Inhaled nitric oxide can improve oxygenation in patients with severe hypoxemia. At high concentrations, nitric oxide displays broad antimicrobial effects. Several trials are testing the effect of nitric oxide on COVID-19.
To date, there's no device available that is able to administer inhaled nitric oxide at concentrations higher than 80 parts per million without the need for dedicated heavy and costly equipment. This device will allow for high-dose inhaled nitric oxide to be delivered outside the hospital setting. Patients with lung colonization due to multi-resistant bacteria, like cystic fibrosis patients, will be able to benefit from this treatment.
Demonstrating the procedure will be Stefano Gianni and Bijan Safaee Fakhr, two postdoc research fellows from my laboratory. To set up the patient interface, connect the built-in elbow port of a snug fitting standard non-invasive ventilation face mask of the appropriate size for the subject to a high efficiency particulate air filter through the 22 millimeter outer diameter 15 millimeter inner diameter connector. To build a Y-piece, use two opposite sense, low resistance 22 millimeter male-female one-way valves to create expiratory and inspiratory limbs on the two distal ends of a 22 millimeter to 22 millimeter and 15 French Y-piece connector with 7.6 millimeter ports.
Position the one-way valve connector to the expiratory limb with the arrow pointing downward to allow a proximal to distal flow only and position the connector for the inspiratory limb with the arrow pointing upward to allow a distal to proximal flow only. Then use a 15 to 22 millimeter two-step adapter to attach the scavenging chamber and tubing assembly to the inspiratory limb of the Y-piece. To prepare the scavenging chamber, connect a 22 by 22 millimeter flexible silicon rubber connector adapter to the proximal end of a scavenger chamber containing 100 grams of calcium hydroxide and connect another 22 by 22 millimeter flexible silicon rubber connector adapter to the distal end of the scavenger and use standard kink-resistant vinyl gas tubing with universal adapters at both ends to connect the oxygen source to the inspiratory limb.
To prepare the nitric oxide reservoir system, connect an aerosol T-piece in a 90 degree ventilator elbow connector without ports and connect the other end of the elbow to three liter latex-free breathing reservoir bag. Attach another one-way inspiratory valve with the arrow pointing up at the distal end of two consecutive 15 millimeter outer diameter by 22 millimeter outer diameter 15 millimeter inner diameter connectors with 7.6 millimeter sampling ports and flip top caps and connect a 15 to 22 millimeter two-step adapter to the proximal end of the system and connect the proximal two-step adapter to the remaining free inlet of the green T-piece from the nitric oxide reservoir system. To attach the air and nitric oxide gas flow lines, use standard kink-resistant Star Lumen vinyl oxygen gas tubing to connect the medical air flow to the most distal gas inlet port and connect the nitric oxide gas flow from an 800 parts per million medical-grade nitric oxide tank to the next port downstream.
To administer nitric oxide to a spontaneously breathing subject, set the air, oxygen, and nitric oxide gas flow according to the table and position the tight fitting mask onto the subject's face similar to a noninvasive ventilation interface setup. Then start the inhalation session for the desired duration. The nitric oxide and nitrogen dioxide concentrations can be traced to assess the stability of the gas delivery during the treatment.
A 33-year-old respiratory therapist working at the ICU at Mass General Hospital during the surge of ICU admission for COVID-19 volunteered to receive nitric oxide as part of the trial involving healthcare workers. The resulting nitric oxide concentration was 160 parts per million at a total gas flow rate of 19.5 liters per minute as measured by three standard 15 liter per minute flow meters and remained stable throughout the entire period of inhalation. Nitrogen dioxide peaked at 0.77 parts per million and was therefore safely below the recommended toxicity threshold.
The possibility of safely delivering high-concentration inhaled nitric oxide opens the field for the application of this therapy to other diseases in which nitric oxide can be an effective treatment.
