GENERATOR Trial: Individualized Ventilation Strategy for Minimally Invasive Surgery
核心洞察
The GENERATOR trial is a multicenter, randomized clinical trial evaluating individualized high PEEP ventilation with recruitment maneuvers (RMs) versus standard low PEEP in patients undergoing minimally invasive abdominal surgery.
The trial aims to determine if the individualized ventilation strategy reduces postoperative pulmonary complications (PPCs) in patients at increased risk.
A total of 1806 patients will be recruited across multiple hospitals in Europe, with the primary endpoint being a composite of PPCs within the first five postoperative days.
The DrivinG prEssure duriNg gEneRal AnesThesia fOr minimally invasive abdominal suRgery (GENERATOR) trial is set to investigate whether an individualized ventilation strategy can reduce postoperative pulmonary complications (PPCs) in patients undergoing minimally invasive abdominal surgery. This international, multicenter, prospective, randomized clinical trial will compare an individualized high positive end-expiratory pressure (PEEP) strategy, titrated to the lowest driving pressure (ΔP) with recruitment maneuvers (RMs), against a standard low PEEP strategy without RMs.
The study, involving 1806 patients across 20 academic and community hospitals in The Netherlands, Germany, Austria, Spain, and Italy, focuses on patients at increased risk for PPCs. Participants are randomized in a 1:1 ratio to either the individualized high PEEP with RMs group or the standard low PEEP group. The primary endpoint is a composite of PPCs until postoperative day 5, including mild and severe respiratory failure, bronchospasm, suspected pulmonary infection, pulmonary infiltrate, aspiration pneumonitis, atelectasis, ARDS (搜索), pleural effusion, cardiopulmonary edema, and pneumothorax.
Ventilation Strategies
In the individualized high PEEP with RMs group, ventilation starts with a PEEP of 10 cm H2O, followed by RMs and a decremental PEEP trial to identify the optimal PEEP level that minimizes ΔP. RMs are performed by increasing PEEP in steps of 5 cm H2O up to 20 cm H2O. The decremental PEEP trial involves decreasing PEEP in steps of 2 cm H2O from 20 cm H2O to 6 cm H2O, while monitoring ΔP. The highest PEEP level with the lowest ΔP is then selected. In the control group, patients receive a standard low PEEP of 5 cm H2O without RMs, a level commonly used in clinical practice.
Inclusion and Exclusion Criteria
Eligible patients are adults (>18 years) scheduled for minimally invasive abdominal surgery and at intermediate or high risk of PPCs based on the ARISCAT score (≥ 26 points) or a combination of age (>40 years) and surgery duration (>2 hours) with planned intra-arterial catheterization. Exclusion criteria include open abdominal surgery, combined abdominal and intra-thoracic surgery, pregnancy, prior mechanical ventilation, expected postoperative ventilation, hemodynamic instability, severe cardiac disease, history of ARDS (搜索), major lung surgery, and severe COPD (搜索).
Secondary Endpoints and Data Collection
Secondary endpoints include intraoperative complications (desaturation, hypotension, arrhythmias), intraoperative fluid strategy, postoperative extrapulmonary complications, all-cause mortality at various time points, and cost-effectiveness parameters such as length of hospital stay and ICU admission. Data is collected preoperatively, intraoperatively, and postoperatively up to 90 days after surgery. The EQ-5D-5L questionnaire will be used to assess health-related quality of life in Dutch patients.
Statistical Analysis and Trial Organization
The sample size calculation is based on an estimated PPC incidence of 30% in the standard low PEEP group and aims to detect a 20% relative risk reduction with the individualized high PEEP strategy. Statistical analysis will be performed using a modified intention-to-treat principle. The trial is overseen by a steering committee and a Data Safety Monitoring Board (DSMB).