Abstract
Background: The effect of higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres aimed at lung expansion as compared with lower PEEP without recruitment manoeuvres aimed at permissive atelectasis on postoperative pulmonary complications (PPCs) in patients undergoing one-lung ventilation (OLV) during thoracic surgery is unclear. We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs. Methods: In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged ≥18 years) with a BMI of less than 35 kg/m2 who were scheduled for open thoracic or video-assisted thoracoscopic surgery under general anaesthesia requiring one-lung ventilation with a double-lumen tube, with a planned operative time of more than 60 min, and an expected duration of one-lung ventilation longer than that of two-lung ventilation. Patients were randomly assigned (1:1), using permuted blocks of random size (4, 6, and 8) and stratified by study site, to receive one-lung ventilation with either a higher PEEP of 10 cm H2O and periodic lung recruitment manoeuvres (high PEEP group) or a lower PEEP of 5 cm H2O without routine recruitment manoeuvres (low PEEP group). All patients received protective tidal volumes of 5 mL/kg predicted body weight during one-lung ventilation and 7 mL/kg predicted body weight during two-lung ventilation. Postoperative assessors were masked to treatment allocation. The primary outcome was a composite of PPCs during the first 5 postoperative days, including aspiration pneumonia, moderate or severe respiratory failure, acute respiratory distress syndrome (ARDS), pulmonary infection, atelectasis, cardiopulmonary oedema, pleural effusion, non-operative pneumothorax, pulmonary infiltrates, prolonged air leak, purulent pleuritis, pulmonary embolism, and pulmonary haemorrhage. A modified intention-to-treat analysis was performed, with patients analysed according to their assigned treatment group, except in cases of withdrawal of informed consent, cancellation of surgery, and or loss to follow-up. This trial is registered with ClinicalTrials.gov (NCT02963025) and is completed. Findings: Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treat analysis after randomisation. The primary outcome occurred in 555 (53·6%) of 1036 patients in the high PEEP group and 592 (56·4%) of 1049 patients in the low PEEP group (absolute risk difference –2·68 percentage points [95% CI –6·36 to 1·01]; p=0·155). Intraoperative complications occurred in 484 (49·8%) of 972 patients in the high PEEP group and in 305 (31·3%) of 974 patients in the low PEEP group (absolute risk difference 18·09 percentage points [95% CI 14·41–21·77]), among which hypotension (360 [37·3%] of 966 patients in the high PEEP group vs 140 [14·3%] of 978 in the low PEEP group) and new arrhythmias (89 [9·9%] of 899 vs 37 [3·9%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [3·3%] of 888 vs 86 [8·8%] of 982). The proportions of patients with extrapulmonary postoperative complications (110 [10·6%] of 1036 vs 107 [10·2%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups. Interpretation: In patients with a BMI of less than 35 kg/m2 undergoing thoracic surgery, one-lung ventilation using higher PEEP with recruitment manoeuvres, compared with lower PEEP without recruitment manoeuvres, did not reduce PPCs. The choice for intraoperative lung expansion or permissive atelectasis should take the individual gas-exchange and haemodynamic conditions into account, which might vary during the intraoperative period. Funding: Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care; Department of Anaesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Technische Universität Dresden (Dresden, Germany); Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasília, Brazil); and the Association of Anaesthetists of GB and Ireland.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 17-28 |
| Number of pages | 12 |
| Journal | The Lancet Respiratory Medicine |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2025 |
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine
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In: The Lancet Respiratory Medicine, Vol. 14, No. 1, 01.2025, p. 17-28.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR)
T2 - a multicentre, international, randomised, controlled, phase 3 trial
AU - Wittenstein, Jakob
AU - Şentürk, Nüzhet Mert
AU - Kiss, Thomas
AU - Schultz, Marcus J.
AU - Serpa Neto, Ary
AU - Gama de Abreu, Marcelo
AU - Cinnella, Gilda
AU - dos Reis Falcão, Luiz Fernando
AU - Cohen, Edmond
AU - El Tahan, Mohamed R.
