Skip to main content
PMC home page
Thorax logoLink to Thorax
. 2002 Nov;57(11):939–944. doi: 10.1136/thorax.57.11.939

A systematic review of the use of opioids in the management of dyspnoea

A Jennings 1, A Davies 1, J Higgins 1, J Gibbs 1, K Broadley 1
PMCID: PMC1746225  PMID: 12403875

Abstract

Background: Opioids are commonly used to treat dyspnoea in palliative medicine but there has been no formal evaluation of the evidence for their effectiveness in the treatment of dyspnoea. A systematic review was therefore carried out to examine this.

Methods: The criteria for inclusion required that studies were double blind, randomised, placebo controlled trials of opioids for the treatment of dyspnoea secondary to any cause. The methods used to identify suitable studies included electronic searching of the literature, hand searching of the literature, and personal contact with relevant individuals and organisations. Random effects meta-analyses were performed on all included studies and on various subgroups (studies involving nebulised opioids or patients with chronic obstructive pulmonary disease (COPD)). Subgroups were compared using meta-regression. Some studies included in the systematic review could not be included in the meta-analysis because insufficient data were presented.

Results: Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness (p=0.0008). Meta-regression indicated a greater effect for studies using oral or parenteral opioids than for studies using nebulised opioids (p=0.02). The subgroup analysis failed to show a positive effect of nebulised opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were essentially similar to the results of the main analysis.

Conclusion: This review supports the continued use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. There are insufficient data from the meta-analysis to conclude whether nebulised opioids are effective, but the results from included studies that did not contribute to the meta-analysis suggest that they are no better than nebulised normal saline.

