Optimal Oxygen Targets in Term Lambs with Meconium Aspiration Syndrome and Pulmonary Hypertension.

Overview

abstract

Optimal oxygen saturation as measured by pulse oximetry (Sp_O₂) in neonatal lung injury, such as meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of newborn (PPHN), is not known. Our goal was to determine the Sp_O₂ range in lambs with MAS and PPHN that results in the highest brain oxygen delivery (bDO₂) and pulmonary blood flow (Qp) and the lowest pulmonary vascular resistance and oxidative stress. Meconium was instilled into endotracheal tubes in 25 near-term gestation lambs, and the umbilical cord was occluded to induce asphyxia and gasping, causing MAS and PPHN. Lambs were randomized into four groups and ventilated for 6 hours with fixed fraction of inspired oxygen (Fi_O₂) = 1.0 irrespective of Sp_O₂, and three groups had Fi_O₂ titrated to keep preductal Sp_O₂ between 85% and 89%, 90% and 94%, and 95% and 99%, respectively. Tissues were collected to measure nitric oxide synthase activity, 3-nitrotyrosine, and 8-isoprostanes. Throughout the 6-hour exposure period, lambs in the 95-99% Sp_O₂ target group had the highest Qp, lowest pulmonary vascular resistance, and highest bDO₂ but were exposed to higher Fi_O₂ (0.5 ± 0.21 vs. 0.29 ± 0.17) with higher lung 3-nitrotyrosine (0.67 [interquartile range (IQR), 0.43-0.73] ng/mcg protein vs. 0.1 [IQR, 0.09-0.2] ng/mcg protein) and lower lung nitric oxide synthase activity (196 [IQR, 192-201] mMol nitrite/mg protein vs. 270 [IQR, 227-280] mMol nitrite/mg protein) compared with the 90-94% target group. Brain 3-nitrotyrosine was lower in the 85-89% target group, and brain/lung 8-isoprostane levels were not significantly different. In term lambs with MAS and PPHN, Qp and bDO₂ through the first 6 hours are higher with target Sp_O₂ in the 95-99% range. However, the 90-94% target range is associated with significantly lower Fi_O₂ and lung oxidative stress. Clinical trials comparing the 90-94% versus the 95-99% Sp_O₂ target range in term infants with PPHN are warranted.