Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19

DOI record: { "DOI": "10.1371/journal.pone.0270646", "ISSN": [ "1932-6203" ], "URL": "http://dx.doi.org/10.1371/journal.pone.0270646", "abstract": "<jats:sec id=\"sec001\">\n<jats:title>Objective</jats:title>\n<jats:p>To compare the efficacy and outcomes with inhaled nitric oxide (iNO) and inhaled epoprostenol (iEPO) in patients with refractory hypoxemia due to COVID-19.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Design</jats:title>\n<jats:p>Retrospective Cohort Study.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Setting</jats:title>\n<jats:p>Single health system multicenter academic teaching hospitals.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Patients OR subjects</jats:title>\n<jats:p>Age group of 18–80 years admitted to the medical ICU.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Interventions</jats:title>\n<jats:p>Mechanically ventilated patients with COVID-19 infection, who received either iNO or iEPO between March 1<jats:sup>st</jats:sup>, 2020, and June 30<jats:sup>th</jats:sup>, 2020.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec006\">\n<jats:title>Measurements and main results</jats:title>\n<jats:p>The primary outcome was the change in the PaO2/FiO2 (P/F) ratio 1 hour after initiation of pulmonary vasodilator therapy. Secondary outcomes include P/F ratios on days 1–3 after initiation, positive response in P/F ratio (increase of at least 20% in PaO2), total days of treatment, rebound hypoxemia (if there was a drop in oxygen saturation after treatment was stopped), ventilator free days (if any patient was extubated), days in ICU, days to extubation, days to tracheostomy, mortality days after intubation, 30-day survival and mortality. 183 patients were excluded, as they received both iNO and iEPO. Of the remaining 103 patients, 62 received iEPO and 41 received iNO. The severity of ARDS was similar in both groups. Change in P/F ratio at one hour was 116 (70.3) with iNO and 107 (57.6) with iEPO (Mean/SD). Twenty-two (53.7%) patients in the iNO group and 25 (40.3%) in the iEPO group were responders to pulmonary vasodilators <jats:italic>n(%)(</jats:italic>p = 0.152) (more than 20% increase in partial pressure of oxygen, Pao2), and 18 (43.9%) and 31 (50%) patients in the iNO and iEPO group (p = 0.685), respectively, had rebound hypoxemia. Only 7 patients in the cohort achieved ventilator free days (3 in the iEPO group and 4 in iNO group).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec007\">\n<jats:title>Conclusions</jats:title>\n<jats:p>We found no significant difference between iNO and iEPO in terms of change in P/F ratio, duration of mechanical ventilation, ICU, in-hospital mortality in this cohort of mechanically ventilated patients with COVID-19. Larger, prospective studies are necessary to validate these results.</jats:p>\n</jats:sec>", "author": [ { "ORCID": "http://orcid.org/0000-0001-7089-8715", "affiliation": [], "authenticated-orcid": true, "family": "Poonam", "given": "Pai B. H.", "sequence": "first" }, { "affiliation": [], "family": "Koscik", "given": "Rebecca", "sequence": "additional" }, { "affiliation": [], "family": "Nguyen", "given": "Trong", "sequence": "additional" }, { "affiliation": [], "family": "Rikhi", "given": "Shefali", "sequence": "additional" }, { "affiliation": [], "family": "Lin", "given": "Hung-Mo", "sequence": "additional" } ], "container-title": "PLOS ONE", "container-title-short": "PLoS ONE", "content-domain": { "crossmark-restriction": false, "domain": [ "www.plosone.org" ] }, "created": { "date-parts": [ [ 2022, 6, 27 ] ], "date-time": "2022-06-27T17:24:46Z", "timestamp": 1656350686000 }, "deposited": { "date-parts": [ [ 2022, 6, 27 ] ], "date-time": "2022-06-27T17:25:05Z", "timestamp": 1656350705000 }, "editor": [ { "affiliation": [], "family": "Torrens", "given": "Christopher", "sequence": "first" } ], "indexed": { "date-parts": [ [ 2022, 6, 27 ] ], "date-time": "2022-06-27T17:42:28Z", "timestamp": 1656351748037 }, "is-referenced-by-count": 0, "issue": "6", "issued": { "date-parts": [ [ 2022, 6, 27 ] ] }, "journal-issue": { "issue": "6", "published-online": { "date-parts": [ [ 2022, 6, 27 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 6, 27 ] ], "date-time": "2022-06-27T00:00:00Z", "timestamp": 1656288000000 } } ], "link": [ { "URL": "https://dx.plos.org/10.1371/journal.pone.0270646", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "340", "original-title": [], "page": "e0270646", "prefix": "10.1371", "published": { "date-parts": [ [ 2022, 6, 27 ] ] }, "published-online": { "date-parts": [ [ 2022, 6, 27 ] ] }, "publisher": "Public Library of Science (PLoS)", "reference": [ { "article-title": "Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China", "author": "D Wang", "journal-title": "JAMA", "key": "pone.0270646.ref001", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)30183-5", "article-title": "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China", "author": "C Huang", "doi-asserted-by": "crossref", "first-page": "497", "issue": "10223", "journal-title": "Lancet", "key": "pone.0270646.ref002", "volume": "395", "year": "2020" }, { "DOI": "10.1001/jamainternmed.2020.0994", "article-title": "Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China", "author": "C Wu", "doi-asserted-by": "crossref", "first-page": "934", "issue": "7", "journal-title": "JAMA Intern Med", "key": "pone.0270646.ref003", "volume": "180", "year": "2020" }, { "DOI": "10.1007/s00134-020-06033-2", "article-title": "COVID-19 pneumonia: different respiratory treatments for different phenotypes?", "author": "L Gattinoni", "doi-asserted-by": "crossref", "first-page": "1099", "journal-title": "Intensive Care Med", "key": "pone.0270646.ref004", "volume": "46", "year": "2020" }, { "DOI": "10.1164/ajrccm.153.3.8630585", "article-title": "Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome", "author": "D Walmrath", "doi-asserted-by": "crossref", "first-page": "991", "issue": "3", "journal-title": "Am J Respir Crit Care Med", "key": "pone.0270646.ref005", "volume": "153", "year": "1996" }, { "DOI": "10.1053/jcan.2001.21974", "article-title": "Hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide and inhaled prostacyclin", "author": "GD Rocca", "doi-asserted-by": "crossref", "first-page": "224", "issue": "2", "journal-title": "J Cardiothorac Vasc Anesth", "key": "pone.0270646.ref006", "volume": "15", "year": "2001" }, { "DOI": "10.1378/chest.14-3161", "article-title": "The use of inhaled prostaglandins in patients with ARDS: a systematic review and meta-analysis", "author": "BM Fuller", "doi-asserted-by": "crossref", "first-page": "1510", "issue": "6", "journal-title": "Chest", "key": "pone.0270646.ref007", "volume": "147", "year": "2015" }, { "DOI": "10.1161/01.CIR.0000134595.80170.62", "article-title": "Inhaled Nitric Oxide", "author": "Fumito Ichinose", "doi-asserted-by": "crossref", "first-page": "3106", "journal-title": "Circulation", "key": "pone.0270646.ref008", "year": "2004" }, { "DOI": "10.1016/j.jcrc.2013.03.006", "article-title": "Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia in critically ill patients", "author": "H Torbic", "doi-asserted-by": "crossref", "first-page": "844", "issue": "5", "journal-title": "J Crit Care", "key": "pone.0270646.ref009", "volume": "28", "year": "2013" }, { "DOI": "10.1177/2045894020973906", "article-title": "Rescue therapy with thrombolysis in patients with severe COVID-19-associated acute respiratory distress syndrome", "author": "LC Price", "doi-asserted-by": "crossref", "issue": "4", "journal-title": "Pulm Circ", "key": "pone.0270646.ref010", "volume": "10", "year": "2020" }, { "article-title": "The Acute Respiratory