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

NCT02963025 | Completed DMC

• 1 other identifier: EK 392092016
• Study Type: interventional
• Target: 2,200
• Locations: 29 countries
• Sites: 79

Brief Summary

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.

Conditions

One-Lung Ventilation

Keywords

Mechanical ventilation; positive end-expiratory pressure; recruitment maneuver; one-lung ventilation; thoracic surgery; postoperative pulmonary complication

Outcome Measures

Primary Outcomes (1)

• The proportion of patients developing one or more postoperative pulmonary complications

  90 days

Study Arms (2)

THE HIGHER PEEP LEVEL

OTHER

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

THE LOWER PEEP LEVEL

OTHER

Mechanical ventilation with VT of 5 ml/kg PBW and the level of PEEP at 5 cmH2O without lung recruitment maneuvers

Procedure: PEEP level

Interventions

PEEP level PROCEDURE

THE HIGHER PEEP LEVEL; THE LOWER PEEP LEVEL

Use of recruitment maneuvers PROCEDURE

THE HIGHER PEEP LEVEL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Technische Universität Dresden: lead
• Istanbul University: collaborator
• European Society of Anaesthesiology and Intensive Care: collaborator

Study Sites (79)

Tufts Medical Center

Boston, Massachusetts, United States

Location

NYC Cornell Medical College

New York, New York, United States

Location

Cleveland Clinic, USA

Cleveland, Ohio, United States

Location

American Hospital Tirana

Tirana, Albania

Location

Medical University of Vienna

Vienna, Austria

Location

Hospital de Amor, Barretos

Barretos, Brazil

Location

Clinics Hospital from the Botucatu Medical School, University of Sao Paulo State

São Paulo, Brazil

Location

Sao Paulo Hospital

São Paulo, Brazil

Location

Pontificia Universidad Catolica de Chile

Santiago, Chile

Location

First Affiliated Hospital of Guangzhou Medical University, China

Guangzhou, China

Location

Anhui Provincial Hospital, First Aff. Hospital, University of Science and Technology of China

Hefei, China

Location

Fudan University, Shanghai Cancer Center

Shanghai, China

Location

Zhongshan Hospital Fudan University

Shanghai, China

Location

West China Hospital Sichuan

Sichuan, China

Location

University Hospital Dubrava

Zagreb, Croatia

Location

University Hospital Zagreb

Zagreb, Croatia

Location

Evangelistria Medical Center, Cyprus

Égkomi, Cyprus

Location

General University Hospital

Prague, Czechia

Location

Mansoura University Hospitals, Egypt

Al Mansurah, Egypt

Location

Tanta University Hospital

Tanta, Egypt

Location

University Hospital of Dijon - François Mitterrand

Dijon, France

Location

University Hospital Aachen

Aachen, Germany

Location

Fachkrankenhaus Coswig

Coswig, Germany

Location

Department of Anesthesiology and Intensive Care, Dresden University of Technology

