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.

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.

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.

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.

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.

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.

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.

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.

Factors to Consider to Study Preductal Oxygen Saturation Targets in Neonatal Pulmonary Hypertension.

There are potential benefits and risks to the infant with higher and lower oxygen saturation (SpO2) targets, and the ideal range for infants with pulmonary hypertension (PH) remains unknown. Targeting high SpO2 can promote pulmonary vasodilation but cause oxygen toxicity. Targeting lower SpO2 may increase pulmonary vascular resistance, especially in the presence of acidosis and hypothermia. We will conduct a randomized pilot trial to compare two ranges of target preductal SpO2 in late-preterm and term infants with hypoxic respiratory failure (HRF) and acute pulmonary hypertension (aPH) of the newborn. We will assess the reliability of a newly created HRF/PH score that could be used in larger trials. We will assess trial feasibility and obtain preliminary estimates of outcomes. Our primary hypothesis is that in neonates with PH and HRF, targeting preductal SpO2 of 95-99% (intervention) will result in lower pulmonary vascular resistance and pulmonary arterial pressures, and lower the need for pulmonary vasodilators (inhaled nitric oxide-iNO, milrinone and sildenafil) compared to targeting SpO2 at 91-95% (standard). We also speculate that a higher SpO2 target can potentially induce oxidative stress and decrease response to iNO (oxygenation and pulmonary vasodilation) for those patients that still require iNO in this range. We present considerations in planning this trial as well as some of the details of the protocol design (Clinicaltrials.gov (NCT04938167)).

Inadequate Bioavailability of Intramuscular Epinephrine in a Neonatal Asphyxia Model.

Background: Over half a million newborn deaths are attributed to intrapartum related events annually, the majority of which occur in low resource settings. While progress has been made in reducing the burden of asphyxia, novel approaches may need to be considered to further decrease rates of newborn mortality. Administration of intravenous, intraosseous or endotracheal epinephrine is recommended by the Newborn Resuscitation Program (NRP) with sustained bradycardia at birth. However, delivery by these routes requires both advanced skills and specialized equipment. Intramuscular (IM) epinephrine may represent a simple, low cost and highly accessible alternative for consideration in the care of infants compromised at birth. At present, the bioavailability of IM epinephrine in asphyxia remains unclear. Methods: Four term fetal lambs were delivered by cesarean section and asphyxiated by umbilical cord occlusion with resuscitation after 5 min of asystole. IM epinephrine (0.1 mg/kg) was administered intradeltoid after 1 min of positive pressure ventilation with 30 s of chest compressions. Serial blood samples were obtained for determination of plasma epinephrine concentrations by ELISA. Results: Epinephrine concentrations failed to increase following administration via IM injection. Delayed absorption was observed after return of spontaneous circulation (ROSC) in half of the studies. Conclusions: Inadequate absorption of epinephrine occurs with IM administration during asphyxial cardiac arrest, implying this route would be ineffective in infants who are severely compromised at birth. Late absorption following ROSC raises concerns for risks of side effects. However, the bioavailability and efficacy of intramuscular epinephrine in less profound asphyxia may warrant further evaluation.

Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension.

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.

Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest.

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.

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.

What is the optimal initial dose of epinephrine during neonatal resuscitation in the delivery room?

The neonatal resuscitation program recommends a wide dose range of epinephrine for newborns who receive chest compressions (endotracheal tube [ET] dose of 0.05-0.1 mg/kg or intravenous [IV] dose of 0.01-0.03 mg/kg), which presents a challenge to neonatal care providers when attempting to determine the optimal initial dose. Dosing errors are common when preparing epinephrine for neonatal resuscitation. Based on animal data, we suggest preparing 0.1 mg/kg or 1 ml/kg of 1 mg/10 ml epinephrine in a 5 ml syringe for ET administration. For IV epinephrine, we suggest preparing an initial dose of 0.02 mg/kg or 0.2 ml/kg of 1 mg/10 ml epinephrine in a 1 ml syringe. A dose of 0.02 mg/kg enables use of a 1 ml syringe for a wide range of birth weights from 500 g to 5 kg. The use of a color-coded syringe may decrease errors in dose preparation.

Randomised trial of epinephrine dose and flush volume in term newborn lambs.

OBJECTIVES: Neonatal 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. DESIGN: Forty 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. RESULTS: Ten 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. CONCLUSIONS: 0.03 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.

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.

Recent Advances in Pathophysiology and Management of Transient Tachypnea of Newborn.

Transient tachypnea of newborn (TTN) results from failure of the newborn to effectively clear the fetal lung fluid soon after birth. TTN represents the most common etiology of respiratory distress in term gestation newborns and sometimes requires admission to the neonatal intensive care unit. TTN can lead to maternal-infant separation, the need for respiratory support, extended unnecessary exposure to antibiotics and prolonged hospital stays. Recent evidence also suggests that TTN may be associated with wheezing syndromes later in childhood. New imaging modalities such as lung ultrasound can help in the diagnosis of TTN and early management with distending pressure using continuous positive airway pressure may prevent exacerbation of respiratory distress.