Optimal PEEP for Postoperative Oxygenation and Lung Aeration (ULTRASVENT-2)

Official title

Effect of Positive End-Expiratory Pressure (PEEP) Level on Postoperative Oxygenation and Lung Aeration Assessed by Lung Ultrasound Monitoring: A Multicenter Randomized Controlled Trial (ULTRASVENT-2)

Overview

The purpose of this multicenter, randomized controlled trial (ULTRASVENT-2) is to evaluate the effect of different positive end-expiratory pressure (PEEP) levels on postoperative oxygenation and lung aeration in adult patients undergoing elective non-cardiac and non-thoracic surgery under general anesthesia. Moving away from traditional binary outcomes, this study utilizes a continuous functional metric, the non-invasive oxygenation index SpO2/FiO2 (S/F ratio), as the primary endpoint to precisely capture the degree of respiratory function preservation. Patients will be stratified into four distinct surgical cohorts based on the type and aggressiveness of the procedure: non-abdominal surgery, major open abdominal surgery, major laparoscopic abdominal surgery, and low-trauma laparoscopic surgery. This adaptive design aims to investigate how protective PEEP strategies interact with varying degrees of surgical trauma and intraoperative pneumoperitoneum, allowing the optimization of mechanical ventilation parameters for routine clinical practice.

Detailed description

Postoperative pulmonary complications remain a significant cause of morbidity and prolonged hospital stay after major surgical interventions under general anesthesia. While positive end-expiratory pressure (PEEP) is widely used to prevent alveolar collapse, the optimal target levels across different surgical sub-types remain controversial in modern anesthesiology. This trial aims to establish robust clinical evidence regarding perioperative lung protection using a comprehensive functional-anatomical approach.

Primary Endpoint and Measurement Standardization:

The primary outcome of the trial is the non-invasive oxygenation index, the S/F ratio (SpO2/Fraction of inspired oxygen), assessed exactly 2 hours post-extubation in the Post-Anesthesia Care Unit (PACU) and tracked dynamically over the first 24 hours of the postoperative period. To eliminate confounding variables and ensure absolute reproducibility across participating centers, the primary endpoint measurement is strictly standardized according to the following criteria:

1. Room Air Breathing (FiO2 0.21): The evaluation is performed while the patient breathes atmospheric air without supplemental oxygen. This eliminates the masking of intrapulmonary shunts and prevents hyperoxia-induced absorption atelectasis. 2. Patient Position: The patient must be placed in a strict supine position. This positioning represents the most physiologically challenging state for the respiratory system, inducing cranial displacement of the diaphragm and maximizing gravity-dependent alveolar collapse. 3. Full Wakefulness Criteria: The measurement is executed only when the patient reaches a full awake status, defined as a modified Post Anesthesia Recovery Score (PARS) greater than 8, with the specific ventilation sub-score being equal to 2 (ability to deep breathe and cough freely). This cognitive and motor filter guarantees that any recorded functional impairment is caused by true parenchymal collapse rather than residual neuromuscular blockade or opioid-induced respiratory depression.

Differentiated Lung Ultrasound (LUS) Track:

To identify the anatomical substrate behind changes in gas exchange, regional lung aeration patterns will be recorded as the key secondary endpoint using a delta LUS score (postoperative score minus preoperative baseline). The diagnostic burden on the investigators is optimized using two parallel diagnostic tracks:

* Express Track (Strata 1 and 4): A rapid, 2-zone simplified protocol focusing exclusively on the most gravity-dependent bilateral dorsal-basal sectors (Zone 6). This assessment takes 2 to 3 minutes and minimizes interference with routine PACU workflows. * Panoramic Mapping Track (Strata 2 and 3): A comprehensive 12-zone thoracic mapping performed under Intensive Care Unit (ICU) conditions. Furthermore, a nested validation sub-study will incorporate high-resolution chest computed tomography (CT) scans performed strictly based on clinical indications (such as refractory hypoxemia or suspected pneumonia). CT data will serve as the gold standard reference to calculate the true sensitivity and specificity of the 12-zone ultrasound findings.