Dresden, 01307, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, Germany

Location

University Hospital Goettingen, Germany

Göttingen, Germany

Location

University Hospital Magdeburg

Magdeburg, Germany

Location

LMU Muenchen

München, Germany

Location

Attikon University Hospital

Athens, Greece

Location

Sotiria Chest Hospital

Athens, Greece

Location

University Hospital of Heraklion

Heraklion, Greece

Location

Patras University Hospital

Pátrai, Greece

Location

University of Debrecen, Department of anesthesiology and Intensive Care

Debrecen, Hungary

Location

Azadi Heart Center, Iraq

Duhok, Iraq

Location

Arcispedale Sant'Anna

Ferrara, Italy

Location

OORR Foggia, University of Foggia

Foggia, Italy

Location

Ospedale Policlinico San Martino

Genova, Italy

Location

AOU G.Martino

Messina, Italy

Location

University Hospital Vanvitelli

Naples, Italy

Location

University Hospital of Parma

Parma, Italy

Location

University School of Medicine Campus Bio-Medico of Rome

Rome, Italy

Location

University-Hospital of Udine

Udine, Italy

Location

Juntendo University Hospital

Tokyo, Japan

Location

Riga East University Hospital, Riga, Latvia

Riga, Latvia

Location

Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico

Tlalpan, Mexico

Location

Academic Medical Center Amsterdam

Amsterdam, Netherlands

Location

VU medical center Amsterdam

Amsterdam, Netherlands

Location

Rijnstate Hospital

Arnhem, Netherlands

Location

Radboud University Medical Centre Nijmegen

Nijmegen, Netherlands

Location

Institutul de Pneumoftiziologie Bucharest

Bucharest, Romania

Location

Department of Anesthesia, College of Medicine, King Saud University Medical City, Saudi-Arabia

Riyadh, Saudi Arabia

Location

Military Medical Academy

Belgrade, Serbia

Location

University Clinical centre of Serbia, Serbia

Belgrade, Serbia

Location

Clinical Center Nis, Clinic for anesthesia and intensive therapy

Niš, Serbia

Location

University of Novi Sad, Serbia

Novi Sad, Serbia

Location

University Medical Centre Ljubljana

Ljubljana, Slovenia

Location

Hospital Clínic. Universitat de Barcelona

Barcelona, Spain

Location

Insular Hospital, Gran Canaria, Spain

Las Palmas de Gran Canaria, Spain

Location

Hospital General Universitario de Valencia

Valencia, Spain

Location

Hospital Universitario de La Ribera

Valencia, Spain

Location

Hospital Álvaro Cunqueiro

Vigo, Spain

Location

University Hospital of Geneva

Geneva, Switzerland

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

Ankara Ataturk Chest Diseases And Chest Surgery Training and Research Hospital

Ankara, Turkey (Türkiye)

Location

Ankara University Medical Faculty

Ankara, Turkey (Türkiye)

Location

University of Health Sciences, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Turkey

Bakırköy, Turkey (Türkiye)

Location

Acıbadem Mehmet Ali Aydınlar University

Istanbul, Turkey (Türkiye)

Location

Istanbul Kartal Dr. Lutfi Kirdar Education and Research Hospital

Istanbul, Turkey (Türkiye)

Location

Istanbul University

Istanbul, Turkey (Türkiye)

Location

Marmara University Medical Faculty

Istanbul, Turkey (Türkiye)

Location

University of Health Science, Konya City Hospital, Turkey

Konya, Turkey (Türkiye)

Location

Celal Bayar University Medical Faculty, Dept of Anesthesiology

Manisa, Turkey (Türkiye)

Location

Mersin University Medical Faculty

Mersin, Turkey (Türkiye)

Location

Pamukkale University Dinizli

Pamukkale, Turkey (Türkiye)

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, United Kingdom

Location

Golden Jubilee National Hospital

Clydebank, United Kingdom

Location

University Hospitals of Leicester

Leicester, United Kingdom

Location

St George's Hospital London

London, United Kingdom

Location

NIHS Sheffield Clinical Research Facility

Sheffield, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 30975217 BACKGROUND

• Writing Committee; Steering Committee; PROTHOR Collaborative Group; PROtective VEntilation Network (PROVE Network) for the Clinical Trial Network of the European Society of Anaesthesiology and Intensive Care. Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR): a multicentre, international, randomised, controlled, phase 3 trial. Lancet Respir Med. 2026 Jan;14(1):17-28. doi: 10.1016/S2213-2600(25)00330-3. Epub 2025 Nov 12.

  PMID: 41240959 DERIVED

Related Links

• Trial Website

Study Officials

• Mert Sentürk

  Istanbul University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 15, 2016
• Study Start: January 1, 2017
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); SL (1); ME (1); IR (1); NL (4); TW (1); CY (1); TU (11); CL (1); AL (1); CR (2); JP (1); SE (4); ES (5); CH (1); RO (1); FR (1); CN (5); CZ (1); BR (3); SA (1); GR (4); HU (1); IT (8); US (3); AU (1); EG (2); LA (1); DE (7)