High-Flow Nasal Cannula Therapy for Exertional Dyspnea in Patients with Cancer: A Pilot Randomized Clinical Trial.

BACKGROUND: Exertional dyspnea is common in patients with cancer and limits their function. The impact of high-flow nasal cannula on exertional dyspnea in nonhypoxemic patients is unclear. In this double-blind, parallel-group, randomized trial, we assessed the effect of flow rate (high vs. low) and gas (oxygen vs. air) on exertional dyspnea in nonhypoxemic patients with cancer. PATIENTS AND METHODS: Patients with cancer with oxygen saturation >90% at rest and exertion completed incremental and constant work (80% maximal) cycle ergometry while breathing low-flow air at 2 L/minute. They were then randomized to receive high-flow oxygen, high-flow air, low-flow oxygen, or low-flow air while performing symptom-limited endurance cycle ergometry at 80% maximal. The primary outcome was modified 0-10 Borg dyspnea intensity scale at isotime. Secondary outcomes included dyspnea unpleasantness, exercise time, and adverse events. RESULTS: Seventy-four patients were enrolled, and 44 completed the study (mean age 63; 41% female). Compared with low-flow air at baseline, dyspnea intensity was significantly lower at isotime with high-flow oxygen (mean change, -1.1; 95% confidence interval [CI], -2.1, -0.12) and low-flow oxygen (-1.83; 95% CI, -2.7, -0.9), but not high-flow air (-0.2; 95% CI, -0.97, 0.6) or low-flow air (-0.5; 95% CI, -1.3, 0.4). Compared with low-flow air, high-flow oxygen also resulted in significantly longer exercise time (difference + 2.5 minutes, p = .009), but not low-flow oxygen (+0.39 minutes, p = .65) or high-flow air (+0.63 minutes, p = .48). The interventions were well tolerated without significant adverse effects. CONCLUSION: Our preliminary findings support that high-flow oxygen improved both exertional dyspnea and exercise duration in nonhypoxemic patients with cancer. (ClinicalTrials.gov ID: NCT02357134). IMPLICATIONS FOR PRACTICE: In this four-arm, double-blind, randomized clinical trial examining the role of high-flow nasal cannula on exertional dyspnea in patients with cancer without hypoxemia, high-flow oxygen, but not high-flow air, resulted in significantly lower dyspnea scores and longer exercise time. High-flow oxygen delivered by high-flow nasal cannula devices may improve clinically relevant outcomes even in patients without hypoxemia.

Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial.

CONTEXT: The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined. OBJECTIVES: We examined the effect of two doses of prophylactic FSS on exertional dyspnea. METHODS: In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%-45% (high dose) or 15%-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function. RESULTS: Thirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected. CONCLUSION: Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials.