The role of inhaled prostacyclin in treating acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a syndrome of acute lung injury that is characterized by noncardiogenic pulmonary edema and severe hypoxemia second to a pathogenic impairment of gas exchange. Despite significant advances in the area, mortality remains high among ARDS patients. High mortality and a limited spectrum of therapeutic options have left clinicians searching for alternatives, spiking interest in selective pulmonary vasodilators (SPVs). Despite the lack of robust evidence, SPVs are commonly employed for their therapeutic role in improving oxygenation in patients who have developed refractory hypoxemia in ARDS. While inhaled epoprostenol (iEPO) also impacts arterial oxygenation by decreasing ventilation-perfusion (V/Q) mismatching and pulmonary shunt flow, this effect is not different from inhaled nitric oxide (iNO). The most effective and safest dose for yielding a clinically significant increase in PaO 2 and reduction in pulmonary artery pressure (PAP) appears to be 20-30 ng/kg/min in adults and 30 ng/kg/min in pediatric patients. iEPO appears to have a ceiling effect above these doses in which no additional benefit may be derived. iNO and iEPO have shown similar efficacy profiles; however, they differ with respect to cost and ease of therapeutic administration. The most beneficial effects of iEPO have been seen in adult patients with secondary ARDS as compared with primary ARDS, most likely due to the difference in etiology of the two disease states, and in patients suffering from baseline right ventricular heart failure. Although iEPO has demonstrated improvements in hemodynamic parameters and oxygenation in ARDS patients, due to the limited number of randomized clinical trials and the lack of studies investigating mortality, the use of iEPO cannot be recommended as standard of care in ARDS. iEPO should be reserved for those refractory to traditional therapies.

An Update on Current Therapeutic Drugs Treating COVID-19

“…Furthermore, in vitro evidence of direct antiviral activity against SARS-CoV was studied and the genetic similarity between SARS-CoV and SARS-CoV-2 suggests their potential effectiveness against SARS-CoV-2 [96]. For iEPO, dosages up to 50 ng/kg per minute have been used [93,94,97,98]. Previous studies reported that to provide a clinically important increase in PaO2 and reduction in pulmonary artery pressure, the most effective and safe dosage appears to be 20-30 ng/kg per minute in adults and 30 ng/kg per minute in pediatric patients [98].…”

“…For iEPO, dosages up to 50 ng/kg per minute have been used [93,94,97,98]. Previous studies reported that to provide a clinically important increase in PaO2 and reduction in pulmonary artery pressure, the most effective and safe dosage appears to be 20-30 ng/kg per minute in adults and 30 ng/kg per minute in pediatric patients [98]. For iNO, therapy was given for ≥ 3 days (30 ppm on day 1, followed by 20 and 10 ppm on days 2 and 3, respectively, then weaned on day 4) in a pilot study on SARS-CoV [99].…”

Effect of iloprost inhalation on postoperative outcome in high-risk cardiac surgical patients: a prospective randomized-controlled multicentre trial (ILOCARD)

“…9,13,14 Iloprost, the stable carbacyclin derivative of prostacyclin (PGI 2 ), is a potent pulmonary vasodilator that lowers RV afterload at least as effectively as inhaled NO. 15 Moreover, iloprost and PGI 2 improved biventricular performance, [16][17][18] exerted anti-inflammatory effects, 19 ameliorated myocardial ischemia-reperfusion injury, 20 improved oxygenation in adult respiratory distress syndrome, 21 attenuated pulmonary ischemiareperfusion injury, 22 improved the pulmonary clearance of endothelin, 23 and reduced oxidative stress and counteracted platelet activation with consecutive microthrombosis. 24 On the background of these beneficial effects, we hypothesized that the prophylactic inhalation of iloprost would improve perioperative morbidity and outcome in patients undergoing elective heart surgery with ECC and at an increased risk for perioperative RV failure.…”

“…Iloprost 110 29 [24][25][26][27][28][29][30][31][32][33][34][35][36][37] 119 26 [20][21][22][23][24][25][26][27][28][29][30][31][32] 121 27 [22][23][24][25][26][27][28][29][30][31][32] 121 30 [25][26][27][28][29][30][31][32][33][34] 114 30 [25][26][27][28]…”

Emerging roles of calcium-activated K channels and TRPV4 channels in lung oedema and pulmonary circulatory collapse

“…, Searcy et al . ). Therefore, there is a clear need for novel therapeutic strategies for these conditions as well as a more profound understanding of the underlying pathophysiological mechanisms.…”