Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19

{ 'indexed': {'date-parts': [[2022, 6, 27]], 'date-time': '2022-06-27T17:42:28Z', 'timestamp': 1656351748037}, 'reference-count': 21, 'publisher': 'Public Library of Science (PLoS)', 'issue': '6', 'license': [ { 'start': { 'date-parts': [[2022, 6, 27]], 'date-time': '2022-06-27T00:00:00Z', 'timestamp': 1656288000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, '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>', 'DOI': '10.1371/journal.pone.0270646', 'type': 'journal-article', 'created': {'date-parts': [[2022, 6, 27]], 'date-time': '2022-06-27T17:24:46Z', 'timestamp': 1656350686000}, 'page': 'e0270646', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19', 'prefix': '10.1371', 'volume': '17', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-7089-8715', 'authenticated-orcid': True, 'given': 'Pai B. H.', 'family': 'Poonam', 'sequence': 'first', 'affiliation': []}, {'given': 'Rebecca', 'family': 'Koscik', 'sequence': 'additional', 'affiliation': []}, {'given': 'Trong', 'family': 'Nguyen', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shefali', 'family': 'Rikhi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hung-Mo', 'family': 'Lin', 'sequence': 'additional', 'affiliation': []}], 'member': '340', 'published-online': {'date-parts': [[2022, 6, 27]]}, 'reference': [ { 'key': 'pone.0270646.ref001', 'article-title': 'Clinical characteristics of 138 hospitalized patients with 2019 novel ' 'coronavirus-infected pneumonia in Wuhan, China', 'author': 'D Wang', 'year': '2020', 'journal-title': 'JAMA'}, { 'issue': '10223', 'key': 'pone.0270646.ref002', 'doi-asserted-by': 'crossref', 'first-page': '497', 'DOI': '10.1016/S0140-6736(20)30183-5', 'article-title': 'Clinical features of patients infected with 2019 novel coronavirus in ' 'Wuhan, China', 'volume': '395', 'author': 'C Huang', 'year': '2020', 'journal-title': 'Lancet'}, { 'issue': '7', 'key': 'pone.0270646.ref003', 'doi-asserted-by': 'crossref', 'first-page': '934', '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', 'volume': '180', 'author': 'C Wu', 'year': '2020', 'journal-title': 'JAMA Intern Med'}, { 'key': 'pone.0270646.ref004', 'doi-asserted-by': 'crossref', 'first-page': '1099', 'DOI': '10.1007/s00134-020-06033-2', 'article-title': 'COVID-19 pneumonia: different respiratory treatments for different ' 'phenotypes?', 'volume': '46', 'author': 'L Gattinoni', 'year': '2020', 'journal-title': 'Intensive Care Med'}, { 'issue': '3', 'key': 'pone.0270646.ref005', 'doi-asserted-by': 'crossref', 'first-page': '991', 'DOI': '10.1164/ajrccm.153.3.8630585', 'article-title': 'Direct comparison of inhaled nitric oxide and aerosolized prostacyclin ' 'in acute respiratory distress syndrome', 'volume': '153', 'author': 'D Walmrath', 'year': '1996', 'journal-title': 'Am J Respir Crit Care Med'}, { 'issue': '2', 'key': 'pone.0270646.ref006', 'doi-asserted-by': 'crossref', 'first-page': '224', 'DOI': '10.1053/jcan.2001.21974', 'article-title': 'Hemodynamic and oxygenation changes of combined therapy with inhaled ' 'nitric oxide and inhaled prostacyclin', 'volume': '15', 'author': 'GD Rocca', 'year': '2001', 'journal-title': 'J Cardiothorac Vasc Anesth'}, { 'issue': '6', 'key': 'pone.0270646.ref007', 'doi-asserted-by': 'crossref', 'first-page': '1510', 'DOI': '10.1378/chest.14-3161', 'article-title': 'The use of inhaled prostaglandins in patients with ARDS: a systematic ' 'review and meta-analysis', 'volume': '147', 'author': 'BM Fuller', 'year': '2015', 'journal-title': 'Chest'}, { 'key': 'pone.0270646.ref008', 'doi-asserted-by': 'crossref', 'first-page': '3106', 'DOI': '10.1161/01.CIR.0000134595.80170.62', 'article-title': 'Inhaled Nitric Oxide', 'author': 'Fumito Ichinose', 'year': '2004', 'journal-title': 'Circulation'}, { 'issue': '5', 'key': 'pone.0270646.ref009', 'doi-asserted-by': 'crossref', 'first-page': '844', 'DOI': '10.1016/j.jcrc.2013.03.006', 'article-title': 'Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia ' 'in critically ill patients', 'volume': '28', 'author': 'H Torbic', 'year': '2013', 'journal-title': 'J Crit Care'}, { 'issue': '4', 'key': 'pone.0270646.ref010', 'doi-asserted-by': 'crossref', 'DOI': '10.1177/2045894020973906', 'article-title': 'Rescue therapy with thrombolysis in patients with severe ' 'COVID-19-associated