Abstract & Commentary
Steroids for COPD Exacerbations: Is High-dose IV Administration Really Necessary?
By David J. Pierson, MD, Editor, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, is Editor for Critical Care Alert.
Synopsis: In an observational study of patients managed for COPD exacerbations in 414 U.S. hospitals, intravenous administration of corticosteroids at high doses conveyed no detectable benefits over oral administration at lower doses, although the great majority of patients received the former.
Source: Lindenauer PK, et al. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA 2010;303:2359-2367.
Although corticosteroids are beneficial in treating severe exacerbations of chronic obstructive pulmonary disease (COPD), studies to date have not shown high-doses (such as methylprednisolone, 2 mg/kg or more per 24 h) administered intravenously (IV) to be superior to lower doses (e.g., prednisone, 40 mg/day) given orally, with respect to clinically important outcomes. Because of the greater patient discomfort, complications, and expense of high-dose IV steroid therapy, current American and European evidence-based practice guidelines recommend lower-dose, oral therapy in the management of COPD exacerbations. Lindenauer and colleagues carried out this study to see how often the latter was used in treating patients hospitalized for this condition, and also to determine whether there was any evidence for an advantage of higher-dose, IV steroid administration.
The authors searched a proprietary database containing data from 414 U.S. hospitals mainly small to midsize urban, nonteaching hospitals for patients admitted because of an exacerbation of COPD (or acute respiratory failure plus COPD) in 2006 and 2007. Of 213,917 such patients, they excluded readmissions; those with other pulmonary diagnoses such as pneumothorax, pneumonia, or pulmonary embolism; those admitted directly to the ICU; and also those who received corticosteroids during the first 2 days at dosages outside the ranges examined: low-dose 20-80 mg prednisone/day by mouth, and high-dose IV 120-800 mg prednisone-equivalent/day. After exclusions, 79,985 patients comprised the study population, 80% of whom were admitted via the emergency department.
Median age of the patients was 69 years, 61% were women, 73% were white, and most were on Medicare. Their median length of stay was 4 days and 1.4% died. The great majority (92%) received high-dose IV steroids, with a median total dose of 600 mg (prednisone equivalents) in the first 2 days compared with 60 mg in those patients who initially received oral steroids. Patients treated with low-dose oral steroids tended to be slightly older, had more comorbidities, and were given antibiotics less often. The 6220 patients who initially received low-dose oral steroids were matched individually with patients in the high-dose IV group by means of a propensity analysis. After all adjustments, these patients were not more likely to experience treatment failure (defined as initiation of mechanical ventilation after the second hospital day, mortality, or readmission for a COPD exacerbation within 30 days) than those treated with high-dose IV steroids (odds ratio, 0.93; 95% confidence interval, 0.84-1.02). Patients treated with low-dose oral steroids had shorter lengths of hospital stay and lower treatment costs. The authors conclude that, among patients hospitalized for a COPD exacerbation, low-dose steroids given orally are not associated with worse outcomes than high-dose IV steroid therapy.
Commentary
This large observational study showed that the vast majority of patients hospitalized because of an exacerbation of COPD were initially treated with high doses of IV corticosteroids in sharp contrast to the recommendations of multiple leading clinical guidelines. This practice was not associated with any detectable clinical benefit and incurred higher hospital costs and longer patient stays.
There were several other findings that I found of interest in their divergence from current recommendations for best practice in managing COPD exacerbations. Of the 213,917 patients screened for the study by virtue of having a discharge diagnosis of COPD exacerbation or acute respiratory failure, 12% never received any steroids. Only 46% of the 80,000 patients in the final cohort had an arterial blood gas measurement during their first 2 hospital days. Long-acting beta-2 agonists (generally considered contraindicated in acute exacerbations) were administered to 40% of the patients. And only 7.3% of the cohort received non-invasive ventilation. Granted, these were patients who were not initially admitted to an ICU, and the 1.4% hospital mortality rate suggests that they did not have exacerbations as severe as those enrolled in most studies of non-invasive ventilation. Still, non-invasive ventilation is the intervention most strongly correlated with improved mortality, fewer intubations, and shorter hospital stays among patients with severe COPD exacerbations.
Why does real-world medical practice differ so markedly from the standard of care as recommended in practice guidelines? With respect to the route and dosing of corticosteroid therapy for COPD exacerbations, the authors of this study offer several possible explanations. Given that steroids hasten recovery in this condition, there may be a natural tendency to assume that larger doses will be more effective than smaller ones, and that parenteral administration will be more certain in onset and magnitude of clinical effect than oral dosing. That neither of these assumptions is true may be unknown to a substantial proportion of clinicians. Another possibility may be less potentially correctable: Some utilization review programs may require the presence of an IV line to justify continued hospitalization at an acute level of care.
Patients with COPD who present with an acute increase in dyspnea and/or sputum quantity, and/or a change in sputum color, should be evaluated clinically to make sure the cause is not pneumonia, pulmonary edema, or some process other than an exacerbation. Those diagnosed with a COPD exacerbation should be assessed for acute respiratory failure (with an arterial blood gas if this is suspected), and consideration given to initial management in the ICU. Non-invasive ventilation is indicated for severe exacerbations, particularly in the presence of acute-on-chronic respiratory acidosis. Otherwise, in addition to maintaining a oxyhemoglobin saturation of 90%-92%, evidence-based management focuses on giving short-acting bronchodilators by aerosol and corticosteroids systemically. However, unless the patient is actively vomiting or on nasogastric suction, the steroids can be low-dose (e.g., 40 mg once daily) and administered by mouth; IV administration of higher doses may increase hyperglycemia and other adverse effects, and is more expensive, but has not been shown to be any more effective.
Although corticosteroids are beneficial in treating severe exacerbations of chronic obstructive pulmonary disease (COPD), studies to date have not shown high-doses (such as methylprednisolone, 2 mg/kg or more per 24 h) administered intravenously (IV) to be superior to lower doses (e.g., prednisone, 40 mg/day) given orally, with respect to clinically important outcomes.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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