Apr 182014

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Systemic steroids in COPD exacerbations requiring ventilator support:

Are we treating our patients, or ourselves?

By Muhammad Adrish, MD

Acute exacerbations of COPD are a major cause of hospitalizations, and are associated with more rapid decline in lung function and reduced survival. Because COPD exacerbations are associated with increased inflammatory responses, corticosteroids have traditionally been used as an integral treatment. In fact, there is insufficient data to to recommend the best dose, method (IV or po) or treatment course of corticosteroids for COPD exacerbations. Guidelines advise the equivalent of 30-40 mg of prednisone per day, based on meta-analyses that suggest steroids accelerate recovery from COPD exacerbations and improve symptoms and lung function.

However, the included studies had a high rate of adverse events (mostly hyperglycemia) and did not show a reduction in the mortality rate. Patients with severe COPD exacerbations were generally excluded, especially those requiring invasive mechanical ventilation. In one of the only studies testing steroids for life-threatening COPD exacerbations, steroids dramatically reduced the need for invasive mechanical ventilation but did not improve mortality.

In a new study in ERJ, Abroug et al randomized 217 patients with severe COPD exacerbations -- all requiring either noninvasive or invasive ventilation -- to receive either prednisone 1 mg/kg or usual care alone. About 25% of patients in each group required invasive ventilation at randomization. This was an open-label trial, so physicians knew who was getting prednisone and who wasn't.

The study did not reach its enrollment target of 300 patients. That said, its findings were firmly negative: no difference in ICU mortality (15% vs. 14% favoring placebo); failure of noninvasive ventilation (16% vs. 13% favoring placebo); ventilator-days (6 days in each) or ICU length of stay (9 vs 8 days favoring placebo).

Patients receiving prednisone had significantly more hyperglycemia, but no serious adverse events (infections, GI bleeding, etc) directly attributable to corticosteroids. 

This study was underpowered and too small to draw conclusions that would change our care practices. Also, its open label design means unmeasured differences in care between the groups could easily have biased the results. Despite these limitations, the results are provocative and interesting and raise questions about the efficacy of corticosteroids as an accepted but not-well-tested therapy for severe COPD exacerbations.

Since the only other relevant study (referenced above) showed steroids protected people from requiring mechanical ventilation, and it was a true placebo controlled trial, it's not quite time to abandon steroids as a core component of care for severe COPD exacerbations.

Regarding treatment courses, the 2013 REDUCE randomized trial in JAMA suggested that a 5 day course of corticosteroids was as good as longer courses for people with COPD exacerbations of moderate severity. A large observational analysis also suggested shorter courses are adequate and cause less hyperglycemia. In response, the 2014 GOLD guidelines now advise 5 days of 40 mg oral prednisolone or prednisone for most COPD exacerbations, not 10-14 days as they previously did.

Prednisone in COPD exacerbation requiring ventilatory support: an open-label randomised evaluation. Eur Respir J 2014 43:717-724; published ahead of print 2013,doi:10.1183/09031936.00002913

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Steroids did not improve outcomes in severe COPD exacerbations (RCT)