Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics, Chongqing, China.
First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
JAMA Pediatr. 2022 Jun 1;176(6):551-559. doi: 10.1001/jamapediatrics.2022.0710.
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.
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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
The NCPAP, NIPPV, or NHFOV treatment was initiated after the first extubation and lasted until discharge.
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.
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; P = .04) and NCPAP (mean difference, 1.5 days; 95% CI, 0.3-2.7 days; P = .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%; P = .003) and NHFOV (risk difference, 12.5%; 95% CI, 7.5%-17.4%; P < .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; P = .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%; P = .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; P = .04), and duration of study intervention (shorter in NHFOV than in NIPPV group; median [25th-75th percentile] difference, -1 [-3 to 0] days; P = .01).
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.
ClinicalTrials.gov Identifier: NCT03181958.
有几种呼吸支持技术可用于最大限度地减少早产儿使用有创机械通气（IMV）。目前尚不清楚在早产儿首次拔管后，与鼻塞持续气道正压通气（NCPAP）或经鼻间歇正压通气（NIPPV）相比，高频振荡通气（NHFOV）是否更有效。
检验假设，即与 NCPAP 或 NIPPV 相比，NHFOV 可降低早产儿拔管后至新生儿重症监护病房出院期间的 IMV 使用率。
设计、地点和参与者：这是一项多中心、基于病理生理学的评估者盲法 3 组随机临床试验，在中国 69 家三级转诊新生儿重症监护病房进行，于 2017 年 12 月 1 日至 2021 年 5 月 31 日期间招募参与者。研究对象为胎龄 25 周零 0 天至 32 周零 6 天且准备拔管的早产儿，随机分为接受 NCPAP、NIPPV 或 NHFOV 治疗。数据分析采用意向治疗原则。
首次拔管后即开始给予 NCPAP、NIPPV 或 NHFOV 治疗，直至出院。
主要结局是总 IMV 持续时间、需要重新插管和无呼吸机天数。选择这些结局来描述无创通气策略对一般 IMV 需求的影响。
共有 1440 名新生儿（出生时平均[标准差]年龄，29.4[1.8]周；860 名男孩[59.7%]）纳入试验。与 NHFOV 相比，NIPPV（平均差异，1.2 天；95%CI，0.01-2.3 天；P = .04）和 NCPAP（平均差异，1.5 天；95%CI，0.3-2.7 天；P = .01）组的 IMV 持续时间更长。与 NCPAP 相比，NIPPV 组需要重新插管的患儿更多（风险差异：8.1%；95%CI，2.9%-13.3%；P = .003）和 NHFOV 组（风险差异，12.5%；95%CI，7.5%-17.4%；P < .001）。与 NCPAP 相比，NIPPV 组无呼吸机天数更少（中位数[25 分位-75 分位]差异，-3[-6 至-1]天；P = .01）。除了使用产后皮质激素（NHFOV 组低于 NCPAP 组；风险差异，7.3%；95%CI，2.6%-12%；P = .002）、每周体重增加（NHFOV 组高于 NCPAP 组；平均差异，-0.9 g/d；95%CI，-1.8 至 0 g/d；P = .04）和研究干预持续时间（NHFOV 组短于 NIPPV 组；中位数[25 分位-75 分位]差异，-1[-3 至 0]天；P = .01）外，其他次要疗效或安全性结局无差异。
本试验结果表明，与 NCPAP 相比，NHFOV 可略微缩短早产儿拔管后至出院期间的 IMV 持续时间，且 NHFOV 和 NIPPV 组的再插管风险均低于 NCPAP 组。这 3 种呼吸支持技术对该患者群体均同样安全。
ClinicalTrials.gov 标识符：NCT03181958。
