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Wiener Medizinische Wochenschrift

, Volume 168, Issue 13–14, pp 333–343 | Cite as

Symptomatic treatment of dyspnea in advanced cancer patients

A narrative review of the current literature
  • Matthäus Strieder
  • Martin Pecherstorfer
  • Gudrun Kreye
review

Summary

Background

Dyspnea is a common, very distressing symptom in advanced cancer patients that challenges them, their relatives, and healthcare professionals. This narrative review summarizes important literature dealing with the evidence for opioids, benzodiazepines, oxygen, and steroids for treating dyspnea in advanced cancer patients.

Methods

A selective literature search was undertaken in PubMed, Embase, and the Cochrane Library and extended with literature from the reference lists of included studies up to April 2016. Inclusion criteria were that patients were suffering from advanced cancer and were receiving either opioids, benzodiazepines, corticosteroids, or oxygen. The outcome of interest was the reduction of dyspnea measured via a visual analogue scale (VAS), a numerical rating scale (NRS), or a Borg scale. This narrative review describes in detail the findings of 13 studies.

Results

Nine studies deal with the effectiveness of opioids for reducing dyspnea in advanced cancer patients. Five of these found a significant benefit to the use of opioids compared to a placebo. Three found no significant improvements, and two favored combinations of opioids and benzodiazepines. Few high-quality studies were available that used benzodiazepines (n = 3, no difference, significant improvement with midazolam + morphine, significant difference for midazolam) or oxygen (n = 2, both without significant difference). Only one study examined treating dyspnea with steroids in patients with advanced cancer, and that study indicated a benefit of steroids compared to a placebo.

Conclusions

Opioids are the drug of choice for treating refractory dyspnea in advanced cancer patients. Neither benzodiazepines nor oxygen showed significant benefit. In addition, there is insufficient literature available to draw a conclusion about the effectiveness of steroids for treating persistent dyspnea in advanced cancer patients.

