Background: The placement of the endotracheal tube (ETT) in neonates is a challenging procedure that currently requires timely confirmation of tip placement by radiographic imaging. Objective: We sought to determine if bedside ultrasound (US) could demonstrate ETT tip location in preterm and term newborns and offer a quick alternative method of ETT positioning. Methods: We conducted a prospective pilot study of 30 newborns admitted to the UC San Diego Medical Center who had their ETT placement confirmed by chest radiographs. After a radiograph, each infant had a US exam with a 13-MHz linear transducer on a portable US machine. To assist localization, gentle longitudinal movement of the ETT of less than 0.5 cm was performed. Measurements from the tip of the ETT tip to the carina were made on chest radiograph and midsagittal US images. Results: Study infants had a mean gestational age of 30.2 ± 4.9 (SD) weeks and mean birth weight of 1,595.2 ± 862 g. US images were taken a mean 2.9 ± 2.2 h after radiographs. Data from 2 infants were excluded for poor radiograph image quality and extreme outlier values. The ETT was visualized by US in all newborns examined. We observed a good correlation between ETT tip-to-carina distance on US and radiograph (r² = 0.68) with minimal bias. Each study took less than 5 min to obtain without any clinical deterioration. Conclusions: Bedside US can visualize the anatomic position of the ETT position in preterm and term infants but further validation is required before routine clinical implementation.

BackgroundEpinephrine administered by low umbilical venous catheter (UVC) or endotracheal tube (ETT) is indicated in neonates who fail to respond to positive pressure ventilation and chest compressions at birth. Pharmacokinetics of ETT epinephrine via fluid‐filled lungs or UVC epinephrine in the presence of fetal shunts is unknown. We hypothesized that epinephrine administered by ETT or low UVC results in plasma epinephrine concentrations and rates of return of spontaneous circulation (ROSC) similar to right atrial (RA) epinephrine.Methods and ResultsForty‐four lambs were randomized into the following groups: RA epinephrine (0.03 mg/kg), low UVC epinephrine (0.03 mg/kg), postcompression ETT epinephrine (0.1 mg/kg), and precompression ETT epinephrine (0.1 mg/kg). Asystole was induced by umbilical cord occlusion. Resuscitation was initiated following 5 minutes of asystole. Thirty‐eight of 44 lambs achieved ROSC (10/11, 9/11, and 12/22 in the RA, UVC, and ETT groups, respectively; subsequent RA epinephrine resulted in a total ROSC of 19/22 in the ETT groups). Median time (interquartile range) to achieve ROSC was significantly longer in the ETT group (including those that received RA epinephrine) compared to the intravenous group (4.5 [2.9–7.4] versus 2 [1.9–3] minutes; P=0.02). RA and low UVC epinephrine administration achieved comparable peak plasma epinephrine concentrations (470±250 versus 450±190 ng/mL) by 1 minute compared to ETT values of 130±60 ng/mL at 5 minutes; P=0.03. Following ROSC with ETT epinephrine alone, there was a delayed peak epinephrine concentration (652±240 ng/mL).ConclusionsThe absorption of ETT epinephrine is low and delayed at birth. RA and low UVC epinephrine rapidly achieve high plasma concentrations resulting in ROSC.

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Objective Continuous chest compressions (CCCs) are more effective during resuscitation in adults. Sustained inflation (SI) 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 (ROSC) in an asphyxial cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs between subjects receiving CCCs during SI 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 CCCs during SI (SI+CCCs). The umbilical cord was occluded to induce asphyxia and asystole. The control group was resuscitated per NRP guidelines. In the SI+CCCs group, SI at 35cm H2O was provided for 30 seconds with 1-second interruptions before another SI was provided. 120 chest compressions/min started after the initial SI. The first dose of IV epinephrine was given at 6 minutes if ROSC was not achieved, and then every 3 minutes until ROSC or for a total of four doses. Measurement and Results All lambs achieved ROSC in a comparable median time (interquartile range) of 390 (225–405) and 345 (204–465) seconds in the SI+CCCs and control groups, respectively. 4/7 (SI+CCCs) and 3/6 (control) lambs required epinephrine to achieve ROSC. Diastolic blood pressures were lower in the SI+CCCs (4 ± 2 mmHg) compared to the control group (7 ± 2 mmHg); 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, SI+CCC is as effective as 3:1 C:V resuscitation in achieving ROSC. Half the lambs achieved ROSC without epinephrine. CCCs during SI reduced diastolic pressures but did not alter gas exchange or carotid blood flow compared to 3:1 C:V resuscitation.

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Neonates suffering from pulmonary hypertension of the newborn (PPHN) continue to represent an important proportion of patients requiring intensive neonatal care, and have an increased risk of morbidity and mortality. The human fetus has evolved to maintain a high pulmonary vascular resistance (PVR) in utero to allow the majority of the fetal circulation to bypass the lungs, which do not participate in gas exchange, towards the low resistance placenta. At birth, oxygen plays a major role in decreasing PVR to enhance pulmonary blood flow and establish the lungs as the organ of gas exchange. The failure of PVR to fall following birth results in PPHN, and oxygen remains the mainstay therapeutic intervention in the management of PPHN. Knowledge gaps on what constitutes the optimal oxygenation target leads to a wide variation in practices, and often leads to excessive oxygen use. Owing to the risk of oxygen toxicity, avoiding hyperoxemia is as important as avoiding hypoxemia in the management of PPHN. Current evidence supports maintaining arterial oxygen tension in the range of 50–80 mm Hg, and oxygen saturation between 90–97% in term infants with hypoxemic respiratory failure. Clinical studies evaluating the optimal oxygenation in the treatment of PPHN will be enthusiastically awaited.

ObjectivesNeonatal 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.DesignForty 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.ResultsTen 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.Conclusions0.03 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.

Epinephrine is the only medication recommended by the International Liaison Committee on Resuscitation for use in newborn resuscitation. Strong evidence from large clinical trials is lacking owing to the infrequent use of epinephrine during neonatal resuscitation. Current recommendations are weak as they are extrapolated from animal models or pediatric and adult studies that do not adequately depict the transitioning circulation and fluid-filled lungs of the newborn in the delivery room. Many gaps in knowledge including the optimal dosing, best route and timing of epinephrine administration warrant further studies. Experiments on a well-established ovine model of perinatal asphyxial cardiac arrest closely mimicking the newborn infant provide important information that can guide future clinical trials.