COPD: exacerbations: no clear role of aminophylline

Clinical bottom line (level 1b-)

  1. Patients with exacerbations of COPD who received aminophylline compared with placebo had no clear improvement in measures of respiratory function, but were more likely to have side-effects (NNH = 3 at 4 days) .
Rice et al: Annals of Internal Medicine 1987; 107: 305-309
Expires November 2003

The study

Double-blinded ?concealed randomised trial without intention-to-treat
Setting: Veterans' Affairs Medical Center, USA

30 patients (aged mean 65, 96% male) with an exacerbation of chronic obstructive pulmonary disease (previously confirmed on spirometry as FEV1 < 2 SD below predicted value and FEV1/FVC < 60%). Exacerbations were defined as worsening dyspnoea usually with increased cough and sputum severe enough to require hospital admission.

Excluded if
  • acute left ventricular failure or pneumonia
  • required immediate mechanical ventilation
  • clinical diagnosis of asthma
  • readily reversible episodes of wheezing and dyspnoea separated by asymptomatic episodes
  • bronchodilator response of >30% on previous spirometry


    • Control Group: (n = 15, 13 analysed): placebo
    Experimental Group: (n = 15, 15 analysed): aminophylline loading dose of 6 mg/kg (3 mg/kg if on theophylline) followed by 0.5 mg/kg infusion adjusted according to theophylline levels
    All patients received metaproterenol every 4 hours, methylprednisolone 0.5 mg/kg every 6 hours, ampicillin 500 mg every 6 hours or trimethoprim-sulphamethoxazole 160/800 mg every 12 hours, and supplemental oxygen
    93% followed for 4 days
    Outcome notes:
    • adverse effects : nausea vomiting

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNH
    (95% CI)
    adverse effects 4 days 1
    (7.69%)    		 7
    (46.7%)    		 -510%
    (-4200% to 14%)    		 -39.0%
    (-68.1% to -9.87%)
    (1 to 10)

  • No significant differences for PEFR, oxygen or carbon dioxide concentrations were noted between the two groups.

    • Comments

    1. The study is too small to show any difference between the two groups. This combined with the short follow-up and lack of clinical outcomes makes these results much less certain.
    2. The study differs from current practice - aminophylline is usually given to patients who fail to respond to initial therapy.

    Citation

    1. Rice KL, Leatherman JW, Duane PG, et al: aminophylline for acute exacerbations of chronic obstructive pulmonary disease: a controlled trial. Annals of Internal Medicine 1987; 107: 305-309
    Search Terms: ?
    Contributor: Bob Phillips & Chris Ball, November 1999
    Reviewer: Mitsuhiro Kamei

    Clinical Question.
    Patient COPD exacerbation
    Intervention or Exposure aminophylline
    Comparison placebo
    Outcome improvement in respiratory function