Fentanyl for the Relief of Refractory Breathlessness: A Systematic Review

Context. Fentanyl is a potent opioid that has been proven to provide effective treatment for breakthrough cancer pain. Although opioids are the only drug group with evidence for the symptomatic treatment of breathlessness, evidence about the efficacy of fentanyl for the relief of breathlessness is unknown. Objectives. We performed a systematic review to evaluate the current evidence for the use of fentanyl for the relief of breathlessness. Methods. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendation for systematic reviews. Four databases (MEDLINE, EMBASE, Cochrane Library, International Pharmaceutical Abstracts) were screened using "fentanyl" and "dyspnoea" (and synonyms) as search terms. Hand search and contact with relevant authors completed the search. Results. A total of 622 references were retrieved, 13 of which met the inclusion criteria for this review. Two randomized controlled trials (RCTs) evaluated fentanyl for breathlessness, but one only included two patients. The other studies were before-after (n = 2) and case studies (n = 9). All studies reported successful relief of breathlessness after fentanyl application, but the only (pilot-) RCT failed to demonstrate a statistically significant difference compared with placebo. The nature and incidence of adverse events were comparable with other opioids, and no respiratory depression was observed. Conclusion. Descriptive studies yielded promising results for the use of fentanyl for the relief of breathlessness; however, efficacy trials are lacking. Fully powered RCTs are warranted to determine the efficacy of fentanyl for breathlessness relief, but these require pilot studies to evaluate effective size, study procedures, and outcome measures. (C) 2013 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.