Inhaled Nitric Oxide for Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: A Systematic Review and Narrative Synthesis

Abstract

Introduction: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. However, its effectiveness in the treatment of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) and severe BPD remains uncertain. Here we systematically reviewed whether iNO treatment increased or decreased mortality and morbidity among preterm infants with severe BPD or BPDPH. Methods: We systematically searched the Ovid MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane CENTRAL, and ICHUSHI databases for randomized and non-randomized studies that compared the effects of iNO in patients with severe BPD or BPD-PH. The primary outcome was mortality. Two authors independently screened the articles and extracted the data. A meta-analysis and certainty of evidence assessment using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation criteria were planned. Results: Among the 1,710 articles, none had a relevant control group and no studies met the eligibility criteria. Using a post hoc analysis, we summarized the ineligible studies that evaluated patients with severe BPD or BPD-PH who received iNO therapy. Although some studies included in the narrative review indicated a decreased pulmonary arterial pressure in patients with severe BPD or BPD-PH at the initiation of iNO therapy, none included a comparator group. Conclusion: Despite the use of iNO in patients with severe BPD and BPD-PH, no published studies compared the outcomes among patients with BPD treated with versus without iNO. Although some studies without comparator groups reported the effectiveness of iNO in patients with severe BPD and BPDPH, our results suggest that iNO therapy should be initiated with caution and careful consideration of the target population.