Keywords

Dyspnea Advanced cancer Opioids Benzodiazepines Steroids 

Abbreviations

COPD

Chronic obstructive pulmonary disease

CRF

Cancer-related fatigue

ESAS

Edmonton Symptom Assessment Scale

ESMO

European Society for Medical Oncology

NH

Nebulized hydromorphone

NRS

Numeric rating scale

NS

Nebulized saline

RCT

Randomized controlled trials

VAS

Visual analog scale

Notes

Conflict of interest

M. Strieder, M. Pecherstorfer, and G. Kreye declare that they have no competing interests.

References

  1. 1.
    Dyspnea ATSCo. Dyspnea. Mechanisms, assessment, and management: a consensus statement. Am J Respir Crit Care Med. 1999;159(1):321–40.CrossRefGoogle Scholar
  2. 2.
    Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, AWMF): Palliativmedizin für Patienten mit einer nicht heilbaren Krebserkrankung L‑, version 1.0, AWMF-Registernummer: 128/001OL.Google Scholar
  3. 3.
    Pohl G, Gaertner J. Pathophysiology and diagnosis of dyspnea in patients with advanced cancer. Wien Med Wochenschr. 2009;159(23–24):571–6.CrossRefGoogle Scholar
  4. 4.
    Parshall MB, Schwartzstein RM, Adams L, Banzett RB, Manning HL, Bourbeau J, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):435–52.CrossRefGoogle Scholar
  5. 5.
    Bausewein C, Simon ST. Shortness of breath and cough in patients in palliative care. Dtsch Arztebl Int. 2013;110(33–34):563–71. quiz 72.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Guirimand F, Sahut d’izarn M, Laporte L, Francillard M, Richard JF, Aegerter P. Sequential occurrence of dyspnea at the end of life in palliative care, according to the underlying cancer. Cancer Med. 2015;4(4):532–9.CrossRefGoogle Scholar
  7. 7.
    Weingartner V, Bausewein C, Higginson IJ, Scheve C, Murtagh FE, Voltz R, et al. Characterizing episodic breathlessness in patients with advanced disease. J Palliat Med. 2013;16(10):1275–9.CrossRefGoogle Scholar
  8. 8.
    Bulbul Y, Ozlu T, Arinc S, Ozyurek BA, Gunbatar H, Senturk A, et al. Assesment of palliative care in lung cancer in Turkey (ASPECT study). Eur Respir J. 2015;  https://doi.org/10.1183/13993003.congress-2015.PA4843.CrossRefGoogle Scholar
  9. 9.
    Currow DC, Smith J, Davidson PM, Newton PJ, Agar MR, Abernethy AP. Do the trajectories of dyspnea differ in prevalence and intensity by diagnosis at the end of life? A consecutive cohort study. J Pain Symptom Manage. 2010;39(4):680–90.CrossRefGoogle Scholar
  10. 10.
    Mercadante S, Aielli F, Adile C, Valle A, Fusco F, Ferrera P, et al. Epidemiology and characteristics of episodic breathlessness in advanced cancer patients: an observational study. J Pain Symptom Manage. 2015;51:17–24.CrossRefGoogle Scholar
  11. 11.
    Kloke M, Cherny N, Committee EG. Treatment of dyspnoea in advanced cancer patients: ESMO Clinical Practice Guidelinesdagger. Ann Oncol. 2015;26(Suppl 5):v169–v73.CrossRefGoogle Scholar
  12. 12.
    Ost DE, Ernst A, Grosu HB, Lei X, Diaz-Mendoza J, Slade M, et al. Therapeutic bronchoscopy for malignant central airway obstruction: success rates and impact on dyspnea and quality of life. Chest. 2015;147(5):1282–98.CrossRefGoogle Scholar
  13. 13.
    Steffen ST, Higginson IJ, Booth S, Harding R, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2010; 1.  https://doi.org/10.1002/14651858.CD007354.pub2.CrossRefGoogle Scholar
  14. 14.
    Simon ST, Higginson IJ, Booth S, Harding R, Weingartner V, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016;  https://doi.org/10.1002/14651858.CD007354.pub3.CrossRefPubMedGoogle Scholar
  15. 15.
    Simon ST, Koskeroglu P, Bausewein C. Pharmacological therapy of refractory dyspnoea : a systematic literature review. Schmerz. 2012;26(5):515–22.CrossRefGoogle Scholar
  16. 16.
    Hui D, Kilgore K, Frisbee-Hume S, Park M, Tsao A, Delgado Guay M, et al. Dexamethasone for dyspnea in cancer patients: a pilot double-blind, randomized, controlled trial. J Pain Symptom Manage. 2016;52(1):8–16.e1.CrossRefGoogle Scholar
  17. 17.
    Allard P, Lamontagne C, Bernard P, Tremblay C. How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. J Pain Symptom Manage. 1999;17(4):256–65.CrossRefGoogle Scholar
  18. 18.
    Jennings AL, Davies AN, Higgins JP, Gibbs JS, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea. Thorax. 2001;57(11):939–44.CrossRefGoogle Scholar
  19. 19.
    Bruera E, MacEachern T, Ripamonti C, Hanson J. Subcutaneous morphine for dyspnea in cancer patients. Ann Intern Med. 1993;119(9):906–7.CrossRefGoogle Scholar
