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Meta-Analysis
. 2022 Oct;37(10):1370-1382.
doi: 10.1177/08850666221118271. Epub 2022 Aug 2.

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

Waleed Khokher  1 , Saif-Eddin Malhas  1 , Azizullah Beran  1 , Saffa Iftikhar  1 , Cameron Burmeister  1 , Mohammed Mhanna  1 , Omar Srour  1 , Rakin Rashid  2 , Nithin Kesireddy  1 , Ragheb Assaly  1   3
Affiliations
Meta-Analysis

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

Waleed Khokher et al. J Intensive Care Med. 2022 Oct.

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.

Keywords: COVID-19; inhaled pulmonary vasodilators; intubation; mortality; refractory hypoxia.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram for the selection of studies.
Figure 2.
Figure 2.
Forest plots for 1-arm meta-analysis: (A) pre- and post-IPVD PaO2/FiO2 ratios, (B) pre- and post-IPVD positive end-expiratory pressure, (C) pre- and post-IPVD lung compliance.
Figure 3.
Figure 3.
Subgroup analysis based on type of IPVD for studies in the 1-arm meta-analysis in regards pre- and post-IPVD PaO2/FiO2 ratios.
Figure 4.
Figure 4.
Forest plots for 2-arm meta-analysis comparing IPVDs to standard therapy: (A) mortality, (B) need for endotracheal intubation, (C) hospital length of stay.
Figure 5.
Figure 5.
Forest plots of responder versus non-responder subgroup analysis: (A) baseline PaO2/FiO2 ratios, (B) mortality, (C) need for endotracheal intubation.
See this image and copyright information in PMC

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