Responsiveness of Inhaled Epoprostenol in Respiratory Failure due to COVID-19

Abstract

Background: Inhaled pulmonary vasodilators are used as adjunctive therapies for the treatment of refractory hypoxemia. Available evidence suggest they improve oxygenation in a subset of patients without changing long-term trajectory. Given the differences in respiratory failure due to COVID-19 and “traditional” ARDS, we sought to identify their physiologic impact. Methods: This is a retrospective observational study of patients mechanically ventilated for COVID-19, from the ICUs of 2 tertiary care centers, who received inhaled epoprostenol (iEpo) for the management of hypoxemia. The primary outcome is change in PaO2/FiO2. Additionally, we measured several patient level features to predict iEpo responsiveness (or lack thereof). Results: Eighty patients with laboratory confirmed SARS-CoV2 received iEpo while mechanically ventilated and had PaO2/FiO2 measured before and after. The median PaO2/FiO2 prior to receiving iEpo was 92 mmHg and interquartile range (74 – 122). The median change in PaO2/FiO2 was 9 mmHg (-9 – 37) corresponding to a 10% improvement (-8 – 41). Fifty-percent (40 / 80) met our a priori definition of a clinically significant improvement in PaO2/FiO2 (increase in 10% from the baseline value). Prone position and lower PaO2/FiO2 when iEpo was started predicted a more robust response, which held after multivariate adjustment. For proned individuals, improvement in PaO2/FiO2 was 14 mmHg (-6 to 45) vs. 3 mmHg (-11 – 20), p = 0.04 for supine individuals; for those with severe ARDS (PaO2/FiO2 < 100, n = 49) the median improvement was 16 mmHg (-2 – 46). Conclusion: Fifty percent of patients have a clinically significant improvement in PaO2/FiO2 after the initiation of iEpo. This suggests it is worth trying as a rescue therapy; although generally the benefit was modest with a wide variability. Those who were prone and had lower PaO2/FiO2 were more likely to respond.

The Use of Inhaled Epoprostenol for Acute Respiratory Distress Syndrome Secondary due to COVID-19: A Case Series

“…This indicates, similar to what was found in the current series, that those select patients will positively respond to iEpo therapy with significant improvements in oxygenation [30]. Another retrospective study by Sonti et al(2021) looked at 80 patients who received iEpo and had P/F ratios measured. Patients were initiated when they had severe ARDS, as evidenced by a P/F ratio of 92 mmHg at baseline.…”

High levels of eicosanoids and docosanoids in the lungs of intubated COVID‐19 patients

“…In contrast, PGE 2 is mostly anti‐inflammatory via the EP 2 and EP 4 receptors 29 and PGI 2 is a recognized microvasculature dilator. In that respect, a retrospective observational study showed that the administration of PGI 2 (epoprostenol) was effective at improving the PaO 2 /FiO 2 ratio in 50% of COVID‐19 patients 30 . Therapies targeting the prostaglandin pathway are numerous and usually effective at controlling inflammation.…”

Inhaled prostacyclin analogues in COVID-19 associated acute respiratory distress syndrome: scientific rationale

“…However, the baseline characteristics were markedly different and early administration of inhalation might be beneficial. Sonti et al [ 27 ] also reported clinically significant improvement in PaO 2 /FiO 2 after the initiation of inhaled epoprostenol in 50% of mechanically ventilated patients. Combination use of inhaled epoprostenol and prone positioning in COVID-19 patients with mechanical ventilation with refractory hypoxemia showed improved oxygenation compared with each treatment individually [ 28 ].…”