Asthma: acute exacerbation: iv aminophylline improved peak flows and reduced nebuliser use in patients admitted with acute severe asthma.

Clinical bottom line (level 1b)

  1. Patients with acute severe asthma admitted to hospital who received iv aminophylline were more likely to have an increase in FEV1 > 20% after 3 hours (NNT = 2 at 3 hours) . This benefit lasted up to 48 hours.
  2. Patients given iv aminophylline also required fewer nebulisers.
  3. The effect of iv aminophylline on adverse effects was unclear.
Huang et al: Annals of Internal Medicine 1993; 119 (12): 1155-1160
Expires November 2002

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: university hospital, USA

21 patients (aged range 22 to 48 years, 52% female) admitted to hospital with an acute exacerbation of asthma who failed to respond to three doses or more of inhaled albuterol and a loading dose of steroids (FEV1 ~ 45% predicted)

Excluded if
  • <18 or >50
  • unable to perform spirometry correctly or consistently
  • intubated
  • pregnant
  • lower respiratory tract infection (lobar consolidation or new pulmonary infiltrate on chest x-ray)
  • pCO2 > 50 mmHg
  • chronic cardiopulmonary disease
  • chronic bronchitis or emphysema
  • FEV1 > 80% predicted


    • Control Group: (n = 11, 11 analysed): placebo
    Experimental Group: (n = 10, 10 analysed): aminophylline : loading dose based on serum theophylline levels measured in the emergency department: 1 mg/kg theophylline for every 2mcg/ml desired increase in serum levels to a target concentration of 15 mcg/ml. This was followed by continuous infusion starting at 0.6 mg/kg/hour adjusted so serum levels 10 to 20 mcg/ml/. Discontinued once patients became asymptomatic or after 48 hours.
    All patients had iv fluids, supplemental oxygen to keep oxygen saturation > 92%, iv methylprednisolone 125mg in the emergency department followed by 60 mg every six hours and nebulised albuterol 2.5 to 5 mg every 0.5 to 4 hours (based on FEV1 and adverse effects)
    100% followed for 48 hours

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    <20% increase in FEV1 3 hours 9
    (81.8%)    		 4
    (40.0%)    		 51%
    (-10% to 78%)    		 41.8%
    (3.85% to 79.8%)    		 2
    (1 to 26)
    tremor 48 hours 1
    (9.09%)    		 3
    (30.0%)    		 -230%
    (-2581% to 59%)    		 -20.9%
    (-54.0% to 12.2%)    		 -5
    (NNT = 8 to infinity;
    NNH = 2 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    FEV1 at 3 hours (%) 10
    (10)     		29
    (23)     		19
    (3 to 35)
    FEV1 at 48 hours (%) 58
    (15)     		75
    (19)     		17
    (1.4 to 33)
    required nebulisers at 48 hours 16.4
    (5.3)     		10.3
    (3.8)     		6.1
    (1.8 to 10)

    Comments

    1. Other studies have failed to show that aminophylline has any effect on pulmonary function tests. Most had very short follow-up (often only an hour) and had short infusions of aminophylline, so may have missed any long-term benefit.
    2. We should consider to add intravenous aminophylline for the treatment of acute severe asthma. But strict dose monitoring is essential to avoid serious adverse effect.

    Citation

    1. Huang D, O'Brien RG, Harman E, et al: Does aminophylline benefit adults admitted to the hospital for an acute exacerbation of asthma. Annals of Internal Medicine 1993; 119 (12): 1155-1160
    Search Terms: acute asthma in Cochrane
    Contributor: Chris Ball and Clare Wotton, November 2000
    Reviewer: Mitsuhiro Kamei

    Clinical Question.
    Patient acute severe asthma
    Intervention or Exposure iv aminophylline
    Comparison placebo
    Outcome peak flow