Asthma: acute exacerbation: more patients improved on epinephrine than metaproterenol.

Clinical bottom line (level 1b)

  1. More patients with severe asthma who received subcutaneous epinephrine compared with inhaled metaproterenol improved after one hour (NNT = 4 at 60 minutes) .
  2. Side-effects were more common in patients given epinephrine (NNH = 6 at 60 minutes) .
  3. More patients who did not respond to initial therapy improved on swapping from metaproterenol to epinephrine than swapping from epinephrine to metaproterenol (NNT = 2 at 60 minutes) .
Appel et al: Journal of Allergy and Clinical Immunology 1989; 84 (1): 90-98
Expires November 2002

The study

Double-blinded concealed randomised trial without intention-to-treat
Setting: emergency department, acute hospital, USA

100 patients (aged ?, 55% female) with severe asthma (PEFR < 150 l/min)

Excluded if
  • history of cigarette smoking, chronic bronchitis, emphysema, significant hypertension, ischaemic heart disease
  • ECG evidence of MI
  • clinical evidence of respiratory failure
  • pregnant


    • Control Group: (n = 46, 46 analysed): 15 mg inhaled metaproterenol and saline injection
    Experimental Group: (n = 54, 54 analysed): inhaled saline and epinephrine 0.3 ml 1:1000 subcutaneous at 0, 30, 60 minutes
    Patients who failed to respond, were then crossed over to the alternative regimen. No patients received iv medication or supplemental oxygen. 30% were on oral steroids.
    100% followed for 60 minutes
    Outcome notes:
    • no improvement : PEFR increase 20% or less, or <120 l/minute
    • side effects : palpitations, tremor, tachycardia, arrhythmia, nervousness

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    no improvement 60 minutes 18
    (39.1%)    		 6
    (11.1%)    		 72%
    (34% to 88%)    		 28.0%
    (11.6% to 44.4%)    		 4
    (2 to 9)
    side effects weeks 33
    (71.7%)    		 48
    (88.9%)    		 -24%
    (-52% to 1%)    		 -17.2%
    (-32.6% to -1.67%)    		 -6
    (-60 to -3)

    Outcome in patients who failed initial treatment
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    no improvement 60 minutes 5
    (27.8%)    		 5
    (83.3%)    		 -200%
    (-586% to -31%)    		 -55.6%
    (-91.9% to -19.3%)    		 -2
    (-5 to -1)

  • Patients who responded generally did so after one or two doses of medication.
  • There was no significant difference in the increase in PEFR for either medication.

    • Comments

    1. Not all patients received iv steroids - this is not like common practice, but steroids are unlikely to have much effect in the first hour.
    2. This study suggests epinephrine should be used as first-line treatment in patients with severe asthma, and should be used as an early option in patients that fail to respond to beta-agonists. But we have many treatment modalities such as short acting beta2-stimulant ( intermittent or continuous use ), intravenous short acting beta2-stimulant, anticholinergic agents and epinephrine available . We need more studies to determine the first line treatment .

    Citation

    1. Appel D, Karpel JP, Sherman M: epinephrine improves expiratory flow rates in patients with asthma who do not respond to inhaled metaproterenol sulfate. Journal of Allergy and Clinical Immunology 1989; 84 (1): 90-98
    Search Terms: acute asthma in Cochrane
    Contributor: Chris Ball and Clare Wotton, November 2000
    Reviewer: Mitsuhiro Kamei

    Clinical Question.
    Patient severe acute asthma
    Intervention or Exposure subcutaneous epinephrine
    Comparison inhaled metaproterenol
    Outcome improvement