AU - Gama de Abreu, Marcelo
AU - Granell Gil, Manuel
AU - Gregoretti, Cesare
AU - Hachenberg, Thomas
AU - Hollmann, Markus W.
AU - Jankovic, Radmilo J.
AU - Kiss, Thomas
AU - Kraßler, Jens
AU - Licker, Marc
AU - Loop, Torsten
AU - Miao, Changhong
AU - Mills, Gary H.
AU - Murrell, Matthew T.
AU - Nandor, Marczin
AU - Neskovic, Vojislava
AU - Nisnevitch-Savarese, Zoulfira
AU - Rossaint, Rolf
AU - Schultz, Marcus J.
AU - Şentürk, Nüzhet Mert
AU - Severgnini, Paolo
AU - Szegedi, Laszlo L.
AU - Tamás, Végh
AU - Vázquez de Anda, Gilberto Felipe
AU - Voyagis, Gregory
AU - Waheedullah, Karzai
AU - Wittenstein, Jakob
AU - Zhong, Jing
AU - Abbenhuis, Jeroen
AU - Abdulmomen, Ahmed
AU - Abdyli, Asead
AU - Abu Elyazed, Mohamed M.
AU - Aguirre Puig, Pilar
AU - Akbudak, Ilknur Hatice
AU - Aksu, Can
AU - Alagöz, Ali
AU - Alhamdi, Malik
AU - Almadhati, Shams
AU - Altorki, Nasser K.
AU - Aragón Alvarez, Sonsoles
AU - Arun, Oguzhan
AU - Azizoglu, Mustafa
AU - Baar, Wolfgang
AU - Balde, Detlef
AU - Balla, Boglárka
AU - Ballı Şeker, Merve
AU - Basheer, Musaab
AU - Bauer, Wolfgang O.
AU - Bence, Johan
AU - Bernardi, Martin H.
AU - Bigatello, Luca M.
AU - Bignami, Elena
AU - Bluth, Thomas
AU - Bonney, Iwona
AU - Bouhemad, Belaid
AU - Bradić, Nikola
AU - Brescianini, Luigi
AU - Bruthans, Jan
AU - Bulte, Carolien S.E.
AU - Cadar, Genoveva
AU - Cakmak, Gul
AU - Calì, Placido
AU - Cantatore, Leonarda Pia
AU - Chai, Xiaoqing
AU - Chang, Yi Ting
AU - Chen, Jiaqi
AU - Christofaki, Maria
AU - Cinnella, Gilda
AU - Coelho Sanches, Luciana
AU - Constantin, Ana
AU - Contreras, Victor
AU - Corsi, Laura
AU - da Silva, Eduardo
AU - Defosse, Jérôme
AU - Deluca, Raffaele
AU - Diaper, John
AU - Didden, Loes
AU - Dimitriou, Evanthia
AU - do Nascimento Junior, Paulo
AU - Domi, Rudin
AU - Dorfinger, Laurin
AU - dos Reis Falcão, Luiz Fernando
AU - Douradinho, Christian
AU - Drnovšek Globokar, Mojca
AU - Duran, Ferdane Melike
AU - Eldawlatly, Abdelazeem
AU - El-Gendy, Hala M.
AU - Elmazny, Maram I.
AU - Elsherif, Salah Eldin I.
AU - Emara, Moataz Maher
AU - Enriquez de los Santos, Sharon Thali
AU - Farnell-Ward, Sarah
AU - Ferrufino, Renan
AU - Gama de Abreu, Marcelo
AU - Gao, Lingling
AU - Geyik, Dogu
AU - Gnezda, Deja
AU - Goeden, Steffie
AU - Gorjup, Kristina
AU - Granell Gil, Manuel
AU - Guido Guerra, Ricardo Eli
AU - Guimarães de Castro Pereira, Maísa
AU - Guinot, Pierre Grégoire
AU - Guven, Aysegul
AU - Hager, Helmut
AU - Han, Ling
AU - Hatipoglu, Zehra
AU - Hayashi, Megumi
AU - Hell, Johannes
AU - Hofland, Jan
AU - Hollmann, Markus W.
