Randomized Controlled Trial

. 2017 Apr 28;18(1):202.

doi: 10.1186/s13063-017-1929-0.

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

T Bluth¹, R Teichmann¹, T Kiss¹, I Bobek², J Canet³, G Cinnella⁴, L De Baerdemaeker⁵, C Gregoretti⁶, G Hedenstierna⁷, S N Hemmes^{8

9}, M Hiesmayr^{10

11

12

13}, M W Hollmann^{8

9}, S Jaber¹⁴, J G Laffey^{15

16

17

18}, M J Licker¹⁹, K Markstaller¹³, I Matot²⁰, G Müller²¹, G H Mills²², J P Mulier²³, C Putensen²⁴, R Rossaint²⁵, J Schmitt²¹, M Senturk²⁶, A Serpa Neto^{27

28}, P Severgnini²⁹, J Sprung³⁰, M F Vidal Melo³¹, H Wrigge³², M J Schultz^{9

33}, P Pelosi³⁴, M Gama de Abreu³⁵; PROBESE investigators; PROtective VEntilation Network (PROVEnet); Clinical Trial Network of the European Society of Anaesthesiology (ESA)

Collaborators, Affiliations

Collaborators

Andreas Güldner, Robert Huhle, Christopher Uhlig, Luigi Vivona, Alice Bergamaschi, Rolf Rossaint, Ana Stevanovic, Tanja Treschan, Maximilian Schaefer, Peter Kienbaum, Rita Laufenberg-Feldmann, Lars Bergmann, Felix Ebner, Luisa Robitzky, Patrick Mölders, Matthias Unterberg, Cornelius Busch, Marc Achilles, Angelika Menzen, Harbert Freesemann, Christian Putensen, Humberto Machado, Carla Cavaleiro, Cristina Ferreira, Daniela Pinho, Marta Carvalho, Sílvia Pinho, Maria Soares, Diogo Sousa Castro, Fernando Abelha, Rui Rabico, Ellise Delphin, Juraj Sprung, Toby N Weingarten, Todd A Kellogg, Yvette N Martin, Travis J McKenzie, Sorin J Brull, J Ross Renew, Harish Ramakrishna, Ana Fernandez-Bustamante, Konstantin Balonov, Harris R Baig, Aalok Kacha, Juan C Pedemonte, Fernando Altermatt, Marcia A Corvetto, Sebastian Paredes, Javiera Carmona, Augusto Rolle, Elke Bos, Charlotte Beurskens, B Veering, Harry Zonneveldt, Christa Boer, Marc Godfried, Bram Thiel, Barbara Kabon, Christian Reiterer, Jaume Canet, Raquel Tolós, Mar Sendra, Miriam González, Noemí Gómez, Carlos Ferrando, Tania Socorro, Ana Izquierdo, Marina Soro, Manuel Granell Gil, María José Hernández Cádiz, Elena Biosca Pérez, Alejandro Suarez-de-la-Rica, Mercedes Lopez-Martinez, Iván Huercio, Emilio Maseda, Julio Yagüe, Alba Cebrian Moreno, Eva Rivas, Manuel Lopez-Baamonde, Hamed Elgendy, Mohamed Sayedalahl, Abdul Razak SIibai, Aysen Yavru, Nukhet Sivrikoz, Meltem Karadeniz, Pelin Corman Dincer, Hilmi Omer Ayanoglu, Gulbin Tore Altun, Ayse Duygu Kavas, Bora Dinc, Bahar Kuvaki, Sule Ozbilgin, Dilek Erdogan, Ceren Koksal, Suheyla Abitagaglu, Caterina Aurilio, Pasquale Sansone, Caterina Maria Pace, Valerio Donatiello, Silvana Mattera, Palange Nazareno, Salvatore Di Colandrea, Savino Spadaro, Carlo Alberto Volta, Riccardo Ragazzi, Stefano Ciardo, Luca Gobbi, Paolo Severgnini, Alessandro Bacuzzi, Elisa Brugnoni, Angelo Gratarola, Camilla Micalizzi, Francesca Simonassi, Patrizia Malerbi, Adrea Carboni, Marc-Joseph Licker, Alexander Dullenkopf, Nicolai Goettel, Visnja Nesek Adam, Maja Karaman Ilić, Vlasta Klaric, Bibiana Vitkovic, Morena Milic, Miro Zupcic, Luc De Baerdemaeker, Stefan De Hert, Bjorn Heyse, Jurgen Van Limmen, Yves Van Nieuwenhove, Els Mertens, Arne Neyrinck, Jan Mulier, David Kahn, Daniela Godoroja, Martin Martin-Loeches, Sergiy Vorotyntsev, Valentyna Fronchko, Idit Matot, Or Goren, Lilach Zac, Thomasz Gaszynski, Jon Laffey, Gary Mills, Pramod Nalwaya, Mark Mac Gregor, Jonathan Paddle, Packianathaswamy Balaji, Francesca Rubulotta, Afeez Adebesin, Mike Margarson, Simon Davies, Desikan Rangarajan, Christopher Newell, Mirjana Shosholcheva, Fotios Papaspyros, Vasiliki Skandalou, Paula Dzurňáková

