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. 2005 Jun 6;60(9):713–717. doi: 10.1136/thx.2004.036046

Intravenous aminophylline in patients admitted to hospital with non-acidotic exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial

N Duffy 1, P Walker 1, F Diamantea 1, P Calverley 1, L Davies 1
PMCID: PMC1747521  PMID: 15939732

Abstract

Background: Intravenous aminophylline is commonly used in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD), despite limited evidence for its efficacy and known risks of toxicity. We hypothesised that adding intravenous aminophylline to conventional treatment would not produce clinically important changes in the speed of spirometric or symptomatic recovery or shorten hospital stay in patients with exacerbations of COPD.

Methods: Eighty patients admitted to hospital with non-acidotic exacerbations of COPD were recruited at admission to a randomised, double blind, placebo controlled study comparing intravenous aminophylline 0.5 mg/kg/hour after an appropriate loading dose with an equivalent volume of 0.9% saline. The primary outcome was the change in post-bronchodilator forced expiratory volume in 1 second (FEV1) over the first 5 days of the admission. Secondary end points were changes in self-reported breathlessness, arterial blood gas tensions, forced vital capacity (FVC), and length of hospital stay.

Results: There was no difference in the post-bronchodilator FEV1 over the first 5 days between the aminophylline and placebo groups. In the aminophylline group, 2 hours of treatment produced a small but significant rise in arterial pH (p = 0.001) and a fall in arterial carbon dioxide tension (p = 0.01) compared with placebo treatment. There were no differences in the severity of breathlessness, post-bronchodilator FVC, or length of hospital stay between the groups. Nausea was a more frequent side effect in the aminophylline group (46% v 22%; p<0.05), but palpitations and headache were noted equally in both groups.

Conclusions: Although intravenous aminophylline produced small improvements in acid-base balance, these did not influence the subsequent clinical course. No evidence was found for any clinically important additional effect of aminophylline treatment when used with high dose nebulised bronchodilators and oral corticosteroids. Given its known toxicity, we cannot therefore recommend the use of intravenous aminophylline in the treatment of non-acidotic COPD exacerbations.

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Selected References

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  1. Barr R. Graham, Rowe Brian H., Camargo Carlos A., Jr Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials. BMJ. 2003 Sep 20;327(7416):643–643. doi: 10.1136/bmj.327.7416.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Calverley P. M. A., Walker Paul. Chronic obstructive pulmonary disease. Lancet. 2003 Sep 27;362(9389):1053–1061. doi: 10.1016/s0140-6736(03)14416-9. [DOI] [PubMed] [Google Scholar]
  3. Chrystyn H., Mulley B. A., Peake M. D. Dose response relation to oral theophylline in severe chronic obstructive airways disease. BMJ. 1988 Dec 10;297(6662):1506–1510. doi: 10.1136/bmj.297.6662.1506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davies L., Angus R. M., Calverley P. M. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet. 1999 Aug 7;354(9177):456–460. doi: 10.1016/s0140-6736(98)11326-0. [DOI] [PubMed] [Google Scholar]
  5. Georgopoulos D., Holtby S. G., Berezanski D., Anthonisen N. R. Aminophylline effects on ventilatory response to hypoxia and hyperoxia in normal adults. J Appl Physiol (1985) 1989 Sep;67(3):1150–1156. doi: 10.1152/jappl.1989.67.3.1150. [DOI] [PubMed] [Google Scholar]
  6. Jones P. W., Quirk F. H., Baveystock C. M., Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321–1327. doi: 10.1164/ajrccm/145.6.1321. [DOI] [PubMed] [Google Scholar]
  7. Lightowler Josephine V., Wedzicha Jadwiga A., Elliott Mark W., Ram Felix S. F. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ. 2003 Jan 25;326(7382):185–185. doi: 10.1136/bmj.326.7382.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Niewoehner D. E., Erbland M. L., Deupree R. H., Collins D., Gross N. J., Light R. W., Anderson P., Morgan N. A. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999 Jun 24;340(25):1941–1947. doi: 10.1056/NEJM199906243402502. [DOI] [PubMed] [Google Scholar]
  9. Nishimura M., Suzuki A., Yoshioka A., Yamamoto M., Akiyama Y., Miyamoto K., Kishi F., Kawakami Y. Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease. Thorax. 1992 Dec;47(12):1025–1029. doi: 10.1136/thx.47.12.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pauwels R. A., Buist A. S., Calverley P. M., Jenkins C. R., Hurd S. S., GOLD Scientific Committee Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001 Apr;163(5):1256–1276. doi: 10.1164/ajrccm.163.5.2101039. [DOI] [PubMed] [Google Scholar]
  11. Rice K. L., Leatherman J. W., Duane P. G., Snyder L. S., Harmon K. R., Abel J., Niewoehner D. E. Aminophylline for acute exacerbations of chronic obstructive pulmonary disease. A controlled trial. Ann Intern Med. 1987 Sep;107(3):305–309. doi: 10.7326/0003-4819-107-2-305. [DOI] [PubMed] [Google Scholar]
  12. Seidenfeld J. J., Jones W. N., Moss R. E., Tremper J. Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease. Ann Emerg Med. 1984 Apr;13(4):248–252. doi: 10.1016/s0196-0644(84)80472-2. [DOI] [PubMed] [Google Scholar]
  13. Wrenn K., Slovis C. M., Murphy F., Greenberg R. S. Aminophylline therapy for acute bronchospastic disease in the emergency room. Ann Intern Med. 1991 Aug 15;115(4):241–247. doi: 10.7326/0003-4819-115-4-241. [DOI] [PubMed] [Google Scholar]
  14. ZuWallack R. L., Mahler D. A., Reilly D., Church N., Emmett A., Rickard K., Knobil K. Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest. 2001 Jun;119(6):1661–1670. doi: 10.1378/chest.119.6.1661. [DOI] [PubMed] [Google Scholar]

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