Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in a third of patients with PPHN. Inhaled NO is less effective in the management of PPHN secondary to congenital diaphragmatic hernia (CDH), extreme prematurity and bronchopulmonary dysplasia (BPD). Intravenous pulmonary vasodilators such as prostacyclin, alprostadil, sildenafil and milrinone have been successfully used in PPHN resistant to iNO. Oral pulmonary vasodilators such as endothelin-receptor antagonist bosentan and phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are used both during acute and chronic phase of PPHN. In the absence of infection, glucocorticoids may also be effective in PPHN. Many of these pharmacologic agents are not approved for use in PPHN and our knowledge is based on case reports and small trials. Large multicenter randomized controlled trials with long-term follow-up are required to evaluate pharmacologic strategies in PPHN.

Background: The oxygenation index (OI = mean airway pressure, MAP × FiO₂ × 100 : PaO₂) is used to assess the severity of hypoxic respiratory failure (HRF) and persistent pulmonary hypertension of the newborn (PPHN). An indwelling arterial line or arterial punctures are necessary to obtain PaO₂ for the calculation of OI. Oxygenation can be continuously and noninvasively assessed using pulse oximetry. The use of the oxygen saturation index (OSI = MAP × FiO₂ × 100 : SpO₂) can be an alternate method of assessing the severity of HRF. Objective: To evaluate the correlation between OSI and OI in the following: (1) neonates with HRF and (2) a lamb model of meconium aspiration syndrome. Methods: Human neonates: a retrospective chart review of 74 ventilated late preterm/term neonates with indwelling arterial access and SpO₂ values in the first 24 h of life was conducted. OSI and OI were calculated and correlated. Lamb model: arterial blood gases were drawn and preductal SpO₂ was documented in 40 term newborn lambs with asphyxia and meconium aspiration. OI and OSI were calculated and correlated with pulmonary vascular resistance (PVR). Results: Mean values of OSI and OI showed a correlation coefficient of 0.952 in neonates (mean value of 308 observations in 74 neonates) and 0.948 in lambs (mean value of 743 observations in 40 lambs). In lambs, with increasing PVR, there was a decrease in OI and OSI. Conclusion: OSI correlates significantly with OI in infants with HRF. This noninvasive measure may be used to assess the severity of HRF and PPHN in neonates without arterial access.

ABSTRACT:The effect of resuscitation with varying levels of O 2 on pulmonary hemodynamics at birth is not well known. We hypothesized that the decrease in pulmonary vascular resistance (PVR) and subsequent response to pulmonary vasoconstrictors and vasodilators will differ following resuscitation with 21%, 50%, or 100%O 2 for 30 min at birth in normal term lambs. Lambs at 141 d gestation were delivered by cesarean section and ventilated with 21% (21% Res; n ϭ 6), 50% (50% Res; n ϭ 6), or 100% O 2 (100% Res; n ϭ 7) for 30 min followed by ventilation with 21% O 2 in all three groups. A greater decrease in PVR was seen with 50% and 100% O 2 ventilation than with 21% O 2 (0.21 Ϯ 0.02, 0.21 Ϯ 0.02, and 0.34 Ϯ 0.05 mm Hg/mL/min/kg, respectively). Subsequent pulmonary vasoconstriction to hypoxia (10% O 2 ) and the thromboxane analog U46619 (0.5 and 1 g/kg/min) was similar in all three groups. After inducing a stable elevation in PVR with U46619, impaired pulmonary vasodilation to inhaled NO (59 Ϯ 4, 65 Ϯ 4, and 74 Ϯ 5% of baseline PVR with 21, 50, and 100%Res, respectively) and acetylcholine infusion (67 Ϯ 8, 75 Ϯ 6, and 87 Ϯ 4% of baseline PVR with 21, 50, and 100%Res, respectively) and rebound pulmonary hypertension following their withdrawal were observed in the 100%Res group. We conclude that, while ventilation with 100% O 2 at birth results in a greater initial decrease in PVR, subsequent pulmonary vasodilation to NO/acetylcholine is impaired. (Pediatr Res 62: 313-318, 2007) F etal pulmonary vascular resistance is high and O 2 plays a crucial role in mediating the pulmonary vascular transition at birth (1). However, the optimal level of O 2 supplementation during resuscitation of a newborn infant remains controversial (2) despite publication of new guidelines (3). During resuscitation of a depressed newborn infant with potentially high PVR, there is concern that room air resuscitation may result in inadequate pulmonary vasodilation. It has been suggested that breathing 100% O 2 dilates constricted pulmonary arteries more efficiently than room air.Previous studies have demonstrated conflicting results regarding the effect of ventilation with different gas mixtures on PVR. Some studies indicate that ventilation with nitrogen, air, and O 2 are similarly effective in reducing fetal PVR in lambs (4,5). Other studies indicate that PVR drops more effectively with 100% O 2 (6) or air (7,8) than with a nitrogen-rich gas. It may be important to find an intermediate level of O 2 that has the advantages of short-term reduction in PVR without the toxicity of 100% O 2 (9,10). Recent studies examined pulmonary hemodynamic responses to 21% or 100% O 2 ventilation, but were conducted on hypoxemic lambs only after 12-72 h of age, after PVR had dropped from high fetal levels immediately after birth (11)(12)(13). Understanding the precise pulmonary hemodynamic response to ventilation with room air, 100% O 2 , and an intermediate level of O 2 exposure (such as 50% O 2 ) in animals at birth is vital for determining the safest protocol ...

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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.