A RANDOMIZED TRIAL OF BILEVEL POSITIVE AIRWAY PRESSURE DEVICE AND HIGH FLOW OXYGEN FOR PERSISTENT DYSPNEA IN

Background: Dyspnea is a common and distressing symptom among patients with advanced cancer. The role of bilevel positive airway pressure (BIPAP) and Vapotherm in the relief of dyspnea have not been well defined. We aimed to determine and to compare the efficacy of BIPAP and VapoTherm for cancer related dyspnea. Methods: In this randomized, open-label, crossover study, we randomly assigned advanced cancer patients with persistent dyspnea >=3/10 to either Vapotherm for 2 hours followed by BiPAP for 2 hours, or BiPAP followed by Vaptherm. A variable washout period was instituted between interventions. The primary end point was change in numeric rating scale before and after each intervention. We planned to enroll 50 patients in total. Results: Among the 803 patients screened over the last 8 months, 62 (26%) were eligible, and 16 (2%) were enrolled so far. Five patients completed the entire study successfully, 4 discontinued the study prematurely due to prolonged relief of dyspnea, and 7 dropped out for various reasons, including inability to tolerate BiPAP (N=3), anxiety (N=2), fatigue (N=1) and pain requiring opioids (N=1). The median baseline numeric rating score for dyspnea was 7/10 (interquartile range (IQR) 5-8), and the median baseline Borg score was 4/10 (3-7). Interim analysis revealed that BiPAP was associated with a median change in numeric rating score of -3 (N=10, IQR -6.3 to -1, p=0.007) and modified Borg score of -1 (N=10, IQR -3 to 0.3, p=0.058), while Vapotherm was associated with a median change in numeric rating score of -2 (N=9, IQR -3 to -1, p=0.011) and modified Borg score of -2.5 (N=8, IQR -5.5 to -0.1, p=0.051). Among the 5 individuals who completed the entire study, 2 preferred Vapotherm, 2 favored BiPAP, and 1 liked both. The respiratory rate decreased and the oxygen saturation improved with both interventions. No significant toxicities were observed. Conclusions: We were successfully able to enroll patients onto this clinic trial. Our preliminary results suggest that BiPAP and Vapotherm are highly efficacious in providing relief for patients with persistent refractory dyspnea. A direct comparison of the two interventions will be done upon study completion. Further research is necessary to confirm our findings.

Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury 3 d to 8 months earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared with untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 months. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C- and Aδ-fibers revealed SCI-induced SA generated in or near the somata of the neurons in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.