Driving pressure during general anesthesia for minimally invasive abdominal surgery (GENERATOR)—study protocol of a randomized clinical trial
Authors:   The GENERATOR–investigators, Dorland Galina , Vermeulen Tom D. , Hollmann Markus W. , Schultz Marcus J. , Hol Liselotte , Nijbroek Sunny G. L. H. , Breel–Tebbutt Jenni S. , Neto Ary Serpa , Mazzinari Guido , Gasteiger Lukas , Ball Lorenzo , Pelosi Paolo , Almac Emre , Navarro Maria P. Argente , Battaglini Denise , Besselink Marc G. , Bokkerink Patty E. M. M. , van den Broek Janneke , Buise Marc P. , Broens Suzanne , Davidson Zoë , Cambronero Oscar Díaz , Dejaco Hannes , Ensink-Tjaberings Petra Y. , Florax Anna A. , de Abreu Marcelo Gama , Godfried Marc B. , Harmon Matthew B. A. , Helmerhorst Hendrik J. F. , Huhn Ragnar , Huhle Robert , Jetten Wesley D. , de Jong Merijn , Koopman Joseph S. H. A. , Koster Stephanie C. E. , de Korte-de Boer Dianne J. , Kuiper Geert-Jan A. J. M. , Trip Charlotte N. Laman , Morariu Aurora M. , Nass Stefan A. , Oei Gezina T. M. L. , Pap−Brugmans Alice C. , Paulus Frederique , Potters Jan-Willem , Rad Mandana , Robba Chiara , Sarton Elise Y. , Servaas Sjoerd , Smit Kirsten F. , Stamkot André , Thiel Bram , Struys Michel M. R. F. , van de Wint Thijs C. , Wittenstein Jakob , Zeillemaker-Hoekstra Miriam , van der Zwan Tim , Hemmes Sabrine N. T. , van Meenen David M. P. , Staier Nikolai , Mörtl Maximilian 
Published: October 2024

Background

Intraoperative driving pressure (ΔP) has an independent association with the development of postoperative pulmonary complications (PPCs) in patients receiving ventilation during general anesthesia for major surgery. Ventilation with high intraoperative positive end–expiratory pressure (PEEP) with recruitment maneuvers (RMs) that result in a low ΔP has the potential to prevent PPCs. This trial tests the hypothesis that compared to standard low PEEP without RMs, an individualized high PEEP strategy, titrated to the lowest ΔP, with RMs prevents PPCs in patients receiving intraoperative protective ventilation during anesthesia for minimally invasive abdominal surgery.

Methods

“DrivinG prEssure duriNg gEneRal AnesThesia fOr minimally invasive abdominal suRgery (GENERATOR)” is an international, multicenter, two–group, patient and outcome–assessor blinded randomized clinical trial. In total, 1806 adult patients scheduled for minimally invasive abdominal surgery and with an increased risk of PPCs based on (i) the ARISCAT risk score for PPCs (≥ 26 points) and/or (ii) a combination of age > 40 years and scheduled surgery lasting > 2 h and planned to receive an intra–arterial catheter for blood pressure monitoring during the surgery will be included. Patients are assigned to either an intraoperative ventilation strategy with individualized high PEEP, titrated to the lowest ΔP, with RMs or one with a standard low PEEP of 5 cm H2O without RMs. The primary outcome is a collapsed composite endpoint of PPCs until postoperative day 5.

Discussion

GENERATOR will be the first adequately powered randomized clinical trial to compare the effects of individualized high PEEP with RMs versus standard low PEEP without RMs on the occurrence of PPCs after minimally invasive abdominal surgery. The results of the GENERATOR trial will support anesthesiologists in their decisions regarding PEEP settings during minimally invasive abdominal surgery.

Trial registration

GENERATOR is registered at ClinicalTrials.gov (study identifier: NCT06101511) on 26 October 2023.