Oxygenator impact on voriconazole in extracorporeal membrane oxygenation circuits

Perfusion ◽  
2020 ◽  
Vol 35 (6) ◽  
pp. 529-533
Author(s):  
Jeffrey J Cies ◽  
Wayne S Moore ◽  
Nadji Giliam ◽  
Tracy Low ◽  
Daniel Marino ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Closed Loop ◽  
Ex Vivo ◽  
Entire Study ◽  
Drug Degradation ◽  
Membrane Oxygenation ◽  
Drug Loss ◽  
In Series

Introduction: To determine the oxygenator impact on alterations of voriconazole in a contemporary neonatal/pediatric (1/4 inch) and adolescent/adult (3/8 inch) extracorporeal membrane oxygenation circuit including the Quadrox-i® oxygenator. Methods: Simulated closed-loop extracorporeal membrane oxygenation circuits (1/4 and 3/8 inch) were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. In addition, 1/4- and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of voriconazole was administered into the circuits, and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24 hour time points. Voriconazole was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation Results: For the 1/4-inch circuit, there was an approximate mean of 64-67% voriconazole loss with the oxygenator in series and mean of 15-20% voriconazole loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean of 44-51% voriconazole loss with the oxygenator in series and a mean of 8-12% voriconazole loss without an oxygenator in series at 24 hours. The reference voriconazole concentrations remained relatively constant during the entire study period demonstrating that the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation. Conclusion: This ex vivo investigation demonstrated substantial voriconazole loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant voriconazole loss in the absence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific voriconazole dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

Oxygenator impact on meropenem/vaborbactam in extracorporeal membrane oxygenation circuits

Perfusion ◽  
2021 ◽  
pp. 026765912110189
Author(s):  
Jeffrey J Cies ◽  
Peter Nikolos ◽  
Wayne S Moore ◽  
Nadji Giliam ◽  
Tracy Low ◽  
...  
Keyword(s):  
Multiple Dose ◽  
Closed Loop ◽  
Ex Vivo ◽  
Extra Corporeal Membrane Oxygenation ◽  
Ecmo Circuit ◽  
Drug Degradation ◽  
Membrane Oxygenation ◽  
In Series

Introduction: To determine the oxygenator impact on alterations of meropenem (MEM)/vaborbactam (VBR) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extra corporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. Methods: 1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of MEM/VBR was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, 8, 12, and 24-hour time points. MEM/VBR was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. Results: For the 1/4-inch circuit, there was an approximate mean 55% MEM loss with the oxygenator in series and a mean 33%–40% MEM loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean 70% MEM loss with the oxygenator in series and a mean 30%–38% MEM loss without an oxygenator in series at 24 hours. For both the 1/4-inch circuit and 3/8-inch circuits with and without an oxygenator, there was <10% VBR loss for the duration of the experiment. Conclusions: This ex-vivo investigation demonstrated substantial MEM loss within an ECMO circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant VBR loss. Further evaluations with multiple dose in-vitro and in-vivo investigations are needed before specific MEM/VBR dosing recommendations can be made for clinical application with ECMO.

scholarly journals Dexmedetomidine extraction by the extracorporeal membrane oxygenation circuit: results from an in vitro study

Perfusion ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 209-216 ◽  
Author(s):  
Samantha H Dallefeld ◽  
Jennifer Sherwin ◽  
Kanecia O Zimmerman ◽  
Kevin M Watt
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Drug Exposure ◽  
In Vitro Study ◽  
Drug Degradation ◽  
Membrane Oxygenation ◽  
Life Threatening ◽  
Patient At Risk ◽  
The Impact

Background: Dexmedetomidine is a sedative administered to minimize distress and decrease the risk of life threatening complications in children supported with extracorporeal membrane oxygenation. The extracorporeal membrane oxygenation circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. Objective: To determine the extraction of dexmedetomidine by the extracorporeal membrane oxygenation circuit. Materials and methods: Dexmedetomidine was studied in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction. Each circuit was primed with human blood according to standard practice for Duke Children’s Hospital, and flow was set to 1 L/min. Dexmedetomidine was dosed to achieve a therapeutic concentration of ~600 pg/mL. Dexmedetomidine was added to a separate tube of blood to serve as a control and evaluate for natural drug degradation. Serial blood samples were collected over 24 hours and concentrations were quantified with a validated assay. Drug recovery was calculated at each time point. Results: Dexmedetomidine was highly extracted by the oxygenator evidenced by a mean recovery of 62-67% at 4 hours and 23-34% at 24 hours in circuits with an oxygenator in-line. In contrast, mean recovery with the oxygenator removed was 96% at 4 hours and 93% at 24 hours. Dexmedetomidine was stable over time with a mean recovery in the control samples of 102% at 24 hours. Conclusion: These results suggest dexmedetomidine is extracted by the oxygenator in the extracorporeal membrane oxygenation circuit which may result in decreased drug exposure in vivo.

scholarly journals Effects of ex vivo Extracorporeal Membrane Oxygenation Circuits on Sequestration of Antimicrobial Agents

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuan Zhang ◽  
Hongbin Hu ◽  
Qing Zhang ◽  
Qing Ou ◽  
Huayou Zhou ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Antimicrobial Agents ◽  
Ex Vivo ◽  
Polymyxin B ◽  
Therapeutic Drug ◽  
Control Groups ◽  
Drug Degradation ◽  
Membrane Oxygenation ◽  
Drug Concentrations

