OBJECTIVE:To determine the impact of early rapid saline bolus during resuscitation on (1) time to achieve return of spontaneous circulation (ROSC), and (2) systemic haemodynamics, oxygenation, myocardial stress markers and pulmonary oedema. DESIGN:Randomised controlled trial. SETTING:Lamb delivery suite. SUBJECTS:Term lambs in haemorrhagic, asphyxial cardiac arrest. INTERVENTIONS:Fetal lambs were exsanguinated (~45 mL/kg) followed by umbilical cord occlusion to arrest. After 5 min of asystole, ventilation was followed by coordinated chest compressions. Asystolic lambs were randomised to epi-first (intravenous epinephrine, 0.02 mg/kg and if no ROSC, a 10 mL/kg saline bolus over 5 min), or bolus-first (10 mL/kg saline bolus over 2 min and if no ROSC, followed by intravenous epinephrine). Haemodynamics and blood gases were monitored. RESULTS:In the epi-first group, none of the lambs achieved ROSC after epinephrine; ROSC occurred in 11/11 lambs during or immediately after saline bolus. In the bolus-first group, none of the lambs achieved ROSC with bolus alone and 8/9 lambs had ROSC after epinephrine. Mean time to ROSC from start of resuscitation was shorter in epi-first (4.9±1.3 vs 6.6±0.9 min, p=0.004), but time to ROSC from the time of epinephrine administration was shorter with bolus-first (86±43 vs 40±21 s, p=0.004). The fetal heart rate did not change significantly despite fetal blood loss. CONCLUSIONS:Our findings support current neonatal resuscitation guidelines of intravenous epinephrine followed by a bolus in neonates with suspected hypovolaemic arrest. Early saline bolus delays epinephrine and ROSC. Careful clinical assessment of haemodynamics in the post-resuscitation phase is critical.

Background: Preterm infants with bradycardia at birth often undergo immediate cord clamping (ICC) followed by resuscitation with positive pressure ventilation (PPV), chest compressions (CCs) and umbilical venous catheter (UVC) epinephrine. Resuscitation with an intact cord (PPV during delayed umbilical cord clamping-DCC) stabilizes cardiac output but delays UVC placement. Objective: To evaluate the feasibility of direct epinephrine injection into the umbilical vein during DCC (DCC + direct-epinephrine) compared with ICC and epinephrine administered through a UVC (ICC + cath-epinephrine), and to explore differences in return of spontaneous circulation (ROSC) and need for CCs between these approaches. Methods: Eleven preterm lambs (125-127 d gestation) were asphyxiated by cord compression to decrease heart rate (HR) to <30/min. In the ICC + cath-epinephrine group, the cord was immediately cut, lambs received PPV followed by CCs if HR < 60/min, and epinephrine was administered after UVC placement. In the DCC + direct-epinephrine group, cord compression was released when HR < 30/min and PPV was initiated. If HR remained <60/min, epinephrine was injected into the UV using a 25G needle. If ROSC was achieved, DCC was continued for 2 min. If HR < 100/min, the cord was cut and resuscitation was continued as outlined above. Plasma epinephrine concentrations were analyzed. Results: All lambs required epinephrine. Time to epinephrine was shorter with DCC + direct-epinephrine, 1.0 (0.7, 1.6) vs. 3.7 min (3.2, 5.2). Fewer lambs with DCC + direct-epinephrine needed CC (2/6 vs. 5/5, p = 0.06). ROSC success and plasma epinephrine concentrations were similar. Post-ROSC, heart rates and mean blood pressures tended to be higher in the ICC + cath-epinephrine group. Conclusions: In this perinatal lamb model of asphyxial bradycardia, resuscitation with an intact cord with direct umbilical venous epinephrine injection is feasible. Larger studies are required to determine whether this approach reduces the need for CC or improves clinically meaningful outcomes.

Objective To assess pulse oximetry saturation (SpO2) to arterial oxygen saturation (SaO2) bias relative to skin pigmentation in newborns and to address potentially occult hypoxemia, defined as SaO2 lower than SpO2. Study design We conducted a prospective, diagnostic accuracy study at 2 tertiary neonatal intensive care units between 2022-2025 to assess SpO2-SaO2 differences in relation to skin pigmentation in newborns. Newborns younger than 10 postnatal days with an arterial catheter undergoing an arterial blood gas collection were enrolled. A pulse oximeter was placed on the extremity corresponding to the arterial sampling site, and SpO2 values were recorded during blood gas collection. Skin pigmentation was measured noninvasively using individual typology angle (ITA), melanin index, and visual assessments. Mean SpO2 was calculated from the 30 seconds immediately preceding arterial sampling or from the most stable 30-second average when timestamps were unavailable and compared with SaO2 to calculate SpO2-SaO2 bias. Results A total of 136 matched SpO2-SaO2 pairs from 70 patients were analyzed, of whom 40% were Black. The overall mean bias was -0·98 ± 2·8% (95% CI -1·4 to -0·52), indicating an underestimation of SaO2 by SpO2. Across categorical skin-pigmentation measures and race, no statistically significant differences in SpO2-SaO2 bias were observed. When analyzed continuously, bias became less negative with lighter skin pigmentation for both ITA and melanin index, reaching significance only for ITA when analyses were restricted to the first measurement per patient (slope +0·016 per ITA unit, 95% CI 0·001-0·032, p=0·041). Occult hypoxemia was rare, occurring in one newborn with light skin pigmentation. Conclusion In this prospective neonatal study with tightly paired measurements, SpO2 slightly underestimated SaO2 but did not demonstrate clinically significant disparities across skin pigmentation.

