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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Complications; Surgery
• Intervention / Treatment: Procedure: Intraoperative ventilation with individualized high PEEP titrated to the lowest ΔP with RMs

• Study Type: Interventional
• Enrollment (Estimated): 1806
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tom Vermeulen, MD; Phone Number: + 31 020 566 2533; Email: t.d.vermeulen@amsterdamumc.nl
• Study Contact Backup: Name: Galina Dorland, MD; Email: g.dorland@amsterdamumc.nl

Study Locations

• Netherlands
  • Noordholland
    • Amsterdam, Noordholland, Netherlands, 1105AZ
      • Recruiting
      • Amsterdam University Medical Center
      • Contact: Tom Vermeulen, Master; Email: t.d.vermeulen@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. age > 18 years; AND
2. scheduled for minimally invasive abdominal surgery; AND
3. 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
4. signed written informed consent

Exclusion criteria:

1. planned for open abdominal surgery;
2. planned for surgery in lateral or prone position;
3. planned for combined abdominal and intra-thoracic surgery
4. confirmed pregnancy;
5. consent for another interventional trial during anesthesia;
6. having received invasive ventilation > 30 minutes within the last five days;
7. any previous lung surgery;
8. 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;
9. history of acute respiratory distress syndrome (ARDS);
10. expected to require postoperative ventilation;
11. expected hemodynamic instability or intractable shock;
12. severe cardiac disease (New York Heart Association class III or IV, acute coronary syndrome or persistent ventricular tachyarrhythmia's).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individualized high PEEP strategy with recruitment maneuvers; 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; 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; Other Names: Individualized high PEEP strategy with recruitment maneuvers
No Intervention: Standard low PEEP strategy without recruitment maneuvers; 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?

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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: University Medical Center Groningen; Maastricht University Medical Center; Medical University Innsbruck; Noordwest Ziekenhuisgroep; The Netherlands Cancer Institute; Leiden University Medical Center; Dijklander Ziekenhuis; Hospital Universitario La Fe; Albert Schweitzer Hospital; Maasstad Hospital; Onze Lieve Vrouwe Gasthuis; Zaans Medical Center; Spaarne Gasthuis; Isala; Ospedale Policlinico San Martino; Medisch Spectrum Twente; University Hospital Carl Gustav Carus; Alrijne Hospital; HagaZiekenhuis
• Investigators: Study Chair: Marcus Schultz, Professor, Amsterdam University Medical Center, location AMC; Principal Investigator: Markus Hollmann, Professor, Amsterdam University Medical Center, location AMC; Principal Investigator: David van Meenen, PhD, Amsterdam University Medical Center, location AMC; Principal Investigator: Sabrine Hemmes, PhD, Amsterdam University Medical Center, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Postoperative pulmonary complications; Mechanical ventilation; Positive end-expiratory pressure; Recruitment maneuver; Driving pressure; Minimally invasive abdominal surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications
• Other Study ID Numbers: NL82971.018.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Interested researchers can contact the Principal Investigator for a collaboration after which an agreement will be discussed.
• IPD Sharing Time Frame: After the main paper has been published. No end-date has been specified for now.
• IPD Sharing Access Criteria: The applicable researcher can contact the Principal investigator with their idea of using the data, preferably accompanied by a statistical analysis plan
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No