Protective Ventilation With Higher Versus Lower PEEP During General Anesthesia for Surgery in Obese Patients

NCT02148692 | Completed DMC

• 1 other identifier: ANE-PROBESE
• Study Type: interventional
• Target: 2,013
• Locations: 16 countries
• Sites: 24

Brief Summary

Postoperative respiratory failure, particularly after surgery under general anesthesia, adds to the morbidity and mortality of surgical patients. Anesthesiologists inconsistently use positive end-expiratory pressure (PEEP) and recruitment maneuvers in the hope that this may improve oxygenation and protect against postoperative pulmonary complications (PPCs), especially in obese patients. While anesthesiologists tend to use PEEP higher than in non-obese patients. While it is uncertain whether a strategy that uses higher levels of PEEP with recruitment maneuvers truly prevents PPCs in these patients, use of higher levels of PEEP with recruitment maneuvers could compromise intra-operative hemodynamics. The investigators aim to compare a ventilation strategy using higher levels of PEEP with recruitment maneuvers with one using lower levels of PEEP without recruitment maneuvers in obese patients at an intermediate-to-high risk for PPCs. We hypothesize that 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 PPCs in obese patients at an intermediate-to-high risk for PPC.

Conditions

Morbid Obesity; Surgery; General Anesthesia

Outcome Measures

Primary Outcomes (5)

• Postoperative pulmonary complications

  Five postoperative days

• Hospital-free days at day 90

  90 postoperative days

• Mortality at day 90

  90 postoperative days

• Postoperative extra-pulmonary complications

  Five postoperative days

• Postoperative wound healing

  Five postoperative days

Secondary Outcomes (4)

• Intra-operative complications

  Surgery period

• Need for postoperative ventilatory support

  Five postoperative days

• Unexpected need for ICU admission or ICU readmission within 30 days

  Five postoperative days

• Need for hospital readmission within 30 days

  30 postoperative days

Study Arms (2)

Higher PEEP

EXPERIMENTAL

PEEP of 12 cmH2O or higher and lung recruitment maneuvers

Procedure: Higher PEEP

Lower PEEP

ACTIVE COMPARATOR

PEEP of 4 cmH2O without lung recruitment maneuvers

Procedure: Lower PEEP

Interventions

Higher PEEP PROCEDURE

Higher PEEP

Lower PEEP PROCEDURE

Lower PEEP

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 or laparoscopic surgery under general anesthesia
• Intermediate-to-high risk for PPCs following surgery, according to the ARISCAT risk score (≥ 26)
• BMI ≥ 35 kg/m2
• Expected duration of surgery ≥ 2 h

You may not qualify if:

• Age \< 18 years
• Previous lung surgery (any)
• Persistent hemodynamic instability, intractable shock (considered hemodynamically unsuitable for the study by the patient's managing physician)
• History of previous severe chronic obstructive pulmonary disease (COPD) (non-invasive ventilation and/or oxygen therapy at home, repeated systemic corticosteroid therapy for acute exacerbations of COPD)
• Recent immunosuppressive medication (patients receiving chemotherapy or radiation therapy up to two months prior to surgery)
• Severe cardiac disease (New York Heart Association class III or IV, acute coronary syndrome or persistent ventricular tachyarrhythmias)
• Invasive mechanical ventilation longer than 30 minutes (e.g., general anesthesia for surgery) within last 30 days
• Pregnancy (excluded by anamneses and/or laboratory analysis)
• Prevalent acute respiratory distress syndrome expected to require prolonged postoperative mechanical ventilation
• Severe pulmonary arterial hypertension, defined as systolic pulmonary artery pressure \> 40 mmHg
• Intracranial injury or tumor
• Neuromuscular disease (any)
• Need for intraoperative prone or lateral decubitus position
• Need for one-lung ventilation
• Cardiac surgery

Sponsors & Collaborators

• Technische Universität Dresden: lead
• European Society of Anaesthesiology: collaborator

Study Sites (24)

Massachusetts General Hospital, Harvard University

Boston, Massachusetts, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Medical University

Vienna, Austria

Location

AZ Sint Jan Brugge-Oostende AV

Bruges, Belgium

Location

Ghent University Hospital

Ghent, Belgium

Location

ABC Medical School

São Paulo, Brazil

Location

Saint Michael's Hospital, University of Toronto

Toronto, Canada

Location

Saint Eloi University Hospital

Montpellier, France

Location

Department of Anesthesiology and Intensive Care, University Hospital Carl Gustav Carus

Dresden, Saxony, 01307, Germany

Location

University of Aachen

Aachen, Germany

Location

University of Bonn

Bonn, Germany

Location

University of Leipzig

Leipzig, Germany

Location

Semmelweis Egyetem

Budapest, Hungary

Location

Tel Aviv Medical Center

Tel Aviv, Israel

Location

University of Foggia

Foggia, Italy

Location

University of Genoa

Genoa, Italy

Location

Città della Salute e della Scienza

Turin, Italy

Location

University of Insubria

Varese, Italy

Location

Academic Medical Center, University of Amsterdam

Amsterdam, Netherlands

Location

Hospital Universitari Germans Trias I Pujol

Barcelona, Spain

Location

University Hospital Uppsala

Uppsala, Sweden

Location

Hôpitaux Universitaires de Genève

Geneva, Switzerland

Location

University of Istanbul

Istanbul, Turkey (Türkiye)

