Current issues of ACP Journal Club are published in Annals of Internal Medicine


Adjunctive aminophylline for acute asthma may reduce unscheduled hospitalization

ACP J Club. 1991 Nov-Dec;115:83. doi:10.7326/ACPJC-1991-115-3-083

Source Citation

Wrenn K, Slovis CM, Murphy F, Greenberg RS. Aminophylline therapy for acute bronchospastic disease in the emergency room. Ann Intern Med. 1991 Aug 15;115:241-7.



To evaluate intravenous aminophylline as an adjunct to treatment with metaproterenol sulfate and methylprednisolone for patients with asthma exacerbation or wheezing.


Randomized, double-blind, placebo-controlled trial for the duration of the emergency department visit.


Emergency department, Grady Memorial Hospital, Atlanta.


Adults presenting with asthma exacerbation or wheezing (including patients with chronic obstructive pulmonary disease [COPD]). Exclusion criteria were use of theophylline-containing products within 24 hours, contraindication to the study drugs, insulin-dependent diabetes, possible myocardial ischemia, or pulmonary edema. 143 patients were randomized and 133 (93%) were included in the analysis.


After measurement of forced expiratory volume at 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR), patients received 3 treatments of nebulized metaproterenol sulfate (0.3 mL of a 5% solution) 15 to 20 minutes apart, and 80 mg of intravenous methylprednisolone sodium succinate. 65 patients also received aminophylline intravenously, 5.6 mg/kg body weight over 20 min, followed by a constant infusion of 0.9 mg/kg per hour. 68 patients received equivalent placebo.

Main outcome measures

FEV1, FVC, and PEFR; patient assessment of "satisfaction" with the regimen; investigator evaluation of response to therapy; time in the emergency department; and admission to the hospital from the emergency department, according to pre-established guidelines.

Main results

At baseline, except for age and smoking history, there were no demographic or clinical differences between the treatment groups. Spirometric measurements after 60 and 120 minutes of treatment showed no differences between the aminophylline and placebo groups (P > 0.2). There were no differences in side effects (P > 0.2), patient satisfaction with treatment (78% vs 77%, P > 0.2), patient improvement on therapy (88% vs 84%, P > 0.2), or time in the emergency department (median, 205 min vs 220 min, P = 0.11) between the aminophylline and placebo groups, respectively. There were fewer hospital admissions in the aminophylline group (6% vs 21%, P = 0.016). {This absolute risk reduction of 15% means that 7 patients would need to be treated with aminophylline, (compared with placebo) in order to prevent 1 additional hospital admission, 95% CI 4 to 33; the relative risk reduction was 70%, CI 19% to 89%.}* The most common reason for admission was failure to clear after 6 h (100% of aminophylline admissions and 77% of placebo-group admissions). In logistic regression, the adjusted odds ratio for the effect of aminophylline on admission rate was 0.22 (CI 0.12 to 0.42).


Adjunctive intravenous aminophylline for patients with acute bronchospastic disease may reduce hospital admissions from the emergency department.

Source of funding: Not stated.

Address for article reprint: Dr. K. Wrenn, University of Rochester Medical Center, Emergency Department, Box 655, 601 Elmwood Avenue, Rochester, NY 14642, USA.

*Numbers calculated from data in article.


In recent years, clinical investigators have re-evaluated the role of intravenous aminophylline in the emergency room treatment of asthma. The National Heart, Lung, and Blood Institute's (NHLBI) recently published National Asthma Education Program Expert Panel Report (1) stated: "When used in combination with repetitively administered β2-agonist bronchodilators, intravenous aminophylline causes increased adverse side effects without affecting additive bronchodilation."

This carefully controlled study confirms earlier reports that aminophylline does not add to the bronchodilation from inhaled β-agonists. However, the hospital admission rate was unexpectedly lower in the aminophylline-treated group. This observation is provocative and unexplained. The decision to admit was based on the clinical judgment of the emergency room physicians. We can only speculate why more patients in the placebo-treated group were admitted when their pulmonary function tests were not worse than those of the aminophylline-treated group. Further, this study was not designed to follow the outcome of patients who were discharged from the emergency room, so the fate of these patients is unknown.

The observation that intravenous aminophylline may reduce hospital admissions for patients with an acute exacerbation of asthma or COPD is worthy of debate and further investigation. The results of this study lend some reinforcement to the weakened forces of aminophylline supporters. However, the authors of this study rightly point out that these findings must be considered preliminary. Clinicians should await the results of additional studies before deciding to administer aminophylline routinely to patients with acute asthma or COPD. In the meantime, physicians should be familiar with the "Guidelines for the Diagnosis and Management of Asthma" published by the NHLBI.

James Li, MD
Mayo ClinicRochester, Minnesota, USA


1. National Heart, Lung, and Blood Institute. National Asthma Education Program Expert Panel Report. Executive Summary: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Maryland: National Institutes of Health; 1991.