Clinical trial NCT06150079: Individualized PEEP Titration on Postoperative Pulmonary Complications
Official title: Effect of Individualized PEEP Titration on Postoperative Pulmonary Complications in Elderly Patients Undergoing Major Laparoscopic Surgery- A Multicenter Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postoperative Pulmonary Complications
Positive End-expiratory Pressure
Elderly
Laparoscopic Surgery
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Geriatric Medical Center
name: Zhongshan Hospital (Xiamen), Fudan University
name: Fudan University
First posted: 2023-11-29
Enrollment: 240
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 65 years or older, of any gender.
2. Scheduled to perform major laparoscopic surgery under general anesthesia.
3. Anticipated duration of surgery ≥ 2 hours.
4. Willingness to sign informed consent or provide a legally authorized representative.

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, or systemic corticosteroid treatment for acute COPD exacerbations.
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 (as 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\[28,29\] indicates poor or unknown functional capacity. Activity examples of METs 3 - 4 are brisk walking (4 - 5 km/h), climbing stairs (≤ 2 flights) with slow pace and gentle cycling (\<16 km/h)).
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 use of immunosuppressive drugs (chemotherapy or radiotherapy within 2 months before surgery).
11. Mechanical ventilation duration \> 30 minutes within the past 30 days (e.g., during 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.

Primary outcomes:
measure: postoperative pulmonary complications
timeFrame: within 7 days after surgery
Secondary outcomes:
measure: airway peak pressure (cmH2O)
timeFrame: intraoperative
measure: plateau pressure
timeFrame: intraoperative
measure: positive end-expiratory pressure
timeFrame: intraoperative
measure: esophageal pressure
timeFrame: intraoperative
measure: driving pressure (cmH2O)
timeFrame: intraoperative
measure: transpulmonary pressure
timeFrame: intraoperative
measure: dynamic lung compliance (mL/cmH20)
timeFrame: intraoperative
measure: static compliance (mL/cmH20)
timeFrame: intraoperative
measure: PaCO2 (mmHg)
timeFrame: before surgery, intraoperative, and in post-anesthetic care unit
measure: PaO2/FiO2 ratio
timeFrame: before surgery, intraoperative, and in post-anesthetic care unit
measure: non-respiratory complications
timeFrame: within 7 days after surgery
measure: QoR-15 scores
timeFrame: day 1 and day 7 after surgery, the day of discharge
measure: unplanned reintubation
timeFrame: day 1 to day 7 after surgery
measure: unplanned transfer to the ICU
timeFrame: day 1 to day 7 after surgery
measure: duration of ICU stay
timeFrame: day 1 after surgery to the day of discharge, assessed up to 90 days
measure: length of hospital stay
timeFrame: from the day of admission to the day of discharge, assessed up to 90 days
measure: Interleukin-6 level
timeFrame: before surgery, before the end of surgery and in post-anesthetic care unit
measure: Clara cell secretory protein-16 level
timeFrame: before surgery, before the end of surgery and in post-anesthetic care unit
measure: soluble receptor for advanced glycation end product level
timeFrame: before surgery, before the end of surgery and in post-anesthetic care unit
measure: angiopoietin-2 level
timeFrame: before surgery, before the end of surgery and in post-anesthetic care unit
measure: plasminogen activator inhibitor-1
timeFrame: before surgery, before the end of surgery and in post-anesthetic care unit
measure: mortality rates
timeFrame: at 90 days after surgery
measure: complications
timeFrame: at 30 days after surgery
measure: vital signs
timeFrame: admission to operating room to day 7 after surgery, and the day of discharge
Other outcomes:
Locations:
city: Shanghai
country: China
facility: 180 Fenglin Road
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Geriatric Medical Center
city: Xiamen
country: China
facility: Zhongshan Hospital (Xiamen), Fudan University
Study officials:
affiliation: Zhongshang Hospital Fudan University
name: Changhong Miao
role: STUDY_DIRECTOR
affiliation: Zhongshang Hospital Fudan University
name: Jing Zhong
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.