In vitro effects of an extracorporeal membrane oxygenation circuit on the sequestration of ϵ-aminocaproic acid.
OBJECTIVE
To assess the in vitro effects of drug sequestration in extracorporeal membrane oxygenation (ECMO) on ϵ-aminocaproic acid (EACA) concentrations.


METHODS
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.


CONCLUSIONS
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.
1 Pharmacy/Anesthesiology, University of Michigan Hospitals and Health Systems, Ann Arbor, MI, USA.
Deborah
D
Wagner
2 University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Miguel
M
Caraballo
3 Extracorporeal Life Support, University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA.
John
J
Waldvogel
3 Extracorporeal Life Support, University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA.
Yuki
Y
Peterson
4 Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Duxin
D
Sun
D015119:Aminocaproic Acid / Q000032:analysis* / Q000378:metabolism; D000933:Antifibrinolytic Agents / Q000032:analysis* / Q000378:metabolism; D015199:Extracorporeal Membrane Oxygenation / Q000295:instrumentation*; D006801:Humans; D010107:Oxygenators, Membrane
D000933:Antifibrinolytic Agents; D015119:Aminocaproic Acid
EACA; ECMO; aminocaproic acid; drug clearance; extracorporeal membrane oxygenation