Epinephrine improves expiratory flow rates in patients with asthma who do not respond to inhaled metaproterenol sulfate

One hundred patients with acute asthma and peak expiratory flow rates (PEFR) <150 L/min were randomized and treated in a double-blind treatment protocol with either metaproterenol sulfate aerosol (MPA) inhalation and placebo injection or epinephrine injection (EPI) and inhaled placebo at entry and at 30 and 60 minutes, and then were treated with the crossover comparison regimen at 120, 150, and 180 minutes. The two groups had similar entry PEFRs and FEV₁ (MPA, 112 L/min; 0.94 L, respectively; EPI, 111 L/min; 0.85 L, respectively) and similar plasma theophylline levels (MPA, 12.2 μg/ml; EPI, 13.8 μg/ml). PEFR and FEV₁ were measured every 30 minutes for 4 hours. Mean expiratory flow rates among both groups were similar at entry and at 120 and 240 minutes. At 120 minutes, flow rates had improved in 28 46 MPA-treated patients (61%) and 48 54 EPI-treated patients (89%). Among these improved patients, flow rates were significantly higher in the MPA-treated group. At 120 minutes, 18 46 MPA-treated patients (39%) and 6 54 EPI-treated patients (11%) had PEFRs <120 L/min and PEFR and FEV₁ <120% of baseline values (p < 0.01). In 13 of these 18 MPA-treated patients who did not improve compared to 1 6 EPI-treated patients who did not improve, PEFRs were >120 L/min, and PEFR and FEV₁ had increased 20% or more above baseline values after treatment with the crossover comparison regimen (p < 0.02). Patients who improved with MPA versus patients who did not improve with MPA had similar entry PEFRs, FEV₁, and plasma theophylline levels, but differed in the duration of their acute illnesses before the study (4 ± 0.5 days, versus 9 ± 1 day; p < 0.013). Among improved patients, expiratory flow rates improved after one or two treatments with either MPA or EPI, and patients who did not improve generally required hospitalization. Adverse side effects occurred frequently during treatment with either agent, but the side effects were never serious. EPI responsiveness among patients not responding to MPA suggests that incomplete penetration of MPA because of mucous plugs and airway edema (rather than β-adrenergic-receptor tolerance) accounted for the lack of response to MPA. MPA nonresponsiveness may be anticipated among those patients with longer acute illness. We recommend that patients with acute asthma who do not improve after MPA be treated with EPI. Patients who do not improve with this treatment can be identified rapidly. They will need other treatment and, quite likely, hospitalization.