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Fentanyl treatment for end-of-life dyspnoea relief in advanced cancer patients

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Abstract

Purpose

We assessed the effects of subcutaneous-endovenous fentanyl on dyspnoea in a cohort of advanced cancer patients.

Methods

We performed a retrospective study in a cohort of advanced cancer patients with dyspnoea at rest who received subcutaneous or intravenous fentanyl. Patients with no shortness of breath at rest or at minimal exertion, no rescue doses per 24 h, were deemed to be responders to fentanyl. The period of assessment was 6 days from the beginning of fentanyl treatment.

Results

Seventy-two patients were evaluated: 65% males, 50% ≥ 75 years, Palliative Performance Scale (PPS) median of 30%. Seventy-six percent of the patients were responders to fentanyl. Fentanyl efficacy was not statistically related to age, gender, cancer type, previous opioid treatment, steroid and midazolam doses and PPS. The median fentanyl dose in responders was 25 mcg/h (interquartile range 12–70). It was significantly related to age (37 vs 12 mcg/h, for ≤ 75 vs > 75 years, respectively; p = 0.02). There was not a significant difference between fentanyl doses of responders and non-responder patients. Thirty-six, 23 and 15 patients had sustained improvements in dyspnoea over 48, 72 and 96 h. Fentanyl had no significant toxicity. The length of inclusion in the study and exclusion were related to low performance status (hazard ratio 0.961; 95%CI 0.927–0.996; Cox-regression) but not to fentanyl doses (hazard ratio 0.875; 95%CI 0.620–1.234; Cox-regression).

Conclusion

Our preliminary data suggest that subcutaneous-endovenous fentanyl may be associated with dyspnoea relief in dying patients. Further research is needed to confirm these findings.

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References

  1. Currow DC, J S, Davidson PM, PJ N, Agar MR, Abernethy AP (2010) Do the trajectories of dyspnea differ in prevalence and intensity by diagnosis at the end of life? A consecutive cohort study. J Pain Symptom Manag 39:680–690

    Article  Google Scholar 

  2. Kehl KA, Kowalkowski JA (2013) A systematic review of the prevalence of signs of impending death and symptoms in the last 2 weeks of life. Am J Hosp Palliat Care 30:601–616

    Article  PubMed  Google Scholar 

  3. Hui D, dos Santos R, Chisholm GB, Bruera E (2015) Symptom expression in the last seven days of life among cancer patients admitted to acute palliative care units. J Pain Symptom Manag 50:488–494

    Article  Google Scholar 

  4. Johnson MJ, Currow DC (2015) Chronic refractory breathlessness is a distinct clinical syndrome. Curr Opin Support Palliat Care 9:203–205

    Article  PubMed  Google Scholar 

  5. Currow DC, Higginson IJ, Johnson MJ (2013) Breathlessness—current and emerging mechanisms, measurement and management: a discussion from an European Association of Palliative Care workshop. Palliat Med 27:932–938

    Article  PubMed  Google Scholar 

  6. Currow DC, Abernethy AP, Allcroft P, Banzett RB, Bausewein C, Booth S, Carrieri-Kohlman V, Davidson P, Disler R, Donesky D, Dudgeon D, Ekstrom M, Farquhar M, Higginson I, Janssen D, Jensen D, Jolley C, Krajnik M, Laveneziana P, McDonald C, Maddocks M, Morelot-Panzini C, Moxham J, Mularski RA, Noble S, O'Donnell D, Parshall MB, Pattinson K, Phillips J, Ross J, Schwartzstein RM, Similowski T, Simon ST, Smith T, Wells A, Yates P, Yorke J, Johnson MJ (2016) The need to research refractory breathlessness. Eur Respir J 47:342–343

    Article  PubMed  Google Scholar 

  7. Smallwood N, Le B, Currow D, Irving L, Philip J (2015) Management of refractory breathlessness with morphine in patients with chronic obstructive pulmonary disease. Intern Med J 45:898–904

    Article  CAS  PubMed  Google Scholar 

  8. Barnes H, McDonald J, Smallwood N, Manser R (2016) Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst Rev 3:Cd011008

    PubMed  Google Scholar 

  9. Ekström M, Bajwah S, Bland JM, Currow DC, Hussain J, Johnson MJ (2017) One evidence base; three stories: do opioids relieve chronic breathlessness? Thorax 73:88–90. https://doi.org/10.1136/thoraxjnl-2016-209868

