Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Following Extubation on Liberation From Respiratory Support in Critically Ill Children
Authors: Padmanabhan Ramnarayan, Alvin Richards-Belle, Laura Drikite, Michelle Saull, Izabella Orzechowska, Robert Darnell, Zia Sadique, Julie Lester, Kevin P. Morris, Lyvonne N. Tume, Peter J. Davis, Mark J. Peters, Richard G. Feltbower, Richard Grieve, Karen Thomas, Paul R. Mouncey, David A. Harrison, Kathryn M. Rowan, Nazima Pathan, Esther Daubney, Deborah White, Nayan Shetty, Dawn Jones, Laura Rad, Laura O'Malley, Kevin Morris, Sarah Fox, Carly Tooke, Afeda Mohamed Ali, Peter Davis, Helen Marley, Rebecca Lean, Laura Dodge, Angela Aramburo, Laura Alcantara, Laura Tos, Helena Sampaio, Siva Oruganti, Susan Bowes, Awen Hughes, Mark J Peters, Lauran O'Neill, Holly Belfield, Samiran Ray, Rohit Saxena, Helen Vander Johnson, Tara McHugh, Gareth Jones, David Armstrong, Laura Fraser, Margrethe Van Dijke, Ian Piper, Jon Lillie, Paul A Wellman, Aleksandra Williams, Tabitha Craen, Joanne Perkins, Christine Mackerness, Aravind Kashyap, Lindsay Cooper, Angela Lawton, Lynda Verhulst, Akash Deep, Ivan C Caro, Eniola Nsirim, Samira N Vahid, Bedangshu Saikia, Rekha Patel, Graham Mason, Claire Jennings, Rebecca Marshall, Danielle Pask, Avishay Sarfatti, Zoe Oliver, Katie Wingfield, Sophie Herrington, Caterina Silvestre, Laura Anderson, Maria Saxton, Helen Fazackerley, Naomi Edmonds, Natasha Thorn, Nosheen Khalid, Hafiza Khatun, Anton Mayer, Alex Howlett, Jade Bryant, Ahmed Osman, Amber Cook, Lorena Caruana, Phillipa C Thomas, Nicholas J Prince, Joana G de Queiroz, Elena Maccarcari, Montserrat R Foguet, Rebecca Mitting, Sarah Darnell, David Inwald, Sam Peters, Lorna Miller, Stefan Sprinckmoller, Abby Koelewyn, Roger Parslow
Journal: JAMA (2022)

<h3>Importance</h3> The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known. <h3>Objective</h3> To evaluate the noninferiority of high-flow nasal cannula (HFNC) therapy as the first-line mode of noninvasive respiratory support following extubation, compared with continuous positive airway pressure (CPAP), on time to liberation from respiratory support. <h3>Design, Setting, and Participants</h3> This was a pragmatic, multicenter, randomized, noninferiority trial conducted at 22 pediatric intensive care units in the United Kingdom. Six hundred children aged 0 to 15 years clinically assessed to require noninvasive respiratory support within 72 hours of extubation were recruited between August 8, 2019, and May 18, 2020, with last follow-up completed on November 22, 2020. <h3>Interventions</h3> Patients were randomized 1:1 to start either HFNC at a flow rate based on patient weight (n = 299) or CPAP of 7 to 8 cm H<sub>2</sub>O (n = 301). <h3>Main Outcomes and Measures</h3> The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio (HR) of 0.75. There were 6 secondary outcomes, including mortality at day 180 and reintubation within 48 hours. <h3>Results</h3> Of the 600 children who were randomized, 553 children (HFNC, 281; CPAP, 272) were included in the primary analysis (median age, 3 months; 241 girls [44%]). HFNC failed to meet noninferiority, with a median time to liberation of 50.5 hours (95% CI, 43.0-67.9) vs 42.9 hours (95% CI, 30.5-48.2) for CPAP (adjusted HR, 0.83; 1-sided 97.5% CI, 0.70-∞). Similar results were seen across prespecified subgroups. Of the 6 prespecified secondary outcomes, 5 showed no significant difference, including the rate of reintubation within 48 hours (13.3% for HFNC vs 11.5 % for CPAP). Mortality at day 180 was significantly higher for HFNC (5.6% vs 2.4% for CPAP; adjusted odds ratio, 3.07 [95% CI, 1.1-8.8]). The most common adverse events were abdominal distension (HFNC: 8/281 [2.8%] vs CPAP: 7/272 [2.6%]) and nasal/facial trauma (HFNC: 14/281 [5.0%] vs CPAP: 15/272 [5.5%]). <h3>Conclusions and Relevance</h3> Among critically ill children requiring noninvasive respiratory support following extubation, HFNC compared with CPAP following extubation failed to meet the criterion for noninferiority for time to liberation from respiratory support. <h3>Trial Registration</h3> isrctn.org Identifier:ISRCTN60048867