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

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.

Study Overview

• Status: Completed
• Conditions: Surgery; Morbid Obesity; General Anesthesia
• Intervention / Treatment: Procedure: Higher PEEP; Procedure: Lower PEEP

• Study Type: Interventional
• Enrollment (Actual): 2013
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Medical University
• Belgium
  • Brugge, Belgium
    • AZ Sint Jan Brugge-Oostende av
  • Ghent, Belgium
    • Ghent University Hospital
• Brazil
  • Sao Paulo, Brazil
    • ABC Medical School
• Canada
  • Toronto, Canada
    • Saint Michael's Hospital, University of Toronto
• France
  • Montpellier, France
    • Saint Eloi University Hospital
• Germany
  • Aachen, Germany
    • University of Aachen
  • Bonn, Germany
    • University of Bonn
  • Leipzig, Germany
    • University of Leipzig
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Department of Anesthesiology and Intensive Care, University Hospital Carl Gustav Carus
• Hungary
  • Budapest, Hungary
    • Semmelweis Egyetem
• Israel
  • Tel Aviv, Israel
    • Tel Aviv Medical Center
• Italy
  • Foggia, Italy
    • University of Foggia
  • Genoa, Italy
    • University of Genoa
  • Turin, Italy
    • Città della Salute e della Scienza
  • Varese, Italy
    • University of Insubria
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center, University of Amsterdam
• Spain
  • Barcelona, Spain
    • Hospital Universitari Germans Trias i Pujol
• Sweden
  • Uppsala, Sweden
    • University Hospital Uppsala
• Switzerland
  • Geneva, Switzerland
    • Hopitaux Universitaires de Geneve
• Turkey
  • Istanbul, Turkey
    • University of Istanbul
• United Kingdom
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospitals
• United States
  • Massachusetts
    • Boston, Massachusetts, United States
      • Massachusetts General Hospital, Harvard University
  • Minnesota
    • Rochester, Minnesota, United States
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Neurosurgery
• Planned reintubation following surgery
• Enrolled in other interventional study or refusal of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Higher PEEP; PEEP of 12 cmH2O or higher and lung recruitment maneuvers	Procedure: Higher PEEP
ACTIVE_COMPARATOR: Lower PEEP; PEEP of 4 cmH2O without lung recruitment maneuvers	Procedure: Lower PEEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-operative complications	complications related to the ventilation strategy (for example: de-saturation, defined as SpO2 ≤ 92%, for > 1 min; hypotension during recruitment maneuvers, as defined by systolic arterial pressure < 90 mmHg for > 2 min)	Surgery period
Need for postoperative ventilatory support	invasive or non-invasive ventilation	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

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: European Society of Anaesthesiology

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: JAMA. 2019 Nov 12;322(18):1829-1830.
• 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. Erratum In: Trials. 2017 Jun 1;18(1):247.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2014
• Primary Completion (ACTUAL): February 1, 2018
• Study Completion (ACTUAL): May 1, 2018

Study Registration Dates

• First Submitted: May 23, 2014
• First Submitted That Met QC Criteria: May 27, 2014
• First Posted (ESTIMATE): May 28, 2014

Study Record Updates

• Last Update Posted (ACTUAL): January 3, 2019
• Last Update Submitted That Met QC Criteria: January 2, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid
• Other Study ID Numbers: ANE-PROBESE