Effects of Inhaled Epoprostenol and Prone Positioning in Intubated Coronavirus Disease 2019 Patients With Refractory Hypoxemia

Li, Jie; Fink, James B.; Augustynovich, Ashley E.; Mirza, Sara; Kallet, Richard H; Dhand, Rajiv

doi:10.1097/cce.0000000000000307

Cited by 17 publications

(31 citation statements)

References 19 publications

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“…The degree to which PP improves V/Q matching via changes in ventilation versus changes in perfusion remains incompletely characterized ( 9 , 10 ). iNO has been demonstrated to improve oxygenation by better matching of perfusion to ventilation, but its effects when used in combination with PP have been infrequently characterized ( 11 , 12 ).…”

mentioning

confidence: 99%

Respiratory Physiology of Prone Positioning With and Without Inhaled Nitric Oxide Across the Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Severity Spectrum

Ziehr

Alladina

Wolf

et al. 2021

Critical Care Explorations

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mentioning

confidence: 99%

Respiratory Physiology of Prone Positioning With and Without Inhaled Nitric Oxide Across the Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Severity Spectrum

Ziehr

Alladina

Wolf

et al. 2021

Critical Care Explorations

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“…Per our institution protocol, iEPO was initiated at a dose of 50 ng/kg/min based on PBW and maintained for a minimum of 24 h after initiation. iEPO weaning was determined by the treating physician(s) and titrated down by 10 ng/kg/min every 30–60 min if the patient’s status remained stable [ 7 ]. In the high concentration group, iEPO dose was titrated by adjusting the pump rate.…”

Section: Methodsmentioning

confidence: 99%

“…In the recent years, the use of a vibrating mesh nebulizer (VMN) with continuous external feed has been increasingly utilized to deliver iEPO in-line during invasive ventilation [ 3 – 7 , 10 – 12 ], as it is powered by electricity with no gas added to the ventilator circuit, and it has little to no residual volume. When a VMN is utilized, iEPO is prepared in a 60 mL syringe and the dose is adjusted by setting different pump rates, depending on the formulation concentration to deliver the desired dose, thereby introducing the formulation to the mesh “drop by drop” which produces aerosol consistently but intermittently.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, there are two major strategies to administer iEPO via VMN: (1) using one high concentration and adjusting the pump rate to deliver a full range of doses. The pump is usually set at a low rate (1–8 mL/h) and the aerosol is generated intermittently [ 7 , 12 ]. (2) preparing different concentrations of medication, then changing the concentration and setting the pump rate (8–20 mL/h) close to the nebulizer output to produce constant and continuous emitted aerosol [ 10 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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In-vitro and in-vivo comparisons of high versus low concentrations of inhaled epoprostenol to adult intubated patients

Augustynovich

Gurnani

et al. 2021

Respir Res

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Background Inhaled epoprostenol (iEPO) has been shown to reduce pulmonary artery pressure and improve oxygenation. iEPO is mainly delivered via a syringe pump with feed tubing connected to a vibrating mesh nebulizer with high or low formulation concentration delivery. Methods An in vitro study and a two-period retrospective case–control study were implemented. The in vitro study compared iEPO delivery via invasive ventilation at low concentrations of 7.5, and 15 mcg/mL and high concentration at 30 mcg/mL, to deliver the ordered dose of 30 and 50 ng/kg/min for three clinical scenarios with predicted body weight of 50, 70 and 90 kg. While in the clinical study, adult patients receiving iEPO via invasive ventilation to treat refractory hypoxemia, pulmonary hypertension, or right ventricular failure were included. 80 patients received low concentration iEPO at multiple concentrations (2.5, 7.5, and 15 mcg/mL, depending on the ordered dose) from 2015 to 2017, while 84 patients received high concentration iEPO at 30 mcg/mL from 2018 to 2019. Results In the in vitro study, there were no significant differences in aerosol deposition between high vs low concentrations of iEPO at a dose of 50 ng/kg/min. In the clinical study, age, gender, ethnicity, and indications for iEPO were similar between high and low concentration groups. After 30–120 min of iEPO administration, both delivery strategies significantly improved oxygenation in hypoxemic patients and reduced mean pulmonary arterial pressure (mPAP) for patients with pulmonary hypertension. However, no significant differences of the incremental changes were found between two delivery groups. Compared to low concentration, high concentration delivery group had better adherence to the iEPO weaning protocol (96% vs 71%, p < 0.001), fewer iEPO syringes utilized per patient (5 [3, 10] vs 12 [6, 22], p = 0.001), and shorter duration of invasive ventilation (6 [3, 12] vs 9 [5, 18] days, p = 0.028). Intensive care unit length of stay and mortality were similar between two groups. Conclusion Compared to low concentration delivery of iEPO, high concentration iEPO via a vibrating mesh nebulizer maintained clinical benefits and increased clinician compliance with an iEPO weaning protocol, required less medication preparation time, and shortened duration of invasive ventilation.

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“…In addition to NSAIDs, other drugs or compounds targeting the formation or function of prostanoids are under consideration as adjuvant therapeutics in COVID-19 patients. Prostacyclin receptor analogs, epoprostenol and iloprost, are approved for the treatment of pulmonary hypertension and have been used in COVID-19 patients for their anti-aggregating and vasodilatory properties ( DeGrado et al, 2020 ; Li et al, 2020 ; Moezinia et al, 2020 ; Sonti et al, 2021 ). Asapiprant (BGE-175), a potent DPR1 antagonist under clinical development for the treatment of allergic rhinitis and asthma, is currently being evaluated in hospitalized COVID-19 patients who are not in respiratory failure (NCT04705597).…”

Section: Introductionmentioning

confidence: 99%

Nonsteroidal anti-inflammatory drugs and glucocorticoids in COVID-19

Ricciotti

Laudański

FitzGerald

2021

Advances in Biological Regulation

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies.

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Effects of Inhaled Epoprostenol and Prone Positioning in Intubated Coronavirus Disease 2019 Patients With Refractory Hypoxemia

Abstract: Supplemental Digital Content is available in the text.

Cited by 17 publications

References 19 publications

Respiratory Physiology of Prone Positioning With and Without Inhaled Nitric Oxide Across the Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Severity Spectrum

Respiratory Physiology of Prone Positioning With and Without Inhaled Nitric Oxide Across the Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Severity Spectrum

In-vitro and in-vivo comparisons of high versus low concentrations of inhaled epoprostenol to adult intubated patients

Nonsteroidal anti-inflammatory drugs and glucocorticoids in COVID-19

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