Effect of Epinephrine Sequestration on the Return of Spontaneous Circulation

Pediatric victims constitute approximately 6% of causalities cared for in combat theaters including Afghanistan and Iraq. Research concerning pediatric resuscitation is limited particularly among intraosseous routes of administration of catecholamine’s. Current pediatric advanced life support (PALS) algorithm recommends intraosseous access placement if intravenous routes are delayed or inaccessible. Our recent study has shown alterations in the pharmacokinetics of epinephrine administered TIO versus IV to pediatric swine in a stage 3 hemorrhagic shock cardiac arrest model. These animals, which were administered the recommended PALS dosing of epinephrine (10 mcg/kg), exhibited a prolonged time to epinephrine maximum concentrations (Tmax) with reduced maximum concentration (Cmax). More importantly, we observed a significant reduction in the frequency of return to spontaneous circulation (ROSC) and ultimately the probability of survival. We
hypothesize that exogenous epinephrine administered via TIO remains sequestered within the tibial medullary cavity due to excessive vasoconstriction and subsequently results in a reduced incidence of ROSC. The proposed study aims are designed to elucidate possible vasoconstrictive mechanisms and explore treatment regimens to ameliorate this phenomenon which may improve the incidence of ROSC. Epinephrine will be administered TIO in a pediatric hypovolemic, cardiac arrest swine model. The following data points will be calculated: frequency and odds of ROSC, Cmax, Tmax, and area under the curve (AUC) for the plot of epinephrine concentration against time. The specific aims of this study are:
1. Determine the effect of bilateral TIO administration of the PALS recommended dose of epinephrine.
2. Determine the effect of unilateral TIO administration of increased dosages epinephrine (20 mcg/kg, 40 mcg/kg).
3. Characterize the contribution of epinephrine metabolism within the tibia.
4. Characterize the contribution of venous vasoconstriction.
5. Determine the contribution of arterial alpha1 receptor-mediated vasoconstriction within the tibia. Results of the present study will provide evidenced-based data for all health care providers and will likely influence current pediatric resuscitation paradigms.
RELEVANCE TO MILITARY NURSING SCIENCE
Treatment of pediatric patients who meet medical rules of engagement can significantly improve relationships between US forces and host nation civilians and troops. The role of advanced practice nurses in the military are expanding and frequently nurses may be the only or best qualified clinician available to treat cardiac arrest among pediatric trauma victims, particularly in austere combat environments. This project offers a tremendous opportunity for nurse scientists to advance research and create knowledge to support evidence-based practice. This scientific foundation will elucidate the mechanism of epinephrine sequestration in the pediatric tibia and offer potential therapeutic strategies to reduce IO vasoconstriction and may improve the probability of ROSC
among pediatric trauma patients. These novel data will offer tremendous insight into current PALS recommendation and possibly be practice changing throughout healthcare. In addition, this grant proposal is a complementary project of the current pediatric study which has yielded exciting scientific data and resulted in numerous publications and presentations. This study supports the mission of Tri-Service Nursing Research Program, which is to positively influence health outcomes in peacetime, wartime, and operations other than war. Specifically, the study will address one of the major priorities of Force Health Protection: to care for all entrusted to our care.