Variability in Uptake Efficiency for Pulsed Versus Constant Concentration Delivery of Inhaled Nitric Oxide

Overview

Journal Med Gas Res

Specialties Anesthesiology
General Medicine
Pharmacology

Date 2014 Jan 24

PMID 24450473

Citations 2

Authors

Andrew R Martin

Chris Jackson

Ira M Katz

Georges Caillibotte

Affiliations

Soon will be listed here.

Abstract

Background: Nitric 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.

Methods: A 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.

Results: Pulsed 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.

Conclusions: Pulsed 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.

Citing Articles

Pulmonary Delivery of Therapeutic and Diagnostic Gases.

Zapol W, Charles H, Martin A, Sa R, Yu B, Ichinose F J Aerosol Med Pulm Drug Deliv. 2018; 31(2):78-87.

PMID: 29451844 PMC: 6421997. DOI: 10.1089/jamp.2017.1431.

Pharmacokinetic analysis of the chronic administration of the inert gases Xe and Ar using a physiological based model.

Katz I, Murdock J, Palgen M, Pype J, Caillibotte G Med Gas Res. 2015; 5:8.

PMID: 26113973 PMC: 4480577. DOI: 10.1186/s13618-015-0029-z.

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