Preliminary study suggests nitric oxide may be a potential treatment for COVID-19 respiratory failure

New research led by Devang K. Sanghavi of the Mayo Clinic in Florida, USA, suggests pre-intubation use of nitric oxide for patients with COVID-19–related hypoxemic respiratory may help reduce patients' mortality. Their findings show that inhaling nitric oxide in this patient population could reduce the need for future intubation and other invasive mechanical ventilation.

According to the researchers, the current study could form the basis for a prospective trial investigating the efficacy of nitric oxide as a coronavirus treatment. Yet, more studies are needed to support its use.

If studied further, the researchers believe administering inhaled nitric oxide early could improve patient outcomes and alleviate the burden on an overwhelmed medical system.

Our study demonstrated that iNO administration pre-intubation did not appear harmful and appears to be safe, complementary to [high flow nasal canula], 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," wrote the team.

The study "Inhaled nitric oxide use in COVID19-induced hypoxemic respiratory failure" is published on the preprint medRxiv* server, while the article undergoes peer review.

How they did it

The study aimed to investigate how pre-intubated nitric oxide improved outcomes in patients with hypoxic respiratory failure due to COVID-19 infection.

About 45 patients hospitalized from June 2020 to December 2020 with COVID-19 pneumonia at a single tertiary care center were given 5-20 ppm of nitric oxide for hypoxemic respiratory failure and a high flow nasal canula. They were given this treatment if they showed pure hypoxemia without increased breathing or respiratory acidosis or if the patient showed any indication of pulmonary hypertension and right ventricular failure.

One group of patients had their nitric oxide delivered at least 1 day before endotracheal intubation. It took an average of 2.1 days since hospital admission to be administered nitric oxide.

The second group had post-intubation nitric oxide started on the same day or after endotracheal intubation and mechanical ventilation. The average time from hospital admission to nitric oxide administration was 4.2 days.

Further analysis also compared survival rates of pre-intubated patients who still required intubation with patients who did not require intubation at all.

Pre-intubation of nitric oxide improved clinical outcomes for COVID-19–induced respiratory failure

Only 11 out of 26 patients (42.3%) were given nitric oxide early on required intubation.

Patients who received pre-intubated nitric oxide spent an average of 4.3 days without a ventilator. In contrast, patients given nitric oxide after post-intubation spent an average of 6.4 days ventilator-free. However, these differences were not statistically significant because of the small sample size.

Patients pre-intubated with nitric oxide spent less time on a ventilator and in the hospital. Having less severe symptoms upon hospital admission was associated with a lesser need for mechanical ventilation in this group.

The average time spent on a ventilator was 12.6 days compared to 19.1 days in post-intubated patients. Additionally, the average hospital stay was 18.3 days in Group 1 compared to 26.2 days in Group 2.

Mortality rates appeared lower in patients pre-intubated with nitric oxide

There were 8 deaths (30.8%) in the pre-intubation group and 9 deaths (47.4%) in the postintubation group.

Patients who required intubation — regardless of when nitric oxide was given — had a higher mortality rate (56.7%) than patients who were not intubated.

Of the 17 people who died, all of them had needed intubation. In contrast, there were 13 patients (46.4%) who required intubation and continued to live. While not statistically significant, less time between hospital admission and nitric oxide administration was correlated with improved survival.

Overall, the research suggests patients with less severe COVID-19 symptoms can benefit from nitric oxide if treatment is delivered early.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.