Original Investigation Caring for the Critically Ill PatientApril 7, 2022
Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Following Extubation on Liberation From Respiratory Support in Critically Ill ChildrenA Randomized Clinical Trial
Padmanabhan Ramnarayan, Alvin Richards-Belle, Laura Drikite, et al
JAMA. Published online April 7, 2022. doi:10.1001/jama.2022.3367
Key Points
Question In critically ill children clinically assessed to require noninvasive respiratory support following extubation, is the first-line use of high-flow nasal cannula (HFNC) therapy noninferior to continuous positive airway pressure (CPAP) in terms of time to liberation from all forms of respiratory support?
Findings In this randomized, noninferiority trial of 600 children clinically assessed to require noninvasive respiratory support following extubation, the median time to liberation was 50.5 hours for HFNC vs 42.9 hours for CPAP. The 1-sided 97.5% confidence limit for the hazard ratio was 0.70, which failed to meet the noninferiority margin of 0.75.
Meaning 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.Abstract
Importance The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known.
Objective 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.
Design, Setting, and Participants 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.
Interventions 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 H2O (n = 301).
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 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.
Results 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%]).
Conclusions and Relevance 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.
Trial Registration isrctn.org Identifier: ISRCTN60048867
