A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects

Summary

This simple and highly adaptable system device for the inhalation of high-concentration nitric oxide (NO) gas does not require mechanical ventilators, positive pressure, or high gas flows. Standard medical consumables and a snug-fitting mask are used to safely deliver NO gas to spontaneously breathing subjects.

Abstract

Nitric Oxide (NO) is administered as gas for inhalation to induce selective pulmonary vasodilation. It is a safe therapy, with few potential risks even if administered at high concentration. Inhaled NO gas is routinely used to increase systemic oxygenation in different disease conditions. The administration of high concentrations of NO also exerts a virucidal effect in vitro. Owing to its favorable pharmacodynamic and safety profiles, the familiarity in its use by critical care providers, and the potential for a direct virucidal effect, NO is clinically used in patients with coronavirus disease-2019 (COVID-19). Nevertheless, no device is currently available to easily administer inhaled NO at concentrations higher than 80 parts per million (ppm) at various inspired oxygen fractions, without the need for dedicated, heavy, and costly equipment. The development of a reliable, safe, inexpensive, lightweight, and ventilator-free solution is crucial, particularly for the early treatment of non-intubated patients outside of the intensive care unit (ICU) and in a limited-resource scenario. To overcome such a barrier, a simple system for the non-invasive NO gas administration up to 250 ppm was developed using standard consumables and a scavenging chamber. The method has been proven safe and reliable in delivering a specified NO concentration while limiting nitrogen dioxide levels. This paper aims to provide clinicians and researchers with the necessary information on how to assemble or adapt such a system for research purposes or clinical use in COVID-19 or other diseases in which NO administration might be beneficial.

Introduction

NO inhalation therapy is regularly used as a life-saving treatment in several clinical settings^1,2,3. In addition to its well-known pulmonary vasodilator effect⁴, NO displays a broad antimicrobial effect against bacteria⁵, viruses⁶, and fungi⁷, particularly if administered at high concentrations (>100 ppm).⁸ During the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak, NO showed potent antiviral activity in vitro and demonstrated therapeutic efficac....

Protocol

NOTE: See the Table of Materials for the materials needed to assemble the delivery system. Sources of medical air, O₂, and NO gases should also be available on site. The device has been developed for investigation use in research protocols that underwent rigorous review by the local Institutional Review Board (IRB). Under no circumstances should providers operate solely based on the indications included in this manuscript, assembling and using this device without seeking prior appropriate institutional regulatory approval. Starting from the proximal end of the device, assemble the pieces in the following order (Figure 1....

Results

A 33-year-old respiratory therapist working at the ICU at MGH during the surge of ICU admission for COVID-19 volunteered to receive NO as part of the trial involving healthcare workers^15,19. The trial tested the efficacy of 160 ppm of NO as a virucidal agent, thereby preventing disease occurrence in lungs at risk for viral contamination. The first session of the inhalation prophylaxis was administered before starting a shift throu.......

Discussion

Given the increasing interest in NO gas therapy for non-intubated patients, including those with COVID-19⁸, the present report describes a novel custom device and how to assemble its components to deliver NO at concentrations as high as 250 ppm. The proposed system is built out of inexpensive consumables and safely delivers a reproducible concentration of NO gas in spontaneously breathing patients. The ease of assembly and use, together with the safety data published elsewhere^16<.......

Materials

Name	Company	Catalog Number	Comments
90° ventilator elbow connector without ports 22 mm ID x 22 mm OD	Teleflex, Wayne, PA, USA	1641
Aerosol tee connector: horizontal ports 22 mm OD, vertical port 11 mm ID/22 mm OD	Teleflex, Wayne, PA, USA	1077
Flexible patient connector for endotracheal or tracheostomy tube (15 mm OD x 22 mm OD/15 mm ID, length 5 cm to 6.5 cm)	Vyaire Medical Inc., Mettawa, IL, USA	3215
High-efficiency particulate air (highly hydrophobic bacterial/viral filter,  HEPA class 13) filter (22 mm ID/15 mm OD x 22 mm OD/15 mm ID connector)	Teleflex, Wayne, PA, USA	28012
Latex-free 3-L breathing reservoir bag	CareFusion, Yorba Linda, CA, USA	5063NL
Nitric Oxide tank 800 ppm medical-grade (size AQ aluminum cylinders containing 2239 L at STP of 800 ppm NO gas balanced with nitrogen, volume 2197 L)	Praxair, Bethlehem PA, USA	MM NO800NI-AQ
One-way valve 22 mm male/female (arrow pointing towards female end)	Teleflex, Wayne, PA, USA	1664	N=2 inspiratory limb (upward arrow)
One-way valve 22 mm male/female (arrow pointing towards male end)	Teleflex, Wayne, PA, USA	1665	N=1 expiratory limb (downward arrow)
Rad-57 Handheld Pulse Oximeter with Rainbow SET Technology	Masimo Corporation, Irvine, CA, USA	3736	Including SpMet Option
Scavenger (ID = 60 mm, internal length = 53 mm, volume = 150 mL) containing 100 g of calcium hydroxide	Spherasorb, Intersurgical Ltd, Berkshire, UK
Silicon rubber flexible connectors 22 mm F x 22 mm F	Tri-anim Health Services, Dublin, OH, USA	301-9000
Snug-fit standard face mask of appropriate size
Star Lumen standard medical grade vynil oxygen tubing with universal connectors	Teleflex, Morrisville, NC, USA	1115	Variable length according to distance from source of gas. 2.1 m length used in protocol
Straight connector with a 7.6 mm sampling port (15 mm OD x 15 mm ID/22 mm OD)	Mallinckrodt, Bedminster, NJ, USA	502041
Two-step adapter (15 mm to 22 mm)	Airlife Auburndale, FL, USA	1824
Y-piece connector with 7.6 mm ports (22 mm to 22 mm and 15 F)	Vyaire Medical Inc., Mettawa, IL, USA	1831