Perioperative lung expansion and pulmonary outcomes after open abdominal surgery versus usual care in the USA (PRIME-AIR): a multicentre, randomised, controlled, phase 3 trial.

We aimed to determine whether a perioperative lung expansion bundle including individualised intraoperative management reduces PPC severity in patients undergoing major open abdominal surgery compared with usual care.

我们旨在确定围手术期肺部扩张方案，包括个体化的术中管理，是否能降低接受重大开放性腹部手术患者术后肺部并发症的严重程度，与常规护理相比。

Methods

In this multicentre, randomised controlled phase 3 trial (PRIME-AIR), we enrolled adult patients (age ≥18 years) scheduled for an elective open abdominal surgery that would last at least 2 h, who were at intermediate or high risk for PPCs on the basis of their Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (a score of ≥26), and who had a BMI below 35 kg/m2 at 17 academic hospitals across ten states in the USA.

在这项多中心、随机对照的III期试验（PRIME-AIR）中，我们招募了计划接受至少2小时的择期开放性腹部手术的成年患者（年龄≥18岁），这些患者根据他们的加泰罗尼亚手术患者呼吸风险评估（ARISCAT）评分（≥26分），处于中度或高度术后肺部并发症（PPCs）风险中，并且在美国十个州的17所学术医院中，他们的体重指数（BMI）低于35 kg/m2。

Participants were randomly assigned (1:1), using permuted block randomisation (a mixture of blocks sizes of 2 and 4; in a 1:2 ratio), stratified by centre, to either usual care or a lung expansion bundle.

参与者被随机分配（1:1），使用混合大小为2和4的置换块随机化（以1:2的比例），按中心分层，接受常规护理或肺部扩张方案。

The bundle comprised preoperative education on PPCs, intraoperative protective ventilation with individualised positive end-expiratory pressure (PEEP) to maximise respiratory system compliance, intraoperative neuromuscular blockade administration and reversal based on patient's weight and neuromuscular transmission monitoring, and postoperative supervised incentive spirometry and mobilisation encouragement.

该综合措施包括术前对术后肺部并发症(PPCs)的教育，术中使用个体化呼气末正压(PEEP)的保护性通气以最大化呼吸系统顺应性，根据患者体重和神经肌肉传递监测进行术中药物神经肌肉阻滞和逆转，以及术后在监督下的激励性肺活量测定和鼓励活动。

Anaesthesiologists at each site were also randomly assigned to either the intervention bundle group or usual care group, and at each site, at least one unmasked and one masked investigator was designated for each participant.

每个地点的麻醉师也被随机分配到综合措施组或常规护理组，且在每个地点，为每位参与者至少指定了一名未蒙面和一名蒙面的研究者。

Assessors were masked to treatment assignment.

评估者对治疗分配情况不知情。

The primary outcome was the highest severity (grade 0-4) of a composite of PPCs by postoperative day 7, including hypoxaemia, respiratory symptoms, atelectasis, bronchospasm, respiratory infection, hypercapnia, pneumonia, pleural effusion, pneumothorax, and ventilatory dependence.

主要结果是术后第7天由一系列术后肺部并发症（PPCs）组成的最高严重程度（0-4级），包括低氧血症、呼吸症状、肺不张、支气管痉挛、呼吸系统感染、高碳酸血症、肺炎、胸腔积液、气胸和呼吸依赖。

The primary endpoint and safety were assessed in the modified intention-to-treat(mITT) population (ie, all participants randomly assigned to treatment who received surgery, and did not withdraw consent or verbal agreement, and excluded those found to be ineligible after randomisation, or for whom consent was not obtained for other reasons).

主要终点和安全性评估是在修改后的意向治疗(mITT)人群中进行的（即，所有被随机分配到治疗并接受手术的参与者，没有撤回同意或口头协议，并排除了在随机化后发现不符合条件的参与者，或者由于其他原因未获得同意的参与者）。

This study is registered with ClinicalTrials.gov, NCT04108130, and is now complete.

这项研究已在ClinicalTrials.gov上注册，注册号为NCT04108130，目前研究已经完成。

Results

Between Jan 24, 2020, and April 5, 2023, we screened 1462 patients, of whom 794 were enrolled and randomly assigned to treatment.