AU - Hu, Jicheng
AU - Hudáček, Kamil
AU - Huti, Gentian
AU - Ilić, Monika
AU - Jankovic, Radmilo J.
AU - Jegarl, Anita
AU - Jiménez Andújar, María José
AU - Jin, Danfeng
AU - Kammerer, Tobias
AU - Karadža, Vjekoslav
AU - Kawagoe, Izumi
AU - Kıran Paudel, Seher İrem
AU - Kiss, Thomas
AU - Koch, Thea
AU - Kolaric, Nevenka
AU - Koning, Nick J.
AU - Kostopanagiotou, Kostas
AU - Kostroglou, Andreas
AU - Kovač, Petra
AU - Kramer, Tim
AU - Kraßler, Jens
AU - Kreft, Tom
AU - Kumrular, Yagmur
AU - Kuut, Marieke
AU - Lan, Lan
AU - Li, Pei Ching
AU - Li, Xue Fei
AU - Li, Lan Tao
AU - Licker, Marc
AU - Liu, Yujia
AU - Longo, Ferdinando
AU - Loop, Torsten
AU - López-Baamonde, Manuel
AU - Luise, Stéphane
AU - Luo, Wenchen
AU - Lv, Hu
AU - Macias Jimenez, Maria de los Angeles
AU - Magalhães, Danielle Dourado
AU - Martuscelli, Matteo
AU - Mavko, Ana
AU - Meco, Basak Ceyda
AU - Mermer, Hasan Alp
AU - Miao, Changhong
AU - Michálek, Pavel
AU - Mills, Gary H.
AU - Miñana Aragón, Encarna
AU - Mirabella, Lucia
AU - Molyneux, Matthew
AU - Montrano, Luigi
AU - Mosqueira, Loreto
AU - Mourisse, Jo
AU - Murrell, Matthew T.
AU - Navarro-Ripoll, Ricard
AU - Negru, Florica
AU - Neskovic, Vojislava
AU - Nikolić, Mario
AU - Norberto de la Vega, Juana Abigail
AU - Noto, Alberto
AU - Nyktari, Vasileia
AU - Orhan Sungur, Mukadder
AU - Ozdemir, Levent
AU - Ozolina, Agnese
AU - Ozturk, Tulun
AU - Pace, Maria Caterina
AU - Pagnussatt Neto, Eugenio
AU - Pálóczi, Balázs
AU - Papaioannou, Alexandra
AU - Papamichail, Konstantinos
AU - Patroniti, Nicolò
AU - Pektaş, Yaser
AU - Pereira Matalobos, Denis
AU - Peršec, Jasminka
AU - Petrović, Stanislava
AU - Pirc, Dejan
AU - Plismanis, Gints
AU - Prata Amendola, Cristina
AU - Pražetina, Marko
AU - Radovic, Nevena
AU - Rauseo, Michela
AU - Richter, Torsten
AU - Rivera Vallejo, Lorena
AU - Rodriguez Ruiz, Juan José
AU - Rondovic, Goran
AU - Rosser, Jon
AU - Sánchez García, Fernando J.
AU - Sansone, Pasquale
AU - Saracoglu, Ayten
AU - Saracoglu, Kemal Tolga
AU - Sazak, Hilal
AU - Scharffenberg, Martin
AU - Schiavoni, Lorenzo
AU - Schilling, Thomas
AU - Schultz, Marcus J.
AU - Sediq, Aras
AU - Semmelmann, Axel
AU - Şentürk, Nüzhet Mert
AU - Sertaç Bingül, Emre
AU - Sertcakacilar, Gokhan
AU - Sfika, Eleni
AU - Shelley, Benjamin
AU - Shin, Sul Hwa
AU - Sidiropoulou, Tatiana
AU - Silva-Jr, João M.
AU - Socci, Laura
AU - Socorro, Tania
AU - Soulioti, Eleftheria
AU - Spadaro, Savino
AU - Špiček-Macan, Jasna
AU - Spray, Dominic
AU - Stamenkovic, Dusica
AU - Stefanakis, Georgios
AU - Stoica, Radu
AU - Stojanovic, Milena
AU - Stopora, Pascal
AU - Sungur, Zerrin
AU - Svareniece-Karjaka, Elizabete
AU - Szamos, Katalin
AU - Tanase, Narcis Valentin
AU - Tanriverdi, Cagin
AU - Tempel, Franz
AU - Terwindt, Lotte E.