Full Text

The Full Text of this article is available as a PDF (166.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Addington-Hall J., McCarthy M. Dying from cancer: results of a national population-based investigation. Palliat Med. 1995 Oct;9(4):295–305. doi: 10.1177/026921639500900404. [DOI] [PubMed] [Google Scholar]
  2. Bar-Or D., Marx J. A., Good J. Breathlessness, alcohol, and opiates. N Engl J Med. 1982 Jun 3;306(22):1363–1364. doi: 10.1056/NEJM198206033062214. [DOI] [PubMed] [Google Scholar]
  3. Beauford W., Saylor T. T., Stansbury D. W., Avalos K., Light R. W. Effects of nebulized morphine sulfate on the exercise tolerance of the ventilatory limited COPD patient. Chest. 1993 Jul;104(1):175–178. doi: 10.1378/chest.104.1.175. [DOI] [PubMed] [Google Scholar]
  4. Berkey C. S., Hoaglin D. C., Mosteller F., Colditz G. A. A random-effects regression model for meta-analysis. Stat Med. 1995 Feb 28;14(4):395–411. doi: 10.1002/sim.4780140406. [DOI] [PubMed] [Google Scholar]
  5. Bredin M., Corner J., Krishnasamy M., Plant H., Bailey C., A'Hern R. Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer. BMJ. 1999 Apr 3;318(7188):901–904. doi: 10.1136/bmj.318.7188.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bruera E., MacEachern T., Ripamonti C., Hanson J. Subcutaneous morphine for dyspnea in cancer patients. Ann Intern Med. 1993 Nov 1;119(9):906–907. doi: 10.7326/0003-4819-119-9-199311010-00007. [DOI] [PubMed] [Google Scholar]
  7. Chua T. P., Harrington D., Ponikowski P., Webb-Peploe K., Poole-Wilson P. A., Coats A. J. Effects of dihydrocodeine on chemosensitivity and exercise tolerance in patients with chronic heart failure. J Am Coll Cardiol. 1997 Jan;29(1):147–152. doi: 10.1016/s0735-1097(96)00446-9. [DOI] [PubMed] [Google Scholar]
  8. Eiser N., Denman W. T., West C., Luce P. Oral diamorphine: lack of effect on dyspnoea and exercise tolerance in the "pink puffer" syndrome. Eur Respir J. 1991 Sep;4(8):926–931. [PubMed] [Google Scholar]
  9. Harris-Eze A. O., Sridhar G., Clemens R. E., Zintel T. A., Gallagher C. G., Marciniuk D. D. Low-dose nebulized morphine does not improve exercise in interstitial lung disease. Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):1940–1945. doi: 10.1164/ajrccm.152.6.8520759. [DOI] [PubMed] [Google Scholar]
  10. Jadad A. R., Moore R. A., Carroll D., Jenkinson C., Reynolds D. J., Gavaghan D. J., McQuay H. J. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1–12. doi: 10.1016/0197-2456(95)00134-4. [DOI] [PubMed] [Google Scholar]
  11. Jankelson D., Hosseini K., Mather L. E., Seale J. P., Young I. H. Lack of effect of high doses of inhaled morphine on exercise endurance in chronic obstructive pulmonary disease. Eur Respir J. 1997 Oct;10(10):2270–2274. doi: 10.1183/09031936.97.10102270. [DOI] [PubMed] [Google Scholar]
  12. Johnson M. A., Woodcock A. A., Geddes D. M. Dihydrocodeine for breathlessness in "pink puffers". Br Med J (Clin Res Ed) 1983 Feb 26;286(6366):675–677. doi: 10.1136/bmj.286.6366.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Leung R., Hill P., Burdon J. Effect of inhaled morphine on the development of breathlessness during exercise in patients with chronic lung disease. Thorax. 1996 Jun;51(6):596–600. doi: 10.1136/thx.51.6.596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Light R. W., Stansbury D. W., Webster J. S. Effect of 30 mg of morphine alone or with promethazine or prochlorperazine on the exercise capacity of patients with COPD. Chest. 1996 Apr;109(4):975–981. doi: 10.1378/chest.109.4.975. [DOI] [PubMed] [Google Scholar]
  15. Masood A. R., Reed J. W., Thomas S. H. Lack of effect of inhaled morphine on exercise-induced breathlessness in chronic obstructive pulmonary disease. Thorax. 1995 Jun;50(6):629–634. doi: 10.1136/thx.50.6.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McCarthy M., Lay M., Addington-Hall J. Dying from heart disease. J R Coll Physicians Lond. 1996 Jul-Aug;30(4):325–328. [PMC free article] [PubMed] [Google Scholar]
  17. Noseda A., Carpiaux J. P., Markstein C., Meyvaert A., de Maertelaer V. Disabling dyspnoea in patients with advanced disease: lack of effect of nebulized morphine. Eur Respir J. 1997 May;10(5):1079–1083. doi: 10.1183/09031936.97.10051079. [DOI] [PubMed] [Google Scholar]
  18. Poole P. J., Veale A. G., Black P. N. The effect of sustained-release morphine on breathlessness and quality of life in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1877–1880. doi: 10.1164/ajrccm.157.6.9711061. [DOI] [PubMed] [Google Scholar]
  19. Santiago T. V., Johnson J., Riley D. J., Edelman N. H. Effects of morphine on ventilatory response to exercise. J Appl Physiol Respir Environ Exerc Physiol. 1979 Jul;47(1):112–118. doi: 10.1152/jappl.1979.47.1.112. [DOI] [PubMed] [Google Scholar]
  20. Schwartzstein R. M., Lahive K., Pope A., Weinberger S. E., Weiss J. W. Cold facial stimulation reduces breathlessness induced in normal subjects. Am Rev Respir Dis. 1987 Jul;136(1):58–61. doi: 10.1164/ajrccm/136.1.58. [DOI] [PubMed] [Google Scholar]
  21. Sutton P. P., Gemmell H. G., Innes N., Davidson J., Smith F. W., Legge J. S., Friend J. A. Use of nebulised saline and nebulised terbutaline as an adjunct to chest physiotherapy. Thorax. 1988 Jan;43(1):57–60. doi: 10.1136/thx.43.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Woodcock A. A., Gross E. R., Gellert A., Shah S., Johnson M., Geddes D. M. Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases. N Engl J Med. 1981 Dec 31;305(27):1611–1616. doi: 10.1056/NEJM198112313052703. [DOI] [PubMed] [Google Scholar]
  23. Young I. H., Daviskas E., Keena V. A. Effect of low dose nebulised morphine on exercise endurance in patients with chronic lung disease. Thorax. 1989 May;44(5):387–390. doi: 10.1136/thx.44.5.387. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES