Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR): a multicentre, international, randomised, controlled, phase 3 trial.

We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs.

我们旨在确定术中肺部扩张策略对预防PPCs的贡献。

Methods

In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged ≥18 years) with a BMI of less than 35 kg/m2 who were scheduled for open thoracic or video-assisted thoracoscopic surgery under general anaesthesia requiring one-lung ventilation with a double-lumen tube, with a planned operative time of more than 60 min, and an expected duration of one-lung ventilation longer than that of two-lung ventilation.

在这项多中心、随机、对照的国际III期试验（PROTHOR）中，我们在28个国家的74个地点招募了成年患者（年龄≥18岁），这些患者BMI小于35 kg/m2，计划接受全身麻醉下的开胸或视频辅助胸腔镜手术，需要使用双腔管进行单肺通气，预计手术时间超过60分钟，且单肺通气时间预期长于双肺通气。

Patients were randomly assigned (1:1), using permuted blocks of random size (4, 6, and 8) and stratified by study site, to receive one-lung ventilation with either a higher PEEP of 10 cm H2O and periodic lung recruitment manoeuvres (high PEEP group) or a lower PEEP of 5 cm H2O without routine recruitment manoeuvres (low PEEP group).

患者按1:1的比例随机分配，使用随机大小为4、6和8的置换块，并根据研究地点进行分层，接受单肺通气，一组使用较高的PEEP（10 cm H2O）和定期的肺复张操作（高PEEP组），另一组使用较低的PEEP（5 cm H2O）而不进行常规的复张操作（低PEEP组）。

All patients received protective tidal volumes of 5 mL/kg predicted body weight during one-lung ventilation and 7 mL/kg predicted body weight during two-lung ventilation.

所有患者在单肺通气期间接受了5 mL/kg预测体重的保护性潮气量，在双肺通气期间接受了7 mL/kg预测体重的保护性潮气量。

Postoperative assessors were masked to treatment allocation.

术后评估者对治疗分配情况不知情。

The primary outcome was a composite of PPCs during the first 5 postoperative days, including aspiration pneumonia, moderate or severe respiratory failure, acute respiratory distress syndrome (ARDS), pulmonary infection, atelectasis, cardiopulmonary oedema, pleural effusion, non-operative pneumothorax, pulmonary infiltrates, prolonged air leak, purulent pleuritis, pulmonary embolism, and pulmonary haemorrhage.

主要结果是术后前5天内PPCs的复合终点，包括吸入性肺炎、中度或重度呼吸衰竭、急性呼吸窘迫综合征（ARDS）、肺部感染、肺不张、心肺水肿、胸腔积液、非手术性气胸、肺浸润、持续性气漏、脓性胸膜炎、肺栓塞和肺出血。

A modified intention-to-treatanalysis was performed, with patients analysed according to their assigned treatment group, except in cases of withdrawal of informed consent, cancellation of surgery, and or loss to follow-up.

进行了改良意向治疗分析，患者根据其分配的治疗组进行分析，除非在撤回知情同意、取消手术或失访的情况下。

This trial is registered with ClinicalTrials.gov (NCT02963025) and is completed.

该试验已在ClinicalTrials.gov注册（NCT02963025），并已完成。

Results

Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treatanalysis after randomisation.

在2017年1月3日至2024年2月12日期间，共有2200名患者被随机分配：1099名患者分配至高PEEP组，1101名患者分配至低PEEP组。在随机分配后，有43名患者从高PEEP组和33名患者从低PEEP组被排除在改良意向治疗分析之外。

The primary outcome occurred in 555 (53·6%) of 1036 patients in the high PEEP group and 592 (56·4%) of 1049 patients in the low PEEP group (absolute risk difference -2·68 percentage points [95% CI -6·36 to 1·01]; p=0·155).

主要结果发生在高PEEP组的1036名患者中的555名（53.6%）和低PEEP组的1049名患者中的592名（56.4%）（绝对风险差异为-2.68个百分点[95% 置信区间-6.36至1.01]；p=0.155）。

Intraoperative complications occurred in 484 (49·8%) of 972 patients in the high PEEP group and in 305 (31·3%) of 974 patients in the low PEEP group (absolute risk difference 18·09 percentage points [95% CI 14·41-21·77]), among which hypotension (360 [37·3%] of 966 patients in the high PEEP group vs 140 [14·3%] of 978 in the low PEEP group) and new arrhythmias (89 [9·9%] of 899 vs 37 [3·9%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [3·3%] of 888 vs 86 [8·8%] of 982).

术中并发症发生在高PEEP组的972名患者中的484名（49.8%）和低PEEP组的974名患者中的305名（31.3%）（绝对风险差异为18.09个百分点[95% 置信区间14.41-21.77]），其中高PEEP组的低血压（高PEEP组的966名患者中的360名[37.3%] vs 低PEEP组的978名患者中的140名[14.3%]）和新发心律失常（高PEEP组的899名患者中的89名[9.9%] vs 低PEEP组的956名患者中的37名[3.9%]）更为常见，而低PEEP组的低氧血症抢救措施更为频繁（高PEEP组的888名患者中的29名[3.3%] vs 低PEEP组的982名患者中的86名[8.8%]）。

The proportions of patients with extrapulmonary postoperative complications (110 [10·6%] of 1036 vs 107 [10·2%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups.

在接受胸外科手术、BMI小于35 kg/m2的患者中，使用较高PEEP并配合肺复张手法的一肺通气，并未比使用较低PEEP而不配合肺复张手法的通气减少术后肺部并发症（PPCs）。

interpretation

In patients with a BMI of less than 35 kg/m2 undergoing thoracic surgery, one-lung ventilation using higher PEEP with recruitment manoeuvres, compared with lower PEEP without recruitment manoeuvres, did not reduce PPCs.

在 BMI 小于 35 kg/m2 的接受胸部手术的患者中，使用较高呼气末正压（PEEP）配合肺复张操作的一肺通气，并未比使用较低PEEP而不配合肺复张操作的减少术后肺部并发症（PPCs）

The choice for intraoperative lung expansion or permissive atelectasis should take the individual gas-exchange and haemodynamic conditions into account, which might vary during the intraoperative period.

在手术期间，应根据个体的气体交换和血流动力学条件来选择术中肺部扩张或允许性肺不张，这些条件在手术过程中可能会发生变化。

funding

Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care; Department of Anaesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Technische Universität Dresden (Dresden, Germany); Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasília, Brazil); and the Association of Anaesthetists of GB and Ireland.

欧洲麻醉学与重症监护学会临床试验网络；德国德累斯顿工业大学卡尔·古斯塔夫·卡鲁斯大学医院麻醉与重症监护科；巴西利亚国家科学技术发展委员会；以及大不列颠及爱尔兰麻醉师协会。