Non-invasive ventilation versus high-flow nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intubation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre, open-label trial
Jean-Pierre Frat, Jean-Damien Ricard, Jean-Pierre Quenot, et al
Lancet Respir Med 2019; 7: 303-312
Background 背景
Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation.
无创通气与高流量氧疗降低气管插管时严重低氧血症风险的作用从未进行过比较。我们旨在确定采用无创通气进行预氧合是否较高流量氧疗能够更有效地降低气管插管时严重低氧血症的风险。
Methods 方法
The FLORALI-2 multicentre, open-label trial was done in 28 intensive care units in France. Adult patients undergoing tracheal intubation for acute hypoxaemic respiratory failure (a partial pressure of arterial oxygen [PaO 2] to fraction of inspired oxygen [FiO 2] ratio of ≤300 mm Hg) were randomly assigned (1:1; block size, four participants) to non-invasive ventilation or high-flow oxygen during preoxygenation, with stratification by PaO 2/FiO 2 ratio (≤200 mm Hg vs >200 mm Hg). Key exclusion criteria were intubation for cardiac arrest, altered consciousness (defined as a Glasgow coma score of less than eight points), other contraindications to non-invasive ventilation (recent laryngeal, oesophageal, or gastric surgery, and substantial facial fractures), pulse oximetry not available, pregnant or breastfeeding women, and refusal to participate. The primary outcome was the occurrence of severe hypoxaemia (pulse oximetry <80%) during the procedure, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02668458.
FLORALI-2是法国28个ICU进行的一项多中心开放试验。将急性低氧性呼吸衰竭（PaO2/FiO2 ≤ 300 mmHg）需接受气管插管的成年患者进行随机分组（1:1，区组大小为4），分别接受无创通气或高流量氧疗进行预氧合，根据PaO2/FiO2比值(≤200 mm Hg vs >200 mm Hg)进行分层。主要排除标准包括因心跳骤停接受气管插管，意识改变（定义为GCS < 8分），无创通气的其他禁忌症（近期喉部、食道或胃部手术，及面部骨折），没有氧饱和度监测，妊娠或哺乳，以及拒绝参加研究。主要预后指标为操作过程中严重低氧血症(SpO2 < 80%)发生率，采用意向治疗分析。试验在 ClinicalTrials.gov注册，注册号NCT02668458。
Findings 结果
Between April 15, 2016, and Jan 8, 2017, 2079 patients were intubated in the 28 participating units, and 322 were enrolled. We excluded five patients with no recorded data, two who withdrew consent or were under legal protection, one who was not intubated, and one who had a cardiac arrest. Of the 313 patients included in the intention-to-treat analysis, 142 were assigned to non-invasive ventilation and 171 to high-flow oxygen therapy. Severe hypoxaemia occurred in 33 (23%) of 142 patients after preoxygenation with non-invasive ventilation and 47 (27%) of 171 with high-flow oxygen (absolute difference −4·2%, 95% CI −13·7 to 5·5; p=0·39). In the 242 patients with moderate-to-severe hypoxaemia (PaO 2/FiO 2 ≤200 mm Hg), severe hypoxaemia occurred less frequently after preoxygenation with non-invasive ventilation than with high-flow oxygen (28 [24%] of 117 patients vs 44 [35%] of 125; adjusted odds ratio 0·56, 0·32 to 0·99, p=0·0459). Serious adverse events did not differ between treatment groups, with the most common immediate complications being systolic arterial hypotension (70 [49%] patients in the non-invasive ventilation group vs 86 [50%] patients in the high-flow oxygen group) and chest infiltrate on x-ray (28 [20%] vs 33 [19%]), and the most common late complications being death at day 28 (53 [37%] vs 58 [34%]) and ventilator-associated pneumonia during ICU stay (31 [22%] vs 35 [20%]).
2016年4月15日至2017年1月8日间，28个参研中心共有2079名患者接受气管插管，322名患者入选研究。5名患者缺乏数据，2名患者撤除知情同意或接受法律监护，1名患者没有接受气管插管，1名患者发生心跳骤停。意向治疗分析纳入313名患者，其中142名患者分至无创通气组，171名患者分至高流量氧疗组。无创通气预氧合后142名患者中33名(23%)及高流量氧疗171名患者中47名(27%)发生严重低氧血症（绝对差异 −4·2%, 95% CI −13·7 to 5·5; p=0·39）。中重度低氧血症(PaO 2/FiO 2 ≤200 mm Hg)的242名患者中，与高流量氧疗相比，无创通气预氧合后严重低氧血症发生率较低（28/117 [24%] vs 44/125 [35%]; 校正后OR 0·56, 0·32 to 0·99, p=0·0459）。两组患者严重不良事件发生率并无差异，最常见的即刻并发症包括收缩压降低（无创通气组70 [49%] 名患者 vs 高流量组86 [50%] 名患者）和胸片肺部浸润影(28 [20%] vs 33 [19%])，最常见的迟发并发症包括28天内死亡 (53 [37%] vs 58 [34%]) 及ICU住院期间发生呼吸机相关性肺炎(31 [22%] vs 35 [20%])。
Interpretation 结论
In patients with acute hypoxaemic respiratory failure, preoxygenation with non-invasive ventilation or high-flow oxygen therapy did not change the risk of severe hypoxaemia. Future research should explore the effect of preoxygenation method in patients with moderate-to-severe hypoxaemia at baseline.
对于急性低氧性呼吸功能衰竭患者，采用无创通气或高流量氧疗进行预氧合，不能改变严重低氧血症的风险。需要进一步研究揭示中重度低氧血症患者预氧合方法的作用。
Funding
French Ministry of Health.
