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.

中文翻译：

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高流量鼻插管治疗与持续气道正压通气治疗对入住儿科重症监护病房的急病儿童呼吸支持解放的影响：一项随机临床试验。

重要性 急性病儿童无创呼吸支持的最佳一线模式尚不清楚。目的 评估高流量鼻插管疗法 (HFNC) 作为急性疾病无创呼吸支持的一线模式，与持续气道正压通气 (CPAP) 相比，对于从各种形式的呼吸支持中解放出来的时间的非劣效性。设计、设置和参与者 在英国 24 个儿科重症监护病房进行的实用、多中心、随机非劣效性临床试验在 2019 年 8 月至2021 年 11 月，最后一次随访于 2022 年 3 月完成。干预 患者被随机分配 1：1 以根据患者体重 (n = 301) 或 7 至 8 cm H2O (n = 299) 的流速开始 HFNC。主要结果和测量 主要结果是从随机化到呼吸支持解放的时间，定义为参与者没有任何形式的呼吸支持（侵入性或非侵入性）的 48 小时周期的开始，根据非劣效性界值进行评估调整后的风险比为 0.75。评估了七项次要结果，包括重症监护病房出院时的死亡率、48 小时内插管和镇静剂的使用。结果 在 600 名随机分配的儿童中，有 5 名（HFNC：1 名；CPAP：4 名）未获得同意，22 名（HFNC：5 名；CPAP：17 名）未开始呼吸支持；573 名儿童（HFNC：295；CPAP：278）被纳入主要分析（中位年龄，9 个月；226 名女孩 [39%]）。HFNC 组的中位解放时间为 52.9 小时（95% CI，46.0-60.9 小时），而 CPAP 组为 47.9 小时（95% CI，40.5-55.7 小时）（绝对差异，5.0 小时 [95% CI - 10.1 至 17.4 小时]；调整后的风险比 1.03 [单侧 97.5% CI，0.86-∞])。这符合非劣效性标准。在 7 个预先指定的次要结果中，有 3 个在 HFNC 组中明显较低：使用镇静剂（27.7% 对 37%；调整后的比值比，0.59 [95% CI，0.39-0.88]）；重症监护平均停留时间（5 天 vs 7.4 天；调整后的平均差，-3 天 [95% CI，-5.1 至 -1 天]）；和平均急性住院时间（13.8 天对 19.5 天；调整后的平均差，-7.6 天 [95% CI，-13.2 至 -1.9 天]）。最常见的不良事件是鼻外伤（HFNC：6/295 [2.0%]；CPAP：18/278 [6.5%]）。结论和相关性 在儿科重症监护病房临床评估需要无创呼吸支持的急性病患儿中，HFNC 与 CPAP 相比达到了从呼吸支持中解放出来的时间的非劣效性标准。试用注册 ISRCTN.org 标识符：ISRCTN60048867。