Objectives: Our ex vivo study was designed to determine the sequestration of teicoplanin, tigecycline, micafungin, meropenem, polymyxin B, caspofungin, cefoperazone sulbactam, and voriconazole in extracorporeal membrane oxygenation (ECMO) circuits.Methods: Simulated closed-loop ECMO circuits were prepared using 2 types of blood-primed ECMO. After the circulation was stabilized, the study drugs were injected into the circuit. Blood samples were collected at 2, 5, 15, 30 min, 1, 3, 6, 12, and 24 h after injection. Drug concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Control groups were stored at 4°C after 3, 6, 12, and 24 h immersing in a water bath at 37°C to observe spontaneous drug degradation.Results: Twenty-six samples were analyzed. The average drug recoveries from the ECMO circuits and control groups at 24 h relative to baseline were 67 and 89% for teicoplanin, 100 and 145% for tigecycline, 67 and 99% for micafungin, 45 and 75% for meropenem, 62 and 60% for polymyxin B, 83 and 85% for caspofungin, 79 and 98% for cefoperazone, 75 and 87% for sulbactam, and 60 and 101% for voriconazole, respectively. Simple linear regression showed no significant correlation between lipophilicity (r2 = 0.008, P = 0.225) or the protein binding rate (r2 = 0.168, P = 0.479) of drugs and the extent of drug loss in the ECMO circuits.Conclusions: In the two ECMO circuits, meropenem and voriconazole were significantly lost, cefoperazone was slightly lost, while tigecycline and caspofungin were not lost. Drugs with high lipophilicity were lost more in the Maquet circuit than in the Sorin circuit. This study needs more in vivo studies with larger samples for further confirmation, and it suggests that therapeutic drug concentration monitoring should be strongly considered during ECMO.

Impact of ex-vivo extracorporeal membrane oxygenation circuitry on daptomycin

Perfusion ◽  
2018 ◽  
Vol 33 (8) ◽  
pp. 624-629 ◽  
Author(s):  
Jeffrey J. Cies ◽  
Wayne S. Moore ◽  
Nadji Giliam ◽  
Tracy Low ◽  
Adela Enache ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Closed Loop ◽  
Ex Vivo ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Ecmo Circuit ◽  
Drug Degradation ◽  
Membrane Oxygenation ◽  
Apparent Volume Of Distribution ◽  
Larger Sample

Background: The objective was to determine the alterations of daptomycin (DAP) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. Methods: Quarter-inch and 3/8-inch, simulated, closed-loop, ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. A one-time dose of DAP was administered into the circuit and serial pre- and post-oxygenator concentrations were obtained at 0-5 minutes and 1, 2, 3, 4, 5, 6 and 24-hour time points. DAP was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation Results: For both the 1/4-inch and 3/8-inch circuits, there was no significant DAP loss at 24 hours. Additionally, the reference DAP concentrations remained relatively constant during the entire 24-hour study period. Conclusion: This ex-vivo investigation demonstrated no significant DAP loss within an ECMO circuit with both sizes of the Quadrox-i oxygenator at 24 hours. Therapeutic concentrations of DAP in the setting of ECMO may be anticipated with current recommended doses, depending on the amount of extracorporeal volume needed for circuit maintenance in comparison to the patient’s apparent volume of distribution. Additional studies with a larger sample size are needed to confirm these findings.

scholarly journals Influence of extracorporeal membrane oxygenation on the pharmacokinetics of ceftolozane/tazobactam: an ex vivo and in vivo study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Camille Mané ◽  
Clément Delmas ◽  
Jean Porterie ◽  
Géraldine Jourdan ◽  
Patrick Verwaerde ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Ex Vivo ◽  
In Vivo Study ◽  
Membrane Oxygenation

scholarly journals Extracorporeal membrane oxygenation and V/Q ratios: an ex vivo analysis of CO2 clearance within the Maquet Quadrox-iD oxygenator

Perfusion ◽  
2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 29-33 ◽  
Author(s):  
Bishoy Zakhary ◽  
Jayne Sheldrake ◽  
Vincent Pellegrino
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Dead Space ◽  
Gas Flow ◽  
Ex Vivo ◽  
Respiratory Acidosis ◽  
Gas Flows ◽  
Membrane Oxygenation ◽  
In Series ◽  
Membrane Oxygenators ◽  
Different Levels

While hypercapnia is typically well treated with modern membrane oxygenators, there are cases where respiratory acidosis persists despite maximal extracorporeal membrane oxygenation support. To better understand the physiology of gas exchange within the membrane oxygenator, CO2 clearance within an adult Maquet Quadrox-iD oxygenator was evaluated at varying blood CO2 tensions and V/Q ratios in an ex vivo extracorporeal membrane oxygenation circuit. A closed blood-primed circuit incorporating two Maquet Quadrox-iD oxygenators in series was attached to a Maquet PLS Rotaflow pump. A varying blend of CO2 and air was connected to the first oxygenator to provide different levels of pre-oxygenator blood CO2 levels (PvCO2) to the second oxygenator. Varying sweep gas flows of 100% O2 were connected to the second oxygenator to provide different V/Q ratios. Exhaust CO2 was directly measured, and then VCO2 and oxygenator dead space fraction (VD/VT) were calculated. VCO2 increased with increasing gas flow rates with plateauing at V/Q ratios greater than 4.0. Exhaust CO2 increased with PvCO2 in a linear fashion with the slope of the line decreasing at high V/Q ratios. Oxygenator dead space fraction varied with V/Q ratio—at lower ratios, dead space fraction was 0.3-0.4 and rose to 0.8-0.9 at ratios greater than 4.0. Within the Maquet Quadrox-iD oxygenator, CO2 clearance is limited at high V/Q ratios and correlated with elevated oxygenator dead space fraction. These findings have important implications for patients requiring high levels of extracorporeal membrane oxygenation support.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

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