Management of Asthma and Chronic Airflow Limitation (Part 8)

Aminophylline in Acute Exacerbations of COPD
Patients with COPD, in severe exacerbations of their disease, are usually treated with oxygen, parenteral antibiotics and steroids, inhaled bronchodilators and intravenously administered aminophylline. The major rationale for the use of aminophylline under these circumstances is the presumption that this drug increases bronchodilatation beyond that achieved by adrenoceptor agonists alone. Until recently, this notion had not been subjected to critical appraisal.
Vozeh and colleagues studied patients with acute exacerbations of COPD or asthma and administered either low- or high-dose aminophylline infusions among other treatment modalities. They were able to show that the high-dose group achieved greater improvement in spirometry than the low-dose group. The major question left unanswered from this trial is whether the addition of theophylline conferred a significant and unique benefit since the study lacked a placebo arm, and suboptimal doses of adrenoceptor agonists probably were used.
This issue was addressed in a recent randomized, double-blind, placebo-controlled trial. Thirty patients with severe exacerbations of COPD (FEVi less than 0.6 L) were studied. Patients received either intravenous aminophylline to achieve a therapeutic serum level or placebo, in addition to nebulized, inhaled metaproterenol (15 mg), intravenously administered methylprednisolone, orally given antibiotics and supplemental oxygen as needed. The baseline characteristics of both groups were similar. At 72 h, both groups had improved to a similar extent with respect to the subjective sensation of dyspnea, arterial blood gas values and spirometry (FEV, and FVC). Almost 50 percent of the aminophylline group experienced side effects attributable to the drug, compared with less than 10 percent in the placebo group, even with theophylline levels within the usually accepted therapeutic range.