  20. 20.
    Davis CPK, A’Hern R, et al. Single dose randomised controlled trial of nebulised morphine in patients with cancer related breathlessness. Palliat Med. 1996;10:64–5.Google Scholar
  21. 21.
    Abernethy AP, Currow DC, Frith P, Fazekas BS, McHugh A, Bui C. Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ. 2003;327(7414):523–8.CrossRefGoogle Scholar
  22. 22.
    Bruera E, Sala R, Spruyt O, Palmer JL, Zhang T, Willey J. Nebulized versus subcutaneous morphine for patients with cancer dyspnea: a preliminary study. J Pain Symptom Manage. 2005;29(6):613–8.CrossRefGoogle Scholar
  23. 23.
    Charles MA, Reymond L, Israel F. Relief of incident dyspnea in palliative cancer patients: a pilot, randomized, controlled trial comparing nebulized hydromorphone, systemic hydromorphone, and nebulized saline. J Pain Symptom Manage. 2008;36(1):29–38.CrossRefGoogle Scholar
  24. 24.
    Hui D, Xu A, Frisbee-Hume S, Chisholm G, Morgado M, Reddy S, et al. Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: a preliminary double-blind, randomized, controlled trial. J Pain Symptom Manage. 2014;47(2):209–17.CrossRefGoogle Scholar
  25. 25.
    Barnes H, McDonald J, Smallwood N, Manser R. Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst Rev. 2016;  https://doi.org/10.1002/14651858.cd011008.pub2.CrossRefPubMedGoogle Scholar
  26. 26.
    Jennings AL, Davies AN, Higgins JP, Gibbs JS, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea. Thorax. 2002;57(11):939–44.CrossRefGoogle Scholar
  27. 27.
    Harrison, TJR. A comparison of the effectiveness of oral lorazepam and placebo in relieving breathlessness associated with advanced cancer [dissertation]. Bristol: Bristol University, 2004.Google Scholar
  28. 28.
    Navigante AH, Cerchietti LC, Castro MA, Lutteral MA, Cabalar ME. Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. J Pain Symptom Manage. 2006;31(1):38–47.CrossRefGoogle Scholar
  29. 29.
    Navigante. Morphine versus midazolam as upfront therapy to relief dyspnea in ambulatory cancer patients while its underlying cause is sought or treated. (unpublished).Google Scholar
  30. 30.
    Navigante AH, Castro MA, Cerchietti LC. Morphine versus midazolam as upfront therapy to control dyspnea perception in cancer patients while its underlying cause is sought or treated. J Pain Symptom Manage. 2010;39(5):820–30.CrossRefGoogle Scholar
  31. 31.
    Uronis HE, Currow DC, McCrory DC, Samsa GP, Abernethy AP. Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis. Br J Cancer. 2008;98(2):294–9.CrossRefGoogle Scholar
  32. 32.
    Ahmedzai SH, Laude E, Robertson A, Troy G, Vora V. A double-blind, randomised, controlled phase II trial of Heliox28 gas mixture in lung cancer patients with dyspnoea on exertion. Br J Cancer. 2004;90(2):366–71.CrossRefGoogle Scholar
  33. 33.
    Booth S, Kelly MJ, Cox NP, Adams L, Guz A. Does oxygen help dyspnea in patients with cancer? Am J Respir Crit Care Med. 1996;153(5):1515–8.CrossRefGoogle Scholar
  34. 34.
    Bruera E, de Stoutz N, Velasco-Leiva A, Schoeller T, Hanson J. Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients. Lancet. 1993;342(8862):13–4.CrossRefGoogle Scholar
  35. 35.
    Bruera E, Sweeney C, Willey J, Palmer JL, Strasser F, Morice RC, et al. A randomized controlled trial of supplemental oxygen versus air in cancer patients with dyspnea. Palliat Med. 2003;17(8):659–63.PubMedGoogle Scholar
  36. 36.
    Philip J, Gold M, Milner A, Di Iulio J, Miller B, Spruyt O. A randomized, double-blind, crossover trial of the effect of oxygen on dyspnea in patients with advanced cancer. J Pain Symptom Manage. 2006;32(6):541–50.CrossRefGoogle Scholar
  37. 37.
    Abernethy AP, McDonald CF, Frith PA, Clark K, Herndon JE 2nd, Marcello J, et al. Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet. 2010;376(9743):784–93.CrossRefGoogle Scholar
  38. 38.
    Yennurajalingam S, Frisbee-Hume S, Palmer JL, Delgado-Guay MO, Bull J, Phan AT, et al. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol. 2013;31(25):3076–82.CrossRefGoogle Scholar
  39. 39.
    Blinderman CDB, Billings JA. Comfort care for patients dying in the hospital. N Engl J Med. 2016;374(17):1692–3.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Matthäus Strieder
    • 1
  • Martin Pecherstorfer
    • 1
  • Gudrun Kreye
    • 1
  1. 1.Department of Internal Medicine 2, Division for Palliative CareUniversity Hospital KremsKremsAustria

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