In vitro effects of an extracorporeal membrane oxygenation circuit on the sequestration of ϵ-aminocaproic acid

Perfusion ◽  
2016 ◽  
Vol 32 (3) ◽  
pp. 226-229 ◽  
Author(s):  
Deborah Wagner ◽  
Miguel Caraballo ◽  
John Waldvogel ◽  
Yuki Peterson ◽  
Duxin Sun
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
In Vitro Study ◽  
Aminocaproic Acid ◽  
P Value ◽  
Ecmo Circuit ◽  
Membrane Oxygenation ◽  
Pediatric Dose ◽  
In Vitro Effects ◽  
Over Time

Objective: To assess the in vitro effects of drug sequestration in extracorporeal membrane oxygenation (ECMO) on ϵ-aminocaproic acid (EACA) concentrations. Methods and Design: This in vitro study will determine changes in EACA concentration over time in ECMO circuits. A pediatric dose of 2,500 mg was administered to whole expired blood in the simulated pediatric ECMO circuit. Blood samples were collected at 0, 30, 60, 360 and 1440-minute intervals after initial administration equilibration from three different sites of the circuit: pre-oxygenator (PRE), post-oxygenator (POST) and PVC tubing (PVC) to determine the predominant site of drug loss. The circuit was maintained for two consecutive days with a re-dose at 24 hours to establish a comparison between unsaturated (New) and saturated (Old) oxygenator membranes. Comparisons between sample sites, sample times and New versus Old membranes were statistically analyzed by a linear mixed-effects model with significance defined as a p-value <0.05. Results: There were no significant differences in EACA concentration with respect to sample site, with PRE and POST samples demonstrating respective mean differences of 0.30 mg/ml and 0.34 mg/ml as compared to PVC, resulting in non-significant p-values of 0.373 [95% CI (-0.37, 0.98)] and 0.324 [95% CI (-0.34, 1.01)], respectively. The comparison of New vs. Old ECMO circuits resulted in non-significant changes from baseline, with a mean difference of 0.50 mg/ml, 95% CI (-0.65, 1.65), p=0.315. Conclusion: The findings of this study did not show any significant changes in drug concentration that can be attributed to sequestration within the ECMO circuit. Mean concentrations between ECMO circuit sample sites did not differ significantly. Comparison between New and Old circuits also did not differ significantly in the change from baseline concentration over time. Sequestration within ECMO circuits appears not to be a considerable factor for EACA administration.

In vitro clearance of dexmedetomidine in extracorporeal membrane oxygenation

Perfusion ◽  
2012 ◽  
Vol 28 (1) ◽  
pp. 40-46 ◽  
Author(s):  
D Wagner ◽  
D Pasko ◽  
K Phillips ◽  
J Waldvogel ◽  
G Annich
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Membrane Oxygenator ◽  
Ecmo Circuit ◽  
Membrane Oxygenation ◽  
Concentration Changes ◽  
Membrane Oxygenators ◽  
Serial Samples ◽  
Ecmo Therapy ◽  
Time Point

Dexmedetomidine (DMET) is a useful agent for sedation, both alone and in combination with other agents, in critically ill patients, including those on extracorporeal membrane oxygenation (ECMO) therapy. The drug is a clonidine-like derivative with an 8-fold greater specificity for the alpha 2-receptor while maintaining respiratory and cardiovascular stability. An in vitro ECMO circuit was used to study the effects of both “new” and “old” membrane oxygenators on the clearance of dexmedetomidine over the course of 24 hours. Once primed, the circuit was dosed with 840 μg of dexmedetomidine for a final concentration of 0.9 μg/ml. Serial samples, both pre- and post-oxygenator, were taken at 5, 60, 360, and 1440 minutes. Concentrations of the drug were expressed as a percentage of the original concentration remaining at each time point, both for new and old circuits. The new circuits were run at a standard flow for 24 hours, after which time the circuit was considered old and re-dosed with dexmedetomidine and the trial repeated. Results show that dexmedetomidine losses occur early in the circuits and then continue to decline. Initial losses in the first hour were 11+-65% and 59-73% pre- and post-oxygenator in the new circuit and 36-50% and 42-72% in the old circuit. The clearance of the drug through the membrane oxygenator exhibits no statistical difference between pre and post or new and old circuits. Dexmedetomidine can be expected to exhibit concentration changes during ECMO therapy. This effect appears to be more related to adsorption to the polyvinyl chloride (PVC) tubing rather than the membrane oxygenator. Dosage adjustments during dexmedetomidine administration during ECMO therapy may be warranted in order to maintain adequate serum concentrations and, hence, the desired degree of sedation.*(Lack of equilibrium)

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.

Influence of Extracorporeal Membrane Oxygenation Circuit on Nutritional Supplements

2020 ◽  
Vol 3 (5) ◽  
pp. 01-09
Author(s):  
AS Thiara
Keyword(s):  
Vitamin A ◽  
Extracorporeal Membrane Oxygenation ◽  
Ex Vivo ◽  
Nutritional Supplements ◽  
Ecmo Support ◽  
Blood Pump ◽  
Ecmo Circuit ◽  
Membrane Oxygenation ◽  
Over Time ◽  
Control Samples

Background The main function of extracorporeal membrane oxygenation (ECMO) is to provide systemic perfusion and gas exchange for patients with severe, acute respiratory or cardiac illness. The ECMO system consists of blood pump and a membrane oxygenator. ECMO oxygenator fibers, blood pump and tubing may bind circulating compounds such as drugs and nutritional components during ECMO support. Any loss of vital nutrients due to adsorption to the ECMO circuits may lead to further nutritional debilitation in critical ill patients. Objective The purpose of study is to analyze the amount of nutritional supplements adsorbed to the ECMO circuit under controlled ex vivo conditions Methods Six identical ECMO circuits were primed with fresh human whole blood and maintained under physiological conditions at 36°C for 24 hours. A dose of nutritional supplement calculated for a 70 kg patient was added. 150 mL volume was drawn from priming bag for control samples and kept under similar conditions. Blood samples were obtained at predetermined time points and analyzed for concentrations of vitamins, minerals, lipids, and proteins. Statistical analyses were performed using mixed models with robust standard errors, which allows for repeated samples within each setup and incomplete data. Results No significant differences were found between the ECMO circuits and controls for any of the measured variables: cobalamin, folate, vitamin A, glucose, concentration of minerals, HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, and total proteins. There was an initial decrease and then and increase in the concentration of cobalamin and folate. Vitamin A concentrations decreased in both groups over time. There was a decrease in concentration of glucose and an increased concentration of lactate dehydrogenase over time in both groups. Conclusion There were no changes in the concentrations of nutritional supplements in an ex vivo ECMO circuit compared to control samples, indicating that parenteral nutrition can be given during ECMO support. However, the time span of this study was limited, and the design made it impossible to investigate any functional and structural changes over time in nutritional supplements which lead to diminished effects through the ECMO circuit.

Sedative clearance during extracorporeal membrane oxygenation

Perfusion ◽  
2005 ◽  
Vol 20 (6) ◽  
pp. 309-315 ◽  
Author(s):  
Varsha Bhatt-Mehta ◽  
Gail Annich
Keyword(s):  
Gas Chromatography ◽  
Extracorporeal Membrane Oxygenation ◽  
Final Concentration ◽  
Ecmo Circuit ◽  
Single Dose Study ◽  
Blood Electrolytes ◽  
Membrane Oxygenation ◽  
Dose Study ◽  
Vitro Model

The effects of polyvinyl chloride (PVC) tubing and membrane oxygenator (MO) on the concentrations of lorazepam and morphine in the neonatal extracorporeal membrane oxygenation (ECMO) circuit were evaluated using an in vitro model that included a closed ECMO circuit with a MO, heat exchanger, bladder and PVC tubing. The circuit was primed with blood, electrolytes, albumin and heparin and maintained at physiologic pH and temperature throughout by frequent measurement of blood gas pH and a temperature probe. Lorazepam and morphine were each studied separately in three separate, but identical circuits for 6 h on the day of circuit prime (new circuit) and then again for 6 h at 24 h (old circuit). Each circuit (new and old) was spiked once with lorazepam to a final concentration of 250 ng/mL or with morphine to a final concentration of 70 ng/mL in the circuit. Serial samples were drawn at baseline and every 30/60 min for 6 h at the site of injection and pre- and post-MO for each circuit. Lorazepam and morphine concentrations were analysed using gas chromatography with electron capture and gas chromatography with mass spectrometry, respectively. The concentrations of morphine and lorazepam at various sample sites and time points were expressed as a percentage of the original concentration. This single-dose study shows that up to 50% of a dose of lorazepam and 40% of a dose of morphine may be extracted by PVC and MO during bypass, depending on the age of the circuit. As the circuits become older, this amount could increase. These data may explain, in part, the higher doses of lorazepam and morphine required to sedate patients during ECMO.

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

Membranes ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 313
Author(s):  
Chris Hoi Houng Chan ◽  
Katrina K. Ki ◽  
Meili Zhang ◽  
Cooper Asnicar ◽  
Hwajin Cho ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Blood Donors ◽  
In Vitro Study ◽  
Flow Rates ◽  
Membrane Oxygenation ◽  
Causative Factors ◽  
The Difference ◽  
Potential Factors ◽  
And Gender

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.

