In December 2018, Neonatology published the results of a multicenter, retrospective observational analysis conducted by Zivanovic and colleagues, titled “Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants without the Need for Rescue with Nasal Continuous Positive Airway Pressure”. The study examined the outcomes of 381 premature infants with RDS across two tertiary neonatal units who had been stabilized on nCPAP and then transitioned to Vapotherm® high velocity therapy for primary respiratory support. The goal was to evaluate the effectiveness of high velocity therapy for primary respiratory support in this patient population without the use of nCPAP as rescue treatment and the analysis found this mode of primary support resulted in intubation rates that were lower or comparable to published data from randomized controlled trials.
In the discussion, the authors note that their findings matched those of Lavizzari et al, whose randomized, controlled trial found high velocity therapy to be non-inferior to nCPAP and Bi-Level PAP in premature infants with mild to moderate RDS. They then note that their findings did not match those of the randomized, controlled trial by Roberts et al. which found high flow nasal cannula (HFNC) to have significantly greater treatment failure as compared to nCPAP in that patient population. The difference in the failure rates at the Roberts trial resulted in the trial enrollment being discontinued on the recommendation of the data safety monitoring board. The authors do point out, however, that the Roberts trial included centers that where unfamiliar with HFNC and also had “permissive failure criteria”.
One significant matter to note which Zivanovic does not, is that an additional difference between the Lavizzari and Roberts trials was that the former was conducted with Vapotherm high velocity therapy exclusively for the non-PAP arm and the latter was effectively conducted with commodity HFNC (6 of 278 patients were treated by high velocity therapy, while the rest were treated by HFNC). Similarly, a randomized, controlled trial by Manley et al., published shortly after the Zivanovic retrospective analysis, also found HFNC to be not noninferior to nCPAP as primary support of premature neonates in special care (level 2) nurseries. Similar to the Roberts trial, Manley and colleagues conducted their study with HFNC exclusively.
Conversely, high velocity therapy has not only been found to be a viable alternative to pressure-based modalities in the neonatal population, but in the adult population as well. Doshi et al. also found high velocity therapy to be noninferior to NiPPV for the treatment of adults in undifferentiated respiratory distress, including hypercapnia. This growing body of clinical literature suggests that there is indeed a difference in outcomes between high velocity therapy and HFNC.
Zivanovic and colleagues framed their study around the importance of a mask-free ventilatory support alternative to nCPAP given that especially premature infants experience a lot of skin breakdown from positive pressure interfaces. When treating this vulnerable population it may be helpful to follow evidence-based practice so as to not inadvertently compromise safety and efficacy. This retrospective analysis offers yet another proof point that high velocity therapy is a safe, effective, and mask-free primary support for premature infants.
No Mask. No Problem. Mask-Free NIV
 Zivanovic, Sanja et al,. Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants without the Need for Rescue with Nasal Continuous Positive Airway Pressure. Neonatology 2019;115:175–181.DOI: 10.1159/000492930
 Lavizarri A, Colnaghi M, Ciuffini F, Veneroni C, Musumeci S, Cortinovis I, Mosca F. “Heated, humidified high-flow nasal cannula vs nasal continuous positive airway pressure for respiratory distress syndrome of prematurity – a randomized clinical noninferiority trial.” JAMA Pediatr. 2016 Aug 8.
 Roberts, Calum T., M.B., Ch.B., Louise S. Owen, M.D., Brett J. Manley, Ph.D., Dag H. Frøisland, Ph.D., Susan M. Donath, M.A., Kim M. Dalziel, Ph.D., Margo A. Pritchard, Ph.D., David W. Cartwright, M.B., B.S., Clare L. Collins, M.D., Atul Malhotra, M.D., and Peter G. Davis, M.D. for the HIPSTER Trial Investigators. “Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants.” New England Journal of Medicine. September 22, 2016; 375:1142-1151.
 Manley, Brett J., et al. Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries. N Engl J Med 2019; 380:2031-2040. DOI: 10.1056/NEJMoa1812077
 Doshi, Pratik et al. High-Velocity Nasal Insufflation in the Treatment of Respiratory Failure: A Randomized Clinical Trial. Annals of Emergency Medicine, 2018. Published online ahead of print.