INHALED PULMONARY VASODILATOR TREATMENT FOR COVID-19: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Coronavirus disease 2019 (COVID-19) has become a leading cause of mortality globally. Inhaled pulmonary vasodilators, epoprostenol (iEPO) and nitric oxide (iNO), are used as adjunctive therapies for the treatment of refractory hypoxemia in patients with acute respiratory distress syndrome (ARDS). Hypoxemia in COVID-19 patients is mainly caused by ventilation-perfusion mismatch, which might be improved by inhaled pulmonary vasodilators. However, the effects of inhaled pulmonary vasodilator therapy on the clinical outcomes of COVID-19 remain unclear. Therefore, we conducted this meta-analysis to evaluate the impact of pulmonary vasodilators, iNO and iEPO, on the oxygenation parameters in COVID-19 patients with refractory hypoxemia. METHODS: We performed a comprehensive literature search using PubMed, Embase, and Cochrane Library databases from inception through April 24, 2021, to include all published studies. All statistical analyses were performed using the Review Manager software (RevMan 5.3). The weighted mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. A P-value <0.05 was considered statistically significant. The primary outcome measure was the change in oxygenation parameter (PaO2/FiO2) pre and post pulmonary vasodilators. RESULTS: A total of seven studies (three and four studies for iEPO and iNO, respectively) involving 211 patients with COVID-19 (140 patients in iEPO group and 71 in iNO) were included. Overall, pulmonary vasodilators showed significant improvement in oxygenation: PaO2/FiO2 (MD: 12.48, 95% CI: 4.51, 20.44, P = 0.002, I2 = 0%). On subgroup analysis, iEPO showed significant improvement in oxygenation: PaO2/FiO2 (MD: 13.39, 95% CI: 2.84, 23.94, P = 0.01, I2 = 0%), however, iNO showed no improvement in oxygenation: PaO2/FiO2 (MD: 12.80, 95% CI: -4.82, 30.42, P = 0.15, I2 = 47%). CONCLUSIONS: Our meta-analysis showed that inhaled epoprostenol improved oxygenation in COVID-19 patients. However, inhaled nitric oxide therapy was not associated with improvement in oxygenation. Major limitation being lack of control arm and adjustment for confounders. Clinical trials are needed to determine the effect of inhaled pulmonary vasodilators on oxygenation parameters and clinical outcomes of COVID-19 patients. CLINICAL IMPLICATIONS: Inhaled pulmonary vasodilators may play a role as rescue therapy in COVID-19 patients with refractory hypoxemia. DISCLOSURES: No relevant relationships by Ziad Abuhelwa, source=Web Response No relevant relationships by Ragheb Assaly, source=Web Response No relevant relationships by Hazem Ayesh, source=Web Response No relevant relationships by Azizullah Beran Beran, source=Web Response No relevant relationships by Sami Ghazaleh, source=Web Response No relevant relationships by Dana Ghazaleh, source=Web Response No relevant relationships by Mohammed Mhanna, source=Web Response No relevant relationships by Asmaa Mhanna, source=Web Response No relevant relationships by Rami Musallam, source=Web Response No relevant relationships by Omar Sajdeya, source=Web Response No relevant relationships by Omar Srour, source=Web Response