Safety and feasibility of intraoperative high PEEP titrated to the lowest driving pressure during anesthesia for minimally invasive abdominal surgery – Interim analysis of GENERATOR

Abstract

Background: The optimal level of positive end–expiratory pressure (PEEP) during minimally invasive abdominal surgery is uncertain. Intraoperative ventilation with individualized high PEEP and recruitment maneuvers can be used to keep the driving pressure (ΔP) low, but can also lead to hypotension. In addition, the resulting ΔP and feasibility of individualized high PEEP in minimally invasive abdominal surgery is unclear. Methods: Planned interim analysis on safety and feasibility of ‘Driving Pressure During General Anesthesia for Minimally Invasive Abdominal Surgery’ (GENERATOR), an ongoing randomized clinical trial that compares individualized high PEEP, titrated to the lowest ΔP, with a standard low PEEP ventilation strategy with respect to postoperative pulmonary complications. The primary endpoint for this analysis was the proportion of patients with intraoperative hypotension. Secondary endpoints were other intraoperative complications, ventilation variables and feasibility parameters. Results: From December 2023 to July 2024, 181 patients were enrolled. Data for analysis were available for 177 patients, of which 87 patients were randomized to individualized high PEEP and 90 to standard low PEEP. Intraoperative hypotension was similar between the individualized high PEEP vs standard low PEEP group (11.5 vs 11.1 %, relative risk ratio 1.0 [95 % CI 0.5–2.4], p = 1.00), while vasopressor use was higher in the intervention group. The median difference in ΔP between both groups was 6 cm H<inf>2</inf>O. Protocol compliance was 81.6 % in the individualized high PEEP group vs 97.8 % in the standard low PEEP group; most instances of non–compliance in the individualized high PEEP group concerned a level of PEEP that was too high. Discussion: In minimally invasive abdominal surgery, a ventilation strategy using individualized high PEEP was not associated with a higher incidence of hypotension, but did show an increased use of vasopressors. The intervention was highly feasible, and led to a lower ΔP. These interim findings warrant confirmation in the main analysis of GENERATOR. Funding: This research was funded by ZonMW, grant number 10390012110091.