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      Oxygen versus air-driven nebulisers for exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial

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          Abstract

          Background

          In exacerbations of chronic obstructive pulmonary disease, administration of high concentrations of oxygen may cause hypercapnia and increase mortality compared with oxygen titrated, if required, to achieve an oxygen saturation of 88–92%. Optimally titrated oxygen regimens require two components: titrated supplemental oxygen to achieve the target oxygen saturation and, if required, bronchodilators delivered by air-driven nebulisation. The effect of repeated air vs oxygen-driven bronchodilator nebulisation in acute exacerbations of chronic obstructive pulmonary disease is unknown. We aimed to compare the effects of air versus oxygen-driven bronchodilator nebulisation on arterial carbon dioxide tension in exacerbations of chronic obstructive pulmonary disease.

          Methods

          A parallel group double-blind randomised controlled trial in 90 hospital in-patients with an acute exacerbation of COPD. Participants were randomised to receive two 2.5 mg salbutamol nebulisers, both driven by air or oxygen at 8 L/min, each delivered over 15 min with a 5 min interval in-between. The primary outcome measure was the transcutaneous partial pressure of carbon dioxide at the end of the second nebulisation (35 min). The primary analysis used a mixed linear model with fixed effects of the baseline PtCO 2, time, the randomised intervention, and a time by intervention interaction term; to estimate the difference between randomised treatments at 35 min. Analysis was by intention-to-treat.

          Results

          Oxygen-driven nebulisation was terminated in one participant after 27 min when the PtCO 2 rose by > 10 mmHg, a predefined safety criterion. The mean (standard deviation) change in PtCO 2 at 35 min was 3.4 (1.9) mmHg and 0.1 (1.4) mmHg in the oxygen and air groups respectively, difference (95% confidence interval) 3.3 mmHg (2.7 to 3.9), p < 0.001. The proportion of patients with a PtCO 2 change ≥4 mmHg during the intervention was 18/45 (40%) and 0/44 (0%) for oxygen and air groups respectively.

          Conclusions

          Oxygen-driven nebulisation leads to an increase in PtCO 2 in exacerbations of COPD. We propose that air-driven bronchodilator nebulisation is preferable to oxygen-driven nebulisation in exacerbations of COPD.

          Trial registration

          Australian New Zealand Clinical Trials Registry number ACTRN12615000389505. Registration confirmed on 28/4/15.

          Electronic supplementary material

          The online version of this article (10.1186/s12890-018-0720-7) contains supplementary material, which is available to authorized users.

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          Most cited references15

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          Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure.

          The effects of the administration of 100% oxygen on minute ventilation (VE) and arterial blood gases were studied in patients with chronic obstructive pulmonary disease during acute respiratory failure. The administration of O2 resulted in an early decrease in VE, which averaged 18% +/- 2 SE of the control VE, and was due to a decrease in both tidal volume (VT) and respiratory frequency (f). This was followed by a slow increase in VE, such that after 15 min of breathing O2, VE rose to 93 +/- 6% of the control room air value, with both VT and f similar to control values. Despite the small difference between VE while breathing room air and that at the fifteenth minute of O2 inhalation, PaCO2 increased by 23 +/- 5 mmHg, and no significant correlation was found between the changes in VE and PaCO2. By the fifteenth minute of O2 inhalation the PaO2 averaged 225 +/- 23 mmHg, and it was concluded that despite the removal of the hypoxic stimulus of O2 inhalation, the activity of the respiratory muscles remained great enough to maintain VE at nearly the same degree as that while breathing room air. Consequently, the changes in PaCO2 after the administration of O2 were mainly due to increased inhomogeneity of VA/Q distribution within the lungs.
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            Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma.

            The effect on Paco2 of high concentration oxygen therapy when administered to patients with severe exacerbations of asthma is uncertain.
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              The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease.

