Driving Pressure During General Anesthesia for Open Abdominal Surgery (DESIGNATION): study protocol of a randomized clinical trial

Abstract

Background: Intraoperative driving pressure (ΔP) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V T ) is kept constant, ΔP may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. ΔP may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods:The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged ≥ 18 years and with a body mass index ≤ 40 kg/m 2 , scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H 2 O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which ΔP is lowest. In both groups of the trial, V T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events.Discussion: DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery. Trial registration: Clinicaltrials.gov, NCT03884543. Registered on 21 March 2019.

Safety and Feasibility of Intraoperative High PEEP Titrated to the Lowest Driving Pressure (ΔP)—Interim Analysis of DESIGNATION

“…The study protocol of DESIGNATION mandated the collection of any episode of intraoperative hypotension, defined as a reduction in mean arterial pressure (MAP) of more than 20% from the baseline measured before the induction of anesthesia, lasting for a duration longer than 3 min [ 9 ]. Excessive use of vasopressors is defined as use of any vasoactive agents, either as a bolus or continuous infusion, in quantities exceeding what was deemed necessary to counteract the vasodilating effects of the employed anesthetics, as assessed by the attending anesthesiologist.…”

“…Our research group is currently conducting an international multicenter randomized clinical trial (‘DESIGNATION’) using this method for titration of PEEP described above [ 9 ]. As of mid-2022, the DESIGNATION study was halfway, and all centers were actively recruiting patients.…”

ΔP-Guided PEEP in the Operating Room––Do We Need More Guidance?

“…The “Driving PrESsure DurIng GeNeral AnesThesIa for Open AbdOmiNal Surgery” (DESIGNATION) study is an international multicenter ongoing randomized clinical trial in which a decremental PEEP trial is used to select the best PEEP, after an initial incremental PEEP trial to 20 cm H 2 O as a recruitment maneuver. 5 In an interim analysis for study conduct, we compared the ΔP at the recruitment maneuver, ie, at 20 cm H 2 O PEEP, and the nadir for PEEP in the successive decremental PEEP trial in a total of 290 patients. While ΔP was 10 (9–12) cm H 2 O at the end of the incremental PEEP trial, the nadir ΔP in the decremental PEEP trial was much lower, only 7 (6–8) cm H 2 O ( P < .01).…”

Management of Intraoperative Mechanical Ventilation to Prevent Postoperative Complications after General Anesthesia: A Narrative Review

“…Expert’s opinion suggests minimizing both the ∆P and the plateau pressure; thus, when different PEEP levels are associated with the “best” ∆P achievable, the lowest one should be set [ 39 ]. Differently, in the ongoing “Designation” trial performed in open abdominal surgery, the highest PEEP associated with the lowest ∆P is set [ 40 ]. Another confounding factor is represented by the selection of PEEP with a decremental or incremental trial.…”