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

Abstract

Background COVID-19 associated acute respiratory distress syndrome (CARDS) is a severe form of SARS CoV-2 infection and affects about 15–30% of hospitalized patients with a high mortality rate. Growing research and data suggest several available drugs with appropriate pharmacological effects to treat COVID-19. Main body Prostacyclin analogues are regiments for pulmonary artery hypertension. Prostacyclin analogues are expected to be beneficial in treating CARDS based on at least four rationales: (1) inhaled prostacyclin analogues improve oxygenation, V/Q mismatch, and act as an ARDS therapy alternative; (2) it alleviates direct SARS-CoV-2-related coagulopathy; (3) increases nitric oxide production; and (4) possible anti-inflammatory effect. Prostacyclin analogues are available in oral, intravenous, and inhaled forms. The inhaled form has the advantage over other forms, such as parenteral administration risks. Previously, a meta-analysis demonstrated the beneficial effects of inhaled prostaglandins for ARDS treatment, such as improved PaO2/FiO2 and PaO2 along with reduced pulmonary artery pressure. Currently, two ongoing randomized controlled trials are evaluating inhaled epoprostenol (VPCOVID [NCT04452669]) and iloprost (ILOCOVID [NCT04445246]) for severe COVID-19 patients. Conclusions Inhaled prostacyclin could be considered in patients with refractory, life-threatening hypoxia despite standard management.

A Comparison of Inhaled Epoprostenol in Patients With Acute Respiratory Distress Syndrome and COVID-19-Associated Acute Respiratory Distress Syndrome

“…Much like previous data on both ARDS and CARDS, an improvement in the PaO 2 /FiO 2 ratio was noted in both groups after the administration of iEPO [5][6][7][8][9][10]. Mechanistically, this is most likely due to a multitude of effects that include vascular smooth muscle relaxation, pulmonary vasodilation, and platelet stabilization [4]. However, those with ARDS had a greater post PaO 2 /FiO 2 ratio as compared to those with CARDS.…”

“…In this limited sample, both those with ARDS and CARDS showed a clinical improvement in their pre/post PaO 2 /FiO 2 ratios. This improvement has been theorized to be related to a more homogenous distribution of iEPO due to the improvement in ventilation/perfusion mismatching [4]. Although a statistically significant difference in the PaO 2 /FiO 2 ratios was noted, no difference in the length of hospitalization or 28-day mortality was seen when the two groups were compared.…”

“…Due to the increase in patients with ARDS and coronavirus disease 2019 (COVID-19), COVID-19-associated acute respiratory distress syndrome (CARDS) was defined based on the Berlin definition [2,3]. Despite a similar medical definition, those with CARDS show unique pathophysiology post-mortem, including widespread pulmonary vascular thrombi and vascular endothelia accompanied by a lack of the more common ARDS-related alveolar damage [4]. It has been hypothesized that the unique findings in those with CARDS could lead to a greater amount of pulmonary hypertension, right ventricular dysfunction, and an increase in ventilation/perfusion mismatching that is not seen in those with ARDS [4].…”

Paroxysmal Finger Hematoma—A Probable Vascular Disorder in Post-COVID-19 Condition: Two Clinical Case Presentations

“…The mechanism included imitation of endogenous prostacyclin-PGI2 and binding to a G-protein, localized in the vascular smooth muscle receptor, which leads to the activation of a cyclic adenosine monophosphate, vascular smooth muscle relaxation [ 12 ]. Also, prostacyclin alleviates coagulopathy by controlling platelet aggregation through elevated nitric oxide production, which promotes vasodilatation and prevents vasoconstriction and platelet aggregation in cases of SARS-CoV-2-infection [ 15 ]. The safety, high-patient tolerability, and effective profile characterize Iloprost as a therapeutic agent with high applicability for treatment and recovery in patients with COVID-19 and AS.…”

A Narrative Review on the Administration of Inhaled Prostaglandins in Critically Ill Adult Patients With Acute Respiratory Distress Syndrome

“…20,21 In contrast, inhaled prostaglandins activate cyclic adenosine monophosphate. [22][23][24][25] Both mechanisms lead to relaxation of smooth muscle and vasodilation of the pulmonary vasculature, increasing blood flow to areas of the lung, which are well-ventilated to improve V/Q matching and oxygenation. [20][21][22][23][24][25] In addition, nitric oxide (NO) and inhaled prostaglandins have anti-inflammatory and antiplatelet effects that are valuable given the release of proinflammatory cytokines and procoagulants associated with the pathology of ARDS.…”