Affiliations

¹ Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany.
² Aneszteziológiai és Intenzív Terápiás Klinika, Semmelweis Egyetem, Budapest, Hungary.
³ Department of Anesthesiology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
⁴ Department of Anesthesiology and Intensive Care Medicine, University of Foggia, Foggia, Italy.
⁵ Department of Anesthesiology, Ghent University Hospital, Ghent, Belgium.
⁶ Department of Biopathology and Medical Biotechnologies, Policlinico "P. Giaccone", Palermo, Italy.
⁷ Section of Clinical Physiology, Department of Medical Sciences, University Hospital, Uppsala, Sweden.
⁸ Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁹ Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
¹⁰ Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
¹¹ Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
¹² Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria.
¹³ Department of Anesthesia, Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria.
¹⁴ Department of Critical Care Medicine and Anesthesiology (SAR B), Saint Eloi University Hospital, Montpellier, France.
¹⁵ Critical Care Medicine Program, Department of Anesthesia, Saint Michael's Hospital, Toronto, ON, Canada.
¹⁶ Department of Anesthesia, University of Toronto, Toronto, ON, Canada.
¹⁷ Department of Physiology, University of Toronto, Toronto, ON, Canada.
¹⁸ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁹ Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital Geneva, Geneva, Switzerland.
²⁰ Department of Anesthesiology and Critical Care, Tel Aviv Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
²¹ Center for Evidence-based Healthcare, University Hospital and Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
²² Operating Services, Critical Care and Anaesthesia (OSCCA), Sheffield Teaching Hospitals and University of Sheffield, Sheffield, UK.
²³ Department of Anesthesiology, AZ Sint Jan Brugge-Oostende AV, Brugge, Belgium.
²⁴ Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany.
²⁵ Department of Anesthesiology, University of Aachen, Aachen, Germany.
²⁶ Department of Anesthesiology and Intensive Care Medicine, Istanbul Medical Faculty, University of Istanbul, Istanbul, Turkey.
²⁷ Department of Critical Care Medicine, Hospital Israelita Albert Einstein, Faculdade de Medicina do ABC, São Paulo, Brazil.
²⁸ Program of Post-Graduation, Research and Innovation, Faculdade de Medicina do ABC, São Paulo, Brazil.
²⁹ Department of Biotechnology and Sciences of Life, University of Insubria, ASST dei Sette Laghi, Ospedale di Cricolo e Fondazione Macchi, Varese, Italy.
³⁰ Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA.
³¹ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³² Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany.
³³ Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
³⁴ Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino - IST, University of Genoa, Genoa, Italy.
³⁵ Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany. mgabreu@uniklinikum-dresden.de.

PMID: 28454590
PMCID: PMC5410049
DOI: 10.1186/s13063-017-1929-0

Randomized Controlled Trial

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

T Bluth et al. Trials. 2017.

. 2017 Apr 28;18(1):202.

doi: 10.1186/s13063-017-1929-0.

