Highlights
1. Intraoperative ventilation using individualized high positive end-expiratory pressure (PEEP) and recruitment maneuvers, guided by driving pressure, did not reduce the incidence of postoperative pulmonary complications (PPCs) compared to a standard low PEEP strategy.
2. The high PEEP group experienced a significantly higher incidence of intraoperative hypotension (54.0% vs 45.0%) and required more frequent use of vasoactive agents (32.0% vs 18.8%).
3. While the individualized strategy improved intraoperative oxygenation and reduced desaturation events, these physiological benefits did not translate into better clinical outcomes for patients undergoing open abdominal surgery.
4. These findings suggest that a simpler, low PEEP strategy remains the standard of care, avoiding the hemodynamic risks associated with aggressive lung recruitment maneuvers.
Background: The Evolution of Lung-Protective Ventilation
Postoperative pulmonary complications (PPCs) represent a significant burden in perioperative medicine, contributing to increased morbidity, mortality, and healthcare costs. For patients undergoing major open abdominal surgery, the risk of PPCs—including atelectasis, pneumonia, and acute respiratory distress syndrome (ARDS)—is particularly high due to the combined effects of general anesthesia, neuromuscular blockade, and surgical manipulation.
Over the last two decades, the concept of lung-protective ventilation (LPV) has transitioned from the intensive care unit to the operating room. The core components of LPV typically include low tidal volumes (Vt) and the application of PEEP. However, the optimal level of PEEP remains a subject of intense debate. While PEEP is intended to prevent end-expiratory alveolar collapse (atelectasis), excessive PEEP can lead to alveolar overdistension and hemodynamic instability by increasing intrathoracic pressure and reducing venous return.
Recent physiological studies have suggested that driving pressure (the difference between plateau pressure and PEEP) is a key predictor of lung injury. By individualizing PEEP to achieve the lowest possible driving pressure—theoretically reflecting the best lung compliance—clinicians hoped to optimize alveolar recruitment while minimizing overdistension. The DESIGNATION trial was designed to provide a definitive answer to whether this individualized approach improves clinical outcomes.
Study Design: The DESIGNATION Randomized Clinical Trial
The DESIGNATION trial was a large-scale, multicenter, randomized clinical trial conducted across 29 sites in five European countries. The study enrolled 1435 adults at increased risk for PPCs (defined by an ARISCAT score of 26 or higher) who were scheduled for elective open abdominal surgery lasting at least 120 minutes.
Intervention vs. Control
Patients were randomized into two groups:
1. Driving Pressure-Guided High PEEP Group (n = 718): These patients received a recruitment maneuver followed by a PEEP titration procedure to identify the PEEP level that resulted in the lowest driving pressure. This individualized PEEP was then maintained throughout the surgery.
2. Standard Low PEEP Group (n = 717): These patients received a fixed PEEP of 5 cm H2O without recruitment maneuvers.
Both groups were ventilated with a low tidal volume of 8 mL/kg of predicted body weight. The primary outcome was a composite of PPCs occurring within the first five postoperative days. This composite included severe respiratory failure, bronchospasm, suspected pulmonary infection, pulmonary infiltrates, aspiration pneumonitis, atelectasis, ARDS, pleural effusion, cardiopulmonary edema, and pneumothorax.
Key Findings: No Clinical Benefit, Increased Hemodynamic Risk
The results of the DESIGNATION trial, published in JAMA, provide clear evidence regarding the efficacy and safety of driving pressure-guided ventilation in the surgical setting.
Primary Outcome Results
In the primary analysis population, the primary composite outcome occurred in 19.8% (142 of 718) of the driving pressure-guided high PEEP group, compared to 17.4% (125 of 717) in the standard low PEEP group. The absolute difference of 2.5% was not statistically significant (95% CI, -1.5% to 6.4%; P = .23). This indicates that the more complex, individualized approach offered no advantage in protecting the lungs over a simple, fixed low PEEP strategy.
Secondary Outcomes and Physiological Effects
While the primary clinical outcome showed no difference, the physiological and safety profiles of the two strategies differed markedly:
1. Hemodynamic Stability: The high PEEP group suffered significantly more intraoperative complications. Hypotension (defined as a decrease in mean arterial pressure of >20% for >3 minutes) occurred in 54.0% of the high PEEP group versus 45.0% in the low PEEP group. Consequently, the use of vasoactive agents was nearly double in the high PEEP group (32.0% vs 18.8%).
2. Oxygenation: The high PEEP group had a lower incidence of intraoperative desaturation (0.8% vs 2.8%). However, this transient physiological benefit did not translate into fewer postoperative complications or shorter hospital stays.
3. Surgical Duration and PEEP Levels: The median PEEP in the individualized group was significantly higher than the 5 cm H2O used in the control group, reflecting the aggressive nature of the recruitment strategy.
Expert Commentary: Interpreting the Data
The failure of individualized high PEEP to improve outcomes in the DESIGNATION trial mirrors findings from previous large-scale perioperative trials, such as the PROVHILO and iPROVE studies. These results suggest that for the majority of patients undergoing abdominal surgery, the “open lung approach” (high PEEP and recruitment maneuvers) may be more harmful than beneficial due to its cardiovascular impact.
The Driving Pressure Paradox
Why did a strategy based on optimizing lung compliance fail? Experts suggest several possibilities. First, in healthy lungs (or lungs without significant pre-existing injury), the benefit of recruiting small areas of atelectasis may be outweighed by the negative effects of cyclic overdistension and the increased intrathoracic pressure. Second, the hemodynamic compromise caused by high PEEP can lead to reduced organ perfusion, potentially counteracting any pulmonary benefit. The significant increase in vasoactive agent requirements in the high PEEP group highlights the physiological strain this strategy places on the right heart and systemic circulation.
Clinical Generalizability
It is important to note that this study focused on open abdominal surgery. Whether these findings apply to laparoscopic surgery—where pneumoperitoneum significantly alters chest wall compliance—remains a topic for further investigation. However, for open procedures, the data now strongly support the use of a standard low PEEP approach (around 5 cm H2O) combined with low tidal volumes.
Conclusion and Summary
The DESIGNATION trial provides high-quality evidence that intraoperative ventilation with driving pressure-guided high PEEP and recruitment maneuvers does not reduce postoperative pulmonary complications in patients undergoing open abdominal surgery. Instead, this strategy increases the risk of intraoperative hemodynamic instability, characterized by hypotension and a higher requirement for vasopressors.
For clinicians, the takeaway is clear: the complexity and risks associated with individualizing PEEP based on driving pressure are not justified by clinical outcomes in this population. A protective ventilation strategy consisting of low tidal volumes and a modest, fixed PEEP remains the most prudent and evidence-based approach for preventing pulmonary complications while maintaining hemodynamic stability.
Funding and Trial Registration
This trial was supported by various academic and clinical research grants across the participating European nations.
Trial Registration: ClinicalTrials.gov Identifier: NCT03884543.
References
1. Writing and Steering Committees for the DESIGNATION–Investigators; Dorland G, Gama de Abreu M, Hemmes SNT, et al. Intraoperative Driving Pressure-Guided High PEEP vs Standard Low PEEP for Postoperative Pulmonary Complications. JAMA. 2025 Dec 3:e2523373. doi: 10.1001/jama.2025.23373.
2. PROVE Network Investigators. High prior to low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet. 2014;384(9942):495-503.
3. Ferrando C, Soro M, Canet J, et al. Individualised perioperative open-lung strategy versus standard protective ventilation in patients undergoing abdominal surgery (iPROVE): a randomised controlled trial. Lancet Respir Med. 2018;6(3):193-203.
4. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755.