Individualized PEEP Titration on Postoperative Pulmonary Complications

Effect of Individualized PEEP Titration on Postoperative Pulmonary Complications in Elderly Patients Undergoing Major Laparoscopic Surgery- A Multicenter Randomized Controlled Clinical Trial

This study aims to investigate the effectiveness and safety of implementing a personalized positive end-expiratory pressure (PEEP) management strategy guided by esophageal pressure (Pes), as well as its potential to reduce the occurrence of postoperative pulmonary complications (PPCs) in elderly patients undergoing laparoscopic surgery.

Study Overview

• Status: Completed
• Conditions: Laparoscopic Surgery; Elderly; Postoperative Pulmonary Complications; Positive End-expiratory Pressure
• Intervention / Treatment: Procedure: Pes-Guided PEEP titration

Detailed Description

This trial is a single-blind, randomized, controlled, multicenter study. Elderly patients undergoing laparoscopic surgery under general anesthesia will be recruited according the inclusion and exclusion criteria. Participants in this study will be randomly assigned into two groups. The total sample size will be 232, with 116 participants in the experimental group and 116 participants in the control group. A stratified block randomization method will be employed, using the ARISCAT score for PPCs risk assessment and individual study centers as stratification factors. Anesthesia routine will be applied during pre-anesthetic preparation, anesthetic induction, maintenance and emergence except intraoperative respiratory management. In the control group, fixed PEEP of 3 cmH2O is applied throughout the procedure without lung recruitment maneuvers. While in the experimental group (Pes-Guided Group), continuous monitoring of end-expiratory esophageal pressure (Pes) is conducted. PEEP is chosen to maintain a positive transpulmonary pressure at end-expiration (PL = PEEP - Pes) after lung recruitment. PEEP titration following lung recruitment should be performed after endotracheal intubation or any procedure that may cause lung collapse, such as pneumoperitoneum, deflation or inflation of the endotracheal tube cuff, changes in position, or endotracheal suctioning. PEEP Titration is also required every hour after the establishment of pneumoperitoneum. Patients will be followed up within 7 days after surgery to assess basic vital signs, potential postoperative pulmonary complications (PPCs). Additionally, postoperative non-respiratory complications will be evaluated. Laboratory tests, the 15-item Quality of Recovery-15 (QoR-15) questionnaire, complications within 30 days after surgery, and 90-day survival rates will also be recorded.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200032
    • 180 Fenglin Road
  • Shanghai, China
    • Shanghai Geriatric Medical Center
  • Xiamen, China
    • Zhongshan Hospital (Xiamen), Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged 65 years or older, male or female
2. Scheduled to perform major laparoscopic surgery under general anesthesia
3. Expected duration of surgery ≥ 2 hours
4. Written informed consent is obtainable either from the patient or from a legal surrogate

Exclusion Criteria:

