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Case Series: Inhaled Nitric Oxide as Rescue Therapy for Nonintubated Patients with Severe COVID-19

Key findings

  • Physicians at Massachusetts General Hospital administered 160 ppm nitric oxide as rescue therapy for five non-intubated adults critically ill with COVID-19
  • Careful monitoring of vital signs did not demonstrate a systemic effect on blood pressure, heart rate or respiratory rate
  • Stable oxygenation during and after the treatment, and bedside monitoring of methemoglobin, showed that the therapy was well tolerated
  • Patients rested comfortably during treatment and reported improvement in breathing

Currently, there is no evidence that using noninvasive ventilation, such as continuous positive airway pressure or high-flow nasal cannula, leads to better outcomes in respiratory distress related to COVID-19. Moreover, noninvasive support is widely considered to generate infectious aerosols that put health care workers at high risk of exposure.

In a recent in vitro study published on Redox Biology, investigators from Uppsala University and Karolinska Institute, showed that nitric oxide inhibits the replication of SARS-CoV-2 in a dose dependent fashion.

In Critical Care ExplorationsLorenzo Berra, MD, anesthesiologist in the Department of Anesthesia, Critical Care and Pain Medicine and medical director for Respiratory Care at Massachusetts General Hospital, and Bijan Safaee Fakhr, MD, research fellow in the Department of Anesthesia, Critical Care and Pain Medicine, and colleagues report on five non-intubated adults who were critically ill with COVID-19 and received high-dose inhaled nitric oxide (NO) as a rescue therapy.

Patient Characteristics

The patients received NO therapy between March 18 and May 20, 2020. All presented with multiple comorbidities and had experienced worsening of symptoms over the days preceding NO initiation, with increased respiratory distress and increased demand for supplemental oxygen despite early proning. They were not considered eligible for other rescue therapies, even within a clinical trial.

Delivery of Nitric Oxide

NO was administered at 160 ppm for 30 minutes twice daily using a custom-made delivery device depicted in the article.

Three of the patients received five to nine treatments. The median methemoglobin level was 0.3% at baseline, the peak value after 30 minutes was 2.0% and the median level five minutes after cessation of therapy was 1.6%. The patients rested comfortably during treatment and reported improvement in breathing. They were discharged after nine to 28 days of hospitalization.

Two patients received only one NO treatment. They presented in severe respiratory distress, unable to maintain peripheral oxygen saturation above 90% despite high supplemental oxygen (10 and 12 L/min) before NO was started. Both patients were transitioned to comfort measurements within 24 hours of the NO treatment and ultimately died.

Cardiopulmonary Function

During and after NO treatments, no changes were observed in average arterial pressure, heart rate or respiratory rate. Oxygenation remained stable whether or not the patient was initially hypoxemic.

A Viable Option

NO treatment can be considered for patients with COVID-19 who have multiple comorbidities and are near respiratory failure. It can be combined with proning and antiviral treatment to slow COVID-19 progression. For patients who have a do-not-intubate order, NO therapy may alleviate suffering by reducing hypoxia and enhancing bronchodilation.

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