Pulmonary Vasodilator Use: Neonatal Management in Very Preterm Infants

Recent findings from United States children’s hospitals reveal a growing trend in using pulmonary vasodilators to manage respiratory complications in very preterm infants. This shift not only enhances oxygenation and reduces pulmonary vascular resistance but also reflects a broader evolution in neonatal intensive care practices.

Integration of Pulmonary Vasodilators in Neonatal Settings

Therapies like inhaled nitric oxide (iNO) and sildenafil are increasingly being incorporated into the treatment of pulmonary hypertension and related conditions in neonatal intensive care units (NICUs). Their adoption represents a meaningful step forward in supporting the delicate cardiopulmonary physiology of very preterm infants. According to clinical guidelines, such as those from NHS Greater Glasgow and Clyde, iNO is typically reserved for cases of hypoxic respiratory failure with pulmonary hypertension, offering rapid vasodilation and improved oxygenation.

These developments have prompted pediatric specialists to revisit established treatment protocols and explore novel strategies that align with the evolving needs of critically ill neonates.

Usage Trends in U.S. Children’s Hospitals

An important 2024 cohort study involving 37,428 very preterm infants from U.S. children’s hospitals found that 6.3% received pulmonary vasodilator therapy—primarily iNO or sildenafil—to address significant respiratory complications (Research Square, 2024). This finding indicates a growing clinical openness to pharmacologic management of neonatal pulmonary hypertension, despite the ongoing absence of standardized national guidelines.

Other observational studies echo this shift, with one recent JAMA Network Open analysis reporting improved short-term oxygenation metrics in infants who responded positively to iNO. However, long-term efficacy and outcome data remain limited, highlighting a critical area for future investigation.

Improving Oxygenation and Reducing Vascular Resistance

The application of pulmonary vasodilators in neonates aims to improve gas exchange and reduce the hemodynamic burden caused by elevated pulmonary vascular resistance. Although large-scale randomized controlled trials remain sparse, NICUs have reported encouraging clinical improvements with the use of these agents, especially in cases of persistent pulmonary hypertension of the newborn (PPHN). An overview published in Perinatology Clinics underscores the physiological rationale for vasodilator use in this population.

Moreover, pharmacoepidemiologic insights into combination therapies—such as sildenafil paired with iNO—suggest further potential in treating more complex or refractory cases, as discussed in a study from Cardiology in the Young.

The Need for Evidence-Based Guidelines

Despite promising clinical outcomes, the field faces notable evidence gaps. As highlighted in a Canadian Paediatric Society position statement, there is insufficient consensus regarding optimal dosing, duration, and patient selection criteria for pulmonary vasodilators in extremely preterm neonates. These gaps pose risks of both under- and over-treatment and emphasize the need for standardized, evidence-based protocols.

Additionally, a Journal of Pediatrics review on pulmonary vascular phenotypes of prematurity calls for precision neonatal medicine approaches to tailor therapies to individual pathophysiologic profiles—especially given the heterogeneity of pulmonary vascular development among preterm infants.

Moving Toward Safer, More Effective Neonatal Care

To ensure the benefits of pulmonary vasodilators are realized safely and consistently, the neonatal care community must invest in longitudinal research, ideally through multicenter trials. These efforts would help define best practices and build robust frameworks for clinical decision-making. Resources like the AARC Clinical Practice Guideline provide a foundation, but updated, neonatal-specific guidance remains urgently needed.

As the use of vasodilators continues to expand, interdisciplinary collaboration among neonatologists, pharmacists, and cardiologists will be vital to optimizing outcomes and minimizing unintended consequences.