BackgroundEpinephrine administered by low umbilical venous catheter (UVC) or endotracheal tube (ETT) is indicated in neonates who fail to respond to positive pressure ventilation and chest compressions at birth. Pharmacokinetics of ETT epinephrine via fluid‐filled lungs or UVC epinephrine in the presence of fetal shunts is unknown. We hypothesized that epinephrine administered by ETT or low UVC results in plasma epinephrine concentrations and rates of return of spontaneous circulation (ROSC) similar to right atrial (RA) epinephrine.Methods and ResultsForty‐four lambs were randomized into the following groups: RA epinephrine (0.03 mg/kg), low UVC epinephrine (0.03 mg/kg), postcompression ETT epinephrine (0.1 mg/kg), and precompression ETT epinephrine (0.1 mg/kg). Asystole was induced by umbilical cord occlusion. Resuscitation was initiated following 5 minutes of asystole. Thirty‐eight of 44 lambs achieved ROSC (10/11, 9/11, and 12/22 in the RA, UVC, and ETT groups, respectively; subsequent RA epinephrine resulted in a total ROSC of 19/22 in the ETT groups). Median time (interquartile range) to achieve ROSC was significantly longer in the ETT group (including those that received RA epinephrine) compared to the intravenous group (4.5 [2.9–7.4] versus 2 [1.9–3] minutes; P=0.02). RA and low UVC epinephrine administration achieved comparable peak plasma epinephrine concentrations (470±250 versus 450±190 ng/mL) by 1 minute compared to ETT values of 130±60 ng/mL at 5 minutes; P=0.03. Following ROSC with ETT epinephrine alone, there was a delayed peak epinephrine concentration (652±240 ng/mL).ConclusionsThe absorption of ETT epinephrine is low and delayed at birth. RA and low UVC epinephrine rapidly achieve high plasma concentrations resulting in ROSC.

Objective Continuous chest compressions (CCCs) are more effective during resuscitation in adults. Sustained inflation (SI) rapidly establishes functional residual capacity in fluid-filled lungs at birth. We sought to compare the hemodynamics and success in achieving return of spontaneous circulation (ROSC) in an asphyxial cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs between subjects receiving CCCs during SI and those receiving conventional 3:1 compression-to-ventilation resuscitation. Design Prospective, randomized, animal model study. Setting An experimental laboratory. Subjects Fourteen newborn term gestation lambs. Interventions Lambs were randomized into two groups: 3:1 compression-to-ventilation (control) and CCCs during SI (SI+CCCs). The umbilical cord was occluded to induce asphyxia and asystole. The control group was resuscitated per NRP guidelines. In the SI+CCCs group, SI at 35cm H2O was provided for 30 seconds with 1-second interruptions before another SI was provided. 120 chest compressions/min started after the initial SI. The first dose of IV epinephrine was given at 6 minutes if ROSC was not achieved, and then every 3 minutes until ROSC or for a total of four doses. Measurement and Results All lambs achieved ROSC in a comparable median time (interquartile range) of 390 (225–405) and 345 (204–465) seconds in the SI+CCCs and control groups, respectively. 4/7 (SI+CCCs) and 3/6 (control) lambs required epinephrine to achieve ROSC. Diastolic blood pressures were lower in the SI+CCCs (4 ± 2 mmHg) compared to the control group (7 ± 2 mmHg); P<0.05. PaCO2, PaO2, and lactate were similar between the groups during the study period. Conclusion In this perinatal cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs, SI+CCC is as effective as 3:1 C:V resuscitation in achieving ROSC. Half the lambs achieved ROSC without epinephrine. CCCs during SI reduced diastolic pressures but did not alter gas exchange or carotid blood flow compared to 3:1 C:V resuscitation.

ObjectivesNeonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest.DesignForty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored.ResultsTen lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush.Conclusions0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

Background The Neonatal Resuscitation Program recommends initial resuscitation of preterm infants with low oxygen (O2) followed by titration to target preductal saturations (SpO2). We studied the effect of resuscitation with titrated O2 on gas exchange, pulmonary and systemic hemodynamics. Methodology Twenty-nine preterm lambs (127d-gestation) were randomized to resuscitation with 21%O2 (n=7), 100%O2 (n=6) or initiation at 21% and titrated to target SpO2 (n=16). Seven healthy term control lambs were ventilated with 21%O2. Results Preductal SpO2 achieved by titrating O2 was within the desired range similar to term lambs in 21%O2. Resuscitation of preterm lambs with 21 and 100%O2 resulted in SpO2 below and above the target respectively. Ventilation of preterm lambs with 100%O2 and term lambs with 21%O2 effectively decreased pulmonary vascular resistance (PVR). In contrast, preterm lambs with 21%O2 and titrated O2 demonstrated significantly higher PVR than term lambs on 21%O2. Conclusion(s) Initial resuscitation with 21%O2 followed by titration of O2 led to suboptimal pulmonary vascular transition at birth in preterm lambs. Ventilation with 100%O2 in preterm lambs caused hyperoxia but reduced PVR similar to term lambs on 21%O2. Studies evaluating initiation of resuscitation at higher O2 concentration followed by titration based on SpO2 in preterm neonates are needed.

PurposeCurrent knowledge about pulmonary/systemic hemodynamics and gas exchange during neonatal resuscitation in a model of transitioning fetal circulation with fetal shunts and fluid-filled alveoli is limited. Using a fetal lamb asphyxia model, we sought to determine whether hemodynamic or gas-exchange parameters predicted successful return of spontaneous circulation (ROSC).MethodsThe umbilical cord was occluded in 22 lambs to induce asphyxial cardiac arrest. Following five minutes of asystole, resuscitation as per AHA-Neonatal Resuscitation Program guidelines was initiated. Hemodynamic parameters and serial arterial blood gases were assessed during resuscitation.ResultsROSC occurred in 18 lambs (82%) at a median (IQR) time of 120 (105–180) seconds. There were no differences in hemodynamic parameters at baseline and at any given time point during resuscitation between the lambs that achieved ROSC and those that did not. Blood gases at arrest prior to resuscitation were comparable between groups. However, lambs that achieved ROSC had lower PaO2, higher PaCO2, and lower lactate during resuscitation. Increase in diastolic blood pressures induced by epinephrine in lambs that achieved ROSC (11 ±4 mmHg) did not differ from those that were not resuscitated (10 ±6 mmHg). Low diastolic blood pressures were adequate to achieve ROSC.ConclusionsHemodynamic parameters in a neonatal lamb asphyxia model with transitioning circulation did not predict success of ROSC. Lactic acidosis, higher PaO2 and lower PaCO2 observed in the lambs that did not achieve ROSC may represent a state of inadequate tissue perfusion and/or mitochondrial dysfunction.