AU - Theilen, Raphael
AU - Tipura, Danijela
AU - Tire, Yasin
AU - Tomaselli, Eleonora
AU - Tsuguie Onari, Neusa
AU - Tunç, Mehtap
AU - Turhan, Özlem
AU - Turktan, Mediha
AU - Ugliola, Daniele
AU - Ulugöl, Halim
AU - Végh, Tamás
AU - Vetrugno, Luigi
AU - Vitali, Costanza
AU - Volta, Carlo Alberto
AU - von Dossow, Vera
AU - Voyagis, Gregory
AU - Voyagis, Gregory
AU - Vukovic, Rade
AU - Vukovic, Anita Z.
AU - Waeschle, Reiner M.
AU - Wall, David
AU - Wang, Hui
AU - Wang, Di
AU - Winroth, Dag
AU - Wittenstein, Jakob
AU - Wu, Qichao
AU - Xu, Peiyao
AU - Yaldır, Olcay
AU - Yamansavcı Sirzai, Esra
AU - Yang, Xinlu
AU - Yapici, Davud
AU - Yıldırım, Ozgucan
AU - Yildirim Guclu, Cigdem
AU - Yu, Hai
AU - Yuksel Tanriverdi, Selvinaz
AU - Zarbock, Alexander
AU - Zeba, Snjezana
AU - Zhang, Yue
AU - Zhang, Xue
AU - Zhang, Zhenyu
AU - Zhang, Jinlin
AU - Zhang, Gong Wei
AU - Zhong, Jing
AU - Ziemann, Sebastian
AU - Abbenhuis, Jeroen
AU - Abdulmomen, Ahmed
AU - Abdyli, Asead
AU - Abu Elyazed, Mohamed M.
AU - Aguirre Puig, Pilar
AU - Akbudak, Ilknur Hatice
AU - Aksu, Can
AU - Alagöz, Ali
AU - Alhamdi, Malik
AU - Almadhati, Shams
AU - Altorki, Nasser K.
AU - Aragón Alvarez, Sonsoles
AU - Arun, Oguzhan
AU - Azizoglu, Mustafa
AU - Baar, Wolfgang
AU - Balde, Detlef
AU - Balla, Boglárka
AU - Balli Seker, Merve
AU - Basheer, Musaab
AU - Bauer, Wolfgang O.
AU - Bence, Johan
AU - Bernardi, Martin H.
AU - Bigatello, Luca M.
AU - Bignami, Elena
AU - Bluth, Thomas
AU - Bonney, Iwona
AU - Bouhemad, Belaid
AU - Bradic, Nikola
AU - Brescianini, Luigi
AU - Bruthans, Jan
AU - Bulte, Carolien S.E.
AU - Cadar, Genoveva
AU - Cakmak, Gul
AU - Calì, Placido
AU - Cantatore, Leonarda Pia
AU - Chai, Xiaoqing
AU - Chang, Yi Ting
AU - Chen, Jiaqi
AU - Christofaki, Maria
AU - Cinnella, Gilda
AU - Coelho Sanches, Luciana
AU - Constantin, Ana
AU - Contreras, Victor
AU - Corsi, Laura
AU - da Silva, Eduardo
AU - Defosse, Jérôme
AU - Deluca, Raffaele
AU - Diaper, John
AU - Didden, Loes
AU - Dimitriou, Evanthia
AU - do Nascimento Junior, Paulo
AU - Domi, Rudin
AU - Dorfinger, Laurin
AU - dos Reis Falcão, Luiz Fernando
AU - Douradinho, Christian
AU - Drnovšek Globokar, Mojca
AU - Duran, Ferdane Melike
AU - Eldawlatly, Abdelazeem
AU - El-Gendy, Hala M.
AU - Elmazny, Maram I.
AU - Elsherif, Salah Eldin I.
