Inhaled pulmonary vasodilators are not associated with improved gas exchange in mechanically ventilated patients with COVID-19: A retrospective cohort study

Lubinsky, Anthony; Brosnahan, Shari B.; Lehr, A.; Elnadoury, Ola; Hagedorn, Jacklyn; Garimella, Bhaskara; Bender, Michael; Amoroso, Nancy; Artigas, Antonio; Bos, Lieuwe D. J.; Kaufman, David A.

doi:10.1016/j.jcrc.2022.153990

Cited by 8 publications

(12 citation statements)

References 34 publications

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“…To begin to describe the efficacy of iEPO for each condition, the authors sought to complete a preliminary assessment in a retrospective cohort. 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].…”

Section: Discussionsupporting

confidence: 73%

“…Despite varying degrees of evidence and support from national organizations, selective pulmonary vasodilators have been used as a rescue medication to improve oxygenation in those with both refractory ARDS and CARDS [5][6][7][8][9][10][11][12]. Inhaled epoprostenol (iEPO), a synthetic prostacyclin analog, is thought to improve oxygenation through selective pulmonary vasodilatation by cyclic guanosine monophosphate and cyclic adenosine monophosphate-mediated smooth muscle relaxation [5][6][7][8][9][10][11][12][13]. Previous data have shown iEPO's ability to alleviate coagulopathy by counteracting the prothrombotic effect of endothelin and decreasing platelet aggregation [14].…”

Section: Introductionmentioning

confidence: 99%

“…Previous data have shown iEPO's ability to alleviate coagulopathy by counteracting the prothrombotic effect of endothelin and decreasing platelet aggregation [14]. Available evidence currently does not show any mortality benefit in those with ARDS or CARDS, but a transient increase in oxygenation has been seen in a subset of both patient populations who have been given iEPO [5][6][7][8][9][10]. Currently, no data directly compare the outcomes of those with ARDS and CARDS who had received iEPO while mechanically ventilated.…”

Section: Introductionmentioning

confidence: 99%

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

Santarelli¹,

Wilks²,

Latu³

et al. 2022

Cureus

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IntroductionAcute respiratory distress syndrome (ARDS) and coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (CARDS) are both characterized by non-cardiogenic pulmonary edema and severe hypoxemia that leads to a high percentage of patients suffering in-hospital mortality. Mechanistically, inhaled epoprostenol (iEPO) has shown a role in the treatment of ARDS and CARDS but little data are available directly comparing the two disease processes. Due to the lack of evidence of iEPO in ARDS and CARDS, the authors sought to compare the pulmonary effects of iEPO for mechanically ventilated patients with CARDS against a case match control of those with ARDS. MethodsA retrospective cohort of all patients receiving iEPO between January 1, 2020, and February 22, 2022, was reviewed. Patients with ARDS were case-matched in a 2:1 allocation ratio of CARDS to ARDS by the number of medical comorbidities and age +/-5 years. Clinical data collected included patient demographics, laboratory values, ventilator settings, length of hospitalization, and 28-day mortality. Comparisons of the effectiveness of iEPO between ARDS and CARDS were conducted using the chi-squared statistic for categorical variables and the Mann-Whitney statistic for continuous variables. ResultsA total of 72 patients were included in the final analysis, with 24 having ARDS and 48 CARDS. The number of medical comorbidities was no different for patients with ARDS or CARDs (p = 0.18), though the frequency of patients diagnosed with coronary artery disease (p=0.007), congestive heart failure (p=0.003), chronic obstructive pulmonary disease (p=0.004), and pulmonary hypertension (p=0.004) did vary between the two groups. A moderate but non-significant difference in pre-iEPO partial pressure of oxygen (PaO 2 )/fraction of inspired oxygen (FiO 2 ) ratio was noted between the groups (0.74 vs 0.65; p=0.33). Following iEPO treatment, patients with ARDS showed a greater PaO 2 /FiO 2 ratio than those with CARDS (0.87 vs 0.70; p=0.02). CARDS patients who received iEPO had a longer length of stay as compared to those with ARDS (17.5 vs 12.5 days; p=0.01). However, no difference was noted in 28-day mortality between the two groups (14 vs 34; p=0.29). ConclusionIn this small sample from a single community hospital, a statistically significant improvement in the PaO 2 /FiO 2 ratio was noted for both those with ARDS and CARDS. However, those with CARDS who were given iEPO had a longer length of stay without a significant difference in mortality as compared to those with traditional ARDS.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Santarelli¹,

Wilks²,

Latu³

et al. 2022

Cureus

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“…Eventually, 18 studies were included in the 1-arm meta-analysis (13 single arm retrospective studies 18 – 30 and 5 case series 31 – 35 ) and three studies 13 , 14 , 36 in the 2-arm meta-analysis. Figure 1 shows the PRISMA flow chart that illustrates how the final studies were selected.…”

Section: Resultsmentioning

confidence: 99%

“… 11 , 37 Recent trials regarding COVID-19 ARDS and IPVD even showed no significant improvement in oxygenation. 21 , 25 IPVD, especially NO, are expensive and their use has not shown much benefit historically, as a meta-analysis by Adhikari et al 38 involving non-COVID-19 patients treated with iNO, commented on lack of mortality benefits. The use of IPVD in COVID-19 ARDS has also become a common practice, without concrete data supporting IPVD use.…”

Section: Discussionmentioning

confidence: 99%

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

Khokher

Malhas

Beran

et al. 2022

J Intensive Care Med

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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.

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Lessons Learned in Mechanical Ventilation/Oxygen Support in Coronavirus Disease 2019

Dragoi

Siuba

Fan

2023

Clinics in Chest Medicine

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Inhaled pulmonary vasodilators are not associated with improved gas exchange in mechanically ventilated patients with COVID-19: A retrospective cohort study

Cited by 8 publications

References 34 publications

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

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

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

Lessons Learned in Mechanical Ventilation/Oxygen Support in Coronavirus Disease 2019

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