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

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06101511
• Collaborator: Onze Lieve Vrouwe Gasthuis (Other), HagaZiekenhuis (Other), Dijklander Ziekenhuis (Other), The Netherlands Cancer Institute (Other), Isala (Other), Maasstad Hospital (Other), Medisch Spectrum Twente (Other), University Medical Center Groningen (Other), Leiden University Medical Center (Other), Hospital Universitario La Fe (Other), Ospedale Policlinico San Martino (Other), University Hospital Carl Gustav Carus (Other), Medical University Innsbruck (Other), Spaarne Gasthuis (Other), Zaans Medical Center (Other), Alrijne Hospital (Other), Albert Schweitzer Hospital (Other), Maastricht University Medical Center (Other), Noordwest Ziekenhuisgroep (Other)
• Enrollment: 1,806
• Arms: 2
• Anticipated Duration (Months): 45

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Complications; Surgery	Procedure: Intraoperative ventilation with individualized high PEEP titrated to the lowest ΔP with RMs	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 1806 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Driving Pressure During General Anesthesia for Minimally Invasive Abdominal Surgery (GENERATOR) - a Randomized Clinical Trial
• Anticipated Study Start Date: Dec 1, 2023
• Anticipated Primary Completion Date: Jun 1, 2027
• Anticipated Study Completion Date: Sep 1, 2027

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Proportion of participants developing one or more postoperative pulmonary complications (PPCs) [The first 5 postoperative days]

   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

Secondary Outcome Measures

1. Intraoperative complications [For the duration of general anesthesia, these outcomes are scored every hour up to a maximum of 18 hours]

   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

2. Intraoperative fluid strategy [During general anesthesia]

   Including the total amount of fluids administered during anesthesia, including the amounts of colloids, crystalloids, and blood products

3. Impaired wound healing [The first 5 postoperative days]

   Impaired wound healing, as judged and mentioned in the medical record by the attending ward physician;

4. Postoperative extrapulmonary complications [The first 5 postoperative days]

   Including: sepsis; septic shock; extrapulmonary infection; anastomotic leak and acute renal failure

5. Mortality [Postoperative day 5, day 30 and day 90]

   All-cause mortality at day 5, day 30 and 90, and in-hospital mortality

6. Length of stay [Postoperatively until the end of the 90 day follow-up period]

   Length of hospital stay (days); length of ICU admission if applicable (days);

7. Oxygen use [The first 5 postoperative days]

   Postoperative supplemental oxygen use (days). Presence, duration and levels of postoperative supplemental oxygen

8. Antibiotics use [The first 5 postoperative days]

   Use of antibiotics for pneumonia (proportion of patients who received antibiotics)

9. Thoracic imaging [The first 5 postoperative days]

   Occurence of imaging (chest X-ray, computed tomography scan). Proportion of patients who underwent thoracic imaging.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Onze Lieve Vrouwe Gasthuis
• HagaZiekenhuis
• Dijklander Ziekenhuis
• The Netherlands Cancer Institute
• Isala
• Maasstad Hospital
• Medisch Spectrum Twente
• University Medical Center Groningen
• Leiden University Medical Center
• Hospital Universitario La Fe
• Ospedale Policlinico San Martino
• University Hospital Carl Gustav Carus
• Medical University Innsbruck
• Spaarne Gasthuis
• Zaans Medical Center
• Alrijne Hospital
• Albert Schweitzer Hospital
• Maastricht University Medical Center
• Noordwest Ziekenhuisgroep

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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prof. Dr. Marcus J. Schultz, Professor of Intensive Care Medicine, Principal Investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• ClinicalTrials.gov Identifier: NCT06101511
• Other Study ID Numbers: NL82971.018.23
• First Posted: Oct 26, 2023
• Last Update Posted: Oct 26, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Prof. Dr. Marcus J. Schultz, Professor of Intensive Care Medicine, Principal Investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): Minimally invasive abdominal surgery; Mechanical ventilation; Positive end-expiratory pressure; Driving pressure; Postoperative pulmonary complications; Recruitment maneuver
• Additional relevant MeSH terms: Postoperative Complications

Study Results

No Results Posted as of Oct 26, 2023