Driving Pressure During General Anesthesia for Minimally Invasive Abdominal Surgery (GENERATOR)

Study Overview
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Brief Summary
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The purpose of this international multicenter, patient and outcome-assessor blinded randomized controlled trial is to determine whether the application of an individualized high Positive End Expiratory Pressure (PEEP) strategy with recruitment maneuvers, aiming at avoiding an increase in the driving pressure during intraoperative ventilation, protects against the development of postoperative pulmonary complications in patients undergoing minimally invasive abdominal surgery.

Official Title
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Driving Pressure During General Anesthesia for Minimally Invasive Abdominal Surgery (GENERATOR) - a Randomized Clinical Trial

Conditions
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Postoperative Complications, Surgery

Intervention / Treatment
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* Procedure: Intraoperative ventilation with individualized high PEEP titrated to the lowest ΔP with RMs


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: age > 18 years; AND scheduled for minimally invasive abdominal surgery; AND at increased (i.e., intermediate or high) risk of PPCs according to the 'Assess Respiratory risk in Surgical Patients in Catalonia' (ARISCAT) risk score (≥ 26 points, see Appendix I); OR at increased risk of PPCs based on the combination of age > 40 years, scheduled surgery lasting > 2 hours and planned to receive an intra-arterial catheter for blood pressure monitoring during the surgery; AND signed written informed consent Exclusion criteria: planned for open abdominal surgery; planned for surgery in lateral or prone position; planned for combined abdominal and intra-thoracic surgery confirmed pregnancy; consent for another interventional trial during anesthesia; having received invasive ventilation > 30 minutes within the last five days; any previous lung surgery; history of previous severe chronic obstructive pulmonary disease (COPD) with (noninvasive) ventilation or oxygen therapy at home or repeated systemic corticosteroid therapy for acute exacerbations of COPD; history of acute respiratory distress syndrome (ARDS); expected to require postoperative ventilation; expected hemodynamic instability or intractable shock; severe cardiac disease (New York Heart Association class III or IV, acute coronary syndrome or persistent ventricular tachyarrhythmia's).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individualized high PEEP strategy with recruitment maneuvers<br>The intervention is intraoperative ventilation using the available ventilator with individualized high positive end-expiratory pressure (PEEP) titrated to the lowest driving pressure (ΔP) with recruitment maneuvers (RMs). After abdominal insufflation, patients randomized to the individualized high PEEP with RMs group will receive a RM followed by a 'decremental PEEP trial'. This is followed by a second RM after which PEEP is set at the level indicated by the decremental PEEP trial. | Procedure: Intraoperative ventilation with individualized high PEEP titrated to the lowest ΔP with RMs<br>* The intervention is intraoperative ventilation using the available ventilator with individualized high PEEP titrated to the lowest ΔP with RMs. After abdominal insufflation, patients randomized to the individualized high PEEP with RMs group will receive a RM followed by a 'decremental PEEP trial'. This is followed by a second RM after which PEEP is set at the level indicated by the decremental PEEP trial<br>* Other names: Individualized high PEEP strategy with recruitment maneuvers;|
| No Intervention: Standard low PEEP strategy without recruitment maneuvers<br>Patients randomized to the standard low PEEP group will receive 5 cm H2O PEEP for the complete duration of general anesthesia. They will neither receive one of the planned RMs nor a decremental PEEP trial. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants developing one or more postoperative pulmonary complications (PPCs) | A composite of the following pulmonary complications: mild respiratory failure; severe respiratory failure; bronchospasm; suspected pulmonary infection; pulmonary infiltrate; aspiration pneumonitis; atelectasis; acute respiratory distress syndrome (ARDS); pleural effusion; cardiopulmonary edema; pneumothorax | The first 5 postoperative days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative complications | Including: any episode of desaturation; any episode of hypotension; any need for vasoactive agents, either as bolus or continuous administration, defined as more than needed to compensate for vasodilating effects of anesthesia as judged by the attending anesthesiologist and any new arrhythmias needing intervention | For the duration of general anesthesia, these outcomes are scored every hour up to a maximum of 18 hours | 
| Intraoperative fluid strategy | Including the total amount of fluids administered during anesthesia, including the amounts of colloids, crystalloids, and blood products | During general anesthesia | 
| Impaired wound healing | Impaired wound healing, as judged and mentioned in the medical record by the attending ward physician; | The first 5 postoperative days | 
| Postoperative extrapulmonary complications | Including: sepsis; septic shock; extrapulmonary infection; anastomotic leak and acute renal failure | The first 5 postoperative days | 
| Mortality | All-cause mortality at day 5, day 30 and 90, and in-hospital mortality | Postoperative day 5, day 30 and day 90 | 
| Length of stay | Length of hospital stay (days); length of ICU admission if applicable (days); | Postoperatively until the end of the 90 day follow-up period | 
| Oxygen use | Postoperative supplemental oxygen use (days). Presence, duration and levels of postoperative supplemental oxygen | The first 5 postoperative days | 
| Antibiotics use | Use of antibiotics for pneumonia (proportion of patients who received antibiotics) | The first 5 postoperative days | 
| Thoracic imaging | Occurence of imaging (chest X-ray, computed tomography scan). Proportion of patients who underwent thoracic imaging. | The first 5 postoperative days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Minimally invasive abdominal surgery, Mechanical ventilation, Positive end-expiratory pressure, Driving pressure, Postoperative pulmonary complications, Recruitment maneuver