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

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.

SUBMITTER: Rawat M

PROVIDER: S-EPMC7528912 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Nasal continuous positive airway pressure (NCPAP) as a primary respiratory therapy in meconium aspiration syndrome (MAS) has not been studied extensively. Nasal continuous positive airway pressure, when applied in newborns with MAS, may resolve atelectasis by sufficiently expanding partially obstructed small airways and stabilizing the collapsing terminal airways to enhance oxygen exchange. Objective:To compare NCPAP vs standard care in neonates with moderate to severe respiratory failure due to MAS in reducing the need for invasive ventilation. Design, Settings, and Participants:This multicenter open-label, parallel-group (1:1 ratio) randomized clinical trial was conducted from August 5, 2014, to May 26, 2016. Data were collected from 3 tertiary care neonatal intensive care units. All infants admitted with respiratory distress, defined as Downe score greater than 4 and peripheral capillary oxygen saturation less than 90%, were assessed for study eligibility if the chest radiograph was suggestive of MAS and they met the other inclusion criteria: gestation longer than 35 weeks, a birth weight greater than 2000 g, and born through meconium-stained amniotic fluid. Interventions:Infants were randomly assigned to either NCPAP or standard care (5-10 L/min hood oxygen). Main Outcomes and Measures:The primary outcome was the need for mechanical ventilation in the first 7 days of life. Results:After excluding 14 infants, 67 infants were randomized to bubble NCPAP and 68 infants to standard care. Baseline characteristics were similar between the 2 groups. Infants randomized to the bubble NCPAP group needed mechanical ventilation less frequently in the first 7 days of life compared with standard care (2 [3.0%] vs 17 [25.0%]); odds ratio, 0.09; 95% CI, 0.02-0.43; P?=?.002). The need for surfactant (3 [4.5%] vs 11 [16.2%]; odds ratio, 0.24; 95% CI, 0.05-0.87) and culture-positive sepsis (4 [6.0%] vs 13 [19.0%]; odds ratio, 0.28; 95% CI, 0.09-0.93) were higher in the standard care group. There was an increased duration of oxygen therapy (median [interquartile range], 45.5 [28.0-78.3] vs 26 [20.0-48.0] hours; P?=?.001) in the standard care group. In the NCPAP group vs standard care group, incidence of persistent pulmonary hypertension (9 [13%] vs 19 [28%]; odds ratio, 0.42; 95% CI, 0.17-1.01) and duration of hospital stay (median [interquartile range], 5.0 [4.0-8.8] vs 4.0 [4.0-6.0] days; P?=?.14) were similar. Conclusions and Relevance:Bubble NCPAP in comparison with standard care for infants with MAS reduces the need for mechanical ventilation in the first 7 days of life. Trial Registration:Clinical Trial Registry, India Identifier: CTRI/2015/03/005631.

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

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