1. BMI ≥ 35 kg/m2.
2. History of pulmonary surgery (of any type).
3. History of severe chronic obstructive pulmonary disease (COPD) requiring non-invasive ventilation and/or home oxygen therapy.
4. Patients on systemic corticosteroid treatment for acute chronic obstructive pulmonary disease exacerbation.
5. Severe pulmonary arterial hypertension, defined as systolic pulmonary artery pressure > 40 mmHg.
6. Heart failure according to the New York Heart Association classification (class III or IV), ongoing hemodynamic instability, or severe shock (determined by the attending internist, cardiac index < 2.5 L/min/m2, or the requirement for positive inotropic drugs to maintain blood pressure).
7. Severe cardiac disease (acute coronary syndrome according to Canadian Cardiovascular Society, atrial flutter/fibrillation, sustained ventricular tachyarrhythmias, metabolic equivalent of tasks (METs) < 4) (METs < 4, determined by the inability to climb ≥ 2 flights of stairs).
8. Severe liver or renal dysfunction (Child-Pugh score 10-15, serum creatinine ≥ 2 mg/dL, or patients requiring peritoneal dialysis or hemodialysis).
9. Neuromuscular disease (of any type).
10. History of bone marrow transplantation or recent history of immunosuppressive drugs (chemotherapy or radiotherapy within 2 months before surgery).
11. Mechanical ventilation duration > 30 minutes within the past 30 days (e.g., surgery under general anesthesia).
12. Requirement for one-lung ventilation.
13. History of acute respiratory distress syndrome with potential need for prolonged postoperative mechanical ventilation.
14. Planned re-intubation after surgery.
15. Pregnancy (excluded by medical history and/or laboratory tests).
16. Brain injury or tumor.
17. Requirement for prone or lateral position during surgery.
18. Severe esophagogastric varices.
19. Enrollment in other interventional studies or refusal to sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; After endotracheal intubation, an esophageal balloon is placed and calibrated for accurate positioning and inflation pressure. Continuous monitoring of end-expiratory esophageal pressure (Pes) is conducted. Fixed PEEP of 3 cmH2O is applied throughout the procedure without lung recruitment maneuvers.
Experimental: Pes-Guided Group; After endotracheal intubation, an esophageal balloon is placed and calibrated for accurate positioning and inflation pressure. Continuous monitoring of end-expiratory esophageal pressure (Pes) is conducted. Lung recruitment is performed at each time point. After lung recruitment, ventilation is adjusted based on the target PEEP. PEEP is chosen to maintain a positive transpulmonary pressure at end-expiration (PL = PEEP - Pes). PEEP titration following lung recruitment should be performed within 1 hour after endotracheal intubation or any procedure that may cause lung collapse, such as pneumoperitoneum, deflation or inflation of the endotracheal tube cuff, changes in position, or endotracheal suctioning.	Procedure: Pes-Guided PEEP titration; Lung recruitment is performed at each time point, involving a switch from volume-controlled (VCV) mode to pressure-controlled (PCV) mode with a pressure setting of 20 cmH2O, RR of 15 bpm, I:E ratio of 1:1, FiO2 of 0.4, and PEEP of 5 cmH2O. During lung recruitment, PEEP is gradually increased in increments of 5 cmH2O, maintained for 5 respiratory cycles until PEEP reaches 20 cmH2O and airway pressure reaches 40 cmH2O, and then maintained for 10 respiratory cycles. After lung recruitment, ventilation is adjusted based on the target PEEP. Each PEEP titration should ensure adequate muscle relaxation, volume status, and hemodynamic stability. PEEP is chosen to maintain a positive transpulmonary pressure at end-expiration (PL = PEEP - Pes). Each PEEP titration should ensure adequate muscle relaxation, volume status, and hemodynamic stability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative pulmonary complications	the incidence of postoperative pulmonary complications	within 7 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
airway peak pressure (cmH2O)	intraoperative mechanical ventilation parameters	intraoperative
driving pressure (cmH2O)	intraoperative mechanical ventilation parameters	intraoperative
dynamic lung compliance (mL/cmH20)	Cdyn = Vt/(Ppeak - PEEP)	intraoperative
unplanned reintubation	the incidence of unplanned reintubation	day 1 to day 7 after surgery
unplanned transfer to the ICU	the incidence of unplanned transfer to the ICU	day 1 to day 7 after surgery
duration of ICU stay	duration of ICU stay	day 1 after surgery to the day of discharge, assessed up to 90 days
length of hospital stay	the number of days from a patient's hospital admission to discharge	from the day of admission to the day of discharge, assessed up to 90 days
plateau pressure	intraoperative mechanical ventilation parameters	intraoperative
positive end-expiratory pressure	intraoperative mechanical ventilation parameters	intraoperative
Interleukin-6 level	biological indices, result from blood sample	before surgery, before the end of surgery and in post-anesthetic care unit
Clara cell secretory protein-16 level	biological indices, result from blood samples	before surgery, before the end of surgery and in post-anesthetic care unit
soluble receptor for advanced glycation end product level	biological indices, result from blood samples	before surgery, before the end of surgery and in post-anesthetic care unit
angiopoietin-2 level	biological indices, result from blood samples	before surgery, before the end of surgery and in post-anesthetic care unit
plasminogen activator inhibitor-1	biological indices, result from blood samples	before surgery, before the end of surgery and in post-anesthetic care unit
static compliance (mL/cmH20)	pulmonary compliance measured at a fixed volume with no airflow and fully relaxed muscles. static compliance = VT / (Pplat - PEEP)	intraoperative
PaO2/FiO2 ratio	the ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2), measured through blood gas analysis	before surgery, intraoperative, and in post-anesthetic care unit
non-respiratory complications	the incidence of stroke, myocardial infarction, acute renal failure, DIC, SIRS, sepsis, septic shock, wound infection	within 7 days after surgery
QoR-15 scores	early quality of recovery	day 1 and day 7 after surgery, the day of discharge
mortality rates	mortality rates	at 90 days after surgery
complications	including postoperative respiratory and non-respiratory complications	at 30 days after surgery
vital signs	vital signs will be recorded at any key time points from admission to operating room to extubation	admission to operating room to day 7 after surgery, and the day of discharge
esophageal pressure (Pes)	a classical and most widely used marker of pleural pressure which is usually measured by air-filled balloons	intraoperative
transpulmonary pressure (PL)	equal to the difference between alveolar pressure and pleural pressure	intraoperative
Vasoactive medications dosages	Vasoactive medications includes norepinephrine, phenylephrine, ephedrine	intraoperative

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Fudan University; Zhongshan Hospital (Xiamen), Fudan University; Shanghai Geriatric Medical Center
• Investigators: Study Director: Changhong Miao, Zhongshang Hospital Fudan University; Principal Investigator: Jing Zhong, Zhongshang Hospital Fudan University

