Abstract
BackgroundNitric oxide (NO) is currently administered using devices that maintain constant inspired NO concentrations. Alternatively, devices that deliver a pulse of NO during the early phase of inspiration may have use in optimizing NO dosing efficiency and in extending application of NO to long-term use by ambulatory, spontaneously breathing patients. The extent to which the amount of NO delivered for a given pulse sequence determines alveolar concentrations and uptake, and the extent to which this relationship varies with breathing pattern, physiological, and pathophysiological parameters, warrants investigation.MethodsA mathematical model was used to analyze inhaled nitric oxide (NO) transport through the conducting airways, and to predict uptake from the alveolar region of the lung. Pulsed delivery was compared with delivery of a constant concentration of NO in the inhaled gas.ResultsPulsed delivery was predicted to offer significant improvement in uptake efficiency compared with constant concentration delivery. Uptake from the alveolar region depended on pulse timing, tidal volume, respiratory rate, lung and dead space volume, and the diffusing capacity of the lung for NO (DLNO). It was predicted that variation in uptake efficiency with breathing pattern can be limited using a pulse time of less than 100 ms, with a delay of less than 50 ms between the onset of inhalation and pulse delivery. Nonlinear variation in uptake efficiency with DLNO was predicted, with uptake efficiency falling off sharply as DLNO decreased below ~50-60 ml/min/mm Hg. Gas mixing in the conducting airways played an important role in determining uptake, such that consideration of bulk convection alone would lead to errors in assessing efficiency of pulsed delivery systems.ConclusionsPulsed NO delivery improves uptake efficiency compared with constant concentration delivery. Optimization of pulse timing is critical in limiting intra- and inter-subject variability in dosing.
Highlights
Nitric oxide (NO) is currently administered using devices that maintain constant inspired nitric oxide (NO) concentrations
It was assumed that zero uptake of NO occurred across the conducting airways, whereas uptake from the alveolar region into the capillaries was modeled with a single transfer factor specifying volume uptake per unit time per unit partial pressure (i.e., DLNO – the diffusing capacity of the lung for NO)
In conclusion, pulsed NO delivery offers significant improvement in uptake efficiency compared with constant concentration delivery
Summary
Nitric oxide (NO) is currently administered using devices that maintain constant inspired NO concentrations. Devices that deliver a pulse of NO during the early phase of inspiration may have use in optimizing NO dosing efficiency and in extending application of NO to long-term use by ambulatory, spontaneously breathing patients. Pulsed systems may have use in optimizing dosing and minimizing total NO usage for intubated, ventilated patients, and in extending application of NO to long-term use by ambulatory, spontaneously breathing patients. These systems are inherently poorly described using the established dose metric of inhaled NO concentration, as the concentration is intentionally varied over each inhalation. The extent to which the amount of NO delivered for a given pulse sequence determines alveolar concentrations and uptake, and the extent to which this relationship varies with breathing pattern, and with physiological and pathophysiological parameters, is presently unclear, and warrants study
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