Insensible Water Loss During Extracorporeal Membrane Oxygenation: An In Vitro Study

ASAIO Journal ◽  
2000 ◽  
Vol 46 (5) ◽  
pp. 620-624 ◽  
Author(s):  
Teresa Camacho ◽  
Balagangadhar R. Totapally ◽  
Karl Hultquist ◽  
Gary Nelson ◽  
Damoon Eawaz ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Water Loss ◽  
In Vitro Study ◽  
Vitro Study ◽  
Membrane Oxygenation

In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation

Perfusion ◽  
2000 ◽  
Vol 15 (1) ◽  
pp. 21-26 ◽  
Author(s):  
H Mulla ◽  
G Lawson ◽  
C von Anrep ◽  
M D Burke ◽  
D U Upton ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Phase 1 ◽  
Drug Binding ◽  
Drug Uptake ◽  
Phase 2 ◽  
Ecmo Circuit ◽  
In Vitro Evaluation ◽  
Membrane Oxygenation ◽  
Sedative Drugs

Sedative agents are routinely administered to critically ill patients, both on and off extracorporeal membrane oxygenation (ECMO), to enable patients to be comfortable and facilitate patient management. It has been observed empirically in our paediatric intensive care unit that doses of sedative drugs required to achieve desired levels of sedation in ECMO patients are far greater than those used in non-ECMO patients. These differences could not simply be accounted for by differences in patient types, clinical status or sedation levels. We therefore undertook an in vitro evaluation of drug binding in ECMO circuits. This study investigated how the polyvinyl chloride (PVC) and silicone rubber components of neonatal ECMO circuits affect drug delivery in patients through drug sorption. Phase 1 investigated drug uptake by the two polymers in static solutions of known concentrations of four commonly used sedative drugs: lorazepam, midazolam, diazepam and propofol. Phase 2 involved the setting up of a complete neonatal ECMO circuit, injecting the drug solutions pre-reservoir at a flow rate of 350 ml/min and collecting samples post-oxygenator for analysis. Phase 1 results revealed significant uptake of drugs with losses in the range 40-98% and in the order propofol • diazepam • midazolam • lorazepam. Phase 2 results were similar and in the first 40 min of running an ECMO circuit only 10% of propofol passed through the circuit. These results may help to explain observed clinical phenomena and raise important issues regarding drug dosing in ECMO patients.

scholarly journals Sequestration of Voriconazole and Vancomycin Into Contemporary Extracorporeal Membrane Oxygenation Circuits: An in vitro Study

2020 ◽  
Vol 8 ◽  
Author(s):  
Genny Raffaeli ◽  
Giacomo Cavallaro ◽  
Karel Allegaert ◽  
Birgit C. P. Koch ◽  
Fabio Mosca ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
In Vitro Study ◽  
Vitro Study ◽  
Membrane Oxygenation

In Vitro Effects of Urokinase — Prevention by Different Inhibitors

1990 ◽  
Vol 64 (03) ◽  
pp. 402-406 ◽  
Author(s):  
M D Oethinger ◽  
E Seifried
Keyword(s):  
In Vitro Study ◽  
Thrombin Time ◽  
Plasma Samples ◽  
Temperature Dependent ◽  
Chloromethyl Ketone ◽  
Control Value ◽  
Dose Time ◽  
In Vitro Effects ◽  
Full Protection

SummaryThe present in vitro study investigated dose-, time- and temperature-dependent effects of two-chain urokinase plasminogen activato(u-PA, urokinase) on normal citrated plasma. When 10 μg/ml u-PA wereadded to pooled normal plasma and incubated for 30 min at an ambient temperature (25° C), α2-antiplas-min decreased to 8% of the control value. Incubation on ice yielded a decrease to 45% of control,whereas α2-antiplasmin was fully consumed at 37° C. Fibrinogen and plasminogen fell to 46% and 39%, respectively, after a 30 min incubation at 25° C. Thrombin time prolonged to 190% of control.Various inhibitors were studied with respect to their suitability and efficacy to prevent these in vitro effects. Aprotinin exhibited a good protective effect on fibrinogen at concentrations exceeding 500 KlU/ml plasma. Its use, however, was limited due to interferences with some haemostatic assays. We could demonstrate that L-Glutamyl-L-Glycyl-L-Arginyl chloromethyl ketone (GGACK) and a specific polyclonal anti-u-PA-antibody (anti-u-PA-IgG) effectively inhibited urokinase-induced plasmin generation without interfering with haemostatic assays. The anti-u-PA-antibody afforded full protection ofα2-antiplasmin at therapeutic levels of u-PA.It is concluded that u-PA in plasma samples from patients during thrombolytic therapy may induce in vitro effects which should be prevented by the use of a suitable inhibitor such as GGACK or specific anti-u-PA-antibody.

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