Distress Syndrome: Mechanisms and Perspective Therapeutic Approaches", "author": "JN Gonzales", "first-page": "1009", "issue": "1", "journal-title": "Austin J Vasc Med", "key": "pone.0270646.ref011", "volume": "2", "year": "2015" }, { "DOI": "10.1097/01.CCM.0000057913.45273.1A", "article-title": "Selective pulmonary vasodilation in acute respiratory distress syndrome", "author": "U Kaisers", "doi-asserted-by": "crossref", "first-page": "S337", "issue": "4", "journal-title": "Crit Care Med", "key": "pone.0270646.ref012", "volume": "31", "year": "2003" }, { "DOI": "10.1177/1060028015595642", "article-title": "Noninferiority of Inhaled Epoprostenol to Inhaled Nitric Oxide for the Treatment of ARDS", "author": "MA Ammar", "doi-asserted-by": "crossref", "first-page": "1105", "issue": "10", "journal-title": "Annals of Pharmacotherapy", "key": "pone.0270646.ref013", "volume": "49", "year": "2015" }, { "DOI": "10.1097/CCE.0000000000000259", "article-title": "Evaluation of the Efficacy and Safety of Inhaled Epoprostenol and Inhaled Nitric Oxide for Refractory Hypoxemia in Patients With Coronavirus Disease 2019", "author": "Jeremy R. DeGrado", "doi-asserted-by": "crossref", "first-page": "e0259", "issue": "10", "journal-title": "Critical Care Explorations", "key": "pone.0270646.ref014", "volume": "2", "year": "2020" }, { "DOI": "10.1007/s00134-020-06022-5", "article-title": "Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)", "author": "W Alhazzani", "doi-asserted-by": "crossref", "first-page": "854", "issue": "5", "journal-title": "Intensive Care Med", "key": "pone.0270646.ref015", "volume": "46", "year": "2020" }, { "DOI": "10.1111/aas.13757", "article-title": "Effects of inhaled nitric oxide in COVID-19–induced ARDS–Is it worthwhile?", "author": "C Lotz", "doi-asserted-by": "crossref", "first-page": "629", "journal-title": "Acta Anaesthesiol Scand", "key": "pone.0270646.ref016", "volume": "65", "year": "2021" }, { "DOI": "10.1097/CCE.0000000000000307", "article-title": "Effects of Inhaled Epoprostenol and Prone Positioning in Intubated Coronavirus Disease 2019 Patients With Refractory Hypoxemia", "author": "J Li", "doi-asserted-by": "crossref", "first-page": "e0307", "issue": "12", "journal-title": "Crit Care Explor", "key": "pone.0270646.ref017", "volume": "2", "year": "2020" }, { "DOI": "10.1177/0885066620976525", "article-title": "Responsiveness of Inhaled Epoprostenol in Respiratory Failure due to COVID-19", "author": "R Sonti", "doi-asserted-by": "crossref", "first-page": "327", "issue": "3", "journal-title": "Journal of Intensive Care Medicine", "key": "pone.0270646.ref018", "volume": "36", "year": "2021" }, { "DOI": "10.4187/respcare.05268", "article-title": "Severity of hypoxemia and other factors that influence the response to aerosolized prostacyclin in ARDS", "author": "RH Kallet", "doi-asserted-by": "crossref", "first-page": "1014", "journal-title": "Respir Care", "key": "pone.0270646.ref019", "volume": "62", "year": "2017" }, { "article-title": "Endothelial dysfunction in sepsis", "author": "J Boisrame'-Helms", "first-page": "150", "journal-title": "Curr Vasc Pharmacol", "key": "pone.0270646.ref020", "volume": "11", "year": "2013" }, { "DOI": "10.1152/ajplung.00195.2020", "article-title": "Novel insights on the pulmonary vascular consequences of COVID-19", "author": "F Potus", "doi-asserted-by": "crossref", "first-page": "L277", "journal-title": "Am J Physiol Lung Cell Mol Physiol", "key": "pone.0270646.ref021", "volume": "319", "year": "2020" } ], "reference-count": 21, "references-count": 21, "relation": {}, "resource": { "primary": { "URL": "https://dx.plos.org/10.1371/journal.pone.0270646" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Multidisciplinary" ], "subtitle": [], "title": "Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1371/journal.pone.corrections_policy", "volume": "17" }