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.

Controversies in neonatology: The efficacy of inhaled nitric oxide in preterm infants with persistent pulmonary hypertension

“…pH in blood gas analysis 4h after commencement of iNO was determined to be significantly increased in reduction in the FiO2 by 20% within 3h of commencing iNO therapy were defined as "positive responders'' and those in which FiO2 increased, remained unchanged or reduced by <20% were defined as "negative responders". If clinical response was not observed to hypoxemia, the dose of iNO was increased to 40 ppm, since NO improvement to oxygenation is largely dose dependent and higher doses of iNO (20-80ppm) may cause progressive pulmonary vasodilatation (15)(16)(17). Blood gases and levels of methemoglobin were analyzed prior to initiation of iNO therapy and every 4h thereafter.…”

Effects of Iloprost on Arterial Oxygenation and Lung Mechanics during One-Lung Ventilation in Supine-Positioned Patients: A Randomized Controlled Study

“…Evidence indicates that ILO administration may be associated with systemic vasodilation and inhibition of platelet aggregation [ 15 ]. Indeed, we frequently observed hypotension during OLV in both groups.…”

A randomised controlled trial on roles of prostaglandin E1 nebulization among patients undergoing one lung ventilation

“…This study showed that once OLV was initiated, the patients’ level of Qs/Qt declined compared to before, which is consistent with the previous research. Inhaling PEG1, a kind of selective pulmonary artery dilator, by ultrasonic atomization during OLV could dilate the pulmonary artery, which causes stealing blood from the shunt area to the non-shunt area, reducing intrapulmonary shunt [ 21 , 22 ]. In addition, a previous study demonstrated that PGE1 could decrease pulmonary shunt and increase PaO 2 in a dose-dependent manner during OLV [ 11 ].…”