Surgical Stratification and Sample Size Design:

Patients will be randomized in a 1:1 ratio to receive either a fixed standard (lower) PEEP or a fixed higher PEEP strategy throughout the intraoperative period (from intubation to extubation). Randomization is performed independently within 4 parallel strata to achieve a total sample size of 320 to 360 patients:

* Strata 1: Non-abdominal surgery (n = 100; PEEP 5 cm H2O versus PEEP 8 cm H2O). * Strata 2: Major open abdominal surgery (n = 60 to 80; PEEP 5 cm H2O versus PEEP 8 cm H2O). * Strata 3: Major laparoscopic abdominal surgery (n = 60 to 80; PEEP 7 cm H2O versus PEEP 12 cm H2O). * Strata 4: Low-trauma laparoscopic surgery (n = 100; PEEP 5 cm H2O versus PEEP 12 cm H2O).

Statistical Analysis Framework:

Data processing will be conducted in the jamovi software environment using General Linear Models (GLM). The analysis will incorporate continuous and categorical baseline covariates (Body Mass Index, age, ASA physical status, and duration of surgery) to reduce residual variance. A key element of the statistical plan is the evaluation of interaction effects between the PEEP level and the specific surgical stratum to determine whether a higher PEEP provides a universal benefit or if its protective role is strictly dependent on the surgical phenotype.

Implementation Protocol Phases:

To guarantee data integrity and eliminate investigator bias, the project is structured into four consecutive logical phases:

Phase 1: Regulatory start, including central registration on ClinicalTrials.gov, Local Ethics Committee (LEC) submission and approval, and prospective publication of the formal Study Protocol manuscript.

Phase 2: Standardized hands-on calibration and training of the core investigator team (4 to 6 specialists) regarding precise zone identification and digital data entry.

Phase 3: A mandatory run-in period dedicated to inter-rater reliability testing. Each investigator must scan a test cohort, and the enrollment of randomized trial patients can begin only after achieving an inter-operator consensus threshold defined as a Cohen's Kappa coefficient greater than or equal to 0.7 and an absolute category agreement greater than or equal to 80%.

Phase 4: Active enrollment utilizing an adaptive recruitment strategy. The trial will commence by enrolling patients in high-volume, low-risk groups (Strata 1 and 4) to seamlessly refine logistical and database processes before activating the complex and labor-intensive ICU-based cohorts (Strata 2 and 3).

Interventions

• Procedure Intraoperative Positive End-Expiratory Pressure (PEEP) Regulation
  Application of fixed PEEP levels calculated according to surgical aggressiveness and the presence of pneumoperitoneum. Standard PEEP arm utilizes PEEP values of 5 cm H2O. Higher PEEP arm utilizes protective PEEP values of 8 or 12 cm H2O. The assigned PEEP strategy is initiated immediately following endotracheal intubation and maintained continuously until extubation.

Primary outcome measures

• Non-invasive oxygenation index (SpO2/FiO2 ratio) [Time frame: Assessed at 3 time points: preoperatively (baseline); exactly 2 hours post-extubation; and 24 hours post-operation.]

Secondary outcome measures (3)

• Incidence of Postoperative Pulmonary Complications (PPCs) [Time frame: From the end of surgery up to 7 days post-operation.]
• Postoperative lung ultrasound score and aeration patterns [Time frame: Exactly 2 hours post-extubation in the Post-Anesthesia Care Unit (PACU) or Intensive Care Unit (ICU).]
• Incidence of Intraoperative Hemodynamic Instability [Time frame: Intraoperatively (from the moment of endotracheal intubation until extubation).]

Eligibility criteria

Inclusion criteria

• Age greater than or equal to 18 years.
• Planned elective non-cardiac and non-thoracic surgical intervention requiring general anesthesia with mechanical ventilation.
• Airway protection utilizing an endotracheal tube.
• Assignment to one of the four specific surgical strata: non-abdominal, major open abdominal, major laparoscopic abdominal, or low-trauma laparoscopic surgery.
• Baseline lung ultrasound showing no pathological findings, corresponding to a total preoperative LUS score of 0.
• Technical feasibility of performing a postoperative lung ultrasound within the first 2 hours after the completion of surgery.
• Signed written informed consent to participate in the clinical trial.