Authors

Collaborators

Andreas Güldner, Robert Huhle, Christopher Uhlig, Luigi Vivona, Alice Bergamaschi, Rolf Rossaint, Ana Stevanovic, Tanja Treschan, Maximilian Schaefer, Peter Kienbaum, Rita Laufenberg-Feldmann, Lars Bergmann, Felix Ebner, Luisa Robitzky, Patrick Mölders, Matthias Unterberg, Cornelius Busch, Marc Achilles, Angelika Menzen, Harbert Freesemann, Christian Putensen, Humberto Machado, Carla Cavaleiro, Cristina Ferreira, Daniela Pinho, Marta Carvalho, Sílvia Pinho, Maria Soares, Diogo Sousa Castro, Fernando Abelha, Rui Rabico, Ellise Delphin, Juraj Sprung, Toby N Weingarten, Todd A Kellogg, Yvette N Martin, Travis J McKenzie, Sorin J Brull, J Ross Renew, Harish Ramakrishna, Ana Fernandez-Bustamante, Konstantin Balonov, Harris R Baig, Aalok Kacha, Juan C Pedemonte, Fernando Altermatt, Marcia A Corvetto, Sebastian Paredes, Javiera Carmona, Augusto Rolle, Elke Bos, Charlotte Beurskens, B Veering, Harry Zonneveldt, Christa Boer, Marc Godfried, Bram Thiel, Barbara Kabon, Christian Reiterer, Jaume Canet, Raquel Tolós, Mar Sendra, Miriam González, Noemí Gómez, Carlos Ferrando, Tania Socorro, Ana Izquierdo, Marina Soro, Manuel Granell Gil, María José Hernández Cádiz, Elena Biosca Pérez, Alejandro Suarez-de-la-Rica, Mercedes Lopez-Martinez, Iván Huercio, Emilio Maseda, Julio Yagüe, Alba Cebrian Moreno, Eva Rivas, Manuel Lopez-Baamonde, Hamed Elgendy, Mohamed Sayedalahl, Abdul Razak SIibai, Aysen Yavru, Nukhet Sivrikoz, Meltem Karadeniz, Pelin Corman Dincer, Hilmi Omer Ayanoglu, Gulbin Tore Altun, Ayse Duygu Kavas, Bora Dinc, Bahar Kuvaki, Sule Ozbilgin, Dilek Erdogan, Ceren Koksal, Suheyla Abitagaglu, Caterina Aurilio, Pasquale Sansone, Caterina Maria Pace, Valerio Donatiello, Silvana Mattera, Palange Nazareno, Salvatore Di Colandrea, Savino Spadaro, Carlo Alberto Volta, Riccardo Ragazzi, Stefano Ciardo, Luca Gobbi, Paolo Severgnini, Alessandro Bacuzzi, Elisa Brugnoni, Angelo Gratarola, Camilla Micalizzi, Francesca Simonassi, Patrizia Malerbi, Adrea Carboni, Marc-Joseph Licker, Alexander Dullenkopf, Nicolai Goettel, Visnja Nesek Adam, Maja Karaman Ilić, Vlasta Klaric, Bibiana Vitkovic, Morena Milic, Miro Zupcic, Luc De Baerdemaeker, Stefan De Hert, Bjorn Heyse, Jurgen Van Limmen, Yves Van Nieuwenhove, Els Mertens, Arne Neyrinck, Jan Mulier, David Kahn, Daniela Godoroja, Martin Martin-Loeches, Sergiy Vorotyntsev, Valentyna Fronchko, Idit Matot, Or Goren, Lilach Zac, Thomasz Gaszynski, Jon Laffey, Gary Mills, Pramod Nalwaya, Mark Mac Gregor, Jonathan Paddle, Packianathaswamy Balaji, Francesca Rubulotta, Afeez Adebesin, Mike Margarson, Simon Davies, Desikan Rangarajan, Christopher Newell, Mirjana Shosholcheva, Fotios Papaspyros, Vasiliki Skandalou, Paula Dzurňáková

