Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Therapy on Liberation From Respiratory Support in Acutely Ill Children Admitted to Pediatric Critical Care Units
Padmanabhan Ramnarayan, Alvin Richards‐Belle, Laura Drikite, Michelle Saull, Izabella Orzechowska, Robert Darnell, Zia Sadique, Julie Lester, Kevin Morris, Lyvonne N. Tume, Peter J. Davis, Mark Peters, Richard Feltbower, Richard Grieve, Karen Thomas, Paul Mouncey, David A Harrison, Kathy Rowan, FIRST-ABC Step-Up RCT Investigators and the Paediatric Critical Care Society Study Group, Nazima Pathan, Deborah White, Esther Daubney, Nayan Shetty, Dawn Jones, Laura O'Malley, Laura Rad, Peter J. Davis, Frances Hutchings, Karen Coy, Sarah Sheedy, Alice Bowerman, Kerry Mahoney, Laura Dodge, Helen Raeside, Pardina Samson-Fessale, Kribashnie Nundlall, Jaime Carungcong, Aravind S Kashyap, Christine Mackerness, Sarah E Daggert, Rob Claydon, Kirsty Mulgrew, Mark Peters, Ana L Pereira Tomas, Holly Belfield, Lauran O'Neill Gutierrez, Hamza Meghari, Emily Beech, Gareth A. Jones, Samiran Ray, Saxena Rohit, Hilary Klonin, Remy Toko, Melony Bowdler-Hayes, Leanne Sherris, Arshid Murad, Armstrong Sonia, Hebbron Kerry, Szekeres Adele, Avishay Sarfatti, Zoe Oliver, Sarah Barton, Melanie James, Lynda Verhulst, Ivan Carlo, Akash Deep, Bedangshu Saikia, Samira Neshat, Rekha Patel, S. Sukhani, Karen Samm, Benila Ravindranathan, Vanessa Zammit, Meleika Hamilton, Shagun Bhatia Shah, Susan E Bowes, Sivakumar Oruganti, Awen Evans, Laura Anderson, Maria Saxton, Helen Fazackerley, Catarina Silvestre, Kamal Patel, Kevin Donnelly, Emma Tagliavini, Vivien Richmond, Helen Coutts, Jessica R. Scott, Ellen Smith, Heather Collier, Angela Aramburo, Laura Alcantara Gemmar, L Tous Sampol, Jenny C Tan, David K Armstrong, Laura Fraser, Margrethe VanDijke, Ian Piper, Graham Mason, Danielle Pask
Abstract
Importance: The optimal first-line mode of noninvasive respiratory support for acutely ill children is not known. Objective: To evaluate the noninferiority of high-flow nasal cannula therapy (HFNC) as the first-line mode of noninvasive respiratory support for acute illness, compared with continuous positive airway pressure (CPAP), for time to liberation from all forms of respiratory support. Design, Setting, and Participants: Pragmatic, multicenter, randomized noninferiority clinical trial conducted in 24 pediatric critical care units in the United Kingdom among 600 acutely ill children aged 0 to 15 years who were clinically assessed to require noninvasive respiratory support, recruited between August 2019 and November 2021, with last follow-up completed in March 2022. Interventions: Patients were randomized 1:1 to commence either HFNC at a flow rate based on patient weight (n = 301) or CPAP of 7 to 8 cm H2O (n = 299). Main Outcomes and Measures: The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which a participant was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio of 0.75. Seven secondary outcomes were assessed, including mortality at critical care unit discharge, intubation within 48 hours, and use of sedation. Results: Of the 600 randomized children, consent was not obtained for 5 (HFNC: 1; CPAP: 4) and respiratory support was not started in 22 (HFNC: 5; CPAP: 17); 573 children (HFNC: 295; CPAP: 278) were included in the primary analysis (median age, 9 months; 226 girls [39%]). The median time to liberation in the HFNC group was 52.9 hours (95% CI, 46.0-60.9 hours) vs 47.9 hours (95% CI, 40.5-55.7 hours) in the CPAP group (absolute difference, 5.0 hours [95% CI -10.1 to 17.4 hours]; adjusted hazard ratio 1.03 [1-sided 97.5% CI, 0.86-∞]). This met the criterion for noninferiority. Of the 7 prespecified secondary outcomes, 3 were significantly lower in the HFNC group: use of sedation (27.7% vs 37%; adjusted odds ratio, 0.59 [95% CI, 0.39-0.88]); mean duration of critical care stay (5 days vs 7.4 days; adjusted mean difference, -3 days [95% CI, -5.1 to -1 days]); and mean duration of acute hospital stay (13.8 days vs 19.5 days; adjusted mean difference, -7.6 days [95% CI, -13.2 to -1.9 days]). The most common adverse event was nasal trauma (HFNC: 6/295 [2.0%]; CPAP: 18/278 [6.5%]). Conclusions and Relevance: Among acutely ill children clinically assessed to require noninvasive respiratory support in a pediatric critical care unit, HFNC compared with CPAP met the criterion for noninferiority for time to liberation from respiratory support. Trial Registration: ISRCTN.org Identifier: ISRCTN60048867.