Effect of Prophylactic Fentanyl Buccal Tablet on Episodic Exertional Dyspnea: A Pilot Double-Blind Randomized Controlled Trial

Abstract

Context Episodic dyspnea is one of the most common, debilitating and difficult-to-treat symptoms. Objective We conducted a pilot study to examine the effect of prophylactic FBT on exercise-induced dyspnea. Methods In this parallel, double-blind randomized placebo-controlled trial, opioid-tolerant patients were asked to complete a 6 minute walk test (6MWT) at baseline, then a second 6MWT 30 minutes after a single dose of FBT (equivalent to 20-50% of their total opioid dose) or matching placebo. We compared dyspnea numeric rating scale (NRS, 0-10, primary outcome), walk distance, vital signs, neurocognitive function and adverse events between the two 6MWTs. Results Among 22 patients enrolled, 20 (91%) completed the study. FBT was associated with a significant within-arm reduction in dyspnea NRS between 0 and 6 minutes (mean change -2.4, 95% confidence interval [CI] -3.5, -1.3) and respiratory rate (mean change -2.6, 95% CI -4.7, -0.4). Placebo was also associated with a non-statistically significant decrease in dyspnea (mean change -1.1). Between arm comparison of dyspnea scores in the second 6MWT favored FBT, albeit not statistically significant (estimate -0.25, P=0.068). Global impression revealed more patients in the FBT group than placebo group reporting their dyspnea was at least “somewhat better” in the second 6MWT (4/9 vs. 0/11, P=0.03). The other secondary outcomes did not differ significantly between arms. Conclusions This study supports that prophylactic FBT was associated with a reduction of exertional dyspnea and was well-tolerated. Our findings support the need for larger trials to confirm the therapeutic potential of rapid-onset opioids.

Palliative Care for Cancer Patients During the COVID-19 Pandemic, With Special Focus on Lung Cancer

“…Morphine has been proven to be an effective treatment for refractory breathlessness ( 30 , 31 ). The risk of a shortage of morphine existed, but other drugs are not effective [oxycodone ( 32 )], or only anecdotal proof of its effectiveness on dyspnea exists [fentanyl ( 33 , 34 )]. To guide physicians in the use of other opioids in the treatment of dyspnea, local guidelines rapidly changed, or expanded with recommendations in times of shortages.…”

Episodic Breathlessness with and without Background Dyspnea in Advanced Cancer Patients Admitted to an Acute Supportive Care Unit

“…This is confirmed by the finding that most episodes were triggered by predictable physical efforts. A series of studies demonstrated that walking-induced EB may be reduced by the prophylactic use of transmucosal or subcutaneous fentanyl, which demonstrated a dose–response relationship in improving both dyspnea and walking distance [ 26 , 27 , 28 , 29 ]. Of interest, the high-dose groups (35–45% of the daily background equivalent opioid dose) were more likely to report at least somewhat better improvement, without producing significant adverse events, confirming the protective role of the level of opioid tolerance reported for breakthrough pain [ 4 ].…”

Polypharmacy Increases Risk of Dyspnea Among Adults With Serious, Life-Limiting Diseases

“…To date, interventions to relieve dyspnea focused on pharmacologic prescriptions including corticosteroids and opioids. [29][30][31][32] A pilot study including 35 patients with cancer randomized to either 7 days of dexamethasone or placebo showed that dexamethasone significantly reduced dyspnea scores by up to 2 points on a 0 to 10 numeric rating scale. 29 The same group also used prophylactic opioids (buccal tablets of fentanyl or nasal spray in pilot studies including approximately 20 patients each) for patients with exertion-related dyspnea.…”