Inhaled Pulmonary Vasodilators in COVID-19 Infection: A Systematic Review and Meta-Analysis

Abstract

Introduction: Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO2), reduce fraction of inspired oxygen (FiO2) requirements, and ultimately increase PaO2/FiO2 (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Methods: Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). Results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Conclusion: Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.

Inhaled Prostacyclins for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

“…This is the first meta-analysis to evaluate inhaled prostacyclins in patients with both non-COVID-19 and COVID-19-related ARDS and the largest metaanalysis evaluating these therapies to date. Previous meta-analyses also found inhaled prostacyclins to improve oxygenation and pulmonary artery pressures and agreed that the data evaluating these therapies is limited and of low quality (12,13).…”

“…Despite demonstrating consistent improvements in oxygenation in published literature, these improvements have been transient and have not resulted in decreased clinical outcomes like hospital length of stay, need for mechanical ventilation, and mortality (12,13). Available literature evaluating inhaled prostacyclins in ARDS is primarily single-center and observational, which limits the generalizability of the results and often does not appropriately control for interventions, which may confound the results of the study.…”

“…We also extracted data for all predefined endpoints of interest including change in Pa o 2 /F io 2 ratio (primary outcome), change in Pa o 2 , and change in mean pulmonary artery pressure (mPAP). We chose change in Pa o 2 /F io 2 ratio as the primary outcome, as it is the most common primary outcome used in observational studies (12, 13). Additionally, we extracted mortality, duration of mechanical ventilation, hospital and ICU length of stay, and adverse effects from all studies reporting these outcomes.…”

“…Data evaluating inhaled prostacyclins has been primarily observational and low quality demonstrating transient improvements in oxygenation without sustained clinical improvements resulting in decreased duration of mechanical ventilation or mortality (12, 13). Given the renewed interest in inhaled prostacyclins due to the COVID-19 pandemic and increased prevalence of ARDS cases, we sought to complete a systematic review and meta-analysis including this new data to evaluate patients with ARDS receiving inhaled pulmonary prostacyclins.…”

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

“…60 Similarly, a meta-analysis observed an improved oxygenation in patients with COVID-19-associated ARDS after the administration of inhaled pulmonary vasodilators, including epoprostenol and NO, though no clear mortality benefit was seen. 65…”