Location

Sheffield Teaching Hospitals

Sheffield, United Kingdom

Location

Related Publications (5)

• Bluth T, Rivas E, Lopez-Baamonde M, Sanahuja JM, Lopez-Hernandez A, Balust J, Weingarten TN, Girrbach F, Simon P, Wrigge H, Wittenstein J, Birr K, Teichmann R, Huhle R, Melchior N, Vivona L, Koch T, Ramakrishna H, Brull S, Serpa Neto A, Schultz MJ, Sprung J, Scharffenberg M, Gama de Abreu M; PROBESE-investigators; Protective Ventilation Network, and the Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care. Association of plasma biomarkers of lung injury with positive end expiratory pressure and postoperative pulmonary complications in obese surgical patients: A substudy of the PROBESE randomised controlled trial. Eur J Anaesthesiol. 2025 Sep 1;42(9):840-850. doi: 10.1097/EJA.0000000000002221. Epub 2025 Jun 20.

  PMID: 40548583 DERIVED

• Scharffenberg M, Mandelli M, Bluth T, Simonassi F, Wittenstein J, Teichmann R, Birr K, Kiss T, Ball L, Pelosi P, Schultz MJ, Gama de Abreu M, Huhle R; PROBESE-investigators; Protective Ventilation Network; Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care. Respiratory mechanics and mechanical power during low vs. high positive end-expiratory pressure in obese surgical patients - A sub-study of the PROBESE randomized controlled trial. J Clin Anesth. 2024 Feb;92:111242. doi: 10.1016/j.jclinane.2023.111242. Epub 2023 Oct 12.

  PMID: 37833194 DERIVED

• Ellenberger C, Pelosi P, de Abreu MG, Wrigge H, Diaper J, Hagerman A, Adam Y, Schultz MJ, Licker M; PROBESE investigators, of the PROtective VEntilation Network (PROVEnet); Clinical Trial Network of the European Society of Anaesthesiology and Intensive Care (ESAIC). Distribution of ventilation and oxygenation in surgical obese patients ventilated with high versus low positive end-expiratory pressure: A substudy of a randomised controlled trial. Eur J Anaesthesiol. 2022 Nov 1;39(11):875-884. doi: 10.1097/EJA.0000000000001741. Epub 2022 Sep 12.

  PMID: 36093886 DERIVED

• Writing Committee for the PROBESE Collaborative Group of the PROtective VEntilation Network (PROVEnet) for the Clinical Trial Network of the European Society of Anaesthesiology; Bluth T, Serpa Neto A, Schultz MJ, Pelosi P, Gama de Abreu M; PROBESE Collaborative Group; Bluth T, Bobek I, Canet JC, Cinnella G, de Baerdemaeker L, Gama de Abreu M, Gregoretti C, Hedenstierna G, Hemmes SNT, Hiesmayr M, Hollmann MW, Jaber S, Laffey J, Licker MJ, Markstaller K, Matot I, Mills GH, Mulier JP, Pelosi P, Putensen C, Rossaint R, Schmitt J, Schultz MJ, Senturk M, Serpa Neto A, Severgnini P, Sprung J, Vidal Melo MF, Wrigge H. Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial. JAMA. 2019 Jun 18;321(23):2292-2305. doi: 10.1001/jama.2019.7505.

  PMID: 31157366 DERIVED

• Bluth T, Teichmann R, Kiss T, Bobek I, Canet J, Cinnella G, De Baerdemaeker L, Gregoretti C, Hedenstierna G, Hemmes SN, Hiesmayr M, Hollmann MW, Jaber S, Laffey JG, Licker MJ, Markstaller K, Matot I, Muller G, Mills GH, Mulier JP, Putensen C, Rossaint R, Schmitt J, Senturk M, Serpa Neto A, Severgnini P, Sprung J, Vidal Melo MF, Wrigge H, Schultz MJ, Pelosi P, Gama de Abreu M; PROBESE investigators; PROtective VEntilation Network (PROVEnet); Clinical Trial Network of the European Society of Anaesthesiology (ESA). Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial. Trials. 2017 Apr 28;18(1):202. doi: 10.1186/s13063-017-1929-0.

  PMID: 28454590 DERIVED

MeSH Terms

Conditions

Obesity, Morbid

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: May 23, 2014
• First Posted: May 28, 2014
• Study Start: July 1, 2014
• Primary Completion: February 1, 2018
• Study Completion: May 1, 2018
• Last Updated: January 3, 2019

Record last verified: 2019-01

Locations

CH (1); HU (1); DE (4); FR (1); TU (1); ES (1); US (2); BE (2); GB (1); BR (1); AU (1); SE (1); CA (1); NL (1); IT (4); IL (1)