Background

The aim was to evaluate the relationship between the direction of the patent ductus arteriosus (PDA) shunt and the pre- and postductal gradient for arterial blood gas (ABG) parameters in a lamb model of meconium aspiration syndrome (MAS) with persistent pulmonary hypertension of the newborn (PPHN).

Methods

PPHN was induced by intermittent umbilical cord occlusion and the aspiration of meconium through the tracheal tube. After delivery, 13 lambs were ventilated and simultaneous 129 pairs of pre- and postductal ABG were drawn (right carotid and umbilical artery, respectively) while recording the PDA and the carotid and pulmonary blood flow.

Results

Meconium aspiration resulted in hypoxemia. The bidirectional ductal shunt had a lower postductal partial arterial oxygen tension ([PaO₂] with lower PaO₂/FiO₂ ratio-97 ± 36 vs. 130 ± 65 mmHg) and left pulmonary flow (81 ± 52 vs. 133 ± 82 mL/kg/min). However, 56% of the samples with a bidirectional shunt had a pre- and postductal saturation gradient of < 3%.

Conclusions

The presence of a bidirectional ductal shunt is associated with hypoxemia and low pulmonary blood flow. The absence of a pre- and postductal saturation difference is frequently observed with bidirectional right-to-left shunting through the PDA, and does not exclude a diagnosis of PPHN in this model.

Neonatal resuscitation (NRP) guidelines suggest targeting 85-95% preductal SpO2 by 10 min after birth. Optimal oxygen saturation (SpO2) targets during resuscitation and in the post-resuscitation management of neonatal meconium aspiration syndrome (MAS) with persistent pulmonary hypertension (PPHN) remains uncertain. Our objective was to compare the time to reversal of ductal flow from fetal pattern (right-to-left), to left-to-right, and to evaluate pulmonary (QPA), carotid (QCA)and ductal (QDA) blood flows between standard (85-94%) and high (95-99%) SpO2 targets during and after resuscitation. Twelve lambs asphyxiated by endotracheal meconium instillation and cord occlusion to induce MAS and PPHN were resuscitated per NRP guidelines and were randomized to either standard (85-94%) or high (95-99%) SpO2 targets. Out of twelve lambs with MAS and PPHN, six each were randomized to standard and high SpO2 targets. Median [interquartile range] time to change in direction of blood flow across the ductus arteriosus from right-to-left, to left-to-right was significantly shorter with high SpO2 target (7.4 (4.4-10.8) min) compared to standard SpO2 target (31.5 (21-66.2) min, p = 0.03). QPA was significantly higher during the first 10 min after birth with higher SpO2 target. At 60 min after birth, the QPA, QCA and QDA were not different between the groups. To conclude, targeting SpO2 of 95-99% during and after resuscitation may hasten reversal of ductal flow in lambs with MAS and PPHN and transiently increase QPA but no differences were observed at 60 min. Clinical studies comparing low and high SpO2 targets assessing hemodynamics and neurodevelopmental outcomes are warranted.

Background

The neonatal resuscitation program (NRP) recommends interrupted chest compressions (CCs) with ventilation in the severely bradycardic neonate. The conventional 3:1 compression-to-ventilation (C:V) resuscitation provides 90 CCs/min, significantly lower than the intrinsic newborn heart rate (120-160 beats/min). Continuous CC with asynchronous ventilation (CCCaV) may improve the success of return of spontaneous circulation (ROSC).

Methods

Twenty-two near-term fetal lambs were randomized to interrupted 3:1 C:V (90 CCs + 30 breaths/min) or CCCaV (120 CCs + 30 breaths/min). Asphyxiation was induced by cord occlusion. After 5 min of asystole, resuscitation began following NRP guidelines. The first dose of epinephrine was given at 6 min. Invasive arterial blood pressure and left carotid blood flow were continuously measured. Serial arterial blood gases were collected.