AU - Emara, Moataz Maher
AU - Enriquez de los Santos, Sharon Thali
AU - Farnell-Ward, Sarah
AU - Ferrufino, Renan
AU - Gama de Abreu, Marcelo
AU - Gao, Lingling
AU - Geyik, Dogu
AU - Gnezda, Deja
AU - Goeden, Steffie
AU - Gorjup, Kristina
AU - Granell Gil, Manuel
AU - Guido Guerra, Ricardo Eli
AU - Guimarães de Castro Pereira, Maísa
AU - Guinot, Pierre Grégoire
AU - Guven, Aysegul
AU - Hager, Helmut
AU - Han, Ling
AU - Hatipoglu, Zehra
AU - Hayashi, Megumi
AU - Hell, Johannes
AU - Hofland, Jan
AU - Hollmann, Markus W.
AU - Hu, Jicheng
AU - Hudácek, Kamil
AU - Huti, Gentian
AU - Ilic, Monika
AU - Jankovic, Radmilo J.
AU - Jegarl, Anita
AU - Jiménez Andújar, María José
AU - Jin, Danfeng
AU - Kammerer, Tobias
AU - Karadža, Vjekoslav
AU - Kawagoe, Izumi
AU - Kiran Paudel, Seher Irem
AU - Kiss, Thomas
AU - Koch, Thea
AU - Kolaric, Nevenka
AU - Koning, Nick J.
AU - Kostopanagiotou, Kostas
AU - Kostroglou, Andreas
AU - Kovac, Petra
AU - Kramer, Tim
AU - Kraßler, Jens
AU - Kreft, Tom
AU - Kumrular, Yagmur
AU - Kuut, Marieke
AU - Lan, Lan
AU - Li, Pei Ching
AU - Li, Xue Fei
AU - Li, Lan Tao
AU - Licker, Marc
AU - Liu, Yujia
AU - Longo, Ferdinando
AU - Loop, Torsten
AU - López-Baamonde, Manuel
AU - Luise, Stéphane
AU - Luo, Wenchen
AU - Lv, Hu
AU - Macias Jimenez, Maria de los Angeles
AU - Magalhães, Danielle Dourado
AU - Martuscelli, Matteo
AU - Mavko, Ana
AU - Meco, Basak Ceyda
AU - Mermer, Hasan Alp
AU - Miao, Changhong
AU - Michálek, Pavel
AU - Mills, Gary H.
AU - Miñana Aragón, Encarna
AU - Mirabella, Lucia
AU - Molyneux, Matthew
AU - Montrano, Luigi
AU - Mosqueira, Loreto
AU - Mourisse, Jo
AU - Murrell, Matthew T.
AU - Navarro-Ripoll, Ricard
AU - Negru, Florica
AU - Neskovic, Vojislava
AU - Nikolic, Mario
AU - Norberto de la Vega, Juana Abigail
AU - Noto, Alberto
AU - Nyktari, Vasileia
AU - Orhan Sungur, Mukadder
AU - Ozdemir, Levent
AU - Ozolina, Agnese
AU - Ozturk, Tulun
AU - Pace, Maria Caterina
AU - Pagnussatt Neto, Eugenio
AU - Pálóczi, Balázs
AU - Papaioannou, Alexandra
AU - Papamichail, Konstantinos
AU - Patroniti, Nicolò
AU - Pektas, Yaser
AU - Pereira Matalobos, Denis
AU - Peršec, Jasminka
AU - Petrovic, Stanislava
AU - Pirc, Dejan
AU - Plismanis, Gints
AU - Prata Amendola, Cristina
AU - Pražetina, Marko
AU - Radovic, Nevena
AU - Rauseo, Michela
AU - Richter, Torsten
AU - Rivera Vallejo, Lorena
AU - Rodriguez Ruiz, Juan José
AU - Rondovic, Goran
AU - Rosser, Jon
AU - Sánchez García, Fernando J.
