Comparison of Analgesic Effects of Nebulized Morphine with Fentanyl Transdermal Patch and Oral Methadone for Cancer Patients in Terminal Stages; a Double-blind Randomized Controlled Study
Introduction: Recent years have witnessed widespread reports on the effectiveness of nebulized morphine for dyspnea, yet there is no evidence for its effectiveness in analgesic therapy. Objective: This study aims to compare effectiveness and side effects of inhalation morphine with oral methadone and transdermal fentanyl in sequential days in end stage cancer patients. Method: This double-blind, randomized controlled study conducted between April and September 2017. Ninety eligible cancer patients presenting to Sayed al-Shohada Hospital were selected non-randomly according to inclusion criteria and then divided to 3 groups in random order. Pain severity was scored by Visual Analog Scale (VAS). Patients were followed up for 3 days and then data were analyzed by SPSS. The benchmark of success was set as marking 4 or below on VAS and a reduction ratio of 50 percent. Results: Pain severity was equal for 3 groups before the first administration (p>0.05), but it decreased significantly from 8.45 (range 6-10) at baseline to 2.46 (range 1-4) at the end of the 3rd day in the nebulized group. The decrease ratio was equal to 70.8% after three days (p<0.05). Pain severity reduced from 8.45 (range 7-10) to 1.8 (range 1-3) (p<0.05) in the methadone group, and reduced from 8.5 (range 6-10) to 2.13 (range 1-3) in the fentanyl group. Conclusion: Our study showed that nebulized morphine, just like oral methadone and transdermal fentanyl, is effective, safe, and well-tolerated for pain management in patients with cancer.
2. Venkat A, Kim D, editors. Ethical tensions in the pain management of an end-stage cancer patient with evidence of opioid medication diversion. HEC forum; 2016: Springer.
3. Fisch MJ, Lee J-W, Weiss M, Wagner LI, Chang VT, Cella D, et al. Prospective, observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer. J Clin Oncol. 2012;30(16):1980-8.
4. Mercadante S, Porzio G, Ferrera P, Fulfaro F, Aielli F, Verna L, et al. Sustained‐release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management. Eur J Pain. 2008;12(8):1040-6.
5. Pergolizzi J, Böger RH, Budd K, Dahan A, Erdine S, Hans G, et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008;8(4):287-313.
6. Menahem S, Shvartzman P. High-dose fentanyl patch for cancer pain. J Am Board Fam Pract. 2004;17(5):388-90.
7. Afsharimani B, Kindl K, Good P, Hardy J. Pharmacological options for the management of refractory cancer pain—what is the evidence? Support Care Cancer. 2015;23(5):1473-81.
8. Clemens KE, Klaschik E. Clinical experience with transdermal and orally administered opioids in palliative care patients—a retrospective study. Jpn J Clin Oncol. 2007;37(4):302-9.
9. Lasheen W, Panneerselvam A, Davis MP. Can we really say that nebulized morphine works? J Pain Symptom Manage. 2006;32(2):101-2.
10. Fulda GJ, Giberson F, Fagraeus L. A prospective randomized trial of nebulized morphine compared with patient-controlled analgesia morphine in the management of acute thoracic pain. J Trauma. 2005;59(2):382-9.
11. Grissa MH, Boubaker H, Zorgati A, Beltaïef K, Zhani W, Msolli MA, et al. Efficacy and safety of nebulized morphine given at 2 different doses compared to IV titrated morphine in trauma pain. Am J Emerg Med. 2015;33(11):1557-61.
12. Arthur AO, Mushtaq N, Mumma S, Thomas SH. Fentanyl buccal tablet versus oral oxycodone for Emergency Department treatment of musculoskeletal pain. J Emerg Med Trauma Acute Care. 2015:6.
13. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 2016;315(15):1624-45.
14. 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.