acute respiratory distress syndrome', 'volume': '10', 'author': 'LC Price', 'year': '2020', 'journal-title': 'Pulm Circ'}, { 'issue': '1', 'key': 'pone.0270646.ref011', 'first-page': '1009', 'article-title': 'The Acute Respiratory Distress Syndrome: Mechanisms and Perspective ' 'Therapeutic Approaches', 'volume': '2', 'author': 'JN Gonzales', 'year': '2015', 'journal-title': 'Austin J Vasc Med'}, { 'issue': '4', 'key': 'pone.0270646.ref012', 'doi-asserted-by': 'crossref', 'first-page': 'S337', 'DOI': '10.1097/01.CCM.0000057913.45273.1A', 'article-title': 'Selective pulmonary vasodilation in acute respiratory distress syndrome', 'volume': '31', 'author': 'U Kaisers', 'year': '2003', 'journal-title': 'Crit Care Med'}, { 'issue': '10', 'key': 'pone.0270646.ref013', 'doi-asserted-by': 'crossref', 'first-page': '1105', 'DOI': '10.1177/1060028015595642', 'article-title': 'Noninferiority of Inhaled Epoprostenol to Inhaled Nitric Oxide for the ' 'Treatment of ARDS', 'volume': '49', 'author': 'MA Ammar', 'year': '2015', 'journal-title': 'Annals of Pharmacotherapy'}, { 'issue': '10', 'key': 'pone.0270646.ref014', 'doi-asserted-by': 'crossref', 'first-page': 'e0259', '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', 'volume': '2', 'author': 'Jeremy R. DeGrado', 'year': '2020', 'journal-title': 'Critical Care Explorations'}, { 'issue': '5', 'key': 'pone.0270646.ref015', 'doi-asserted-by': 'crossref', 'first-page': '854', '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)', 'volume': '46', 'author': 'W Alhazzani', 'year': '2020', 'journal-title': 'Intensive Care Med'}, { 'key': 'pone.0270646.ref016', 'doi-asserted-by': 'crossref', 'first-page': '629', 'DOI': '10.1111/aas.13757', 'article-title': 'Effects of inhaled nitric oxide in COVID-19–induced ARDS–Is it ' 'worthwhile?', 'volume': '65', 'author': 'C Lotz', 'year': '2021', 'journal-title': 'Acta Anaesthesiol Scand'}, { 'issue': '12', 'key': 'pone.0270646.ref017', 'doi-asserted-by': 'crossref', 'first-page': 'e0307', 'DOI': '10.1097/CCE.0000000000000307', 'article-title': 'Effects of Inhaled Epoprostenol and Prone Positioning in Intubated ' 'Coronavirus Disease 2019 Patients With Refractory Hypoxemia', 'volume': '2', 'author': 'J Li', 'year': '2020', 'journal-title': 'Crit Care Explor'}, { 'issue': '3', 'key': 'pone.0270646.ref018', 'doi-asserted-by': 'crossref', 'first-page': '327', 'DOI': '10.1177/0885066620976525', 'article-title': 'Responsiveness of Inhaled Epoprostenol in Respiratory Failure due to ' 'COVID-19', 'volume': '36', 'author': 'R Sonti', 'year': '2021', 'journal-title': 'Journal of Intensive Care Medicine'}, { 'key': 'pone.0270646.ref019', 'doi-asserted-by': 'crossref', 'first-page': '1014', 'DOI': '10.4187/respcare.05268', 'article-title': 'Severity of hypoxemia and other factors that influence the response to ' 'aerosolized prostacyclin in ARDS', 'volume': '62', 'author': 'RH Kallet', 'year': '2017', 'journal-title': 'Respir Care'}, { 'key': 'pone.0270646.ref020', 'first-page': '150', 'article-title': 'Endothelial dysfunction in sepsis', 'volume': '11', 'author': "J Boisrame'-Helms", 'year': '2013', 'journal-title': 'Curr Vasc Pharmacol'}, { 'key': 'pone.0270646.ref021', 'doi-asserted-by': 'crossref', 'first-page': 'L277', 'DOI': '10.1152/ajplung.00195.2020', 'article-title': 'Novel insights on the pulmonary vascular consequences of COVID-19', 'volume': '319', 'author': 'F Potus', 'year': '2020', 'journal-title': 'Am J Physiol Lung Cell Mol Physiol'}], 'container-title': 'PLOS ONE', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://dx.plos.org/10.1371/journal.pone.0270646', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 6, 27]], 'date-time': '2022-06-27T17:25:05Z', 'timestamp': 1656350705000}, 'score': 1, 'resource': {'primary': {'URL': 'https://dx.plos.org/10.1371/journal.pone.0270646'}}, 'subtitle': [], 'editor': [{'given': 'Christopher', 'family': 'Torrens', 'sequence': 'first', 'affiliation': []}], 'short-title': [], 'issued': {'date-parts': [[2022, 6, 27]]}, 'references-count': 21, 'journal-issue': {'issue': '6', 'published-online': {'date-parts': [[2022, 6, 27]]}}, 'URL': 'http://dx.doi.org/10.1371/journal.pone.0270646', 'relation': {}, 'ISSN': ['1932-6203'], 'subject': ['Multidisciplinary'], 'container-title-short': 'PLoS ONE', 'published': {'date-parts': [[2022, 6, 27]]}}