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Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study

Al Sulaiman et al., Critical Care, doi:10.1186/s13054-022-04158-y
Oct 2022  
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Mortality -40% Improvement Relative Risk Mortality, day 30 -18% Nitric Oxide  Al Sulaiman et al.  ICU PATIENTS Is very late treatment with nitric oxide beneficial for COVID-19? Retrospective 815 patients in Saudi Arabia (March 2020 - July 2021) Higher mortality with nitric oxide (not stat. sig., p=0.1) c19early.org Al Sulaiman et al., Critical Care, Oct 2022 Favorsnitric oxide Favorscontrol 0 0.5 1 1.5 2+
Retrospective 815 COVID-19 ICU patients in Saudi Arabia, showing significant improvement in oxygenation. There was no significant difference in mortality, and ICU and hospitalization time was longer.
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects (early treatment may be more beneficial).
risk of death, 40.0% higher, HR 1.40, p = 0.10, treatment 44 of 56 (78.6%), control 52 of 125 (41.6%), adjusted per study, in-hospital mortality, multivariable, Cox proportional hazards.
risk of death, 18.0% higher, HR 1.18, p = 0.45, treatment 41 of 56 (73.2%), control 44 of 122 (36.1%), adjusted per study, multivariable, Cox proportional hazards, day 30.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Al Sulaiman et al., 3 Oct 2022, retrospective, Saudi Arabia, peer-reviewed, mean age 62.5, 29 authors, study period 1 March, 2020 - 31 July, 2021. Contact: alsulaimankh@hotmail.com (corresponding author).
This PaperNitric OxideAll
Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study
Khalid Al Sulaiman, Ghazwa B Korayem, Ali F Altebainawi, Shmeylan Al Harbi, Abdulrahman Alissa, Abdullah Alharthi, Raed Kensara, Amjaad Alfahed, Ramesh Vishwakarma, Hussain Al Haji, Naif Almohaimid, Omar Al Zumai, Fahad Alrubayan, Abdulmajid Asiri, Nasser Alkahtani, Abdulaziz Alolayan, Samiah Alsohimi, Nawal Melibari, Alaa Almagthali, Seba Aljahdali, Abeer A Alenazi, Alawi S Alsaeedi, Ghassan Al Ghamdi, Omar Al Faris, Joud Alqahtani, Jalal Al Qahtani, Khalid A Alshammari, Khalil I Alshammari, Ohoud Aljuhani
Critical Care, doi:10.1186/s13054-022-04158-y
Background: Inhaled nitric oxide (iNO) is used as rescue therapy in patients with refractory hypoxemia due to severe COVID-19 acute respiratory distress syndrome (ARDS) despite the recommendation against the use of this treatment. To date, the effect of iNO on the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill COVID-19 patients with moderate-to-severe ARDS. Methods: This multicenter, retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. Eligible patients with moderate-to-severe ARDS were subsequently categorized into two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary endpoint was the improvement in oxygenation parameters 24 h after iNO use. Other outcomes were considered secondary. Propensity score matching (1:2) was used based on the predefined criteria. Results: A total of 1598 patients were screened, and 815 were included based on the eligibility criteria. Among them, 210 patients were matched based on predefined criteria. Oxygenation parameters (PaO 2 , FiO 2 requirement, P/F ratio, oxygenation index) were significantly improved 24 h after iNO administration within a median of six days of ICU admission. However, the risk of 30-day and in-hospital mortality were found to be similar between the two groups (HR: 1.18; 95% CI: 0.77, 1.82; p = 0.45 and HR: 1.40; 95% CI: 0.94, 2.11; p= 0.10, respectively). On the other hand, ventilator-free days (VFDs) were significantly fewer, and ICU and hospital LOS were significantly longer in the iNO group.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s13054-022-04158-y. Additional file 1. Outcomes definition(s). Author contributions All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. All authors read and approved the final manuscript. Declarations Ethics approval and consent to participate The study was approved in December 2020 by King Abdullah International Medical Research Center Institutional Review Board, Riyadh, Saudi Arabia (Ref.# RC20.638.R). Participants' confidentiality was strictly observed throughout the study by using anonymous unique serial number for each subject and restricting data only to the investigators. Informed consent was not required due to the research's method as per the policy of the governmental and local research center. Consent for publication Not applicable. Competing interests No author has a conflict of interest in this study. • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for..