Publications and helpful links

General Publications

• Fernandez-Bustamante A, Frendl G, Sprung J, Kor DJ, Subramaniam B, Martinez Ruiz R, Lee JW, Henderson WG, Moss A, Mehdiratta N, Colwell MM, Bartels K, Kolodzie K, Giquel J, Vidal Melo MF. Postoperative Pulmonary Complications, Early Mortality, and Hospital Stay Following Noncardiothoracic Surgery: A Multicenter Study by the Perioperative Research Network Investigators. JAMA Surg. 2017 Feb 1;152(2):157-166. doi: 10.1001/jamasurg.2016.4065.
• Canet J, Gallart L, Gomar C, Paluzie G, Valles J, Castillo J, Sabate S, Mazo V, Briones Z, Sanchis J; ARISCAT Group. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology. 2010 Dec;113(6):1338-50. doi: 10.1097/ALN.0b013e3181fc6e0a.
• Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, Pelosi P, Talmor D, Grasso S, Chiumello D, Guerin C, Patroniti N, Ranieri VM, Gattinoni L, Nava S, Terragni PP, Pesenti A, Tobin M, Mancebo J, Brochard L; PLUG Working Group (Acute Respiratory Failure Section of the European Society of Intensive Care Medicine). The application of esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014 Mar 1;189(5):520-31. doi: 10.1164/rccm.201312-2193CI.
• Ferrando C, Soro M, Unzueta C, Suarez-Sipmann F, Canet J, Librero J, Pozo N, Peiro S, Llombart A, Leon I, India I, Aldecoa C, Diaz-Cambronero O, Pestana D, Redondo FJ, Garutti I, Balust J, Garcia JI, Ibanez M, Granell M, Rodriguez A, Gallego L, de la Matta M, Gonzalez R, Brunelli A, Garcia J, Rovira L, Barrios F, Torres V, Hernandez S, Gracia E, Gine M, Garcia M, Garcia N, Miguel L, Sanchez S, Pineiro P, Pujol R, Garcia-Del-Valle S, Valdivia J, Hernandez MJ, Padron O, Colas A, Puig J, Azparren G, Tusman G, Villar J, Belda J; Individualized PeRioperative Open-lung VEntilation (iPROVE) Network. Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial. Lancet Respir Med. 2018 Mar;6(3):193-203. doi: 10.1016/S2213-2600(18)30024-9. Epub 2018 Jan 19.
• Tusman G, Bohm SH, Warner DO, Sprung J. Atelectasis and perioperative pulmonary complications in high-risk patients. Curr Opin Anaesthesiol. 2012 Feb;25(1):1-10. doi: 10.1097/ACO.0b013e32834dd1eb.
• Hegeman MA, Hemmes SN, Kuipers MT, Bos LD, Jongsma G, Roelofs JJ, van der Sluijs KF, Juffermans NP, Vroom MB, Schultz MJ. The extent of ventilator-induced lung injury in mice partly depends on duration of mechanical ventilation. Crit Care Res Pract. 2013;2013:435236. doi: 10.1155/2013/435236. Epub 2013 Apr 17.
• Zhang C, Xu F, Li W, Tong X, Xia R, Wang W, Du J, Shi X. Driving Pressure-Guided Individualized Positive End-Expiratory Pressure in Abdominal Surgery: A Randomized Controlled Trial. Anesth Analg. 2021 Nov 1;133(5):1197-1205. doi: 10.1213/ANE.0000000000005575.
• Fernandez-Bustamante A, Sprung J, Parker RA, Bartels K, Weingarten TN, Kosour C, Thompson BT, Vidal Melo MF. Individualized PEEP to optimise respiratory mechanics during abdominal surgery: a pilot randomised controlled trial. Br J Anaesth. 2020 Sep;125(3):383-392. doi: 10.1016/j.bja.2020.06.030. Epub 2020 Jul 16.
• Cammarota G, Lauro G, Sguazzotti I, Mariano I, Perucca R, Messina A, Zanoni M, Garofalo E, Bruni A, Della Corte F, Navalesi P, Bignami E, Vaschetto R, Mojoli F. Esophageal Pressure Versus Gas Exchange to Set PEEP During Intraoperative Ventilation. Respir Care. 2020 May;65(5):625-635. doi: 10.4187/respcare.07238.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2023
• Primary Completion (Actual): November 18, 2024
• Study Completion (Actual): February 9, 2025

Study Registration Dates

• First Submitted: November 11, 2023
• First Submitted That Met QC Criteria: November 27, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: B2023-334R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data generated during the study will be made available on reasonable request to qualified researchers, following publication of the primary results, and in accordance with institutional and ethical guidelines.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No