Noninvasive High-Frequency Oscillatory Ventilation vs Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation as Postextubation Support for Preterm Neonates in China
Authors: Xingwang Zhu, HongBo Qi, Zhichun Feng, Yuan Shi, Daniele De Luca, Yuan Shi, Daniele De Luca, Xingwang Zhu, Zhichun Feng, Hongbo Qi, Xiaoyun Zhong, Sijie Song, Lan Zhang, Li Li, Huiqiang Liu, Xiaomei Tong, Xiaojing Xu, LiFeng Cui, Ming Yi, Zhoujie Peng, Jie Li, Dongmei Chen, Weifeng Zhang, Xinzhu Lin, Bin Wang, Weimin Huang, Guangliang Bi, Shaoru He, Yumei Liu, Jie Yang, Weiwei Gao, Wuhua Liang, Yaoxun Wu, Xinnian Pan, Qiufen Wei, Yujun Chen, Bingmei Wei, Ling Liu, Xinghui Zheng, Ding Xu, Fan Wang, Bin Yi, Jingyun Shi, Yuning Li, Li Jiang, Chunming Jiang, Chenghe Tang, Hong Xiong, Huiqing Sun, Wenqing Kang, Dapeng Liu, Falin Xu, Kaihui Xing, Ning Yang, Fang Liu, Shaoguang Lv, Hanchu Liu, Wenchao Yuan, Rui Cheng, Xian Shen, Hui Wu, Laishuan Wang, Zhenying Yang, Xiao Zhang, Jiang Xue, Zhankui Li, Rong Ju, Jin Wang, Wenbin Dong, Xiaoxiu Ye, Benqing Wu, Jun Zheng, Xiuying Tian, Mingxia Li, Yanping Zhu, Nuerya Rejiafu, Long Li, Yangfang Li, Canlin He, Hongying Mi, Kun Liang, Hong Cao, Linlin Xia, Chuanfeng Li, Zhaoqing Yin, Le Su, Yanxiang Chen, Liping Shi, Chenhong Wang, Jiajun Zhu, Xuefeng Zhang, Xirong Gao, Bo Lv, Chongde Liu, Xiaorong Wang, Liping Chen, Lin Li, Chunli Zhang, Jia Chen, Qiyu Li, Qin Lv, Yanhong Li, Yong Ji, Yanjiang Chen, Jianhua Sun, Jun Bu, Danni Zhong, Zongyan Cao, Shuping Han, Xiaohui Chen, Caiyun Gao, Hongbin Zhu, Zhenguang Li, Hongwei Wu, Xiuyong Cheng, Juhua Li, Long Chen, Huanhuan Li
Journal: JAMA Pediatrics (2022)

<h3>Importance</h3> Several respiratory support techniques are available to minimize the use of invasive mechanical ventilation (IMV) in preterm neonates. It is unknown whether noninvasive high-frequency oscillatory ventilation (NHFOV) is more efficacious than nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV) in preterm neonates after their first extubation. <h3>Objective</h3> To test the hypothesis that NHFOV is more efficacious than NCPAP or NIPPV in reducing IMV after extubation and until neonatal intensive care unit discharge among preterm neonates. <h3>Design, Setting, and Participants</h3> This multicenter, pathophysiology-based, assessor-blinded, 3-group, randomized clinical trial was conducted in 69 tertiary referral neonatal intensive care units in China, recruiting participants from December 1, 2017, to May 31, 2021. Preterm neonates who were between the gestational age of 25 weeks plus 0 days and 32 weeks plus 6 days and were ready to be extubated were randomized to receive NCPAP, NIPPV or NHFOV. Data were analyzed on an intention-to-treat basis. <h3>Interventions</h3> The NCPAP, NIPPV, or NHFOV treatment was initiated after the first extubation and lasted until discharge. <h3>Main Outcomes and Measures</h3> Primary outcomes were total duration of IMV, need for reintubation, and ventilator-free days. These outcomes were chosen to describe the effect of noninvasive ventilation strategy on the general need for IMV. <h3>Results</h3> A total of 1440 neonates (mean [SD] age at birth, 29.4 [1.8] weeks; 860 boys [59.7%]) were included in the trial. Duration of IMV was longer in NIPPV (mean difference, 1.2; 95% CI, 0.01-2.3 days;<i>P</i> = .04) and NCPAP (mean difference, 1.5 days; 95% CI, 0.3-2.7 days;<i>P</i> = .01) compared with NHFOV. Neonates who were treated with NCPAP needed reintubations more often than those who were treated with NIPPV (risk difference: 8.1%; 95% CI, 2.9%-13.3%;<i>P</i> = .003) and NHFOV (risk difference, 12.5%; 95% CI, 7.5%-17.4%;<i>P</i> &lt; .001). There were fewer ventilator-free days in neonates treated with NCPAP than in those treated with NIPPV (median [25th-75th percentile] difference, −3 [−6 to −1] days;<i>P</i> = .01). There were no differences between secondary efficacy or safety outcomes, except for the use of postnatal corticosteroids (lower in NHFOV than in NCPAP group; risk difference, 7.3%; 95% CI, 2.6%-12%;<i>P</i> = .002), weekly weight gain (higher in NHFOV than in NCPAP group; mean difference, −0.9 g/d; 95% CI, −1.8 to 0 g/d;<i>P</i> = .04), and duration of study intervention (shorter in NHFOV than in NIPPV group; median [25th-75th percentile] difference, −1 [−3 to 0] days;<i>P</i> = .01). <h3>Conclusions and Relevance</h3> Results of this trial indicated that NHFOV, if used after extubation and until discharge, slightly reduced the duration of IMV in preterm neonates, and both NHFOV and NIPPV resulted in a lower risk of reintubation than NCPAP. All 3 respiratory support techniques were equally safe for this patient population. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03181958