Affiliations

¹ Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany.
² Aneszteziológiai és Intenzív Terápiás Klinika, Semmelweis Egyetem, Budapest, Hungary.
³ Department of Anesthesiology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
⁴ Department of Anesthesiology and Intensive Care Medicine, University of Foggia, Foggia, Italy.
⁵ Department of Anesthesiology, Ghent University Hospital, Ghent, Belgium.
⁶ Department of Biopathology and Medical Biotechnologies, Policlinico "P. Giaccone", Palermo, Italy.
⁷ Section of Clinical Physiology, Department of Medical Sciences, University Hospital, Uppsala, Sweden.
⁸ Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁹ Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
¹⁰ Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
¹¹ Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
¹² Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria.
¹³ Department of Anesthesia, Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria.
¹⁴ Department of Critical Care Medicine and Anesthesiology (SAR B), Saint Eloi University Hospital, Montpellier, France.
¹⁵ Critical Care Medicine Program, Department of Anesthesia, Saint Michael's Hospital, Toronto, ON, Canada.
¹⁶ Department of Anesthesia, University of Toronto, Toronto, ON, Canada.
¹⁷ Department of Physiology, University of Toronto, Toronto, ON, Canada.
¹⁸ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁹ Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital Geneva, Geneva, Switzerland.
²⁰ Department of Anesthesiology and Critical Care, Tel Aviv Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
²¹ Center for Evidence-based Healthcare, University Hospital and Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
²² Operating Services, Critical Care and Anaesthesia (OSCCA), Sheffield Teaching Hospitals and University of Sheffield, Sheffield, UK.
²³ Department of Anesthesiology, AZ Sint Jan Brugge-Oostende AV, Brugge, Belgium.
²⁴ Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany.
²⁵ Department of Anesthesiology, University of Aachen, Aachen, Germany.
²⁶ Department of Anesthesiology and Intensive Care Medicine, Istanbul Medical Faculty, University of Istanbul, Istanbul, Turkey.
²⁷ Department of Critical Care Medicine, Hospital Israelita Albert Einstein, Faculdade de Medicina do ABC, São Paulo, Brazil.
²⁸ Program of Post-Graduation, Research and Innovation, Faculdade de Medicina do ABC, São Paulo, Brazil.
²⁹ Department of Biotechnology and Sciences of Life, University of Insubria, ASST dei Sette Laghi, Ospedale di Cricolo e Fondazione Macchi, Varese, Italy.
³⁰ Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA.
³¹ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³² Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany.
³³ Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
³⁴ Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino - IST, University of Genoa, Genoa, Italy.
³⁵ Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany. mgabreu@uniklinikum-dresden.de.

PMID: 28454590
PMCID: PMC5410049
DOI: 10.1186/s13063-017-1929-0

Erratum in

Erratum to Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial.
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, Müller G, Mills GH, Mulier JP, Putensen C, Rossaint R, Schmitt J, Senturk M, Neto AS, Severgnini P, Sprung J, Vidal Melo MF, Wrigge H, Schultz MJ, Pelosi P, Gama de Abreu M; PROBESE investigators, and the PROtective VEntilation Network (PROVEnet) and on behalf of the Clinical Trial Network of the European Society of Anaesthesiology (ESA). Bluth T, et al. Trials. 2017 Jun 1;18(1):247. doi: 10.1186/s13063-017-1987-3. Trials. 2017. PMID: 28571581 Free PMC article. No abstract available.

Abstract

Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients.

Methods/design: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m² scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH₂O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH₂O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint.

Discussion: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs.

Trial registration: ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016.

Keywords: Mechanical ventilation; Obesity; Positive end-expiratory pressure; Postoperative pulmonary complication; Recruitment maneuver.

PubMed Disclaimer

Figures

**Fig. 1**
Consolidated Standards of Reporting Trials (CONSORT) diagram for the PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) trial. *PEEP* Positive end-expiratory pressure

**Fig. 2**
Lung recruitment maneuver protocol. *Ppeak* Peak airway pressure, *Pplat* Plateau airway pressure, *PEEP* Positive end-expiratory pressure, Vt Tidal volume normalized for predicted body weight, RR Respiratory rate, *I:E* Ratio between inspiratory and expiratory time

**Fig. 3**
Schedule of enrollment, interventions, and assessments. *POD* Postoperative day, *PEEP* Positive end-expiratory airway pressure, RM Recruitment maneuver, *SpO* ₂ Peripheral oxyhemoglobin saturation measured by pulse oximetry

**Fig. 4**
Effect size (Z) according to enrollment of patients in the PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) trial

See this image and copyright information in PMC

References

1. Mazo V, Sabate S, Canet J, Gallart L, de Abreu MG, Belda J, et al. Prospective external validation of a predictive score for postoperative pulmonary complications. Anesthesiology. 2014;121:219–31. doi: 10.1097/ALN.0000000000000334. - DOI - PubMed
1. Serpa Neto A, Hemmes SN, Barbas CS, Beiderlinden M, Fernandez-Bustamante A, Futier E, et al. Incidence of mortality and morbidity related to postoperative lung injury in patients who have undergone abdominal or thoracic surgery: a systematic review and meta-analysis. Lancet Respir Med. 2014;2:1007–15. doi: 10.1016/S2213-2600(14)70228-0. - DOI - PubMed
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Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

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Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

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