COPD: exacerbation: methylxanthines improve symptoms but causes nausea and vomiting

Clinical bottom line (level 1a-)

  1. Patients attending emergency departments with COPD exacerbations who receive methylxanthines compared with placebo feel symptomatically better (NNT = 8 at hours) , but are more likely to develop nausea and vomiting (NNH = 14 at hours) .
  2. There is no clear effect on admission to hospital or subsequent relapse.
Barr et al: Cochrane Library 2001; 1 : -
Expires October 2003

The study

Systematic review of all randomised controlled trials of
  • Patients: COPD exacerbation
  • Intervention: methylxanthines (oral or intravenous) - oral theophylline, iv aminophylline or iv doxofylline compared with placebo (with or without standard care, including beta-2 agonists, iptratropium, antibiotics, and corticosteroids)
Outcome:

Articles found in ?all languages using Cochrone Airways COPD Registry based on Medline, Embase, CINAHL, CENTRAL and hand-searching of 20 respiratory journals, (search terms: methyl-xanthine OR theophylline OR aminophylline OR doxofylline AND acute OR emerg* OR exacerbation* OR sudden ) and and contacting primary authors and content experts. Bibliographies from included stuides, known reviews and texts were searched.

Selection criteria: see above
Appraisal criteria: by 2 independent reviewers: using Cochrane approach and Jadad criteria
Articles excluded if:
  • failure to report pulmonary function or admission results
  • patients with asthma, cystic fibrosis, bronchiectasis or other lung diseases
4 studies found involving 172 patients

The evidence

Outcome Time to outcome CER OR
(95% CI)		 NNT
(95% CI)
hospital admission hours 4/16
(0.25%)		 0.30
(0.05 to 1.69) 		6
(NNT = 13 to infinity;
NNH = 2 to infinity)
return to emergency department 7 days 6/95
(6.3%)		 1.57
(0.48 to 5.11) 		-31
(NNT = 5 to infinity;
NNH = 31 to infinity)
nausea and vomiting hours 2/88
(2.3%)		 4.53
(1.49 to 13.76) 		14
(5 to 93)
symptomatic improvement reported by patient weeks 56/75
(74.7%)		 2.46
(1.04 to 5.80) 		8
(5 to 140)

  • There was no clear difference in FEV1 between patients treated with methyl-xanthines and placebo at 2 hours (-8 m/s: 95% CI: -85 to 69)

Comments

  1. The studies were too small to demonstrate any differences between the two groups for hospital admissions or subsequent relapses.

Citation

  1. Barr RG, Rowe BH, Camargo CA: methyl-xanthines for exacerbations of chronic obstructive pulmonary disease. Cochrane Library 2001; 1 : -
Search Terms: COPD in Cochrane Library
Contributor: Chris Ball, October 2001
Reviewer:

Clinical Question.
Patient COPD exacerbation
Intervention or Exposure methyl-xanthines: aminophylline, theophylline
Comparison placebo
Outcome hospital admission, relapse, symptomatic improvement