High flow oxygen for dyspnea in hospitalized patients with cancer: A 4x4 crossover randomized clinical trial.

Abstract

12077 Background: Dyspnea is common in hospitalized cancer patients and highly distressing. High flow oxygen (HFOx) is administered for oxygenation in this setting; however, its effect on dyspnea has not been well examined, particularly among non-hypoxemic patients. In this phase II trial, we assessed the effect of HFOx, high flow air (HFAir), low flow oxygen (LFOx) and low flow air (LFAir) on dyspnea. We hypothesized that HFO and HFA can alleviate dyspnea. Methods: This double-blind, 4x4 crossover clinical trial enrolled hospitalized patients with cancer who were dyspneic (NRS ≥3 at rest) and non-hypoxemic (SpO2>90% on room air). Patients were randomized to 10 minutes of HFOx, HFAir, LFOx and LFAir in different orders. The flow rate was titrated between 20-60 L/min in the high flow groups and 2 L/min in the low flow groups. The primary outcome was dyspnea 0-10 numeric rating scale (NRS) “now”, where 0=none and 10=worst. Secondary outcomes included modified Borg scale dyspnea intensity and unpleasantness, adverse effects, and overall preference. We compared among the interventions with a linear mixed model adjusting for time, treatment effect, period effect and carryover effect. Results: 17 patients completed 55 interventions in a random order. Mean age 51, 58% female, mean baseline dyspnea NRS 6.3 (SD 1.7). The absolute change of dyspnea NRS between 0 and 10 minutes was -1.8 (SD 1.7) for HFOx, -1.8 (2.0) for HFAir, -0.5 (0.8) for LFOx and -0.6 (1.2) for LFAir. In mixed model analysis, HFOx group provided greater dyspnea relief than LFOx (mean difference [95% CI] -0.80 [-1.45, -0.15], P=0.02) and LFAir (-1.24 [-1.90, -0.57], P<0.001). HFAir also provided a significantly greater dyspnea relief than LFOx (-0.95 [-1.61, -0.30], P=0.005) and LFAir (-1.39 [-2.05, -0.73], P<0.001). No difference was found between HFOx and HFAir nor between LFOx and LFAir. There was no significant carryover effect. Dyspnea Borg scale intensity and unpleasantness showed similar changes. Oxygen saturation increased in the HFOx group (97.2% to 99.7%) and LFOx group (95.5% to 98.2%) but not HFAir nor LFAir groups. HFOx was well tolerated. At the end of the study, 7 (54%), 4 (31%), 1 (8%) and 1 (8%) patients blindly preferred HFOx, HFAir, LFOx and LFAir, respectively. Conclusions: For the first time, we found that HFOx and HFAir provided a rapid and clinically significant reduction of dyspnea at rest in hospitalized cancer patients even when they were non-hypoxemic, supporting a role for high flow devices to provide palliation beyond oxygenation. Larger studies are needed to confirm these findings. Clinical trial information: NCT02932332 .