, differences in ECMO techniques and equipment, and the heterogeneity of underlying pathologies. 13 Ex-vivo studies have demonstrated to be a feasible and efficient alternative to answering key questions regarding drug sequestration and adsorption. [13][14][15][16][17] Decrease in drug concentration over time in a closed loop ex-vivo ECMO circuit can be attributed either to sequestration or organ-independent metabolism, whereas in invivo ECMO studies, changes in drug concentrations are confounded by changes in hepatic or renal clearance, drug interactions, underlying disease pathologies, and use of other extracorporeal methods (i.e.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of an ex-vivo neonatal extracorporeal membrane oxygenation circuit on antiepileptic drug sequestration

et al. 2021

View full text Add to dashboard Cite

Antiepileptic dosing information used to manage neonatal patients receiving extracorporeal membrane oxygenation (ECMO) is limited. The objective of this study is to quantify the extent of sequestration of various antiepileptic drugs using an ex-vivo neonatal ECMO circuit. Two neonatal closed-loop ECMO circuits were prepared using a Rotaflow centrifugal pump, custom polyvinylchloride tubing and a Quadrox-i Neonatal membrane oxygenator. After 5 minutes of circuit priming and stabilization with normal saline/albumin or expired human whole blood, single boluses of levetiracetam (200 mg), lacosamide (20 mg), and phenytoin (200 mg) were injected into the circuit. To account for spontaneous drug degradation, two polyvinylchloride beakers were filled with normal saline/albumin or expired human whole blood and equivalent antiepileptic drug doses were prepared. Simultaneous pharmacokinetic samples were collected from the control solution and the pre-centrifugal pump, pre-oxygenator, and post-oxygenator sampling ports from each circuit. Similar drug recovery profiles were observed among the three sampling sites investigated. Percent drug sequestration after a 24-hour circuit flow period was relatively similar between the two different circuits and ranged between 5.5%–13.2% for levetiracetam, 18.4%–22.3% for lacosamide, and 24.5%–30.2% for phenytoin. A comparison at 12 and 24 hours demonstrated similar percent drug sequestration across all three drugs in each circuit. Percent drug sequestrations for levetiracetam and lacosamide were less than 20% and for phenytoin were as high as 30% based on the sampling following single bolus dose administration into a neonatal ECMO circuit. Careful consideration of patient clinical status should be taken in consideration when optimizing antiepileptic therapy in neonates receiving ECMO.

show abstract

Ex vivo models for research in extracorporeal membrane oxygenation: a systematic review of the literature

Cited by 5 publications

References 54 publications

Prediction of Insufficient Beta-Lactam Concentrations in Extracorporeal Membranous Oxygenation Patients

Prediction of Insufficient Beta-Lactam Concentrations in Extracorporeal Membranous Oxygenation Patients

Extracorporeal Membrane Oxygenation-Induced Hemolysis: An In Vitro Study to Appraise Causative Factors

Evaluation of an ex-vivo neonatal extracorporeal membrane oxygenation circuit on antiepileptic drug sequestration

Contact Info

Product

Resources

About