              The detailed mechanisms of oxygen-induced hypercapnia were examined in 22 patients during an acute exacerbation of chronic obstructive pulmonary disease. Ventilation, cardiac output, and the distribution of ventilation-perfusion (V A/Q ) ratios were measured using the multiple inert gas elimination technique breathing air and then 100% oxygen through a nose mask. Twelve patients were classified as retainers (R) when Pa(CO(2)) rose by more than 3 mm Hg (8.3 +/- 5.6; mean +/- SD) after breathing 100% oxygen for at least 20 min. The other 10 patients showed a change in Pa(CO(2)) of -1.3 +/- 2.2 mm Hg breathing oxygen and were classified as nonretainers (NR). Ventilation fell significantly from 9.0 +/- 1.5 to 7.2 +/- 1.2 L/min in the R group breathing oxygen (p = 0.007), whereas there was no change in ventilation in the NR group (9.8 +/- 1.8 to 9.9 +/- 1.8 L/min). The dispersion of V A/Q ratios as measured by log SD of blood flow (log SD Q) increased significantly in both R (0.96 +/- 0. 17 to 1.13 +/- 0.17) and NR (0.77 +/- 0.20 to 1.04 +/- 0.23, p < 0.05) groups breathing oxygen, whereas log SD of ventilation (log SD Q ) increased only in the R group (0.97 +/- 0.24 to 1.20 +/- 0.46, p < 0.05). This study suggests that an overall reduction in ventilation characterizes oxygen-induced hypercapnia, as an increased dispersion of blood flow from release of hypoxic vasoconstriction occurred to a significant and similar degree in both groups. The significant increase in wasted ventilation (alveolar dead space) in the R group only may be secondary to the higher carbon dioxide tension, perhaps related to bronchodilatation.
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                Author and article information

                Contributors
                George.Bardsley@mrinz.ac.nz
                Janine.Pilcher@mrinz.ac.nz
                Steve.McKinstry@mrinz.ac.nz
                Philippa.Shirtcliffe@ccdhb.org.nz
                James.berryspc@gmail.com
                James.Fingleton@mrinz.ac.nz
                Mark.Weatherall@otago.ac.nz
                +64-4-805 0230 , richard.beasley@mrinz.ac.nz
                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                1471-2466
                3 October 2018
                3 October 2018
                2018
                : 18
                : 157
                Affiliations
                [1 ]ISNI 0000 0001 0244 0702, GRID grid.413379.b, Capital and Coast District Health Board, ; Wellington, New Zealand
                [2 ]ISNI 0000 0004 0445 6830, GRID grid.415117.7, Medical Research Institute of New Zealand, ; Box 7902, Wellington, PO 6242 New Zealand
                [3 ]ISNI 0000 0001 2292 3111, GRID grid.267827.e, Victoria University Wellington, ; Wellington, New Zealand
                [4 ]ISNI 0000 0004 1936 7830, GRID grid.29980.3a, Wellington School of Medicine & Health Sciences, , University of Otago Wellington, ; Wellington, New Zealand
                Author information
                http://orcid.org/0000-0003-0056-4298
                http://orcid.org/0000-0002-9500-7744
                http://orcid.org/0000-0003-4497-6892
                http://orcid.org/0000-0002-4611-2687
                http://orcid.org/0000-0002-1246-6188
                http://orcid.org/0000-0001-9148-196X
                http://orcid.org/0000-0002-0051-9107
                http://orcid.org/0000-0003-0337-406X
                Article
                720
                10.1186/s12890-018-0720-7
                6171193
                30285695
                4d121509-473a-45b3-98e9-f6199883196b
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 April 2018
                : 10 September 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001505, Health Research Council of New Zealand;
                Award ID: 14-835
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Respiratory medicine
                air,bronchodilator agents,hypercapnia,nebulisation,oxygen
                Respiratory medicine
                air, bronchodilator agents, hypercapnia, nebulisation, oxygen

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