Inhaled nitric oxide use in COVID19-induced hypoxemic respiratory failure
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Abstract
Introduction
Nitric Oxide (NO) is an endogenous vasodilator that is synthesized by the vascular endothelium. Due to its vasodilatory effect and short half-life, the use of NO as an exogenous inhaled medication (iNO) to target the pulmonary vasculature, in conditions with increased pulmonary vascular resistance, has been studied.
The use of iNO in patients with ARDS secondary to COVID-19 has therapeutic importance in improving oxygenation. It also has potential anti-viral, anti-inflammatory, and anti-thrombotic properties.
Herein, we want to share our experience of use of iNO in hypoxemic respiratory failure secondary to COVID 19 pneumonia. We hypothesized that iNO may be beneficial at preventing intubation, decreasing invasive mechanical ventilation duration, and consequently improve outcomes including hospital mortality.
Methods
This is a descriptive hypothesis generating study of patients admitted for COVID-19 pneumonia who received iNO for hypoxemic respiratory failure, at a single tertiary care center. We collected information on patient demographics, co-morbidities, iNO treatment, need for intubation, arterial blood gas analysis, laboratory values, hospital length of stay, and mortality. Patients were divided into two groups based on the timing of iNO administration: group 1 - “pre-intubation” (i.e. iNO started at least 1 day prior to endotracheal intubation, if any) and group 2 - “post-intubation” (i.e. iNO started on the same day as or after endotracheal intubation and mechanical ventilation).
Result
A total of 45 (group 1, n=26 [57.8%] vs group2, n=19 [42.2%]) COVID 19 patients who had iNO use. The mean time from hospital admission to iNO administration(days) in group 1 was 2.1 (±1.8) vs 4.2 (±5.9) in group 2. The mean hospital length of stay from the beginning of iNO treatment until discharge or death was 18.3 vs 26.2 days, with 8 deaths (30.8%) vs 9 deaths (47.4%) in group 1 vs group 2, respectively.
Discussion
Our study is unable to demonstrate comparably outcomes benefit of iNO. Although there was a trend towards decreased need for invasive mechanical ventilation in group 1[Only 11 (42.3%) patients were intubated out of 26 who received iNO early after hospital admission (2.3 days)], no statistical significance could be achieved because of small sample size.
Our study demonstrated that iNO administration pre-intubation did not appear harmful and appears to be safe, complementary to HFNC, signalling the domain where systematic investigation is required to confirm or not the potential for iNO to improve patient outcomes in the management of COVID 19-induced hypoxemic respiratory failure.
Conclusion
This study showcases the potential benefit of early pre-intubation use of iNO in COVID patients with hypoxemic respiratory failure. This study could conclusively form the basis for a prospective trial and could have a tremendous impact in improving patient outcomes.
Highlights
Inhaled nitric oxide can be used in the treatment COVID 19 induced hypoxemic respiratory failure.
Inhaled nitric oxide use can lower the burden on overwhelmed medical system.
Inhaled nitric oxide use may lower the need for intubation and subsequent invasive mechanical ventilation.
Article activity feed
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SciScore for 10.1101/2021.08.19.21262314: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Study Limitations: This is retrospective study with small sample size; hence desired results were not statistically significant. The effects of iNO were not charted in terms of patient outcomes. We collected SOFA score on admission. Therefore, the severity …
SciScore for 10.1101/2021.08.19.21262314: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Study Limitations: This is retrospective study with small sample size; hence desired results were not statistically significant. The effects of iNO were not charted in terms of patient outcomes. We collected SOFA score on admission. Therefore, the severity of patient condition may have deteriorated or improved after 24 hrs. Potential confounders include the novel nature of this virus with rapidly changing standards of medical care, which are not included in this study.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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