In Reply:
We thank you for your elegant and insightful commentaries on our article.
Physiologically, patients with COPD are classified as dry lung, contrasting with subjects with ARDS and pneumonia, who are classified as wet lung. This classification is used because COPD patients present similar behavior with respect to shunt, hypoxic vascular response, alveolar ventilation/perfusion (V̇A/Q̇) distribution, and response to 100% oxygen.1 Patients with COPD exacerbation, whether requiring ventilatory support or not, exhibit low amounts of shunt (usually < 10%), suggesting that the efficiency of collateral ventilation is very high or that complete airway obstruction does not occur functionally except in a few airways that are completely occluded by bronchial secretions.1 In addition, these patients have an increased hypoxic vascular response. Finally, COPD causes severe V̇A/Q̇ mismatching and nonuniform patterns (four different patterns) of V̇A/Q̇ distribution. The distribution of both V̇A and pulmonary blood flow, namely V̇A/Q̇ mismatching, remains the most important cause of arterial hypoxemia, with or without hypercapnia, in both stable COPD and with COPD exacerbation.2 The mechanisms that may contribute to CO2 retention include a decrease in hypoxic ventilatory response consequent to the administration of oxygen, an increase in dead space consequent to release of hypoxic vasoconstriction and thus worsening of V̇A/Q̇ relationships, and the Haldane effect (for any given amount of CO2 bound to hemoglobin, PaCO2 is considerably higher in the presence of high vs low SpO2).3
Dr Briones Claudett's main question concerns the clinical applicability of our findings in the short follow-up time of subjects after setting the FIO2 to 1.0. Hyperoxia increases pulmonary dead space. However, using the multiple inert-gas elimination technique (breathing air and then 100% oxygen through a nose mask) in 22 subjects with COPD exacerbation, Robinson et al4 also showed a decrease in V̇A (expiratory minute volume of 9 ± 2 L/min vs 7.2 ± 1.6 L/min, P < .05) and an increase in low V̇A/Q̇ units. They concluded that the major mechanism differentiating CO2-retaining patients from CO2-nonretaining patients is depression of ventilation rather than redistribution of blood flow caused by release of hypoxic vasoconstriction and that an increase in alveolar dead space could be secondary and not the cause of hypercapnia. However, we agree with González, Vulliez, and De Vito that our subjects may have received indiscriminate oxygen therapy at baseline (pre-100% FIO2). The high basal PaO2 values (101.4 ± 21.7 mm Hg) in our subjects could have abolished the effect of hypoxemic pulmonary vasoconstriction reflex with a consequent increase in V̇A/Q̇ mismatching. However, we believe that this increases the likelihood of re-taining CO2, which did not occur in our subjects.
Dr Briones Claudett questions the short follow-up of subjects in our study. Santos et al5 evaluated the pulmonary gas exchange response to oxygen breathing in 8 subjects with acute lung injury and 4 subjects with COPD, and did not demonstrate changes in PaCO2 (39 ± 6 mm Hg vs 44 ± 8 mm Hg, P = not significant) after 60 min of 100% FIO2. The methodology used by these authors was replicated in our study because it intentionally alters the FIO2 with the objective assessment of respiratory and hemodynamic parameters. Unlike the previously cited article,4 Briones Claudett et al6,7 performed two elegant studies with subjects with COPD and hypercapnic encephalopathy and did not change the supply of oxygen during the study period. Rather, they evaluated the respiratory response (PaCO2) of the different ventilatory strategies and different ventilatory pressures. Diaz et al8 also evaluated the effect of noninvasive ventilation (NIV) on pulmonary gas exchange during COPD exacerbation for only 30 min.
In response to González, Vulliez, and De Vito, Diaz et al8 reported that improvement in respiratory blood gases during NIV was essentially due to higher V̇A and not to improvement in V̇A/Q̇ relationships and that the increase in alveolar-arterial oxygen difference was explained by the increase in respiratory exchange ratio due to an increased clearance of body stores of CO2 during NIV. In conclusion, we agree that the traditional theory that oxygen administration to CO2-retaining patients causes loss of hypoxic drive, resulting in hypoventilation and ventilatory failure, is a myth, particularly during NIV.9
We agree with Dr Briones Claudett's criticism of the lack of spirometric data from our subjects, and we believe this is a flaw in our study.
In conclusion, our study had the clear objective of evaluating the safety of brief increases in FIO2 (during respiratory therapy procedures and during O2 saturation decreases secondary to maladjustments or interface leaks) in CO2-retaining subjects with COPD and undergoing NIV.10 No other clinical objective exists in sustained increases in FIO2, except temporarily, because in cases of persistent refractory hypoxemia, endotracheal intubation and mechanical ventilation are mandatory.
Footnotes
The authors have disclosed no conflicts of interest.
- Copyright © 2014 by Daedalus Enterprises