Exclusion criteria

• Planned cardiac or thoracic surgery (e.g., coronary artery bypass grafting, valve replacement, heart transplantation, lung resection, esophageal surgery).
• Pneumothorax diagnosed before or during the surgical procedure.
• Inability to adequately visualize the target dorsal-basal lung zones by ultrasound due to physical limitations (e.g., morbid obesity, massive surgical dressings, anatomical anomalies, or dermatological lesions in the scanning area).
• Presence of hydrothorax detected on the baseline preoperative ultrasound.
• Confirmed perioperative aspiration of gastric contents or other foreign material.
• Any pathological changes identified during the baseline ultrasound of the dorsal-basal lung regions (a total preoperative LUS score greater than 0).
• Requirement for massive blood transfusion during the surgery, defined according to local institutional criteria.
• Surgical interventions directly involving or violating the diaphragm.
• Expected inability to conduct reliable postoperative clinical and ultrasound assessments (e.g., need for deep sedation preventing wakefulness and contact, or planned transfer to another facility).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Russia · 1 center

• Moscow Multi-disciplinary Clinical Center "Kommunarka" — Moscow

Publications

• L D, Kumar R, Patel N, Ayub A, Rewari V, Subramaniam R, Roy KK. Effect of Lung Compliance-Based Optimum Pressure Versus Fixed Positive End-Expiratory Pressure on Lung Atelectasis Assessed by Modified Lung Ultrasound Score in Laparoscopic Gynecological Surgery: A Prospective Randomized Controlled Trial. Cureus. 2023 Jun 12;15(6):e40278. doi: 10.7759/cureus.40278. eCollection 2023 Jun. PMID 37448389
• Miskovic A, Lumb AB. Postoperative pulmonary complications. Br J Anaesth. 2017 Mar 1;118(3):317-334. doi: 10.1093/bja/aex002. PMID 28186222
• Zhang Y, Zhu J, Xi C, Wang G. Effect of driving pressure-guided individualized positive end-expiratory pressure (PEEP) ventilation strategy on postoperative atelectasis in patients undergoing laparoscopic surgery as assessed by ultrasonography: study protocol for a prospective randomized controlled trial. Trials. 2025 Mar 26;26(1):106. doi: 10.1186/s13063-025-08819-5. PMID 40140868
• Frassanito L, Sonnino C, Pitoni S, Zanfini BA, Catarci S, Gonnella GL, Germini P, Vizzielli G, Scambia G, Draisci G. Lung ultrasound to monitor the development of pulmonary atelectasis in gynecologic oncologic surgery. Minerva Anestesiol. 2020 Dec;86(12):1287-1295. doi: 10.23736/S0375-9393.20.14687-X. Epub 2020 Nov 11. PMID 33174404
• Ma J, Sun M, Song F, Wang A, Tian X, Wu Y, Wang L, Zhao Q, Liu B, Wang S, Qiu Y, Hou H, Deng L. Effect of ultrasound-guided individualized positive end-expiratory pressure on the severity of postoperative atelectasis in elderly patients: a randomized controlled study. Sci Rep. 2024 Nov 15;14(1):28128. doi: 10.1038/s41598-024-79105-8. PMID 39548165
• Liao B, Liao W, Yin S, Liu S, Wu X. Effect of ultrasound-guided lung recruitment to reduce pulmonary atelectasis after non-cardiac surgery under general anesthesia: a systematic review and meta-analysis of randomized controlled trials. Perioper Med (Lond). 2024 Mar 27;13(1):23. doi: 10.1186/s13741-024-00379-7. PMID 38539248
• Wu XZ, Xia HM, Zhang P, Li L, Hu QH, Guo SP, Li TY. Effects of ultrasound-guided alveolar recruitment manoeuvres compared with sustained inflation or no recruitment manoeuvres on atelectasis in laparoscopic gynaecological surgery as assessed by ultrasonography: a randomized clinical trial. BMC Anesthesiol. 2022 Aug 16;22(1):261. doi: 10.1186/s12871-022-01798-z. PMID 35974310

Identifiers

NCT: NCT07613177 · ULTRASVENT-2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