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
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'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>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 '
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'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 '
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'were considered secondary. Propensity score matching (1:2) was used based on the predefined '
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' <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 '
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'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: '
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'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, '
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' <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. '
'Moreover, iNO use is associated with higher odds of AKI, pneumonia, longer LOS, and\xa0fewer '
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