Therapeutic Role of Nitric Oxide in Respiratory Disease

Thomas E. Siddons, BSc, Mohammed Asif, MA, BMBCh, FRCS, and Tim W. Higenbottam, MD, MA, BSc, FRCP, University of Sheffield, Sheffield, United Kingdom

In This Article

How Is Nitric Oxide Delivered?

Conventional Delivery Methods

Ensuring a constant and predictable concentration of inhaled NO with a ventilator is difficult. Mixing the gases in the inspiratory limb of the ventilator does not deliver a consistent amount; as a result, the amount of NO delivered may exceed the intended dose. The dose of inhaled NO may also vary if the patient's ventilatory pattern changes.

The chemiluminescence analyzers that are typically used to monitor the concentration of NO are too slow to detect the relatively rapid changes that occur. Determining where in the delivery circuit monitoring with these analyzers should occur is also disputed.

Systems that premix NO before entering the ventilator circuit maintain a constant concentration of NO regardless of tidal volume or ventilatory pattern or whether the patient is spontaneously breathing.[28] Premixing has resulted in build-up of NO2 but this problem can be minimized by using low NO concentrations (<20 ppm) and by decreasing the volume of the mixing vessel.

The site at which NO should be monitored depends on the speed of the analyzer. Gas samples from the trachea can only be deemed valid if measured using a rapid-response analyzer.[29] Slower analyzers give a time-weighted average, which tends to underestimate the peak inspired concentration of NO. If NO is sampled in the inspiratory circuit, the measured concentrations are found to be somewhat lower than those measured in the trachea.

The dose of inhaled NO delivered to a ventilated patient is affected to a greater or lesser degree by four things: the design of the ventilator circuit, the response time of the analyzer, where in the circuit the concentration of NO is analyzed, and the ventilatory pattern. To optimize the accuracy of NO delivery, inspired gas should be premixed rather than injected into the inspiratory circuit and should be rapidly analyzed from tracheal samples. .

New Delivery Methods

The problem of treating with NO is essentially one of delivering a reliable concentration of the gas on a breath-by-breath basis during mechanical ventilation. New approaches to this problem, such as the INOvent delivery system, have been developed on the basis of mass flow control.[30] This system measures the inspiratory gas flow by using a hot film anemometer placed in the inspiratory limb of the circuit and delivers an appropriate flow of NO. This device controls the mass, rather than the volume or velocity, of gases flowing through it. The rate of response must be rapid to ensure accurate delivery of a flowing mass. This method has proved to be particularly efficient--measured NO concentrations are easily more precise than those required for clinical use. Equivalent inhaled NO systems are made by Siemens and Drager and also use mass flow devices.


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