Protective Ventilation With High Versus Low PEEP During One-lung Ventilation for Thoracic Surgery

PROtective Ventilation With High Versus Low PEEP During One-lung Ventilation for THORacic Surgery PROTHOR: A Randomized Controlled Trial

One-lung ventilation (OLV) with resting of the contralateral lung may be required to allow or facilitate thoracic surgery. However, OLV can result in severe hypoxemia, requiring a mechanical ventilation approach that is able to maintain adequate gas exchange, while protecting the lungs against postoperative pulmonary complications (PPCs). During OLV, the use of lower tidal volumes is helpful to avoid over-distension, but can result in increased atelectasis and repetitive collapse-and-reopening of lung units, particularly at low levels of positive end-expiratory pressure (PEEP).

Anesthesiologists inconsistently use PEEP and recruitment maneuvers (RM) in the hope that this may improve oxygenation and protect against PPC. Up to now, it is not known whether high levels of PEEP combined with RM are superior to lower PEEP without RM for protection against PPCs during OLV.

Hypothesis: An intra-operative ventilation strategy using higher levels of PEEP and recruitment maneuvers, as compared to ventilation with lower levels of PEEP without recruitment maneuvers, prevents postoperative pulmonary complications in patients undergoing thoracic surgery under standardized one-lung ventilation.

Study Overview

• Status: Completed
• Conditions: One-Lung Ventilation
• Intervention / Treatment: Procedure: PEEP level; Procedure: Use of recruitment maneuvers

• Study Type: Interventional
• Enrollment (Actual): 2200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Albania
  • Tirana, Albania
    • American Hospital Tirana
• Austria
  • Vienna, Austria
    • Medical University of Vienna
• Brazil
  • Barretos, Brazil
    • Hospital de Amor, Barretos
  • São Paulo, Brazil
    • São Paulo Hospital
  • São Paulo, Brazil
    • Clinics Hospital from the Botucatu Medical School, University of Sao Paulo State
• Chile
  • Santiago, Chile
    • Pontificia Universidad Catolica de Chile
• China
  • Guangzhou, China
    • First Affiliated Hospital of Guangzhou Medical University, China
  • Hefei, China
    • Anhui Provincial Hospital, First Aff. Hospital, University of Science and Technology of China
  • Shanghai, China
    • Zhongshan Hospital Fudan University
  • Shanghai, China
    • Fudan University, Shanghai Cancer Center
  • Sichuan, China
    • West China Hospital Sichuan
• Croatia
  • Zagreb, Croatia
    • University Hospital Zagreb
  • Zagreb, Croatia
    • University Hospital Dubrava
• Cyprus
  • Égkomi, Cyprus
    • Evangelistria Medical Center, Cyprus
• Czechia
  • Prague, Czechia
    • General University Hospital
• Egypt
  • Al Mansurah, Egypt
    • Mansoura University Hospitals, Egypt
  • Tanta, Egypt
    • Tanta University Hospital
• France
  • Dijon, France
    • University Hospital of Dijon - François Mitterrand
• Germany
  • Aachen, Germany
    • University Hospital Aachen
  • Coswig, Germany
    • Fachkrankenhaus Coswig
  • Dresden, Germany, 01307
    • Department of Anesthesiology and Intensive Care, Dresden University of Technology
  • Freiburg im Breisgau, Germany
    • University Hospital Freiburg
  • Göttingen, Germany
    • University Hospital Goettingen, Germany
  • Magdeburg, Germany
    • University Hospital Magdeburg
  • München, Germany
    • LMU Muenchen
• Greece
  • Athens, Greece
    • Attikon University Hospital
  • Athens, Greece
    • Sotiria Chest Hospital
  • Heraklion, Greece
    • University Hospital of Heraklion
  • Pátrai, Greece
    • Patras University Hospital
• Hungary
  • Debrecen, Hungary
    • University of Debrecen, Department of Anesthesiology and Intensive Care
• Iraq
  • Dihok, Iraq
    • Azadi Heart Center, Iraq
• Italy
  • Ferrara, Italy
    • Arcispedale Sant'Anna
  • Foggia, Italy
    • OORR Foggia, University of Foggia
  • Genova, Italy
    • Ospedale Policlinico San Martino
  • Messina, Italy
    • AOU G.Martino
  • Naples, Italy
    • University Hospital Vanvitelli
  • Parma, Italy
    • University Hospital of Parma
  • Rome, Italy
    • University School of Medicine Campus Bio-Medico of Rome
  • Udine, Italy
    • University-Hospital of Udine
• Japan
  • Tokyo, Japan
    • Juntendo University Hospital
• Latvia
  • Riga, Latvia
    • Riga East University Hospital, Riga, Latvia
• Mexico
  • Tlalpan, Mexico
    • Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center Amsterdam
  • Amsterdam, Netherlands
    • VU medical center Amsterdam
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Nijmegen, Netherlands
    • Radboud University Medical Centre Nijmegen
• Romania
  • Bucharest, Romania
    • Institutul de Pneumoftiziologie Bucharest
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Department of Anesthesia, College of Medicine, King Saud University Medical City, Saudi-Arabia
• Serbia
  • Belgrade, Serbia
    • Military Medical Academy
  • Belgrade, Serbia
    • University Clinical centre of Serbia, Serbia
  • Niš, Serbia
    • Clinical Center Nis, Clinic for anesthesia and intensive therapy
  • Novi Sad, Serbia
    • University of Novi Sad, Serbia
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre Ljubljana
• Spain
  • Barcelona, Spain
    • Hospital Clínic. Universitat de Barcelona
  • Las Palmas de Gran Canaria, Spain
    • Insular Hospital, Gran Canaria, Spain
  • Valencia, Spain
    • Hospital General Universitario de Valencia
  • Valencia, Spain
    • Hospital Universitario de La Ribera
  • Vigo, Spain
    • Hospital Alvaro Cunqueiro
• Switzerland
  • Geneva, Switzerland
    • University Hospital of Geneva
• Taiwan
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye)
    • Ankara University Medical Faculty
  • Ankara, Turkey (Türkiye)
    • Ankara Ataturk Chest Diseases And Chest Surgery Training and Research Hospital
  • Bakırköy, Turkey (Türkiye)
    • University of Health Sciences, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Turkey
  • Istanbul, Turkey (Türkiye)
    • Acıbadem Mehmet Ali Aydınlar University
  • Istanbul, Turkey (Türkiye)
    • Istanbul Kartal Dr. Lutfi Kirdar Education and Research Hospital
  • Istanbul, Turkey (Türkiye)
    • Istanbul University
  • Istanbul, Turkey (Türkiye)
    • Marmara University Medical Faculty
  • Konya, Turkey (Türkiye)
    • University of Health Science, Konya City Hospital, Turkey
  • Manisa, Turkey (Türkiye)
    • Celal Bayar University Medical Faculty, Dept of Anesthesiology
  • Mersin, Turkey (Türkiye)
    • Mersin University Medical Faculty
  • Pamukkale, Turkey (Türkiye)
    • Pamukkale University Dinizli
• United Kingdom
  • Bristol, United Kingdom
    • University Hospitals Bristol NHS Foundation Trust
  • Clydebank, United Kingdom
    • Golden Jubilee National Hospital
  • Leicester, United Kingdom
    • University Hospitals of Leicester
  • London, United Kingdom
    • St George's Hospital London
  • Sheffield, United Kingdom
    • NIHS Sheffield Clinical Research Facility
• United States
  • Massachusetts
    • Boston, Massachusetts, United States
      • Tufts Medical Center
  • New York
    • New York, New York, United States
      • NYC Cornell Medical College
  • Ohio
    • Cleveland, Ohio, United States
      • Cleveland Clinic, USA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV (no emergency surgery)
• BMI < 35 kg/m2
• age ≥ 18 years
• expected duration of surgery > 60 min
• planned lung separation with double lumen tube (DLT, not for study purpose only)
• most of ventilation time during surgery expected to be in OLV

