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 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.

Electrographic Seizures and Brain Injury in Children Requiring Extracorporeal Membrane Oxygenation.

BACKGROUND: Single-center studies suggest that up to 30% of children undergoing extracorporeal membrane oxygenation have electrographic seizures. The aim of this study was to characterize seizure prevalence, seizure risk factors, and brain injury prevalence in the pediatric extracorporeal membrane oxygenation population at a tertiary care children's hospital. METHODS: We performed a retrospective systematic review of medical records for 86 consecutive children (neonates to age 21 years) who received Neurology consults and continuous video electroencephalography while undergoing extracorporeal membrane oxygenation from November 2015 to September 2018. RESULTS: Continuous video electroencephalography was initiated in 86 of 170 children who required extracorporeal membrane oxygenation (51%); median duration of continuous vodeo electroencephalography was four days. Nineteen of 86 had electroencephalography-confirmed seizures (22%). Sixteen of 19 had seizures within the first 48 hours on continuous video electroencephalography. Interictal epileptiform discharges were a significant risk factor for seizures; 89% of those with seizures versus 46% of those without had interictal epileptiform discharges (P < 0.001, Fisher's exact test). Children with seizures also had higher pericannulation lactate (median 6.7, interquartile range of 4.3 to 19.0 for those with, and median 4.0, interquartile range of 2.0 to 7.3 for those without; P = 0.02, Mann-Whitney U test). Seizures were associated with hemorrhage on neuroimaging (68% of children with seizures had intracranial hemorrhage versus 34% of those without, P = 0.01, chi-square test). CONCLUSION: Approximately half the children undergoing extracorporeal membrane oxygenation received continuous video electroencephalography during the study period, and 22% had seizures. Interictal epileptiform discharges and elevated pre-extracorporeal membrane oxygenation lactate levels were risk factors for seizures; seizures were associated with intracranial hemorrhage.