Steroids for COPD Exacerbations: Oral or IV?

Abstract & Commentary

By David J. Pierson, MD

Synopsis: This study of oral versus intravenous prednisolone in patients hospitalized with exacerbations of COPD showed no differences in any outcome variable between the two forms of administration.

Source: de Jong YP, et al. Oral or IV prednisolone in the treatment of COPD exacerbations: A randomized, controlled, double-blind study. Chest. 2007;132:1741-1747.

De jong and colleagues, in the Netherlands, conducted a prospective, randomized, double-blind, double-dummy, placebo-controlled, parallel-group clinical study of intravenous vs oral corticosteroids in the treatment of patients hospitalized because of an exacerbation of chronic obstructive pulmonary disease (COPD). All patients with known COPD who were admitted to a single institution during the 2-year study period were considered for inclusion. Patients were excluded if they had asthma, significant comorbidity, poor compliance, or previous study enrollment, and also if the exacerbation was severe, as defined by arterial pH 7.25 or less or PCO2 70 mm Hg or more. Patients received 5 days of either intravenous or oral prednisolone 60 mg as the active medication; they also received nebulized ipratropium and albuterol 4 times daily and oral amoxicillin-clavulanate. Prednisolone was given orally to all patients after the first 5 days, with the daily dose tapered to zero over the next week.

Treatment failure, the primary outcome, was defined as death, admission to ICU, readmission for COPD, or intensification of pharmacological therapy during a 90-day follow-up. The study was designed as a non-inferiority trial, with sample sizes calculated to detect a difference of 15% in the primary outcome. Secondary outcomes included spirometry, length of hospital stay, health status, as measured by the St George's Respiratory Questionnaire, and a measure of health-related quality of life.

During the study period, 435 potentially eligible patients were admitted 581 times. After exclusions, 210 patients (48%) were included, 107 of whom received prednisolone intravenously and 103 of whom received it by mouth. Final data analysis included 99 and 94 of these patients, respectively. The patients were demographically and clinically similar: three-fourths were men, mean age 70 years, and mean FEV1 approximately 1.0 L (37% of predicted, or GOLD stage 3). Most of them had received oral corticosteroids in the month prior to admission, although only about 10% took them chronically. About 12% were on long-term oxygen therapy at home.

Mean duration of hospitalization was about 11 days; 7 patients died. Treatment failure, the primary study outcome, occurred in 62% of the patients who received steroids intravenously, as compared to 56% in those who received them orally, with no differences in early vs late treatment failure. No differences in secondary outcome variables — including changes in FEV1, health status, quality of life, or duration of hospitalization — achieved or approached statistical significance. De Jong et al concluded that orally-administered prednisolone is not inferior to its intravenous counterpart, and that the former is preferable because of its lower cost and greater convenience.


As confirmed by a Cochrane review of numerous published, placebo-controlled studies,1 the systemic administration of corticosteroids to patients with COPD exacerbations hastens physiologic recovery, reduces morbidity, and improves other outcomes, both in ambulatory patients and those ill enough to be admitted to the hospital. In exacerbations, steroids also decrease the incidence of treatment failure and the likelihood of relapse in the succeeding 1 to 3 months. Thus, a short course of systemic steroids is the current standard of care for this condition.

Although once-daily prednisone (or prednisolone, as used in this study) is generally used in treating exacerbations in outpatients, it has been common practice to administer steroids intravenously when patients are sick enough to be admitted to the hospital — despite the fact that they are virtually 100% bioavailable when taken by mouth. Nearly all studies of corticosteroids in hospitalized COPD patients have used intravenous administration, and such patients typically receive the drug in 2 or 4 divided daily doses.

Hospitalization for exacerbations accounts for the largest component of health care costs for COPD. In the United States, some 750,000 hospitalizations for COPD exacerbations occur each year. Thus, if the findings of this study are valid, oral rather than intravenous administration could have important implications in terms of the use of monetary and other resources.

This study's results agree with my own personal bias that hospitalized patients with COPD exacerbations can be treated as effectively with oral as with intravenous steroids, as long as they can take medication by mouth and are not actively vomiting. However, the present study falls short of being the final word on the subject. De Jong et al acknowledge that their own a priori criteria for the non-inferiority of oral administration were not met because of insufficient patient enrollment during the study period; they achieved only 74% power (vs the planned 80%) to assure non-inferiority of oral prednisolone. And they excluded patients with severe hypercapnia or acidemia, which is the population of greatest interest to intensivists. In addition, although there are no good data to suggest that higher steroid doses are more effective in this condition, the 60 mg daily prednisolone dose is lower than that initially used by many American clinicians in treating hospitalized patients.

As a side note, I know of no data supporting the use of inhaled steroids in COPD exacerbations. Given the lower overall potency of these agents, as compared to usual doses of systemically-given preparations for patients already receiving inhaled steroids prior to the exacerbation, it would make sense to discontinue them until the daily oral prednisone dose is reduced below about 15-20 mg. It has also become commonplace in some intensive care units to administer inhaled steroids to intubated patients who have COPD, whether exacerbated or not. To my knowledge, this practice, which is both expensive and time-consuming for staff, is supported by no evidence at all. Given the inefficiency of aerosol delivery via endotracheal tube (which reduces drug delivery by a factor of 5 to 10 in comparison with optimal oral technique), it is most unlikely that the administered agent reaches the patient's lungs in any biologically significant amount.


1. Wood-Baker R, et al. Oral corticosteroids for acute exacerbations of chronic obstructive pulmonary disease (Cochrane Review). The Cochrane Library. Oxford: Update Software 2003; Issue 3.