Rescue Treatment With High-Dose Gaseous Nitric Oxide in Spontaneously Breathing Patients With Severe Coronavirus Disease 2019

Abstract

Treatment options are limited for patients with respiratory failure due to coronavirus disease 2019. Conventional oxygen therapy and awake proning are options, but the use of high-flow nasal cannula and continuous positive airway pressure are controversial. There is an urgent need for effective rescue therapies. Our aim is to evaluate the role of inhaled nitric oxide 160 ppm as a possible rescue therapy in nonintubated coronavirus disease 2019 patients.

Design: Retrospective evaluation of coronavirus disease 2019 patients in respiratory distress receiving nitric oxide gas as rescue therapy.

Setting: Massachusetts General Hospital, between March 18, 2020, and May 20, 2020, during the local coronavirus disease 2019 surge.

Patients: Coronavirus disease 2019 patients at high risk for acute hypoxemic respiratory failure with worsening symptoms despite use of supplemental oxygen and/or awake proning.

Interventions: Patients received nitric oxide at concentrations of 160 ppm for 30 minutes twice per day via a face mask until resolution of symptoms, discharge, intubation, or the transition to comfort measures only.

Measurements and main results: Between March 18, 2020, and May 20, 2020, five patients received nitric oxide inhalation as a rescue therapy for coronavirus disease 2019 at Massachusetts General Hospital. All received at least one dosage. The three patients that received multiple treatments (ranging from five to nine) survived and were discharged home. Maximum methemoglobin concentration after 30 minutes of breathing nitric oxide was 2.0% (1.7-2.3%). Nitrogen dioxide was below 2 ppm. No changes in mean arterial pressure or heart rate were observed during or after nitric oxide treatment. Oxygenation and the respiratory rate remained stable during and after nitric oxide treatments. For two patients, inflammatory marker data were available and demonstrate a reduction or a cessation of escalation after nitric oxide treatment.

Conclusions: Nitric oxide at 160 ppm may be an effective adjuvant rescue therapy for patients with coronavirus disease 2019.

Keywords: acute respiratory failure; coronavirus disease 2019; nitric oxide; rescue therapy.

Conflict of interest statement

Dr. Wiegand receives a salary from the German Research Foundation number WI5162/2-1. Dr. Carroll receives funding from unitaid (an international organisation that invests in innovations to prevent, diagnose and treat HIV/AIDS, tuberculosis and malaria more quickly, affordably and effectively) as a principal investigator in a multi-institutional study working to decentralize laboratories to diagnose and treat tuberculosis in low-resource settings. Dr. Zapol is on the scientific advisory board of Third Pole, which has licensed patents on electric nitric oxide (NO) generation from Massachusetts General Hospital. Dr. Kacmarek is a consultant for Medtronic and Orange Med and has received research grants from Medtronic and Venner Medical (Dänischenhagen, Germany). Dr. Berra receives salary support from K23 HL128882/National Heart Lung and Blood Institute National Institutes of Health as principal investigator for his work on hemolysis and NO; he receives technologies and devices from inhaled NO (iNO) Therapeutics LLC, Praxair, and Masimo Corp; and he receives a grant from iNO Therapeutics LLC. Dr. Fakhr has disclosed that he does not have any potential conflicts of interest.

Figures

Figure 1.

Nitric oxide (NO) delivery device and administration. A, NO delivery device build from respiratory care components for spontaneously breathing patients. Main components are tubings for medical air, NO in nitrogen and oxygen, sampling lines for oxygen content, NO and nitrogen dioxide (No2) concentration, one-way valves, high efficiency particulate air (HEPA) filter, scrubber with soda lime, and mask. B, NO administration in an adult patient using one of our delivery devices.

Figure 2.

Vital variables and laboratory variables in severe coronavirus disease 2019 patients receiving nitric oxide (NO) treatment. Cardiopulmonary variables of patients receiving 160 parts per million NO with no negative effect on mean arterial pressure (MAP) (A), heart rate (B), or respiratory rate (C) (data shown as median and 95% CI). Oxygenation was not impaired and showed to be stable for normoxemic and hypoxemic cases (D). Course of laboratory results in patient 1 (E) and patient 2 (F). bpm = beats per minute, CRP = C-reactive protein, Spo2 = oxygen saturation.