Exclusion Criteria:

• COPD GOLD grades III and IV, lung fibrosis, documented bullae, severe emphysema, pneumothorax
• uncontrolled asthma
• Heart failure NYHA Grade 3 and 4, Coronary Heart Disease CCS Grade 3 and 4
• previous lung surgery
• documented pulmonary arterial hypertension >25mmHg MPAP at rest or > 40 mmHg syst. (estimated by ultrasound)
• documented or suspected neuromuscular disease (thymoma, myasthenia, myopathies, muscular dystrophies, others)
• planned mechanical ventilation after surgery
• bilateral procedures
• lung separation with other method than DLT (e.g. difficult airway, tracheostomy)
• surgery in prone position
• persistent hemodynamic instability, intractable shock
• intracranial injury or tumor
• enrollment in other interventional study or refusal of informed consent
• pregnancy (excluded by anamnesis and/or laboratory analysis)
• esophagectomy, pleural surgery only, sympathectomy surgery only, chest wall surgery only, mediastinal surgery only, lung transplantation
• presence before induction of anaesthesia of one of the adverse events, listed as postoperative pulmonary complications (aspiration, moderate respiratory failure, infiltrates, pulmonary infection, atelectasis, cardiopulmonary edema, pleural effusion, pneumothorax, pulmonary embolism, purulent pleuritis, lung hemorrhage)
• documented preoperative hypercapnia > 45mmHg (6kPa)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: THE HIGHER PEEP LEVEL; Mechanical ventilation with VT of 5 ml/kg PBW and the level of PEEP at 10 cmH2O with lung recruitment maneuvers	Procedure: PEEP level; Procedure: Use of recruitment maneuvers
Other: THE LOWER PEEP LEVEL; Mechanical ventilation with VT of 5 ml/kg PBW and the level of PEEP at 5 cmH2O without lung recruitment maneuvers	Procedure: PEEP level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients developing one or more postoperative pulmonary complications	90 days

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: Istanbul University; European Society of Anaesthesiology and Intensive Care
• Investigators: Principal Investigator: Mert Sentürk, Istanbul University Hospital

Publications and helpful links

General Publications

• Kiss T, Wittenstein J, Becker C, Birr K, Cinnella G, Cohen E, El Tahan MR, Falcao LF, Gregoretti C, Granell M, Hachenberg T, Hollmann MW, Jankovic R, Karzai W, Krassler J, Loop T, Licker MJ, Marczin N, Mills GH, Murrell MT, Neskovic V, Nisnevitch-Savarese Z, Pelosi P, Rossaint R, Schultz MJ, Serpa Neto A, Severgnini P, Szegedi L, Vegh T, Voyagis G, Zhong J, Gama de Abreu M, Senturk M; PROTHOR investigators; Research Workgroup PROtective VEntilation Network (PROVEnet) of the European Society of Anaesthesiology (ESA). Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial. Trials. 2019 Apr 11;20(1):213. doi: 10.1186/s13063-019-3208-8.

Helpful Links

• Trial Website

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: November 10, 2016
• First Submitted That Met QC Criteria: November 10, 2016
• First Posted (Estimated): November 15, 2016

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: one-lung ventilation; thoracic surgery; Mechanical ventilation; positive end-expiratory pressure; recruitment maneuver; postoperative pulmonary complication
• Other Study ID Numbers: EK 392092016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Study Protocol

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No