Inhaled pulmonary vasodilators: a narrative review

Abstract

Pulmonary hypertension (PH) is a severe disease that affects people of all ages. It can occur as an idiopathic disorder at birth or as part of a variety of cardiovascular and pulmonary disorders. Inhaled pulmonary vasodilators (IPV) can reduce pulmonary vascular resistance (PVR) and improve RV function with minimal systemic effects. IPV includes inhaled nitric oxide (iNO), inhaled aerosolized prostacyclin, or analogs, including epoprostenol, iloprost, treprostinil, and other vasodilators. In addition to pulmonary vasodilating effects, IPV can also be used to improve oxygenation, reduce inflammation, and protect cell. Off-label use of IPV is common in daily clinical practice. However, evidence supporting the inhalational administration of these medications is limited, inconclusive, and controversial regarding their safety and efficacy. We conducted a search for relevant papers published up to May 2020 in four databases: PubMed, Google Scholar, EMBASE and Web of Science. This review demonstrates that the clinical using and updated evidence of IPV. iNO is widely used in neonates, pediatrics, and adults with different cardiopulmonary diseases. The limitations of iNO include high cost, flat dose-response, risk of significant rebound PH after withdrawal, and the requirement of complex technology for monitoring. The literature suggests that inhaled aerosolized epoprostenol, iloprost, treprostinil and others such as milrinone and levosimendan may be similar to iNO. More research of IPV is needed to determine acceptable inclusion criteria, long-term outcomes, and management strategies including time, dose, and duration.

Keywords: Pulmonary hypertension (PH); epoprostenol; iloprost; nitric oxide; treprostinil.

Figure 1

IPV. IPV, inhaled pulmonary vasodilators; iNO, inhaled nitric oxide; PVR, pulmonary vascular resistance; PPHN, persistent pulmonary hypertension of the newborn; BPD, bronchopulmonary dysplasia; ECMO, extracorporeal membrane oxygenation; CA, cardiac arrest; IRI, ischemia-reperfusion injury; ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; SCD, sickle cell disease.