Results

Baseline characteristics between groups were similar. Rate of and time to ROSC was similar between groups. CCCaV was associated with a higher PaO₂ (partial oxygen tension) (22 ± 5.3 vs. 15 ± 3.5 mmHg, p < 0.01), greater left carotid blood flow (7.5 ± 3.1 vs. 4.3 ± 2.6 mL/kg/min, p < 0.01) and oxygen delivery (0.40 ± 0.15 vs. 0.13 ± 0.07 mL O₂/kg/min, p < 0.01) compared to 3:1 C:V.

Conclusions

In a perinatal asphyxiated cardiac arrest lamb model, CCCaV showed greater carotid blood flow and cerebral oxygen delivery compared to 3:1 C:V resuscitation.

Impact

In a perinatal asphyxiated cardiac arrest lamb model, CCCaV improved carotid blood flow and oxygen delivery to the brain compared to the conventional 3:1 C:V resuscitation. Pre-clinical studies assessing neurodevelopmental outcomes and tissue injury comparing continuous uninterrupted chest compressions to the current recommended 3:1 C:V during newborn resuscitation are warranted prior to clinical trials.

The combination of perinatal acidemia with postnatal hyperoxia is associated with a higher incidence of hypoxic-ischemic encephalopathy (HIE) in newborn infants. In neonatal cardiac arrest, current International Liaison Committee on Resuscitation (ILCOR) and Neonatal Resuscitation Program (NRP) guidelines recommend increasing inspired O2 to 100% during chest compressions (CC). Following the return of spontaneous circulation (ROSC), gradual weaning from 100% O2 based on pulse oximetry (SpO2) can be associated with hyperoxia and risk for cerebral tissue injury owing to oxidative stress. We hypothesize that compared to gradual weaning from 100% O2 with titration based on preductal SpO2, abrupt or rapid weaning of inspired O2 to 21% after ROSC or use of 21% O2 during CC followed by upward titration of inspired O2 to achieve target SpO2 after ROSC will limit hyperoxia after ROSC. Nineteen lambs were randomized before delivery and asphyxial arrest was induced by umbilical cord occlusion. There was no difference in oxygenation during chest compressions between the three groups. Gradual weaning of inspired O2 from 100% O2 after ROSC resulted in supraphysiological PaO2 and higher cerebral oxygen delivery compared to 21% O2 during CC or 100% O2 during CC followed by abrupt weaning to 21% O2 after ROSC. The use of 21% O2 during CC was associated with very low PaO2 after ROSC and higher brain tissue lactic acid compared to other groups. Our findings support the current recommendations to use 100% O2 during CC and additionally suggest the benefit of abrupt decrease in inspired oxygen to 21% O2 after ROSC. Clinical studies are warranted to investigate optimal oxygen titration after chest compressions and ROSC during neonatal resuscitation.

Background

Cerebral oxygen delivery (cDO₂) is low during chest compressions (CC). We hypothesized that gas exchange and cDO₂ are better with continuous CC with high frequency percussive ventilation (CCC + HFPV) compared to conventional 3:1 compressions-to-ventilation (C:V) resuscitation during neonatal resuscitation in preterm lambs with cardiac arrest induced by umbilical cord compression.

Methods

Fourteen lambs in cardiac arrest were randomized to 3:1 C:V resuscitation (90CC + 30 breaths/min) per the Neonatal Resuscitation Program guidelines or CCC + HFPV (120CC + HFPV continuously). Intravenous epinephrine was given every 3 min until return of spontaneous circulation (ROSC).

Results

There was no difference in the incidence and time to ROSC between both groups. Median (IQR) PaCO₂ was significantly lower with CCC + HFPV during CC, at ROSC and 15 min post-ROSC-[104 (99-112), 83 (77-99), and 43 (40-64)], respectively compared to 3:1 C:V-[149 (139-167), 153 (143-168), and 153 (138-178) mmHg. PaO₂ and cDO₂ were higher with CCC + HFPV during CC and at ROSC. PaO₂ was similar 15 min post-ROSC with a lower FiO₂ in the CCC + HFPV group 0.4 (0.4-0.5) vs. 1 (0.6-1).

Conclusion

In preterm lambs with perinatal cardiac-arrest, continuous chest compressions with HFPV does not improve ROSC but enhances gas exchange and increases cerebral oxygen delivery compared to 3:1 C:V during neonatal resuscitation.