AU - Sansone, Pasquale
AU - Saracoglu, Ayten
AU - Saracoglu, Kemal Tolga
AU - Sazak, Hilal
AU - Scharffenberg, Martin
AU - Schiavoni, Lorenzo
AU - Schilling, Thomas
AU - Sediq, Aras
AU - Semmelmann, Axel
AU - Sentürk, Nüzhet Mert
AU - Sertaç Bingül, Emre
AU - Sertcakacilar, Gokhan
AU - Sfika, Eleni
AU - Shelley, Benjamin
AU - Shin, Sul Hwa
AU - Sidiropoulou, Tatiana
AU - Silva-Jr, João M.
AU - Socci, Laura
AU - Socorro, Tania
AU - Soulioti, Eleftheria
AU - Spadaro, Savino
AU - Špicek-Macan, Jasna
AU - Spray, Dominic
AU - Stamenkovic, Dusica
AU - Stefanakis, Georgios
AU - Stoica, Radu
AU - Stojanovic, Milena
AU - Stopora, Pascal
AU - Sungur, Zerrin
AU - Svareniece-Karjaka, Elizabete
AU - Szamos, Katalin
AU - Tanase, Narcis Valentin
AU - Tanriverdi, Cagin
AU - Tempel, Franz
AU - Terwindt, Lotte E.
AU - Theilen, Raphael
AU - Tipura, Danijela
AU - Tire, Yasin
AU - Tomaselli, Eleonora
AU - Tsuguie Onari, Neusa
AU - Tunç, Mehtap
AU - Turhan, Özlem
AU - Turktan, Mediha
AU - Ugliola, Daniele
AU - Ulugöl, Halim
AU - Végh, Tamás
AU - Vetrugno, Luigi
AU - Vitali, Costanza
AU - Volta, Carlo Alberto
AU - von Dossow, Vera
AU - Voyagis, Gregory
AU - Voyagis, Gregory
AU - Vukovic, Rade
AU - Vukovic, Anita Z.
AU - Waeschle, Reiner M.
AU - Wall, David
AU - Wang, Hui
AU - Wang, Di
AU - Winroth, Dag
AU - Wittenstein, Jakob
AU - Wu, Qichao
AU - Xu, Peiyao
AU - Yaldir, Olcay
AU - Yamansavci Sirzai, Esra
AU - Yang, Xinlu
AU - Yapici, Davud
AU - Yildirim, Ozgucan
AU - Yildirim Guclu, Cigdem
AU - Yu, Hai
AU - Yuksel Tanriverdi, Selvinaz
AU - Zarbock, Alexander
AU - Zeba, Snjezana
AU - Zhang, Yue
AU - Zhang, Xue
AU - Zhang, Zhenyu
AU - Zhang, Jinlin
AU - Zhang, Gong Wei
AU - Zhong, Jing
AU - Ziemann, Sebastian
N1 - Publisher Copyright: © 2025 Elsevier Ltd
PY - 2025/1
Y1 - 2025/1
N2 - Background: The effect of higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres aimed at lung expansion as compared with lower PEEP without recruitment manoeuvres aimed at permissive atelectasis on postoperative pulmonary complications (PPCs) in patients undergoing one-lung ventilation (OLV) during thoracic surgery is unclear. We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs. Methods: In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged ≥18 years) with a BMI of less than 35 kg/m2 who were scheduled for open thoracic or video-assisted thoracoscopic surgery under general anaesthesia requiring one-lung ventilation with a double-lumen tube, with a planned operative time of more than 60 min, and an expected duration of one-lung ventilation longer than that of two-lung ventilation. Patients were randomly assigned (1:1), using permuted blocks of random size (4, 6, and 8) and stratified by study site, to receive one-lung ventilation with either a higher PEEP of 10 cm H2O and periodic lung recruitment manoeuvres (high PEEP group) or a lower PEEP of 5 cm H2O without routine recruitment manoeuvres (low PEEP group). All patients received protective tidal volumes of 5 mL/kg predicted body weight during one-lung ventilation and 7 mL/kg predicted body weight during two-lung ventilation. Postoperative assessors were masked to treatment allocation. The primary outcome was a composite of PPCs during the first 5 postoperative days, including aspiration pneumonia, moderate or severe respiratory failure, acute respiratory distress syndrome (ARDS), pulmonary infection, atelectasis, cardiopulmonary oedema, pleural effusion, non-operative pneumothorax, pulmonary infiltrates, prolonged air leak, purulent pleuritis, pulmonary embolism, and pulmonary haemorrhage. A modified intention-to-treat analysis was performed, with patients analysed according to their assigned treatment group, except in cases of withdrawal of informed consent, cancellation of surgery, and or loss to follow-up. This trial is registered with ClinicalTrials.gov (NCT02963025) and is completed. Findings: Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treat analysis after randomisation. The primary outcome occurred in 555 (53·6%) of 1036 patients in the high PEEP group