Influence of FIO2 on PaCO2 in COPD Patients With Chronic CO2 Retention
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* Romina N González
* Gastón G Morel Vulliez
* Eduardo L De Vito

*To the Editor*:

We have read with interest the original article entitled “Influence of FIO2 on PaCO2 During Noninvasive Ventilation in Patients with COPD.”1 In this article, the authors prospectively evaluated 17 CO2-retaining COPD subjects recovering from acute respiratory crisis on noninvasive ventilation (NIV) with FIO2 of ≤ 0.5, and they studied the response of PaCO2 to an FIO2 of 1.0. The authors found that during NIV with an “FIO2 sufficient to maintain a normal PaO2,” a further increase in FIO2 did not result in an increased PaCO2.

The accentuation of hypercapnia when oxygen is administered to hypercapnic COPD patients is a concern due to increased CO2 retention and respiratory acidosis. NIV seems to be a more effective treatment for carbon dioxide retention in these patients.2

We feel the need to make some remarks on this study. Table 2 shows that before an increase in FIO2 to 1.0, the PaO2 values were 101.4 ± 21.7 mm Hg and after increased significantly to 290.5 ± 35.7 mm Hg (SpO2 94.3 ± 2.2% and 98.8 ± 0.8%, respectively). Both PaO2 and SpO2 were significantly elevated compared with the usual values for COPD patients with chronic CO2 retention. In fact, we could say that a PaO2 of 100–120 mm Hg (21.7 is the upper SD) may well be the result of indiscriminate oxygen therapy. With those high PaO2 values, the mechanisms for the increase in PaCO2 may have been generated as well, and further increases in PaO2 could not have had any additional effect on PaCO2. We wonder what the PaCO2 would be with breathing ambient air, under baseline conditions. It is in this situation when the previously described increase in PaCO2 is expected. Hypercapnia becomes dangerous somewhere in the range of 80–120 mm Hg.3

The mechanisms of CO2 retention in patients with COPD have been described.4–7 These mechanisms do not have the same relevance in every CO2-retaining patient with COPD. First, the traditional theory that oxygen administration to CO2-retaining patients causes loss of hypoxic drive, resulting in hypoventilation and ventilatory failure, is a myth. This mechanism does not suffice to justify the 20% increase in PaCO2, and it may be canceled due to the concomitant decrease in CO2 production.3 In the subjects studied by Savi et al,1 the use of NIV could prevent such a mechanism from occurring.

Deoxygenated hemoglobin binds CO2 with greater affinity than oxygenated hemoglobin. Hence, oxygen induces a rightward shift in the CO2 dissociation curve, which is called the Haldane effect, and is very important in canceling severe hypoxia (up to 25% increased PaCO2), but it is negligible in the absence of the Haldane effect (∼5% increased PaCO2).

An underventilated lung usually has low oxygen content, which leads to localized vasoconstriction, limiting blood flow to that lung. The main mechanism of CO2 retention occurs because supplemental oxygen abolishes localized vasoconstriction, limiting blood flow at a low ventilation/perfusion ratio.

The administered oxygen flow is not important, but the PaCO2 (and, indirectly, the PaO2) achieved is. Because the mechanisms described are of different relevancy in individual subjects, it might have been important to provide the blood gas report with the target SpO2 of 88–92% (regardless of FIO2) and to observe changes with increasing FIO2.

The results of the article are supportive of the authors' hypothesis that increasing the FIO2 in CO2-retaining subjects with COPD on NIV does not cause clinically important changes in CO2 retention.1 This is relevant new information. We think these considerations should be taken into account when analyzing these results.

## Footnotes

*   The authors have disclosed no conflicts of interest.

*   Copyright © 2014 by Daedalus Enterprises

## References

1.  1. Savi A, Gasparetto Maccari J, Frederico Tonietto T, Peçanha Antonio AC, Pinheiro de Oliveira R, de Mello Rieder M, et al. Influence of FIO2 on PaCO2 during noninvasive ventilation in patients with COPD. Respir Care 2014;59(3):383–387.
    
    [Abstract/FREE Full Text](http://rc.rcjournal.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoicmVzcGNhcmUiO3M6NToicmVzaWQiO3M6ODoiNTkvMy8zODMiO3M6NDoiYXRvbSI7czoyNDoiL3Jlc3BjYXJlLzU5LzcvZTEwNS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

2.  2. Murphy R, Driscoll P, O'Driscoll R. Emergency oxygen therapy for the COPD patient. Emerg Med J 2001;18(5):333–339.
    
    [FREE Full Text](http://rc.rcjournal.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NzoiZW1lcm1lZCI7czo1OiJyZXNpZCI7czo4OiIxOC81LzMzMyI7czo0OiJhdG9tIjtzOjI0OiIvcmVzcGNhcmUvNTkvNy9lMTA1LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

3.  3. Kim V, Benditt JO, Wise RA, Sharafkhaneh A. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008;5(4):513–518.
    
    [PubMed](http://rc.rcjournal.com/lookup/external-ref?access_num=18453364&link_type=MED&atom=%2Frespcare%2F59%2F7%2Fe105.atom) 

4.  4. Sassoon CS, Hassell KT, Mahutte CK. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987;135(4):907–911.
    
    [PubMed](http://rc.rcjournal.com/lookup/external-ref?access_num=3565937&link_type=MED&atom=%2Frespcare%2F59%2F7%2Fe105.atom) 
    
    [Web of Science](http://rc.rcjournal.com/lookup/external-ref?access_num=A1987K046900028&link_type=ISI) 

5.  5. Abdo WF, Heunks LM. Oxygen-induced hypercapnia in COPD: myths and facts. Crit Care 2012;16(5):323.
    
    [PubMed](http://rc.rcjournal.com/lookup/external-ref?access_num=23106947&link_type=MED&atom=%2Frespcare%2F59%2F7%2Fe105.atom) 

6.  6. De Vito EL. [Causes of CO2 retention in patients with chronic obstructive lung disease]. Medicina 1993;53(4):350–356. *Article in Spanish*.
    
    

7.  7. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, Derenne JP. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis 1980;122(5):747–754.
    
    [PubMed](http://rc.rcjournal.com/lookup/external-ref?access_num=6778278&link_type=MED&atom=%2Frespcare%2F59%2F7%2Fe105.atom) 
    
    [Web of Science](http://rc.rcjournal.com/lookup/external-ref?access_num=A1980KS56900011&link_type=ISI)