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. A referenced 1996 prospective crossover trial (N=8) compared iEPO and iNO in mechanically ventilated ARDS patients with pulmonary hypertension (PAP ≥30 mm Hg), using escalating doses of each agent. Both reduced PAP dose-dependently; iEPO lowered mean PAP from 35.1 to 29.6 mm Hg and PVR without systemic effects, while improving PaO₂/FiO₂ at 10 and 25 ng/kg/min. iNO produced more consistent oxygenation gains (PaO₂ from 116 ± 47 to 167 ± 86 mm Hg at 8 ppm) and reduced shunt, though it had limited PVR impact. Individual responses varied, with iEPO benefiting some iNO non-responders. Another referenced 1996 randomized crossover study (N=16) in severe ARDS showed both agents improved PaO₂/FiO₂ (by 29 mm Hg with iNO, 21 mm Hg with iEPO; p <0.01) and reduced shunt (~33% to ~26%; p <0.05). PAP decreased more with iEPO (–3.1 mm Hg vs. –1.8 mm Hg; p <0.05), without affecting systemic hemodynamics. No rebound hypoxemia was reported. [1], [2], [3]
Regarding safety, iEPO in general 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 (IV) epoprostenol. Overall, while iEPO may improve certain parameters in ARDS patients, their benefits have not been consistently substantiated. [1]
A 2022 multicenter, retrospective observational analysis evaluated comparative effectiveness between iNO and iEPO in patients with acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV). Utilizing the Premier Healthcare Database from 2016 to 2020, the investigators identified 11,200 adult patients with ARF or ARDS who were treated with either iEPO or iNO after the initiation of IMV. To emulate a cluster-randomized trial and reduce confounding by indication, the primary analysis was restricted to a subset of 3,478 patients admitted to hospitals that exclusively used one of the two therapies, 1,812 patients at iEPO-only hospitals and 1,666 at iNO-only hospitals. The primary endpoint was successful extubation within 28 days, defined rigorously based on cessation of IMV billing codes prior to death or discharge. Results demonstrated no statistically significant difference in the likelihood of successful extubation between patients receiving iNO versus iEpo (adjusted subdistribution hazard ratio [SHR] for iNO, 0.97; 95% confidence interval [CI], 0.80–1.18). Similarly, adjusted analyses revealed no differences in rates of death or hospice discharge (aOR, 0.99; 95% CI, 0.77–1.29), renal replacement therapy (RRT) initiation (adjusted SHR, 0.69; 95% CI, 0.44–1.08), or median PaO2:FIO2 ratio improvement one day post-initiation (adjusted median difference for iNO vs iEpo, –6 mm Hg; 95% CI, –21 to 9 mm Hg). Inhaled vasodilator-specific costs were significantly higher for iNO (adjusted median cost difference, $3,255; 95% CI, $1,568–$4,942), but this disparity did not translate into a statistically significant difference in total hospitalization costs. Among hospitals in the cohort, 34.3% exclusively used iNO, 38.9% exclusively used iEPO, and only 26.7% employed both agents, with 94.7% of the variation in initial vasodilator use explained by hospital site alone. These findings collectively underscore that in real-world practice, clinical outcomes associated with iNO and iEPO appear comparable when accounting for institutional-level treatment allocation. [4]
A 2020 systematic review and meta-analysis compared the efficacy of inhaled nitric oxide (NO) with aerosolized prostacyclin and its analogues in managing pulmonary hypertension (PH) post-cardiac or pulmonary surgery. This meta-analysis included data from seven randomized controlled trials and prospective studies conducted before December 2019, encompassing a total of 195 patients. The studies primarily assessed changes in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Patients were divided into two groups based on the intervention received—either inhaled NO or inhaled prostacyclin (or its analogues). The analysis aimed to determine if these treatments offered comparable outcomes for patients experiencing PH in the perioperative or postoperative setting. The results from these studies demonstrated no significant difference in the improvement of MPAP or PVR between the groups treated with inhaled NO and those treated with inhaled prostacyclin or its analogues. Specifically, the pooled difference in mean change for MPAP was 0.10 with a 95% confidence interval ranging from -3.98 to 3.78, while the pooled standardized difference in mean change for PVR was 0.27 with a 95% confidence interval of -0.60 to 0.05. Additionally, secondary outcomes such as heart rate and cardiac output also showed no statistically significant differences between the two treatment modalities. These findings suggest that inhaled prostacyclin and its analogues can be considered viable alternatives to inhaled NO for managing PH following surgical interventions. [5]
A 2020 single-center, retrospective cohort analysis conducted at a 755-bed academic medical center examined the comparative effectiveness and cost implications of fixed-dose iEPO versus iNO for adult patients with moderate-to-severe ARDS. The investigation reviewed data from 239 mechanically ventilated patients between January 2014 and October 2018 who received either iNO or a fixed-dose regimen of iEPO. Patients receiving ECMO or treated for pulmonary embolism (PE) were excluded to isolate a homogeneous ARDS population. The fixed-dose iEPO protocol utilized a continuous nebulization technique with a vibrating mesh system, consistently delivering epoprostenol without adjusting for patient weight. The primary endpoint was the change in PaO2:FIO2 at 4 hours post-initiation. The results showed the mean increase in PaO2:FIO2 at 4 hours was statistically comparable between iEPO (31.4 ± 54.6 mm Hg) and iNO (32.4 ± 42.7 mm Hg; p = 0.88), with responder rates, defined as PaO2:FIO2 improvement of ≥10%, also similar (64.7% vs. 66.0%, p = 0.84). Improvements in oxygenation were sustained up to 72 hours with both agents. Notable findings included significantly lower mean FIO2 and tidal volumes within the first 24 hours in the iEPO group. Additionally, iEPO was associated with more mechanical ventilation-free days (p = 0.003), although hospital and ICU lengths of stay and mortality rates were similar between groups. Total drug acquisition costs were markedly lower with iEPO, translating to an estimated annual cost-savings exceeding USD 1 million compared to iNO. This investigation demonstrated that a fixed-dose iEPO strategy offers comparable clinical efficacy to iNO while significantly reducing financial burden in critically ill ARDS patients. [6]