Neonatal resuscitation with continuous chest compressions and high frequency percussive ventilation in preterm lambs.

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.

Caffeine pharmacokinetics following umbilical vein injection during delayed cord clamping in preterm lambs.

BACKGROUND: Spontaneous breathing during and after delayed cord clamping (DCC) stabilizes cardiopulmonary transition at birth. Caffeine stimulates breathing and decreases apnea in premature newborns. We evaluated the pharmacokinetics and physiological effects of early caffeine administration-direct injection into the umbilical vein (UV) during DCC or administered through a UV catheter (UVC) after delivery. METHODS: Eighteen extremely premature lambs (125-127d, term gestation 145d) were exteriorized and instrumented. Lambs received caffeine-citrate at high (40 mg/kg) or standard-dose (20 mg/kg) via direct UV (DUV) injection during DCC, or via the UVC. RESULTS: Mean peak plasma caffeine concentrations were lower with high-dose DUV compared to UVC (18 ± 4.3 vs. 46 ± 12 mg/L, p < 0.05). With standard-dose caffeine, mean peak plasma levels were 7.48 ± 2.6 with DUV and 28.73 ± 9.4 mg/L with UVC. The volume of distribution was higher in the DUV group compared to UVC (2.5 ± 1.0 vs. 0.69 ± 0.15 L/kg) with an estimated 39 ± 18% entering the maternal circulation. Maternal peak concentrations were 0.79 ± 0.71 and 1.43 ± 0.74 mg/L with standard and high-dose DUV, respectively. CONCLUSIONS: Caffeine injected directly into the UV during DCC is feasible but achieves lower concentrations due to high volume of distribution including maternal circulation. Further trials evaluating DUV caffeine injection should use higher caffeine doses. IMPACT: Respiratory stimulation with early caffeine may reduce the need for intubation in preterm infants. In the preterm lambs, caffeine injection directly into the umbilical vein during delayed cord clamping is feasible. Plasma caffeine concentrations are less than half when administered directly into the umbilical vein during delayed cord clamping compared to administration via an umbilical venous catheter following birth likely attributed to a larger volume of distribution or injection site leak. There were no significant hemodynamic alterations following caffeine injection.

Perinatal Azithromycin Provides Limited Neuroprotection in an Ovine Model of Neonatal Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Hypoxic-ischemic brain injury/encephalopathy affects about 1.15 million neonates per year, 96% of whom are born in low- and middle-income countries. Therapeutic hypothermia is not effective in this setting, possibly because injury occurs significantly before birth. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal azithromycin administration in near-term lambs following global ischemic injury to support earlier treatment approaches. METHODS: Ewes and their lambs of both sexes (n=34, 141-143 days) were randomly assigned to receive azithromycin or placebo before delivery as well as postnatally. Lambs were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Outcomes were assessed over a 6-day period. RESULTS: While maternal azithromycin exhibited relatively low placental transfer, azithromycin-treated lambs recovered spontaneous circulation faster following the initiation of cardiopulmonary resuscitation and were extubated sooner. Additionally, peri- and postnatal azithromycin administration was well tolerated, demonstrating a 77-hour plasma elimination half-life, as well as significant accumulation in the brain and other tissues. Azithromycin administration resulted in a systemic immunomodulatory effect, demonstrated by reductions in proinflammatory IL-6 (interleukin-6) levels. Treated lambs exhibited a trend toward improved neurodevelopmental outcomes while histological analysis revealed that azithromycin supported white matter preservation and attenuated inflammation in the cingulate and parasagittal cortex. CONCLUSIONS: Perinatal azithromycin administration enhances neonatal resuscitation, attenuates neuroinflammation, and supports limited improvement of select histological outcomes in an ovine model of hypoxic-ischemic brain injury/encephalopathy.

Differential Alveolar and Systemic Oxygenation during Preterm Resuscitation with 100% Oxygen during Delayed Cord Clamping.

