Correspondence

Noninvasive Ventilation for Exacerbations of Chronic Obstructive Pulmonary Disease

N Engl J Med 1996; 334:735-736March 14, 1996

Article

To the Editor:

The study by Brochard et al. (Sept. 28 issue)1 showed an impressive decrease in the need for endotracheal intubation in patients with acute exacerbations of chronic obstructive pulmonary disease treated with noninvasive positive-pressure ventilation (26 percent of whom required intubation), as compared with patients receiving standard therapy (74 percent of whom required intubation). We agree that noninvasive positive-pressure ventilation may be an important adjunct in managing exacerbations of chronic obstructive pulmonary disease, but several flaws in the study by Brochard et al. raise questions about the magnitude of the benefit of noninvasive positive-pressure ventilation, and thus about the strength of their conclusions. Although the patients enrolled in the study were clearly quite ill, an intubation rate of 74 percent seems unusually high for patients receiving standard treatment. Two factors that may account for this high rate are inadequate use of oxygen and suboptimal medical treatment for exacerbations of chronic obstructive pulmonary disease.

Patients assigned to standard treatment received oxygen limited to a maximal flow rate of 5 liters per minute, delivered by nasal prongs, to maintain a level of arterial oxygen saturation above 90 percent. Limiting the flow of oxygen to this rate may have resulted in inadequate oxygenation in some patients in this group, necessitating intubation for hypoxemia simply because of the oxygen-delivery protocol. Such a limitation was not imposed in the noninvasive-ventilation group. In addition, a Venturi face mask is the preferred means of administering oxygen to patients with chronic obstructive pulmonary disease,2 in order to regulate the fraction of inspired oxygen as precisely as possible and maintain a minimally acceptable value for the partial pressure of oxygen without causing further hypercarbia and respiratory acidosis.3 Oxygen delivered by noninvasive positive-pressure ventilation can be controlled more precisely than oxygen delivered by nasal prongs. The lower average value for the partial pressure of oxygen and the higher average value for the partial pressure of carbon dioxide in the standard-treatment group, as compared with the values in the noninvasive-treatment group, at one hour (the period during which most intubations were performed) are consistent with both possible reasons for inadequate use of oxygen.

Only 60 percent or less of the patients in each group received corticosteroids, about 30 percent did not receive sympathomimetic agents, and it appears that no patients received anticholinergic agents, all of which are standard therapies for exacerbations of chronic obstructive pulmonary disease.2,4,5 Although applicable to both groups, a delayed response to treatment would tend to increase the need for intubation and cause the relative benefit of noninvasive positive-pressure ventilation to be overestimated. Furthermore, among the patients who received sympathomimetic agents, an unspecified proportion received intravenous rather than inhaled agents. No information is given about the routes of administration or doses of these medications in the two groups. If there were substantial differences in treatment, they may have contributed to the difference in the rates of intubation.

Thus, although we agree that noninvasive positive-pressure ventilation may be of value in managing acute exacerbations of chronic obstructive pulmonary disease, it remains uncertain what the true benefit of this approach would be if it were compared with a more standard approach to management.

Mark J. Baumel, M.D.
Richard J. Schwab, M.D.
Ronald G. Collman, M.D.
Hospital of the University of Pennsylvania, Philadelphia, PA 19104

5 References

1. 1

   Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995;333:817-822
   Full Text | Web of Science | Medline

2. 2

   Snider GL, Faling LJ, Rennard SI. Chronic bronchitis and emphysema. In: Murray JF, Nadel JA, eds. Textbook of respiratory medicine. 2nd ed. Vol. 2. Philadelphia: W.B. Saunders, 1994:1372-3.
   

3. 3

   Dunn WF, Nelson SB, Hubmayr RD. Oxygen-induced hypercarbia in obstructive pulmonary disease. Am Rev Respir Dis 1991;144:526-530
   CrossRef | Web of Science | Medline

4. 4

   Curtis JR, Hudson LD. Emergent assessment and management of acute respiratory failure in COPD. Clin Chest Med 1994;15:481-500
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5. 5

   Higgins BG, Powell RM, Cooper S, Tattersfield AE. Effect of salbutamol and ipratropium bromide on airway calibre and bronchial reactivity in asthma and chronic bronchitis. Eur Respir J 1991;4:415-420
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We agree with Dr. Baumel and his colleagues that the efficacy of noninvasive ventilation should be compared with optimal medical management. As they emphasize, oxygen therapy is aimed at improving oxygenation without inducing a major increase in hypercarbia.1 In this respect, there is no documented difference among various techniques of oxygen supplementation, provided that arterial oxygen saturation is carefully monitored. Indeed, the important variable to control is not the fraction of inspired oxygen itself but its effect on the partial pressure of oxygen, which drives changes in the partial pressure of carbon dioxide.

In our study, an adjustment in oxygen administration was based on the criterion of maintaining a level of oxygen saturation above 90 percent, as assessed by continuous pulse oximetry. At one hour, the partial pressure of oxygen had risen from 39 to 58 mm Hg in the standard-treatment group and from 41 to 66 mm Hg in the noninvasive-ventilation group (not a significant difference). Severe hypoxemia contributed to the need for endotracheal intubation in 10 patients in the standard-treatment group; all but 2 of these patients, however, also presented with a low pH, which was a criterion for intubation, and a higher rate of oxygen flow could have had a detrimental effect on the partial pressure of carbon dioxide in these patients. Therefore, although oxygen therapy may have been suboptimal, we do not believe this factor played a major part in the higher rate of endotracheal intubation in the standard-treatment group.

We clearly lack good information about the role of different drug regimens in the prevention of endotracheal intubation.2 At the time of our study, ipratropium bromide was not available for aerosolization at all the participating centers. The use of other medications as first-line therapy was similar in the two groups and was also similar in intubated and nonintubated patients. All the patients in the standard-treatment group received at least one bronchodilator. Sympathomimetic agents, corticosteroids, and aminophylline were administered in 71, 60, and 61 percent of the intubated patients, respectively, in the standard-treatment group, and these percentages were similar to or slightly higher than those among the nonintubated patients. Medications were given intravenously to intubated patients. In the noninvasive-ventilation group, the proportion of intubated patients receiving these medications was higher (91 percent) than the proportion of nonintubated patients (53 percent, P = 0.08), presumably because of more severe respiratory failure on admission. It is difficult to draw firm conclusions about the influence of medical therapy on the frequency of intubation in this study.

Laurent Brochard, M.D.
Hôpital Henri Mondor, 94010 Créteil, France

Jordi Mancebo, M.D.
Hospital Sant Pau, 08025 Barcelona, Spain

2 References

1. 1

   Warren PM, Flenley DC, Millar JC, Avery A. Respiratory failure revisited: acute exacerbations of chronic bronchitis between 1961-68 and 1970-76. Lancet 1980;1:467-470
   CrossRef | Web of Science | Medline

2. 2

   Derenne JP, Fleury B, Pariente R. Acute respiratory failure of chronic obstructive pulmonary disease. Am Rev Respir Dis 1988;138:1006-1033
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   M. Carrera, E. Sala, B.G. Cosío, A.G.N. Agustí. (2005) Tratamiento hospitalario de los episodios de agudización de la EPOC. Una revisión basada en la evidencia. Archivos de Bronconeumología 41:4, 220-229
   CrossRef

2. 2

   Robert M. Jasmer, Michael A. Matthay. (2000) Cost-effectiveness of noninvasive ventilation for acute chronic obstructive pulmonary disease: Cashing in too quickly. Critical Care Medicine 28:6, 2170-2171
   CrossRef