BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity and quality of life. The most common causes are infective, and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti-inflammatory agents.
OBJECTIVES: To assess the effects of corticosteroids administered orally or parenterally for treatment of acute exacerbations of COPD, and to compare the efficacy of parenteral versus oral administration.
SEARCH METHODS: We carried out searches using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials), and checked references of included studies and trials registries. We conducted the last search in May 2014.
SELECTION CRITERIA: Randomised controlled trials comparing corticosteroids administered orally or parenterally with an appropriate placebo, or comparing oral corticosteroids with parenteral corticosteroids in the treatment of people with acute exacerbations of COPD. Other interventions (e.g. bronchodilators and antibiotics) were standardised for both groups. We excluded clinical studies of acute asthma.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS: Sixteen studies (n = 1787) met inclusion criteria for the comparison systemic corticosteroid versus placebo and 13 studies contributed data (n = 1620). Four studies (n = 298) met inclusion criteria for the comparison oral corticosteroid versus parenteral corticosteroid and three studies contributed data (n = 239). The mean age of participants with COPD was 68 years, median proportion of males 82% and mean forced expiratory volume in one second (FEV1) per cent predicted at study admission was 40% (6 studies; n = 633). We judged risk of selection, detection, attrition and reporting bias as low or unclear in all studies. We judged risk of performance bias high in one study comparing systemic corticosteroid with control and in two studies comparing intravenous corticosteroid versus oral corticosteroid.Systemic corticosteroids reduced the risk of treatment failure by over half compared with placebo in nine studies (n = 917) with median treatment duration 14 days, odds ratio (OR) 0.48 (95% confidence interval (CI) 0.35 to 0.67). The evidence was graded as high quality and it would have been necessary to treat nine people (95% CI 7 to 14) with systemic corticosteroids to avoid one treatment failure. There was moderate-quality evidence for a lower rate of relapse by one month for treatment with systemic corticosteroid in two studies (n = 415) (hazard ratio (HR) 0.78; 95% CI 0.63 to 0.97). Mortality up to 30 days was not reduced by treatment with systemic corticosteroid compared with control in 12 studies (n = 1319; OR 1.00; 95% CI 0.60 to 1.66).FEV1, measured up to 72 hours, showed significant treatment benefits (7 studies; n = 649; mean difference (MD) 140 mL; 95% CI 90 to 200); however, this benefit was not observed at later time points. The likelihood of adverse events increased with corticosteroid treatment (OR 2.33; 95% CI 1.59 to 3.43). Overall, one extra adverse effect occurred for every six people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased (OR 2.79; 95% CI 1.86 to 4.19). For general inpatient treatment, duration of hospitalisation was significantly shorter with corticosteroid treatment (MD -1.22 days; 95% CI -2.26 to -0.18), with no difference in length of stay the intensive care unit (ICU) setting.Comparison of parenteral versus oral treatment showed no significant difference in the primary outcomes of treatment failure, relapse or mortality or for any secondary outcomes. There was a significantly increased rate of hyperglycaemia in one study (OR 4.89; 95% CI 1.20 to 19.94).
AUTHORS' CONCLUSIONS: There is high-quality evidence to support treatment of exacerbations of COPD with systemic corticosteroid by the oral or parenteral route in reducing the likelihood of treatment failure and relapse by one month, shortening length of stay in hospital inpatients not requiring assisted ventilation in ICU and giving earlier improvement in lung function and symptoms. There is no evidence of benefit for parenteral treatment compared with oral treatment with corticosteroid on treatment failure, relapse or mortality. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.
It is always good to see a Cochrane review. I believe that most practitioners know that IV and PO steroids are equipotent. That the parenteral delivery increases risk of side effects, I didn't know.
Most practitioners who treat patients experiencing exacerbations of COPD know that corticosteroids are very helpful, but not all know that there is no advantage to administering these parenterally rather than orally.
This is a very active area of research given the relatively close benefit: harm ratios with corticosteroids. Questions are now whether oral steroids are better than high-dose inhaled, what is the optimal duration of course for exacerbation, why do steroids increase the rate of pneumonia while decreasing 'exacerbations', what are the long-term benefits and harms?
Updated Cochrane meta-analysis of systemic steroids for COPD exacerbations, finding that they reduce treatment failure and relapse, shorten length of stay and improve lung function and symptoms faster. Also finds little benefit of IV over oral steroids. Already well known - there have been no new RCTs of this is nearly a decade, except for 2 small trials in ICU patients that are too limited to add much that is useful.
This paper is a re-do of several previous meta-analyses with the addition of 9 new papers and the inclusion of ventilated patients in the analysis. The findings confirm the existing standard of care. I do not see any methodologic caveats that would give cause to question the bottom line.
Very important information for general internists and probably many respirologists. Provides excellent evidence that oral steroids can (and should) replace systemic as standard of care.