High-flow warm humidified oxygen versus standard low-flow nasal cannula oxygen for moderate bronchiolitis (HFWHO RCT): an open, phase 4, randomised controlled trial

Summary

Background 背景

Bronchiolitis is the most common lung infection in infants and treatment focuses on management of respiratory distress and hypoxia. High-flow warm humidified oxygen (HFWHO) is increasingly used, but has not been rigorously studied in randomised trials. We aimed to examine whether HFWHO provided enhanced respiratory support, thereby shortening time to weaning off oxygen.

支气管炎是婴儿最常见的肺部感染，治疗重点在于纠正呼吸窘迫与缺氧。高流量加温加湿氧疗(HFWHO)的使用日益普遍，但是尚未经过随机试验的研究。我们旨在验证采用HFWHO加强呼吸支持能否缩短脱离氧疗的时间。

Methods 方法

In this open, phase 4, randomised controlled trial, we recruited children aged less than 24 months with moderate bronchiolitis attending the emergency department of the John Hunter Hospital or the medical unit of the John Hunter Children's Hospital in New South Wales, Australia. Patients were randomly allocated (1:1) via opaque sealed envelopes to HFWHO (maximum flow of 1 L/kg per min to a limit of 20 L/min using 1:1 air–oxygen ratio, resulting in a maximum FiO2 of 0·6) or standard therapy (cold wall oxygen 100% via infant nasal cannulae at low flow to a maximum of 2 L/min) using a block size of four and stratifying for gestational age at birth. The primary outcome was time from randomisation to last use of oxygen therapy. All randomised children were included in the primary and secondary safety analyses. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12612000685819.

在这项开放，4期，随机对照试验中，我们入选了澳大利亚新南威尔士州John Hunter医院急诊科或John Hunter儿童医院内科就诊的合并中度支气管炎的不足24个月儿童。采用不透明的密闭信封，设置区组大小为4，并根据生产时孕周分层，将患者(1:1)随机分为HFWHO组（最大流量1 L/kg/min，上限为20 L/min，采用1:1的空气与氧气比例，可达到的最大FiO2为0.6）或标准治疗组（冷的墙壁供氧100%，经婴儿鼻导管给予低流量氧疗，最大流量2 L/min）。主要预后指标为从随机分组至最终停止氧疗的时间。所有接受随机分组的儿童均纳入主要及次要安全性分析。此研究在澳大利亚新西兰临床试验注册网，注册号ACTRN12612000685819。

Findings 结果

From July 16, 2012, to May 1, 2015, we randomly assigned 202 children to either HFWHO (101 children) or standard therapy (101 children). Median time to weaning was 24 h (95% CI 18–28) for standard therapy and 20 h (95% CI 17–34) for HFWHO (hazard ratio [HR] for difference in survival distributions 0·9 [95% CI 0·7–1·2]; log rank p=0·61). Fewer children experienced treatment failure on HFWHO (14 [14%]) compared with standard therapy (33 [33%]; p=0·0016); of these children, those on HFWHO were supported for longer than were those on standard therapy before treatment failure (HR 0·3; 95% CI 0·2–0·6; p<0·0001). 20 (61%) of 33 children who experienced treatment failure on standard therapy were rescued with HFWHO. 12 (12%) of children on standard therapy required transfer to the intensive care unit compared with 14 (14%) of those on HFWHO (difference −1%; 95% CI –7 to 16; p=0·41). Four adverse events occurred (oxygen desaturation and condensation inhalation in the HFWHO group, and two incidences of oxygen tubing disconnection in the standard therapy group); none resulted in withdrawal from the trial. No oxygen-related serious adverse events occurred. Secondary effectiveness outcomes are reported in the Results section.

从2012年7月16日至2015年5月1日，我们将202名患儿随机分为HFWHO组(n = 101)或标准治疗组(n = 101)。标准治疗组脱离氧疗的中位时间为24 h (95% CI 18–28) ，HFWHO组为 20 h (95% CI 17–34) （生存分布的风险比 [HR] 0·9 [95% CI 0·7–1·2]; log rank p=0·61）。HFWHO组(14 [14%])较标准治疗组更少患儿治疗失败 (33 [33%]; p=0·0016)；在这些患儿中，HFWHO组患者在治疗失败前接受支持治疗时间更长(HR 0·3; 95% CI 0·2–0·6; p<0·0001)。标准治疗组治疗失败的33个患儿中20名(61%)使用HFWHO进行挽救治疗。标准治疗组12名(12%)患儿需要转入ICU，HFWHO组为14名(14%)（差异 −1%；95% CI –7 to 16; p=0·41）。共发生4例不良事件（HFWHO组低氧及冷凝水吸入，标准治疗组2例吸氧管路脱开）；均未造成从试验中退出。未发现氧疗相关严重不良事件。次要疗效预后指标见结果部分。

Interpretation 结论

HFWHO did not significantly reduce time on oxygen compared with standard therapy, suggesting that early use of HFWHO does not modify the underlying disease process in moderately severe bronchiolitis. HFWHO might have a role as a rescue therapy to reduce the proportion of children requiring high-cost intensive care.

与标准治疗相比，HFWHO不能显著缩短氧疗时间，提示早期使用HFWHO不能改变中度支气管炎的疾病进程。HFWHO可以做为挽救治疗措施，减少需要收入ICU的患儿比例。

Funding

Hunter Children's Research Foundation, John Hunter Hospital Charitable Trust, and the University of Newcastle Priority Research Centre GrowUpWell.