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To date, the effect of iNO on ' 'the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS ' 'remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill ' 'COVID-19 patients with moderate-to-severe ARDS.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>This multicenter, retrospective cohort study included critically ill ' 'adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. ' 'Eligible patients\xa0with\xa0moderate-to-severe ARDS\xa0were subsequently categorized into ' 'two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary ' 'endpoint was the improvement in oxygenation parameters 24\xa0h after iNO use. Other outcomes ' 'were considered secondary. Propensity score matching (1:2) was used based on the predefined ' 'criteria.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>A total of 1598 patients were screened, and 815 were included based ' 'on the eligibility criteria. Among them, 210 patients were matched based on predefined ' 'criteria. Oxygenation parameters (PaO<jats:sub>2</jats:sub>, FiO<jats:sub>2</jats:sub> ' 'requirement, P/F ratio, oxygenation index) were\xa0significantly improved 24\xa0h after iNO ' 'administration within a median of six\xa0days of ICU admission. However, the risk of\xa0' '30-day and in-hospital mortality were\xa0found to be similar between the two groups (HR: ' '1.18; 95% CI: 0.77, 1.82; <jats:italic>p</jats:italic>\u2009=\u20090.45 and HR: 1.40; 95% CI: ' '0.94, 2.11; <jats:italic>p</jats:italic>=\u20090.10, respectively). On the other hand, ' 'ventilator-free days (VFDs) were significantly fewer, and \xa0ICU and hospital LOS were ' 'significantly longer in the iNO group. In addition, patients who received iNO had higher odds ' 'of acute kidney injury (AKI) (OR (95% CI): 2.35 (1.30, 4.26), <jats:italic>p</jats:italic> ' 'value\u2009=\u20090.005) and hospital/ventilator-acquired pneumonia (OR (95% CI): 3.2 (1.76, ' '5.83), <jats:italic>p</jats:italic> value\u2009=\u20090.001).</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusion</jats:title>\n' ' <jats:p>In critically ill COVID-19 patients with moderate-to-severe ARDS, iNO ' 'rescue therapy is associated with improved oxygenation parameters but no mortality benefits. 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' '2021;126:e72–5.', 'journal-title': 'Br J Anaesth'}, { 'key': '4158_CR19', 'doi-asserted-by': 'publisher', 'first-page': '508', 'DOI': '10.1186/s13054-020-03222-9', 'volume': '24', 'author': 'G Tavazzi', 'year': '2020', 'unstructured': 'Tavazzi G, Pozzi M, Mongodi S, et al. Inhaled nitric oxide in patients ' 'admitted to intensive care unit with COVID-19 pneumonia. Crit Care. ' '2020;24:508.', 'journal-title': 'Crit Care'}, { 'key': '4158_CR20', 'doi-asserted-by': 'publisher', 'first-page': 'a558', 'DOI': '10.1016/j.chest.2021.07.539', 'volume': '160', 'author': 'A Beran', 'year': '2021', 'unstructured': 'Beran A, Mhanna M, Srour O, et al. Inhaled pulmonary vasodilator ' 'treatment for COVID-19: a systematic review and meta-analysis. Chest. ' '2021;160:a558.', 'journal-title': 'Chest'}, { 'key': '4158_CR21', 'unstructured': 'COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) ' 'Treatment Guidelines. National Institutes of Health. [Internet]. 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Respir ' 'Care. 2011;56:1341–9.', 'journal-title': 'Respir Care'}, { 'key': '4158_CR24', 'first-page': '1717', 'volume': '55', 'author': 'RM DiBlasi', 'year': '2010', 'unstructured': 'DiBlasi RM, Myers TR, Hess DR. Evidence-based clinical practice ' 'guideline: inhaled nitric oxide for neonates with acute hypoxic ' 'respiratory failure. Respir Care. 2010;55:1717–45.', 'journal-title': 'Respir Care'}, { 'issue': '1', 'key': '4158_CR25', 'doi-asserted-by': 'publisher', 'first-page': '5', 'DOI': '10.1093/toxsci/59.1.5', 'volume': '59', 'author': 'B Weinberger', 'year': '2001', 'unstructured': 'Weinberger B, Laskin DL, Heck DE, Laskin JD. The toxicology of inhaled ' 'nitric oxide. Toxicol Sci. 2001;59(1):5–16. ' 'https://doi.org/10.1093/toxsci/59.1.5.', 'journal-title': 'Toxicol Sci'}, { 'key': '4158_CR26', 'doi-asserted-by': 'publisher', 'first-page': '40', 'DOI': '10.5492/wjccm.v1.i2.40', 'volume': '1', 'author': 'C-Y Lin', 'year': '2012', 'unstructured': 'Lin C-Y, Chen Y-C. 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Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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