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Inhaled nitric oxide: how to deliver it?


Clinical applications of inhaled nitric oxide (inhNO) therapy gave rise to the development of delivery systems applicable to routine clinical care. This study reviewed the various components necessary for an adequate clinical use of inhNO, covering the NO gas mixture cylinders, inhNO delivery techniques and specifications.


Computerized search (CURRENT CONTENTS, MEDLINE) of published original research and review articles (~260), conference abstracts and compendiums up to December 1997 (~60), personal files with clinical and experimental use, and contact with expert informants were selected in technical, experimental and clinical reports from the recent English, French, German, and Spanish literature if pertaining to the administration of inhNO.


The production of NO gas mixture cylinders must be certified with respect to gas purity, stability, and concentration (limits between 100 and 1000 parts-per-million), guaranteed calibration, and specific color. In order to maintain a safe and constant concentration of NO in inspired gas, NO would need to be injected proportionally to the flow in the main circuit and followed by adequate mixing of NO and N2/O2. This would be expected to occur with: (1) mixing a constant proportion of N2, O2 and NO pre-ventilator (or with a gas mixing chamber): with this system, flow in the inspiratory limb could be continuous or phasic, constant or variable, and not be expected to effect NO concentration; but drawbacks are inability to precisely adjust preventilator mixing, increased time availability for creation of toxic NO2 gas, and putative deterioration of the ventilator internal components by the oxidative gas; (2) NO is injected in the inspiratory limb with some limitations: at a continuous and constant rate of NO and gas flow for infant ventilators; sequentially (during inspiration only) of an adult phasic flow ventilator where main circuit flow is at a constant rate (volume ventilation, square wave flow, and patient heavily sedated or sedated/paralyzed); (3) with variable flow rate (decelerating, ramp, and sine) for volume-, pressure-controlled ventilation or variation in patient ventilatory effort, NO injection in the inspiratory limb is titrated using an ultrafast response system that consists of an inspiratory limb pneumotach (or thermoanemometer) generating an electrical signal to a mass flow meter that adjusts the NO injection on a millisecond basis as flow varies within or between breaths. The synchronized delivery allows a precise and constant administration of NO with a minimal production of NO2 and oxidation danger.


The great expectancies generated by inhNO action have led researchers to design personal inhNO delivery system but only with mitigated results. At present, biomedical companies are finding a financial interest in designing a delivery system which will suit the needs of clinicians considering the effect of the ventilatory mode, ventilatory settings, NO delivery device being used, and injection site.

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Troncy, E., Francœur, M. & Blaise, G. Inhaled nitric oxide: how to deliver it?. Crit Care 2 (Suppl 1), P115 (1998).

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