Discussion
critically ill, inflammation, hypoxia, ARDS, pulmonary microthrombi
CRITICALLY ILL, HYPOXIA, INFLAMMATION, INFILTRATES, SECONDARY, DIFFUSE PULMONARY FIBROSIS, ARDS, COMPLICATIONS
In this randomized controlled trial involving patients with ARDS, we addressed the question of whether inhaled prostacyclin would improve the lung function, as measured by oxygenation in the blood. We were able to show improved oxygenation on Day 5 of treatment in a population with ARDS however, the effect was not significant. The observed effect of prostacyclin was not associated with improved secondary outcomes in the intervention group, and neither the overall outcome nor the incidence of secondary complications was significantly different between groups.In addition to extensive inflammation within the alveolar space, the central hallmark of ARDS is hypoxia [As mentioned above, this randomized study documents the effect of prostacyclin on patients with ARDS including COVID-19-induced ARDS. COVID-19-induced ARDS is an entity characterized by additional features compared to classical ARDS. Patients with COVID-19 present widespread pulmonary microthrombi and inflammatory infiltrates with diffuse pulmonary fibrosis [Of course, our trial also has several limitations. First, the trial was started before the COVID-19 pandemic to evaluate the effects of prostacyclin on oxygenation and outcomes of critically ill patients with ARDS. Then, shortly after the start of the trial, the first wave of patients with COVID-19-induced ARDS were treated in Germany and German ICUs, including ours. Given the potential differences in the pathologies of ARDS and COVID-19-induced ARDS, this factor might have significant implications for therapy with prostacyclin. However, we decided to include all patient groups with ARDS and not exclude patients with COVID-19, since our trial should also take advantage of the opportunity to compare patients with different ARDS etiologies and their responses to prostacyclin treatment. Second, our sample size was moderate, and our study was probably underpowered. This interpretation seems justified, as we obtained the expected effect, i.e., a superiority of 21 mmHg in PaOIn conclusion, among patients with severe ARDS, inhaled prostacyclin showed a tendency to improve oxygenation, especially in COVID-19-induced ARDS. This change was not associated with a survival benefit but was associated with an improvement of secondary outcomes in the treated patient population. Larger clinical trials will evaluate the effect of prostacyclin on the overall outcomes of patients with ARDS.