2020年1月24日至2023年4月5日期间，我们筛查了1462名患者，其中794名被纳入并随机分配接受治疗。

The mITT population included 751 participants, of whom 379 (50%) were in the intervention bundle group and 372 (50%) were in the usual care group.

mITT人群包括751名参与者，其中379名（50%）在综合干预组，另外372名（50%）在常规护理组。

Mean age was 61·8 years (SD 12·8); 360 (48%) of 751 patients were female and 391 (52%) were male; 572 (76%) were White, 44 (6%) were Black, 35 (5%) were Asian, and ten (1%) were other races or more than one race.

平均年龄为61.8岁（标准差12.8）；751名患者中，360名（48%）为女性，391名（52%）为男性；572名（76%）为白人，44名（6%）为黑人，35名（5%）为亚洲人，10名（1%）为其他种族或多种族。

Adherence to bundle components was high (72-98%).

对捆绑组件的依从性很高（72-98%）。

Patients in the intervention bundle group received higher mean PEEP (7·5 cmH2O [SD 2·5] vs 5·6 cmH2O [1·4]) and more frequent per-protocol dosing of neuromuscular blockade (334 [88%] of 379 vs 214 [58%] of 372) and reversal (322 [86%] of 375 who received reversal medication vs 250 [70%] of 358) than did those in the usual care group.

干预包组的患者接受了更高的平均PEEP（7.5 cmH2O [标准差2.5] 对比 5.6 cmH2O [标准差1.4]）以及更频繁的按方案剂量的神经肌肉阻滞（334 [88%] of 379 vs 214 [58%] of 372）和逆转（322 [86%] of 375 接受逆转药物 vs 250 [70%] of 358），相较于常规护理组的患者。

By postoperative day 7, the most common PPC severity was grade 2 (211 [56%] of 379 in intervention bundle group vs 225 [60%] of 372 in the usual care group).

至术后第7天，最常见的PPC严重程度为2级（干预包组379人中有211人[56%]，常规护理组372人中有225人[60%]）。

Mean PPC severity was similar in both groups (1·60 [SD 0·94] vs 1·53 [0·93]; mean difference 0·07 [95% CI -0·03 to 0·18]; p=0·19).

两组的平均PPC严重程度相似（1·60 [标准差 0·94] 对比 1·53 [0·93]；平均差异 0·07 [95% 置信区间 -0·03 至 0·18]；p=0·19）。

Occurrence of serious adverse events was similar in both groups.

两组中严重不良事件的发生率相似。

At 7 days postoperatively, one (<1%) patient in the intervention bundle group and two (1%) in the usual care group had died; at 30 days, cumulatively, one (<1%) patient and four (1%) patients had died; and at 90 days, cumulatively, six (2%) patients and five (1%) patients had died, respectively.

术后第7天，干预包组有1名（<1%）患者死亡，常规护理组有2名（1%）患者死亡；术后第30天，累计来看，干预包组有1名（<1%）患者死亡，常规护理组有4名（1%）患者死亡；术后第90天，累计来看，干预包组有6名（2%）患者死亡，常规护理组有5名（1%）患者死亡。

Adverse events occurred in 71 (19%) of 379 patients in the intervention bundle group and 54 (14%) of 372 in the usual care group, and 35 (9%) patients in each group had serious adverse events.

在干预包组的379名患者中，有71名（19%）发生了不良事件，在常规护理组的372名患者中，有54名（14%）发生了不良事件，且两组各有35名（9%）患者发生了严重不良事件。

interpretation

In patients with a BMI of less than 35 kg/m2 who are at moderate-to-high risk of PPCs and undergoing prolonged major open abdominal surgery, a perioperative lung expansion bundle did not reduce PPC severity compared with usual care provided at US academic hospitals.

在体重指数小于35 kg/m2且面临中到高术后肺部并发症（PPCs）风险的患者中，如果他们接受的是长期的主要开放式腹部手术，与美国学术医院提供的常规护理相比，围手术期肺扩张方案并未减少PPCs的严重程度。

funding

US National Institutes for Health National Heart, Lung, and Blood Institute.

美国国家卫生研究院国家心肺血液研究所