High-Velocity nasal insufflation is a viable alternative to noninvasive positive pressure ventilation (NIPPV) for treating moderate-to-severe hypercapnic respiratory distress in emergency department patients with COPD.


This multi-center randomized controlled trial demonstrates that high velocity therapy is a viable alternative to Noninvasive Positive Pressure Ventilation (NiPPV) for treating moderate-to-severe hypercapnic respiratory distress in emergency department (ED) patients with COPD, with significant benefits for patient comfort and tolerability, according to results from the HYPERACT (HYPERcapnia: A Randomized Clinical Trial) study published in Academic Emergency Medicine.

Led by Principal Investigators Dr. Andrew Meltzer and Dr. David Yamane, the HYPERACT trial challenges long-standing respiratory care practices, offering a new approach to managing acute COPD exacerbations. The findings were initially presented by Dr. Yamane at the Society of Critical Care Medicine’s Annual Congress, where he received the prestigious Star Research Award.

Dr. Yamane, who is also the Associate Professor of Emergency Medicine at George Washington University, reflected on the study’s transformative impact: “The results of the HYPERACT trial were both surprising and practice changing. At George Washington, we’ve already begun integrating high velocity therapy into our protocols, and the difference in patient comfort and outcomes is evident. This therapy is an invaluable tool for emergency care teams managing COPD patients with hypercapnic respiratory distress.”

Dr. Andrew Meltzer, also a professor at George Washington University, further comments, “Well, it isn’t so surprising. When a patient arrives to the ED gasping for air, a mask-based therapy is terrifying. It’s only one study, but I hope this is enough to encourage other physicians to consider high velocity therapy.”

Key Study Highlights

  • Primary Outcome: High velocity therapy was non-inferior to NiPPV in reducing dyspnea (as measured on a modified Borg Scale) over four hours.
  • Secondary Outcomes: Comparable improvements in pH and pCO2 between high velocity therapy and NiPPV (with baseline CO2 up to 120 mmHg).
  • Patient Comfort: Statistically superior comfort ratings for high velocity therapy at all time points.
  • Discharge Rates: 11% of patients on high velocity therapy were discharged home directly from the ED, compared to none in the NiPPV group.
  • Tolerance: High velocity therapy was better tolerated, with fewer patients discontinuing therapy due to intolerance (11% vs.19% with NiPPV).

HYPERACT is the first multi-center RCT to focus on patients with moderate-to-severe hypercapnic respiratory failure. By addressing limitations of traditional mask-based therapies, such as discomfort, aspiration risk, and cardiovascular instability, high velocity therapy offers a patient-friendly alternative that aligns with evidence-based medicine.

Commenting on the study, Dr. Jessica Whittle, Vapotherm’s Chief Medical Officer, said: “Publishing the HYPERACT trial is an important milestone, but it isn’t enough. The next step is ensuring clinicians are educated on these findings and equipped to implement evidence-based medicine in their practices. This study challenges the status quo and highlights the importance of considering innovative solutions like high velocity therapy.”