Impact statement

Ventilation is the most important intervention in newborn resuscitation. Currently recommended 3:1 compression-to-ventilation ratio is associated with hypercarbia and poor oxygen delivery to the brain. Providing uninterrupted continuous chest compressions during high frequency percussive ventilation is feasible in a lamb model of perinatal cardiac arrest, and demonstrates improved gas exchange and oxygen delivery to the brain. This is the first study in premature lambs evaluating high frequency percussive ventilation with asynchronous chest compressions and lays the groundwork for future clinical studies to optimize gas exchange and hemodynamics during chest compressions in newborns.

Background

An umbilical venous catheter (UVC) is the preferred route of epinephrine administration during neonatal resuscitation but requires specialized equipment, expertise, and time.

Hypothesis

Direct injection of epinephrine into the umbilical vein (UV) followed by milking a ~20 cm segment of cut umbilical cord to flush the epinephrine (DUV + UCM) will lead to a quicker administration and earlier return of spontaneous circulation (ROSC) compared with epinephrine given through a UVC.

Design

Eighteen near-term asphyxiated lambs were randomized to receive a low-UVC or DUV + UCM of epinephrine at 0.02 or 0.03 mg/kg doses.

Outcome measures

A total of 16/18 lambs achieved ROSC with a similar mean (±SEM) time to ROSC [DUV + UCM vs. low-UVC (4.67 ± 0.67 vs. 3.99 ± 0.58 min); p = 0.46]. Two out of ten lambs in the DUV + UCM group required UVC placement for additional epinephrine. The administration of the first dose of epinephrine was similar (DUV + UCM-2.97 ± 0.48 vs. UVC-4.23 ± 0.58 min; p = 0.12). Both methods yielded similar epinephrine concentrations (peak concentrations of 253 ± 63 and 328 ± 80 ng/mL for DUV + UCM and UVC EPI, respectively).

Conclusions

DUV + UCM resulted in a ROSC success of 78% following the first epinephrine dose and showed similar epinephrine concentrations to UVC. Clinical studies evaluating DUV + UCM as an alternate route for epinephrine while intravenous access is being established are warranted.

Background

The Neonatal Resuscitation Program (NRP) recommends using 100% O₂ during chest compressions and adjusting FiO₂ based on SpO₂ after return of spontaneous circulation (ROSC). The optimal strategy for adjusting FiO₂ is not known.

Methods

Twenty-five near-term lambs asphyxiated by umbilical cord occlusion to cardiac arrest were resuscitated per NRP. Following ROSC, lambs were randomized to gradual decrease versus abrupt wean to 21% O₂ followed by FiO₂ titration to achieve NRP SpO₂ targets. Carotid blood flow and blood gases were monitored.

Results

Three minutes after ROSC, PaO₂ was 229 ± 32 mmHg in gradual wean group compared to 57 ± 13 following abrupt wean to 21% O₂ (p < 0.001). PaO₂ remained high in the gradual wean group at 10 min after ROSC (110 ± 10 vs. 67 ± 12, p < 0.01) despite similar FiO₂ (~0.3) in both groups. Cerebral O₂ delivery (C-DO₂) was higher above physiological range following ROSC with gradual wean (p < 0.05). Lower blood oxidized/reduced glutathione ratio (suggesting less oxidative stress) was observed with abrupt wean.

Conclusion

Weaning FiO₂ abruptly to 0.21 with adjustment based on SpO₂ prevents surge in PaO₂ and C-DO₂ and minimizes oxidative stress compared to gradual weaning from 100% O₂ following ROSC. Clinical trials with neurodevelopmental outcomes comparing post-ROSC FiO₂ weaning strategies are warranted.

Impact

In a lamb model of perinatal asphyxial cardiac arrest, abrupt weaning of inspired oxygen to 21% prevents excessive oxygen delivery to the brain and oxidative stress compared to gradual weaning from 100% oxygen following return of spontaneous circulation. Clinical studies assessing neurodevelopmental outcomes comparing abrupt and gradual weaning of inspired oxygen after recovery from neonatal asphyxial arrest are warranted.

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.