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

Abstract

Background

Postoperative pulmonary complications (PPCs) are a leading cause of morbidity, death, and increased use of health-care resources. 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.

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. 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. 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. 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. Assessors were masked to treatment assignment. 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. 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). This study is registered with ClinicalTrials.gov, NCT04108130, and is now complete.

Findings

Between Jan 24, 2020, and April 5, 2023, we screened 1462 patients, of whom 794 were enrolled and randomly assigned to treatment. 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. 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. Adherence to bundle components was high (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. 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). 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). Occurrence of serious adverse events was similar in both groups. 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. 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.

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.

Funding

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