Inhaled nitric oxide reduces the utilization of extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn

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Abstract
Objective To determine if the use of inhaled nitric oxide therapy reduces the need for extracorporeal membrane oxygenation (ECMO) in persistent pulmonary hypertension of the newborn. Design A matched cohort study with retrospective data extraction. Setting Pediatric and neonatal intensive care units at a medical school-affiliated children's hospital serving as a regional referral center for respiratory failure. Patients Records of all neonates transferred for rescue therapy for persistent pulmonary hypertension during the study period were analyzed, with inclusion in the study based on defined gas exchange parameters, and with exclusion from the study based on the presence of congenital heart disease, diaphragmatic hernia, or lethal chromosomal abnormality. Assignment to cohorts was based on availability of inhaled nitric oxide therapy: group 1 patients were admitted when inhaled nitric oxide was unavailable; group 2 patients were admitted when inhaled nitric oxide was available. Interventions Standard criteria (alveolar-arterial oxygen tension gradient of >600 torr [>80 kPa], or oxygenation index of >40) were used to trigger initial evaluation for ECMO when these criteria were met for 2 hrs, and ECMO was initiated if these criteria continued to be met for 12 hrs, or if cardiovascular instability occurred. Ventilator management in all patients was directed to improve arterial oxygenation, such that ECMO criteria were no longer met. Patients in group 2 only were treated with inhaled nitric oxide after meeting ECMO evaluation criteria, and they continued to receive inhaled nitric oxide if a quantifiable improvement in gas exchange occurred. Measurements and Main Results Fifty patients qualified for inclusion in the analysis (29 patients in group 1, and 21 patients in group 2). In group 1, 21 (72%) patients met ECMO criteria, and 16 (76%) patients required ECMO therapy. In group 2, 16 (76%) patients met ECMO criteria, 15 patients received inhaled nitric oxide therapy, and only four (25%) patients required ECMO therapy (p = .003 compared with group 1). Treatment with inhaled nitric oxide resulted in an initial increase in PaO2, without adverse effects, in all of the treated patients. The reduction in ECMO utilization in group 2 was achieved with a higher rate of complication-free survival (survival without oxygen requirement at 28 days, p = .018; survival without intracranial hemorrhage, p = .048), and a lower hospital cost per survivor (p = .021), compared with group 1 patients. Conclusion In neonates with persistent pulmonary hypertension, therapy with inhaled nitric oxide reliably and safely improves oxygenation, thereby resulting in a decreased need for ECMO therapy, improved patient outcome, and lower hospital costs. (Crit Care Med 1997; 25:352-359)