    Article  PubMed  Google Scholar 

  10. Johnson MJ, Abernethy AP, Currow DC (2012) Gaps in the evidence base of opioids for refractory breathlessness. A future work plan? J Pain Symptom Manag 43:614–624

    Article  CAS  Google Scholar 

  11. Simon ST, Köskeroglu P, Gaertner J, Voltz R (2013) Fentanyl for the relief of refractory breathlessness: a systematic review. J Pain Symptom Manag 46:874–886

    Article  Google Scholar 

  12. Jansen K, Haugen DF, Pont L, Ruths S (2017) Safety and effectiveness of palliative drug treatment in the last days of life—a systematic literature review. J Pain Symptom Manag 55:508–521

    Article  Google Scholar 

  13. Schug SA, Ting S (2017) Fentanyl formulations in the management of pain: an update. Drugs 77:747–763

    Article  PubMed  Google Scholar 

  14. Benitez-Rosario MA, Martin AS, Feria M (2005) Oral transmucosal fentanyl citrate in the management of dyspnea crises in cancer patients. J Pain Symptom Manag 30:395–397

    Article  Google Scholar 

  15. Sitte T, Bausewein C (2008) Intranasal fentanyl for episodic breathlessness. J Pain Symptom Manag 36(6):e3–e6

    Article  Google Scholar 

  16. Gauna AA, Kang SK, Triano ML, Swatko ER, Vanston VJ (2008) Oral transmucosal fentanyl citrate for dyspnea in terminally ill patients: an observational case series. J Palliat Med 11:643–648

    Article  PubMed  Google Scholar 

  17. Kornick CA, Santiago-Palma J, Schulman G, O'Brien PC, Weigand S, Payne R, Manfredi PL (2003) A safe and effective method for converting patients from transdermal to intravenous fentanyl for the treatment of acute cancer-related pain. Cancer 97:3121–3214

    Article  PubMed  Google Scholar 

  18. Pereira J, Lawlor P, Vigano A, Dorgan M, Bruera E (2001) Equianalgesic dose ratios for opioids. A critical review and proposals for long-term dosing. J Pain Symptom Manag 22:672–678

    Article  CAS  Google Scholar 

  19. Ekström M, Currow DC, Johnson MJ (2015) Outcome measurement of refractory breathlessness: endpoints and important differences. Curr Opin Support Palliat Care 9:238–243

    Article  PubMed  Google Scholar 

  20. Navigante AH, Cerchietti LC, Castro MA, Lutteral MA, Cabalar ME (2006) Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. J Pain Symptom Manag 31:38–47

    Article  CAS  Google Scholar 

  21. Mercadante S, Portenoy RK (2016) Breakthrough cancer pain: twenty-five years of study. Pain 157:2657–2663

    Article  CAS  PubMed  Google Scholar 

  22. Takeyasu M, Miyamoto A, Kato D, Takahashi Y, Ogawa K, Murase K, Mochizuki S, Hanada S, Uruga H, Takaya H, Morokawa N, Kishi K (2016) Continuous intravenous morphine infusion for severe dyspnea in terminally ill interstitial pneumonia patients. Intern Med 55:725–729

    Article  CAS  PubMed  Google Scholar 

  23. Pang GS, Qu LM, Tan YY, Yee AC (2016) Intravenous fentanyl for dyspnea at the end of life: lessons for future research in dyspnea. Am J Hosp Palliat Care 33:222–227

    Article  CAS  PubMed  Google Scholar 

  24. Hui D, Xu A, Frisbee-Hume S, Chisholm G, Morgado M, Reddy S, Bruera E (2014) Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: a preliminary double-blind, randomized, controlled trial. J Pain Symptom Manag 47:209–217

    Article  Google Scholar 

  25. Hui D, Kilgore K, Park M, Williams J, Liu D, Bruera E (2016) Impact of prophylactic fentanyl pectin nasal spray on exercise-induced episodic dyspnea in cancer patients: a double-blind, randomized controlled trial. J Pain Symptom Manag 52:459–468

    Article  Google Scholar 

  26. Hui D, Kilgore K, Frisbee-Hume S, Park M, Liu D, Balachandran DD, Bruera E (2017) Effect of prophylactic fentanyl buccal tablet on episodic exertional dyspnea: a pilot double-blind randomized controlled trial. J Pain Symptom Manag 54:798–805

    Article  Google Scholar 

  27. Simon ST, Kloke M, Alt-Epping B, Gärtner J, Hellmich M, Hein R, Piel M, Cornely OA, Nauck F, Voltz R (2016) EffenDys-fentanyl buccal tablet for the relief of episodic breathlessness in patients with advanced cancer: a multicenter, open-label, randomized, morphine-controlled, crossover, phase II trial. J Pain Symptom Manag 52:617–625

