Does Oxygen Increase CO2 Retention in Hypercapnic COPD Patients?

Abstract & Commentary

Synopsis: Traditional teaching related to the use of oxygen therapy for hypercapnic patients with COPD may be incorrect.

Source: Gomersall CD, et al. Oxygen therapy for hypercapnic patients with chronic obstructive pulmonary disease and acute respiratory failure: A randomized, controlled pilot study. Crit Care Med. 2002; 30:113-116.

The objective of this study was to investigate the effect of oxygen therapy on outcome and on symptomatic hypercapnia. Patients admitted with a clinical diagnosis of an acute exacerbation of COPD, a PaO2 < 50 mm Hg, and PaCO2 > 50 mm Hg while breathing room air was randomized to receive oxygen therapy by 1 of 2 protocols. Patients received oxygen therapy titrated to PaO2 > 50 mm Hg (low oxygen group; n = 17) or PaO2 > 70 mm Hg (high oxygen group; n = 17). Patients in the low-oxygen group also received doxapram (an intravenous respiratory stimulant) if they developed a pH < 7.20, whereas those in the high-oxygen group received doxapram if they developed symptomatic acidosis. Administration of bronchodilators, corticosteroids, and antibiotics was standardized. Two patients in the low-oxygen tension group required mechanical ventilation and another one died. No patients in the high-oxygen group had a poor outcome (difference not significant). No patient in either group became comatose or developed an acute cardiac arrhythmia.

Comment by Dean R. Hess, PhD, RRT

Traditional teaching for physicians, nurses, and respiratory therapists warns of the dangers of oxygen therapy for acutely ill, hypercapnic COPD patients. Emotional vignettes are espoused in which a patient with COPD is given oxygen and stops breathing. Clinicians-in-training thus enter their practice with the fear of potentially killing the unsuspecting patient with COPD by oxygen therapy—death by nasal cannula! Such practice is taught as indefensible. Indeed, I suspect that, unfortunately, the withholding of oxygen therapy may have harmed countless patients, thus subjecting them to unnecessary hypoxemia. I find this in contradiction to the evidence that oxygen therapy prolongs life in hypoxemic patients with COPD. In fact, oxygen is the only therapy known to improve survival in stable patients with COPD. However, it may be inappropriate to compare the risks and benefits during stable COPD to those that occur with an acute exacerbation.

The traditional teaching is that the predominant respiratory drive in hypercapnic COPD patients is the low PaO2—the so-called "hypoxic drive." Oxygen therapy raises the PaO2 and suppresses the hypoxic drive, thus lowering the minute ventilation with a subsequent respiratory acidosis. The common impression among clinicians is that the drive to breathe is suppressed in patients with COPD. However, this is not supported by the evidence, which shows that respiratory drive in patients with COPD is often increased.1 Airflow obstruction (asphyxia) and hypercapnia result in an increased respiratory drive. Moreover, it has been reported that there is no correlation between changes in PaCO2 and changes in respiratory drive (as measured by mouth occlusion pressure, P0.1) when oxygen is administered to COPD patients.

The PaCO2 may increase in some patients with COPD when oxygen is administered. Accordingly, it is prudent to monitor the oxygen dose administered and arterial blood gases; pulse oximetry may not be an appropriate substitute for arterial blood gases in this setting. There are several explanations for an increase in PaCO2 that may occur.2-5 Due to the Haldane effect, an increase in hemoglobin oxygen saturation may off-load CO2 from hemoglobin, increasing PaCO2. The increase in PaCO2 might also be due to changes in ventilation:perfusion (V/Q) matching in the lungs, an increase in dead space, and, perhaps in some patients, a decreased respiratory drive.

The results of this study by Gomersall and associates suggest that the traditional teaching related to oxygen therapy for hypercapnic patients with an acute exacerbation of chronic obstructive pulmonary disease might be incorrect. However, a few caveats are important. First, they did not test the effect of a high PaO2, such as might occur if 100% oxygen is administered. Second, the study is relatively small (n = 34). Although a large randomized, controlled study is required to confirm the results of this study, such may not be forthcoming as a power analysis suggests that this would require a sample size of more than 1000 patients. 


1. Aubier M, et al. Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1980;122: 191-199.

2. West JB. Causes of carbon dioxide retention in lung disease. N Engl J Med. 1971;284:1232-1236.

3. Sassoon CSH, et al. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis. 1987;135:907-911.

4. Aubier M, et al. 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;122:747-754.

5. Simpson SQ. Oxygen-induced acute hypercapnia in chronic obstructive pulmonary disease: What’s the problem? Crit Care Med. 2002;30:258-259.