OBJECTIVE: Delayed cord clamping (DCC) and 21 to 30% O2 resuscitation is recommended for preterm infants but is commonly associated with low pulmonary blood flow (Qp) and hypoxia. 100% O2 supplementation during DCC for 60 seconds followed by 30% O2 may increase Qp and oxygen saturation (SpO2). STUDY DESIGN: Preterm lambs (125-127 days of gestation) were resuscitated with 100% O2 with immediate cord clamping (ICC, n = 7) or ICC + 30% O2, and titrated to target SpO2 (n = 7) or DCC + 100% O2 for 60 seconds, which followed by cord clamping and 30% O2 titration (n = 7). Seven preterm (23-27 weeks of gestation) human infants received continuous positive airway pressure (CPAP) + 100% O2 for 60 seconds during DCC, cord clamping, and 30% O2 supplementation after cord clamping. RESULTS: Preterm lambs in the ICC + 100% O2 group resulted in PaO2 (77 ± 25 mm Hg), SpO2 (77 ± 11%), and Qp (27 ± 9 mL/kg/min) at 60 seconds. ICC + 30% O2 led to low Qp (14 ± 3 mL/kg/min), low SpO2 (43 ± 26%), and PaO2 (19 ± 7 mm Hg). DCC + 100% O2 led to similar Qp (28 ± 6 mL/kg/min) as ICC + 100% O2 with lower PaO2. In human infants, DCC + CPAP with 100% O2 for 60 seconds, which followed by weaning to 30% resulted in SpO2 of 92 ± 11% with all infants >80% at 5 minutes with 100% survival without severe intraventricular hemorrhage. CONCLUSION: DCC + 100% O2 for 60 seconds increased Qp probably due to transient alveolar hyperoxia with systemic normoxia due to "dilution" by umbilical venous return. Larger translational and clinical studies are warranted to confirm these findings. KEY POINTS: · Transient alveolar hyperoxia during delayed cord clamping can enhance pulmonary vasodilation.. · Placental transfusion buffers systemic oxygen tension and limits hyperoxia.. · Use of 100% oxygen for 60 seconds during DCC was associated with SpO2 ≥80% by 5 minutes..

Defining Longer-Term Outcomes in an Ovine Model of Moderate Perinatal Hypoxia-Ischemia.

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable. Here, we describe an umbilical cord occlusion (UCO) model of moderate HIE with a 6-day follow-up. Near-term lambs (n = 27) were resuscitated after the induction of 5 min of asystole. Following recovery, lambs were assessed to define neurodevelopmental outcomes. At the end of this period, lambs were euthanized, and brains were harvested for histological analysis. Compared with prior models that typically follow lambs for 3 days, the observation of neurobehavioral outcomes for 6 days enabled identification of animals that recover significant neurological function. Approximately 35% of lambs exhibited severe motor deficits throughout the entirety of the 6-day course and, in the most severely affected lambs, developed spastic diparesis similar to that observed in infants who survive severe neonatal HIE (severe, UCOs). Importantly, and similar to outcomes in human neonates, while initially developing significant acidosis and encephalopathy, the remainder of the lambs in this model recovered normal motor activity and exhibited normal neurodevelopmental outcomes by 6 days of life (improved, UCOi). The UCOs group exhibited gliosis and inflammation in both white and gray matters, oligodendrocyte loss, neuronal loss, and cellular death in the hippocampus and cingulate cortex. While the UCOi group exhibited more cellular death and gliosis in the parasagittal cortex, they demonstrated more preserved white matter markers, along with reduced markers of inflammation and lower cellular death and neuronal loss in Ca3 of the hippocampus compared with UCOs lambs. Our large animal model of moderate HIE with prolonged follow-up will help further define pathophysiologic drivers of brain injury while enabling identification of predictive biomarkers that correlate with disease outcomes and ultimately help support development of therapeutic approaches to this challenging clinical scenario.

Continuous chest compressions with asynchronous ventilations increase carotid blood flow in the perinatal asphyxiated lamb model.

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.

Randomized trial of oxygen weaning strategies following chest compressions during neonatal resuscitation.

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.

Hemoglobin oxygen saturation targets in the neonatal intensive care unit: Is there a light at the end of the tunnel? 1.

