(1) Background: Optimal initial oxygen (O₂) concentration in preterm neonates is controversial. Our objectives were to compare the effect of delayed cord clamping with ventilation (DCCV) to early cord clamping followed by ventilation (ECCV) on O₂ exposure, gas exchange, and hemodynamics in an asphyxiated preterm ovine model. (2) Methods: Asphyxiated preterm lambs (127–128 d) with heart rate <90 bpm were randomly assigned to DCCV or ECCV. In DCCV, positive pressure ventilation (PPV) was initiated with 30–60% O₂ and titrated based on preductal saturations (SpO₂) with an intact cord for 5 min, followed by clamping. In ECCV, the cord was clamped, and PPV was initiated. (3) Results: Fifteen asphyxiated preterm lambs were randomized to DCCV (N = 7) or ECCV (N = 8). The inspired O₂ (40 ± 20% vs. 60 ± 20%, p < 0.05) and oxygen load (520 (IQR 414–530) vs. 775 (IQR 623–868), p-0.03) in the DCCV group were significantly lower than ECCV. Arterial oxygenation and carbon dioxide (PaCO₂) levels were significantly lower and peak pulmonary blood flow was higher with DCCV. (4) Conclusion: In asphyxiated preterm lambs, resuscitation with an intact cord decreased O₂ exposure load improved ventilation with an increase in peak pulmonary blood flow in the first 5 min.

The current guidelines recommend the use of 100% O₂ during resuscitation of a neonate requiring chest compressions (CC). Studies comparing 21% and 100% O₂ during CC were conducted in postnatal models and have not shown a difference in incidence or timing of return of spontaneous circulation (ROSC). The objective of this study is to evaluate systemic oxygenation and oxygen delivery to the brain during CC in an ovine model of perinatal asphyxial arrest induced by umbilical cord occlusion. Pulseless cardiac arrest was induced by umbilical cord occlusion in 22 lambs. After 5 min of asystole, lambs were resuscitated with 21% O₂ as per Neonatal Resuscitation Program (NRP) guidelines. At the onset of CC, inspired O₂ was either increased to 100% O₂ (n = 25) or continued at 21% (n = 9). Lambs were ventilated for 30 min post ROSC and FiO₂ was gradually titrated to achieve preductal SpO₂ of 85–95%. All lambs achieved ROSC. During CC, PaO₂ was 21.6 ± 1.6 mm Hg with 21% and 23.9 ± 6.8 mm Hg with 100% O₂ (p = 0.16). Carotid flow was significantly lower during CC (1.2 ± 1.6 mL/kg/min in 21% and 3.2 ± 3.4 mL/kg/min in 100% oxygen) compared to baseline fetal levels (27 ± 9 mL/kg/min). Oxygen delivery to the brain was 0.05 ± 0.06 mL/kg/min in the 21% group and 0.11 ± 0.09 mL/kg/min in the 100% group and was significantly lower than fetal levels (2.1 ± 0.3 mL/kg/min). Immediately after ROSC, lambs ventilated with 100% O₂ had higher PaO₂ and pulmonary flow. It was concluded that carotid blood flow, systemic PaO₂, and oxygen delivery to the brain are very low during chest compressions for cardiac arrest irrespective of 21% or 100% inspired oxygen use during resuscitation.

The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

Background: Current neonatal resuscitation guidelines recommend the use of epinephrine for bradycardia/arrest not responding to ventilation and chest compressions. Vasopressin is a systemic vasoconstrictor and is more effective than epinephrine in postnatal piglets with cardiac arrest. There are no studies comparing vasopressin with epinephrine in newly born animal models with cardiac arrest induced by umbilical cord occlusion. Objective: To compare the effect of epinephrine and vasopressin on the incidence and time to return of spontaneous circulation (ROSC), hemodynamics, plasma drug levels, and vasoreactivity in perinatal cardiac arrest. Design/Methods: Twenty-seven term fetal lambs in cardiac arrest induced by cord occlusion were instrumented and resuscitated following randomization to epinephrine or vasopressin through a low umbilical venous catheter. Results: Eight lambs achieved ROSC prior to medication. Epinephrine achieved ROSC in 7/10 lambs by 8 ± 2 min. Vasopressin achieved ROSC in 3/9 lambs by 13 ± 6 min. Plasma vasopressin levels in nonresponders were much lower than responders after the first dose. Vasopressin caused in vivo increased pulmonary blood flow and in vitro coronary vasoconstriction. Conclusions: Vasopressin resulted in lower incidence and longer time to ROSC compared to epinephrine in a perinatal model of cardiac arrest supporting the current recommendations for exclusive use of epinephrine in neonatal resuscitation.

Resuscitation with 21% O₂ may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO₂. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147–150 d). Lambs without PPHN were ventilated with 21% O₂, titrated O₂ to maintain target oxygenation or 21% O₂ + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O₂, titrated O₂ or 50% O₂ + iNO. Resuscitation with 21% O₂ in preterm lambs and 50%O₂ in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO₂ in preterm lambs ventilated with 21% O₂ similar to that achieved by titrated O₂ (41 ± 9% at 30 min). Inhaled NO increased PaO₂ to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O₂, titrated O₂ up to 100% and 50% O₂ + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO₂ required to achieve target PaO₂.

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation–SI vs. positive pressure ventilation–V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC—immediate, DCC—60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2–3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.