    Article  Google Scholar 

  28. Maeda T, Hayakawa T (2016) Combined effect of opioids and corticosteroids for alleviating dyspnea in terminal cancer patients: a retrospective review. J Pain Palliat Care Pharmacother 30:106–110

    Article  PubMed  Google Scholar 

  29. Hui D, Kilgore K, Frisbee-Hume S, Park M, Tsao A, Delgado Guay M, Lu C, William W Jr, Pisters K, Eapen G, Fossella F, Amin S, Bruera E (2016) Dexamethasone for dyspnea in cancer patients: a pilot double-blind, randomized, controlled trial. J Pain Symptom Manag 52:8–16

    Article  Google Scholar 

  30. Mori M, Shirado AN, Morita T, Okamoto K, Matsuda Y, Matsumoto Y, Yamada H, Sakurai H, Aruga E, Kaneishi K, Watanabe H, Yamaguchi T, Odagiri T, Hiramoto S, Kohara H, Matsuo N, Katayama H, Nishi T, Matsui T, Iwase S (2017) Predictors of response to corticosteroids for dyspnea in advanced cancer patients: a preliminary multicenter prospective observational study. Support Care Cancer 25:1169–1181

    Article  PubMed  Google Scholar 

  31. Hardy J, Randall C, Pinkerton E, Flatley C, Gibbons K, Allan S (2016) A randomised, double-blind controlled trial of intranasal midazolam for the palliation of dyspnoea in patients with life-limiting disease. Support Care Cancer 24:3069–3076

    PubMed  Google Scholar 

  32. Simon ST, Higginson IJ, Booth S, Harding R, Weingärtner V, Bausewein C (2016) Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev 10:CD007354

    PubMed  Google Scholar 

  33. Allard P, Lamontagne C, Bernard P, Tremblay C (1999) How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. J Pain Symptom Manag 17:256–265

    Article  CAS  Google Scholar 

  34. Johnson MJ, Bland JM, Oxberry SG, Abernethy AP, Currow DC (2013) Opioids for chronic refractory breathlessness: patient predictors of beneficial response. Eur Respir J 42:758–766

    Article  PubMed  Google Scholar 

  35. Hui D, Glitza I, Chisholm G, Yennu S, Bruera E (2013) Attrition rates, reasons, and predictive factors in supportive care and palliative oncology clinical trials. Cancer 119:1098–1105

    Article  PubMed  Google Scholar 

  36. Currow DC, Rowett D, Doogue M, To TH, Abernethy AP (2012) An international initiative to create a collaborative for pharmacovigilance in hospice and palliative care clinical practice. J Palliat Med 15:282–286

    Article  PubMed  Google Scholar 

  37. Sanderson C, Quinn SJ, Agar M, Chye R, Clark K, Doogue M, Fazekas B, Lee J, Lovell MR, Rowett D, Spruyt O, Currow DC (2016) Pharmacovigilance in hospice/palliative care: net effect of pregabalin for neuropathic pain. BMJ Support Palliat Care 6:323–330

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Palliative Care Unit, Hospital Universitario NS La Candelaria, Crta del Rosario 145, 38010, Tenerife, SC, Spain

    Miguel Angel Benítez-Rosario & Inmaculada Rosa-González

  2. School of Health Science (Medicine), Universidad de La Laguna, Tenerife, Spain

    Miguel Angel Benítez-Rosario, Enrique González-Dávila & Emilio Sanz

  3. Statistical Department, Universidad de La Laguna, Tenerife, Spain

    Enrique González-Dávila

  4. Department of Pharmacology, Universidad de La Laguna, Tenerife, Spain

    Emilio Sanz

Authors
  1. Miguel Angel Benítez-Rosario
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  2. Inmaculada Rosa-González
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  3. Enrique González-Dávila
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  4. Emilio Sanz
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Corresponding author

Correspondence to Miguel Angel Benítez-Rosario.

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The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Human Research Ethics Committee of Hospital Universitario La Candelaria. For this type of study formal consent is not required.

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Benítez-Rosario, M.A., Rosa-González, I., González-Dávila, E. et al. Fentanyl treatment for end-of-life dyspnoea relief in advanced cancer patients. Support Care Cancer 27, 157–164 (2019). https://doi.org/10.1007/s00520-018-4309-8

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  • DOI: https://doi.org/10.1007/s00520-018-4309-8

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