The optimal oxygenation target needed to prevent the extremes of hypoxia and oxygen toxicity in premature and sick newborns has been the subject of much research and debate. The advent of the pulse oximeter has allowed the continuous monitoring of oxyhemoglobin saturation and the delivery of oxygen with greater precision. Well-run, large clinical trials to determine the safest oxygen concentration have led to several revisions in guidelines for neonatal care. However, monitoring of oxyhemoglobin saturation has its limitations and does not provide a comprehensive assessment of tissue oxygenation. To identify optimal oxygen therapy, various other factors (partial pressure of arterial carbon dioxide, hemoglobin concentration, blood pH, and tissue metabolic demand) that influence perfusion and tissue oxygenation need to be considered.

Effect of various inspired oxygen concentrations on pulmonary and systemic hemodynamics and oxygenation during resuscitation in a transitioning preterm model.

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 (127 d 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 the initiation of resuscitation at a higher O2 concentration followed by titration based on SpO2 in preterm neonates are needed.

Continuous capnography monitoring during resuscitation in a transitional large mammalian model of asphyxial cardiac arrest.

BACKGROUND: In neonates requiring chest compression (CC) during resuscitation, neonatal resuscitation program (NRP) recommends against relying on a single feedback device such as end-tidal carbon dioxide (ETCO2) or saturations (SpO2) to determine return of spontaneous circulation (ROSC) until more evidence becomes available. METHODS: We evaluated the role of monitoring ETCO2 during resuscitation in a lamb model of cardiac arrest induced by umbilical cord occlusion (n = 21). Lambs were resuscitated as per NRP guidelines. Systolic blood pressure (SBP), carotid and pulmonary blood flows along with ETCO2 and blood gases were continuously monitored. Resuscitation was continued for 20 min or until ROSC (whichever was earlier). Adequate CC was arbitrarily defined as generation of 30 mmHg SBP during resuscitation. ETCO2 thresholds to predict adequacy of CC and detect ROSC were determined. RESULTS: Significant relationship between ETCO2 and adequate CC was noted during resuscitation (AUC-0.735, P < 0.01). At ROSC (n = 12), ETCO2 rapidly increased to 57 ± 20 mmHg with a threshold of ≥32 mmHg being 100% sensitive and 97% specific to predict ROSC. CONCLUSION: In a large mammalian model of perinatal asphyxia, continuous ETCO2 monitoring predicted adequacy of CC and detected ROSC. These findings suggest ETCO2 in conjunction with other devices may be beneficial during CC and predict ROSC.

Continuous Chest Compressions During Sustained Inflations in a Perinatal Asphyxial Cardiac Arrest Lamb Model.

OBJECTIVE: Continuous chest compressions are more effective during resuscitation in adults. Sustained inflation 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 in an asphyxial cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs between subjects receiving continuous chest compressions during sustained inflation 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 continuous chest compressions during sustained inflation. The umbilical cord was occluded to induce asphyxia and asystole. The control group was resuscitated per NRP guidelines. In the sustained inflation + continuous chest compressions group, sustained inflation at 35 cm H2O was provided for 30 seconds with 1-second interruptions before another sustained inflation was provided. One hundred twenty chest compressions/min started after the initial sustained inflation. The first dose of IV epinephrine was given at 6 minutes if return of spontaneous circulation was not achieved and then every 3 minutes until return of spontaneous circulation or for a total of four doses. MEASUREMENT AND RESULTS: All lambs achieved return of spontaneous circulation in a comparable median time (interquartile range) of 390 seconds (225-405 s) and 345 seconds (204-465 s) in the sustained inflation + continuous chest compressions and control groups, respectively. Four of seven (sustained inflation + continuous chest compressions) and three of six (control) lambs required epinephrine to achieve return of spontaneous circulation. Diastolic blood pressures were lower in the sustained inflation + continuous chest compressions (4 ± 2 mm Hg) compared to the control group (7 ± 2 mm Hg), 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, sustained inflation + continuous chest compressions is as effective as 3:1 compression-to-ventilation resuscitation in achieving return of spontaneous circulation. Half the lambs achieved return of spontaneous circulation without epinephrine. continuous chest compressions during sustained inflation reduced diastolic pressures but did not alter gas exchange or carotid blood flow compared to 3:1 compression-to-ventilation resuscitation.

Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration.

