Associate Professor of Pediatrics University of Washington University of Washington Seattle, Washington, United States
Background: The Neonatal Resuscitation Program recommends administration of epinephrine by umbilical venous (UV) catheter or intraosseous (IO) needle for bradycardia not responding to positive pressure ventilation and chest compressions at birth. Relative pharmacokinetics and efficacy of IO as compared to UV administration in a perinatal asphyxia model remain unknown.
Objective: To determine efficacy, absorption, bioavailability and pharmacokinetics of IO as compared to UV epinephrine in a neonatal ovine asphyxia model
Design/Methods: 17 term lambs were instrumented and delivered by c-section prior to umbilical occlusion to induce asphxial arrest. IO and UV access were established during asphyxia and confirmed by blood aspiration. Lambs were randomized to receive epinephrine (0.03 mg/kg followed by 2 mL flush) via IO or UV route. Resuscitation was initiated after 5 min of asystole (+ 2 min for PEA with heart rate > 40/min) following NRP guidelines. Blinded administration of epinephrine (or concurrent saline via alternative route) was performed at 5 min and every 3 min thereafter with ongoing chest compressions. Continuous hemodynamics were monitored with serial blood sampling for blood gas analysis and determination of epinephrine concentrations by ELISA. Data were analyzed by 2-way ANOVA with post hoc Bonferroni.
Results: 17 lambs were studied with comparable demographics in the IO and UV cohorts. There were no differences in rates of return of spontaneous circulation (ROSC) or average number of epinephrine doses. However, there was a trend towards earlier ROSC in the IO cohort with median time (IQR) to ROSC of 363 (353-368) and 432 (365-469) sec for IO and UV respectively (p = 0.058) (Table 1). Epinephrine levels were comparable at ROSC with IO and UV administration (Figure 1), however comparison of concentrations from lambs who received only one dose of epinephrine identified higher peak with UV administration (Figure 2). While route of administration did not impact systolic BPs, less tachycardia, higher diastolic BPs, and higher carotid artery flows were present after IO epinephrine. Slightly lower pulmonary artery flows were also noted (Figure 3). Conclusion(s): IO epinephrine resulted in comparable pharmacokinetics and efficacy to UV administration with tendency towards early ROSC and improved hemodynamics, supporting the use of this alternative route of administration in neonatal resuscitation (particularly by non-neonatal emergency medical providers unfamiliar with UV catheter placement).
TABLE 1: Baseline Characteristics and ROSC
Data are presented as mean ± SD or median (IQR). Epi = epinephrine, ROSC = return of spontaneous circulation, PPV = positive pressure ventilation.
Figure 1: Plasma epinephrine concentrations in relation to time of ROSC
Data are presented as mean ± SD. Vertical grey bar denotes time of ROSC.
Figure 2: Plasma epinephrine concentrations following single dose of epinephrine
Data are presented as mean ± SD. * p < 0.05 by 2-way ANOVA with post hoc Bonferroni.
Figure 3: Hemodynamic parameters following ROSC
Data are presented as mean ± SD. p values by 2-way ANOVA. Carotid, pulmonary and ductal data represent mean flows.
Authors/Institutions: Sara Berkelhamer, University of Washington, Seattle, Washington, United States; Justin Helman, University at Buffalo, Grand Island, New York, United States; Sylvia F. Gugino, University at Buffalo, Sanborn, New York, United States; Pedro J. Rivera-Hernandez, University at Buffalo - Oishei Childrens Hospital, Buffalo, New York, United States; Jayasree Nair, SUNY Buffalo, Buffalo, New York, United States; Lori Nielsen, SUNY Buffalo, Buffalo, New York, United States; Satyan Lakshminrusimha, UC Davis, Sacramento, California, United States; Carmon Koenigsknecht, University at Buffalo, Buffalo, New York, United States