INTRODUCTION:Survival from cardiac arrest is directly and consistently linked to the quality of chest compressions (CC). Although compressor fatigue is well established, neonatal resuscitation guidelines (NRP) do not offer specific recommendations on rotation intervals beyond suggesting provider changes every 2-5 min. By comparison, Pediatric Advanced Life Support recommends a strict 2-min rotation to prevent fatigue and maintain high-quality CC. METHODS:Prospective observational data from resuscitation of asphyxiated cardiac-arrested neonatal lambs to evaluate changes in chest compression rate, blood pressure, carotid blood flow with duration of CC by a single compressor. Forty-one near-term lambs were asphyxiated by umbilical cord occlusion until asystole resuscitated using NRP's synchronized three CC to one ventilation algorithm. RESULTS:The error rate of providing >3 or <3 CC between ventilations was <1%. The CC rate and the percentage of lambs that received NRP's goal CC rate of 90/min decreased over time (p < 0.005). After 91-120 s of chest compressions, CC rate decreased by 4% [3%,6%], carotid flow decreased by 21% [7%,35%], systolic blood pressure decreased by 3.1 [1.1,5.0] mm Hg or 10% [3%,16%], and mean blood pressure decreased by 1.0 [0.3,1.7] or 7% [2%,12%] at the 95% confidence interval compared to baseline CC during the first 30 s (p < 0.05). CONCLUSIONS:Extended duration of CC beyond 2 min is associated with a decrease in carotid blood flow, CC rate, systolic and mean arterial blood pressure. To maintain optimal cerebral perfusion in an ovine model of cardiac arrest, rotating compressors every 2 min may minimize fatigue-induced decrease in CC efficacy.

Clinically significant fetomaternal hemorrhage (FMH) can have devastating consequences on the newborn infant. Acute FMH close to childbirth can present with hypovolemia, shock, metabolic acidosis, and encephalopathy. Chronic FMH can be associated with congestive heart failure, pulmonary edema, hydrops and hepatomegaly. Early recognition and timely management of FMH are crucial in improving outcomes. This review article summarizes the epidemiology, pathogenesis, diagnosis, management and outcomes of clinically significant FMH. Current knowledge gaps in diagnosis and management of FMH are additionally described.

INTRODUCTION:Gas exchange and perfusion are impaired during neonatal cardiopulmonary resuscitation. Continuous chest compressions with asynchronous ventilation (CCCaV) improve oxygenation and hemodynamics in term animal models compared to synchronized 3:1 compressions-to-ventilation (C:V). We hypothesized that CCCaV improves gas exchange and hemodynamics in preterm lambs. METHODS:Sixteen extremely preterm (124-126 days gestation) lambs were asphyxiated to cardiac arrest by umbilical cord occlusion. Lambs were randomized to 3:1 C:V following the International Liaison Committee on Resuscitation algorithm or CCCaV (120 compressions and 40 asynchronized ventilations per minute). Epinephrine was given 3 min into resuscitation and repeated every 3 min until return of spontaneous circulation (ROSC). RESULTS:All lambs achieved ROSC with no difference in time to ROSC. There was no difference in cerebral oxygen delivery (C-DO2) in lambs resuscitated with CCCaV versus 3:1 C:V (0.05 [0.041] vs. 0.03 [0.031] mL O2/kg/min, respectively) during chest compressions. CCCaV yielded higher arterial oxygen content (CaO2 2.07 [1.00] vs. 1.07 [0.69] mL O2/dL), mean arterial pressure (14.2 [2.6] vs. 13.2 [2.3] mm Hg), and diastolic pressure (8.1 [1.8] vs. 7.1 [1.4] mm Hg) during chest compressions compared to 3:1 C:V. There was no difference in plasma reduced to oxidized glutathione [GSH/GSSG ratio] between groups at 10 min post-ROSC. DISCUSSION:CCCaV in asystolic preterm lambs did not alter C-DO2, frequency, or time to ROSC compared to standard 3:1 C:V resuscitation but increased CaO2, mean, and diastolic arterial pressure compared to 3:1 C:V without increasing plasma oxidative stress markers.

GA gestational age at birth, NBW not breathing well, BW breathing well, IVH intraventricular hemorrhage, DR delivery room, RR relative risk, MD mean difference, Hct hematocrit, PMA postmenstrual age, Copyright Satyan Lakshminrusimha.

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.

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.

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.

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 O-2 to 100% during chest compressions (CC). Following the return of spontaneous circulation (ROSC), gradual weaning from 100% O-2 based on pulse oximetry (SpO(2)) can be associated with hyperoxia and risk for cerebral tissue injury owing to oxidative stress. We hypothesize that compared to gradual weaning from 100% O-2 with titration based on preductal SpO(2), abrupt or rapid weaning of inspired O-2 to 21% after ROSC or use of 21% O-2 during CC followed by upward titration of inspired O-2 to achieve target SpO(2) 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 O-2 from 100% O-2 after ROSC resulted in supraphysiological PaO2 and higher cerebral oxygen delivery compared to 21% O-2 during CC or 100% O-2 during CC followed by abrupt weaning to 21% O-2 after ROSC. The use of 21% O-2 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% O-2 during CC and additionally suggest the benefit of abrupt decrease in inspired oxygen to 21% O-2 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.

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.