THE ROLE OF HYPOVENTILATION AND VENTILATION-PERFUSION REDISTRIBUTION IN OXYGEN-INDUCED HYPERCAPNIA DURING ACUTE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

To the Editor :

We read with great interest the article by Robinson and colleagues that appeared in the May 2000 issue of the Journal (1). In this article, the authors concluded that the major mechanism of hypercapnia in patients who retain CO₂ was a reduction in overall ventilation, as opposed to a redistribution of perfusion caused by the release of hypoxic pulmonary vasoconstriction (HPV).

The authors identified a group of patients as retainers if their Pa_CO2 increased more than 3 mm Hg. This, however, makes the physiologic differences between retainers and nonretainers less clear. From a clinical standpoint, most physicians would not classify a patient whose Pa_CO2 went from 43 mm Hg to 46 mm Hg as a retainer (subject 14).

Furthermore, the mean Pa_O2 in the group of retainers was lower than that in the nonretainer group (54.5 versus 62.7 mm Hg, respectively) and neither group was particularly hypoxemic (1). This is in sharp contrast to the patients in the study by Aubier and colleagues, where the mean Pa_O2 was 38 mm Hg (2). As HPV does not seem to play a physiologic role until Pa_O2 is lower than 55-60 mm Hg (3), it is unlikely that there would be release of HPV in the nonretainer group, and only a mild release of HPV in the retainer group. Additionally, the Haldane effect, which as with HPV is more prominent at lower partial pressures of oxygen, may have contributed to hypercapnia, and deserves mention.

Robinson and colleagues also found that retainers had a significantly greater change in alveolar dead space while on oxygen as compared to non-retainers. Our interpretation of these data is that / distribution changed due to a release of HPV in the retainer group, supporting the conclusions of Aubier and others (2, 4, 5). This effect may have been limited to the retainer group for the reasons outlined above. Finally, we were unclear as to why they concluded that the reduction in minute volume was more significant than changes in / matching due to release of HPV, when neither of these variables was quantified as compared to the total change in Pa_CO2.

This was the first study of its kind, and the authors should be commended on their techniques and innovative examination of a perplexing physiologic problem. However, we believe the categorization of their groups of responders and nonresponders, as well as their interpretations of the results, are subject to continued discussion and refinement.

Harvard Medical School, Boston, Massachusetts

1. Robinson TD, Freiberg DB, Regnis JA, Young IH. The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 1524-1529 [Abstract/Free Full Text].

2. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, Derenne JP. Efforts 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 [Medline].

3. Cutais M, Rounds S. Hypoxic pulmonary vasoconstriction: physiologic significance, mechanism, and clinical relevance. Chest 1990; 97: 706-718 [Free Full Text].

4. Hanson CW III,, Marshall BE, Frasch HF, Marshall C. Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease. Crit Care Med 1996; 24: 23-28 [Medline].

5. Sassoon CS, Hassell KT, Mahutie CK. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987; 135: 907-911 [Medline].

From the Authors:

We thank Drs. Feller-Kopman and Schwartzstein for their comments on our recent article (1).

The choice of a 3 mm Hg rise in Pa_CO2 as hypercapnia was made with reference to the reproducibility of the electrode, as noted in the paper, so that a 3 mm Hg or greater rise could be regarded as real. We feel that this resulted in a reasonable separation of the patients, as the largest rise in CO₂ in the "nonretainers" was 1.9 mm Hg and most actually had a fall in Pa_CO2. Subject 14 did rise from a Pa_CO2 in the normal range to 46 mm Hg, which would clinically be regarded as abnormal.

It is necessary to distinguish between the local P_O2 in the low / regions of the lung, which would be well within the operating range for hypoxic pulmonary vasoconstriction (HPV) in our patients, and the final mixed Pa_O2 which will be kept relatively high by the redistribution mechanism. In any case, a number of studies have shown that HPV is present even in patients with mild COPD and that it has an important role in preserving / matching (2, 3). Release of HPV with oxygen administration would be expected to increase blood flow to low / regions, manifest as an increase in log 3D Q in our MIGET data, and this occurred equally in our CO₂ retainer (R) and nonretainer (NR) groups.

While there was some attendant increase in alveolar dead space with oxygen administration in the NR group, there was a larger and statistically significant increase in this dead space, and decrease in ventilation in the R group, which distinguished them from the NR patients. There may be another separate mechanism causing this larger increase in alveolar dead space in the R group, causally unrelated to the decrease in ventilation. However, we prefer the more economic hypothesis that the two are connected through an increase in alveolar PCO₂.

Model calculations of the relative contributions to the rise in Pa_CO2 in the R group revealed about 43% due to the increase in alveolar dead space, 46% due to the decrease in overall ventilation and the remaining 11% due to the Haldane effect (6%) and changes in cardiac output (5%).

In summary, we believe that our data are entirely consistent with those of Aubier (4) and others. However, the application of MIGET to this physiologic problem has allowed the further dissection of the above mechanisms. We conclude that the equal changes in log SD Q in the R and NR groups is evidence that release of HPV is not a distinguishing mechanism. Hypoventilation and a large increase in alveolar dead space are distinguishing mechanisms and they may be causally related.

Royal Prince Alfred Hospital, Sydney, Australia

1. Robinson TD, Freiberg DB, Regnis JA, Young IH. The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 1524-1529 .

2. Agusti AN, Barbera JA, Roca J, Wagner PD, Guitart R, Rodriguez-Roisin R. Hypoxic pulmonary vasoconstriction and gas exchange during exercise in chronic obstructive pulmonary disease. Chest 1990; 97: 268-275 [Abstract/Free Full Text].

3. Barbera JA, Ramirez J, Roca J, Wagner PD, Sachez-Lioret J, Rodriguez-Roisin R. Lung structure and gas exchange in mild chronic obstructive pulmonary disease. Am Rev Respir Dis 1990; 141: 895-901 [Medline].

4. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, Derenne J-P. 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 .