Inhaled nitric oxide use in COVID19-induced hypoxemic respiratory failure
Authors: Giri Abhishek R. , Yarrarapu Siva Naga S. , Kaur Nirmaljot , Hochwald Alex , Crook Julie , Helgeson Scott , Harrison Michael F. , Patel Neal , Guru Pramod K. , Lowman Philip , Moreno-Franco Pablo , Lee Augustine , Sanghavi Devang K. 
Published: August 2021

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.