A 2023 systematic review and meta-analysis aimed to assess the change in partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio after administration of an inhaled prostacyclin in patients with acute respiratory distress syndrome (ARDS). A total of 23 studies were included with a study population of N=1658 subjects, assessing the efficacy of inhaled prostacyclin in patients with and without COVID-19 ARDS. It also assessed inhaled epoprostenol, inhaled alprostadil, and inhaled iloprost. There was a significant improvement in Pao2/Fio2 from baseline (mean deviation [MD], 40.35; 95% confidence interval [CI], 26.14 to 54.56 mm Hg; p <0.00001; I^2 = 95%; very low-quality evidence), as well as an increase in Pao2 (MD, 12.68; 95% CI, 2.89 to 24.48 mm Hg; p = 0.01; I^2 = 96%; very low-quality evidence). Additionally, there was a decrease in mean pulmonary artery pressure (mPAP) (MD, –3.67; 95% CI, –5.04 to –2.31 mm Hg; p <0.00001; I^2 = 68%; very low-quality evidence). For non-COVID-19 ARDS specifically, Pao2/Fio2 improvement was also notable (MD, 33.83; 95% CI, 30.48 to 37.18 mm Hg; p <0.00001; I^2 = 95%). Overall, this data suggests that inhaled prostacyclins improve oxygenation and pulmonary artery pressures in patients with ARDS; however, these improvements have not resulted in decreased clinical outcomes like hospital length of stay, need for mechanical ventilation, and mortality. [1]
Another meta-analysis, published in 2015, assessed the effectiveness of inhaled prostaglandins in improving pulmonary physiology and mortality in patients with ARDS, while also evaluating potential adverse effects. A total of 25 studies were included in the analysis. Results indicated that one randomized controlled trial (RCT) found no significant difference in the change in mean PaO2 to FiO2 ratio when comparing inhaled alprostadil to placebo. However, the analysis of the remaining studies demonstrated that inhaled prostaglandins were associated with a 39.0% improvement in the PaO2 to FiO2 ratio (95% CI 26.7% to 51.3%) and a 21.4% increase in PaO2 (95% CI 12.2% to 30.6%). Additionally, there was a decrease in pulmonary artery pressure by -4.8 mm Hg (95% CI -6.8 to -2.8 mmHg). However, high levels of bias and heterogeneity were noted among the studies. Regarding adverse effects, the authors noted that they were variably reported. Twenty studies mentioned adverse effects or lack thereof, while 11 studies reported no impact on systemic hemodynamics. Five studies documented hypotension (rates ranging from 12.5% to 33.3%), with a significant difference noted between prospective studies (0.69%) and observational studies (17.4%; p<0.001). Additionally, three studies reported thrombocytopenia, anemia, or transfusion requirements. Based on these findings, it was suggested that inhaled prostaglandins may improve oxygenation and decrease pulmonary artery pressures in ARDS, though there may also be associated risks. [2]
A 2017 Cochrane review evaluated the benefits and harms of aerosolized prostacyclin in adults and children with ARDS. Two RCTs involving 81 participants were included (one involving 14 children and the other 67 adults), both with very low-quality evidence. The pediatric trial reported no difference in mortality between the intervention and control groups, but it was limited by a cross-over design. The adult trial reported no significant improvement in the PaO2/FiO2 ratio, with a mean difference of -25.35 (95% CI -60.48 to 9.78; p= 0.16) No adverse events, such as bleeding or organ dysfunction, were reported in either trial. The limited number of RCTs prevented further subgroup and sensitivity analyses. Overall, it was concluded that the evidence was too imprecise to determine whether aerosolized prostacyclin has a meaningful effect on mortality, and further research is needed to evaluate its routine use in ARDS. [3]
A 2015 review discussed the role of inhaled prostacyclin as a treatment for ARDS. Overall, there appears to be a lack of robust evidence on selective pulmonary vasodilators (SPVs), a class that includes inhaled prostacyclins, and their use in ARDS management. In a study comparing inhaled epoprostenol (iEPO) and nitric oxide (NO) (N= 8), both agents demonstrated a dose-dependent reduction in mean pulmonary artery pressure (PAP). Notably, iEPO led to at least a 10% decrease in PAP at all doses in all eight patients with ARDS and pulmonary hypertension. Additionally, iEPO significantly increased PaO2 at doses of 10 and 25 ng/kg/min, though it had no effect at 1 ng/kg/min. However, intrapulmonary shunt flow remained unchanged. Another study found that iEPO significantly reduced PAP from 35.0 to 31.9 mmHg (p<0.05). Another prospective study concluded that there was no significant difference between various iEPO doses on oxygenation indices. The authors noted that iEPO reduced PaO2/FiO2 (from 146 ± 16 to 135 mmHg ± 17; p<0.05) and PaO2 (from 87 ± 2 to 79 mmHg ± 2; p<0.02) in patients with primary ARDS, whereas in secondary ARDS, there was an increase in PaO2/FiO2 (from 161 ± 23 to 171 mmHg ± 22; p<0.01) and PaO2 (from 76 ± 4 to 84 mmHg ± 4; p<0.01). Regarding safety, iEPO has not been associated with cytotoxic effects compared to iNO. However, iEPO may worsen ventilation-perfusion (V/Q) mismatch, cause hypotension, inhibit platelet aggregation, and induce tachycardia. These effects may be minimized or avoided due to iEPO’s pulmonary selectivity and mode of administration. Hypotension, for instance, is more common in patients receiving intravenous epoprostenol. Evidence on iloprost is limited and conflicting; while one study suggested it produces effects similar to iNO, it was associated with marked bronchoconstriction and other adverse effects. In contrast, a case series in infants receiving iloprost showed significant oxygenation improvement without bronchoconstriction. Overall, while these agents may improve certain parameters in ARDS patients, their benefits have not been consistently substantiated. [4]