BACKGROUND: The Neonatal Resuscitation Program (NRP) recommends upper and lower limits of preductal saturations (SpO2) extrapolated from studies in infants resuscitated in room air. These limits have not been validated in asphyxia and lung disease. METHODS: Seven control term lambs delivered by cesarean section were ventilated with 21% O2. Thirty lambs with asphyxia with meconium aspiration were randomly assigned to resuscitation with 21% O2 (n = 6), 100% O2 (n = 6), or initiation with 21% O2 followed by variable FIO2 to maintain NRP target SpO2 ranges (n = 18). Hemodynamic and ventilation parameters were recorded for 15 min. RESULTS: Control lambs maintained preductal SpO2 near the lower limit of NRP target range. Asphyxiated lambs had low SpO2 (38 ± 2%), low arterial pH (6.99 ± 0.01), and high PaCO2 (96 ± 7 mm Hg) at birth. Resuscitation with 21% O2 resulted in SpO2 values below the target range with low pulmonary blood flow (Qp) compared to variable FIO2 group. The increase in PaO2 and Qp with variable FIO2 resuscitation was similar to control lambs. CONCLUSION: Maintaining SpO2 as recommended by NRP by actively adjusting inspired O2 leads to effective oxygenation and higher Qp in asphyxiated lambs with lung disease. Our findings support the current NRP SpO2 guidelines for O2 supplementation during resuscitation of an asphyxiated neonate.

The Precision Between Transcutaneous Carbon Dioxide Versus PaCO2 in Infants Undergoing Therapeutic Hypothermia.

BACKGROUND: Infants with hypoxic-ischemic encephalopathy are often treated with therapeutic hypothermia and high-frequency ventilation. Fluctuations in PaCO2 during therapeutic hypothermia are associated with poor neurodevelopmental outcomes. Transcutaneous CO2 monitors offer a noninvasive estimate of PaCO2 represented by transcutaneously measured partial pressure of carbon dioxide (PtcCO2 ). We aimed to assess the precision between PtcCO2 and PaCO2 values in neonates undergoing therapeutic hypothermia. METHODS: This was a retrospective chart review of 10 neonates who underwent therapeutic hypothermia requiring respiratory support over 2 y. A range of 2-27 simultaneous PtcCO2 and PaCO2 pairs of measurements per neonate were analyzed via linear mixed models and a Bland-Altman plot for multiple observations per neonate. RESULTS: A linear mixed-effect model demonstrated that PtcCO2 and PaCO2 (controlling for sex) were similar. The 95% CI of the mean difference ranged from -2.3 to 5.7 mm Hg (P = .41). However, precision was poor as the PtcCO2 ranged from > 18 mm Hg to < 13 mm Hg than PaCO2 values for 95% of observations. CONCLUSIONS: The neonates' PtcCO2 was as much as 18 mm Hg higher to 13 mm Hg lower than the PaCO2 95% of the time. Transcutaneous CO2 monitoring may not be a good trending tool, nor is it appropriate for estimating PaCO2 in patients undergoing therapeutic hypothermia.

Pneumothorax in a term newborn.

With the advent of surfactant and gentle ventilation, the incidence of neonatal pneumothorax has decreased over the last two decades. Pneumothorax associated with respiratory distress syndrome is more common in preterm infants, but term infants often present with isolated pneumothorax. The use of CPAP or non-invasive respiratory support in the delivery room for a term infant with respiratory distress increases transpulmonary pressures and increases the risk of pneumothorax. Prompt diagnosis with a high index of suspicion, quick evaluation by transillumination, chest X-ray or lung ultrasound is critical. Management includes observation, needle thoracocentesis and if necessary, chest tube placement. This manuscript reviews the incidence, pathogenesis, diagnosis and management of a term infant with isolated pneumothorax, summarizing the combination of established knowledge with new understanding, including data on diagnostic modes such as ultrasound, reviewing preventative measures, and therapeutic interventions such as needle thoracocentesis and a comparison of pigtail vs. straight chest tubes.

Direct Umbilical Vein Injection of Epinephrine with Cut-Cord Milking in an Ovine Model of Neonatal Resuscitation.

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.

Randomized Trial of 21% versus 100% Oxygen during Chest Compressions Followed by Gradual versus Abrupt Oxygen Titration after Return of Spontaneous Circulation in Neonatal Lambs.

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.