Epinephrine Administration in a Pediatric Swine Normovolemic Cardiac Arrest Model

This study will expand our current study, which is determining the effects of administration of epinephrine by intraosseous (IO), intravenous (IV), and by endotracheal (ET) routes in a hypovolemic, pediatric model of cardiac arrest. This study will the same except we will investigate intraosseous (IO), intravenous (IV), and by endotracheal (ET) routes in a normovolemic, pediatric model of cardiac arrest. The outcome variables are mean concentration (MC) over time, concentration maximum (Cmax), time to maximum concentration (Tmax), Area under the curve (AUC) of epinephrine, and return and time of spontaneous circulation (ROSC). Yorkshire Cross Swine (7 per group, total 49 + 7 for model development = 56 subjects) weighing between 20 and 30 kg will be used to simulate children between 5 and 6 years of age. The groups will consist of Sternal IO (SIO), Tibia IO (TIO), Humerus IO (HIO), intravenous (IV), ET, and two control groups (CPR only and CPR + defibrillation). All swine will be sedated, anesthetized, and placed on mechanical ventilation with monitors applied. Arterial and venous catheters will be inserted and the appropriate IO device. After 5 minutes of stabilization, we will place the swine into cardiac arrest by direct electrical current. After 2 minutes, CPR will be initiated and continued for 2 minutes. Epinephrine (0.01 mg/kg of 1:10,000) will be administered by IO or IV route depending on group assignment. The ET group will receive 0.1 mg/kg of 1:1000 concentration. One baseline and samples at 30, 60, 90, 120, 150, 180, 240, and 300 seconds will be collected. After the samples are collected, we will continue CPR and defibrillate at 2 J/kg and repeat at 4J/kg every 2 minutes or until ROSC. Epinephrine will be repeated every 4 minutes and defibrillation will continue every 2 minutes for 30 minutes or until ROSC occurs. This study will produce the data to determine the effectiveness of different routes of administration of epinephrine in a normovolemic model. The following research questions will guide the study:
1. Are there significant differences in MC, AUC, Cmax, and Tmax of epinephrine when administered by HIO, TIO, SIO, and IV routes?
2. Are there significant differences in the frequency and odds of the occurrence of ROSC in HIO, TIO, SIO, IV, CPR + defibrillation, and CPR only groups?
3. Are there significant differences in the time to ROSC between HIO, TIO, SIO, IV, CPR + defibrillation, and CPR only groups?
4. Are there significant differences in normovolemic and hypovolemic groups?
A Multivariate Analyses of Variance (MANOVA) will be used to analyze data relative to questions 1 and 3 and part of 4. The Least Significant Difference Post-Hoc test will be used to determine significance between the groups. A Fisher’s Exact test and an Odds Ratio will be used to answer question 2 and part of 4.
RELEVANCE
An estimated 6.3 million children under the age of 15 years died in 2017. Based on limited evidence, the American Heart Association recommends epinephrine be administered by IV, and if not accessible, IO or ET routes used. Our current research indicates that both the HIO and TIO routes are not effective in the hypovolemic pediatric model. No research has investigated the variables addressed in proposed study. This study will provide evidence for making clinical decisions relative to a normovolemic, pediatric, cardiac arrest model.