and 592 (56·4%) of 1049 patients in the low PEEP group (absolute risk difference –2·68 percentage points [95% CI –6·36 to 1·01]; p=0·155). Intraoperative complications occurred in 484 (49·8%) of 972 patients in the high PEEP group and in 305 (31·3%) of 974 patients in the low PEEP group (absolute risk difference 18·09 percentage points [95% CI 14·41–21·77]), among which hypotension (360 [37·3%] of 966 patients in the high PEEP group vs 140 [14·3%] of 978 in the low PEEP group) and new arrhythmias (89 [9·9%] of 899 vs 37 [3·9%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [3·3%] of 888 vs 86 [8·8%] of 982). The proportions of patients with extrapulmonary postoperative complications (110 [10·6%] of 1036 vs 107 [10·2%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups. Interpretation: In patients with a BMI of less than 35 kg/m2 undergoing thoracic surgery, one-lung ventilation using higher PEEP with recruitment manoeuvres, compared with lower PEEP without recruitment manoeuvres, did not reduce PPCs. The choice for intraoperative lung expansion or permissive atelectasis should take the individual gas-exchange and haemodynamic conditions into account, which might vary during the intraoperative period. Funding: Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care; Department of Anaesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Technische Universität Dresden (Dresden, Germany); Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasília, Brazil); and the Association of Anaesthetists of GB and Ireland.
AB - Background: The effect of higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres aimed at lung expansion as compared with lower PEEP without recruitment manoeuvres aimed at permissive atelectasis on postoperative pulmonary complications (PPCs) in patients undergoing one-lung ventilation (OLV) during thoracic surgery is unclear. We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs. Methods: In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged ≥18 years) with a BMI of less than 35 kg/m2 who were scheduled for open thoracic or video-assisted thoracoscopic surgery under general anaesthesia requiring one-lung ventilation with a double-lumen tube, with a planned operative time of more than 60 min, and an expected duration of one-lung ventilation longer than that of two-lung ventilation. Patients were randomly assigned (1:1), using permuted blocks of random size (4, 6, and 8) and stratified by study site, to receive one-lung ventilation with either a higher PEEP of 10 cm H2O and periodic lung recruitment manoeuvres (high PEEP group) or a lower PEEP of 5 cm H2O without routine recruitment manoeuvres (low PEEP group). All patients received protective tidal volumes of 5 mL/kg predicted body weight during one-lung ventilation and 7 mL/kg predicted body weight during two-lung ventilation. Postoperative assessors were masked to treatment allocation. The primary outcome was a composite of PPCs during the first 5 postoperative days, including aspiration pneumonia, moderate or severe respiratory failure, acute respiratory distress syndrome (ARDS), pulmonary infection, atelectasis, cardiopulmonary oedema, pleural effusion, non-operative pneumothorax, pulmonary infiltrates, prolonged air leak, purulent pleuritis, pulmonary embolism, and pulmonary haemorrhage. A modified intention-to-treat analysis was performed, with patients analysed according to their assigned treatment group, except in cases of withdrawal of informed consent, cancellation of surgery, and or loss to follow-up. This trial is registered with ClinicalTrials.gov (NCT02963025) and is completed. Findings: Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treat analysis after randomisation. The primary outcome occurred in 555 (53·6%) of 1036 patients in the high PEEP group and 592 (56·4%) of 1049 patients in the low PEEP group (absolute risk difference –2·68 percentage points [95% CI –6·36 to 1·01]; p=0·155). Intraoperative complications occurred in 484 (49·8%) of 972 patients in the high PEEP group and in 305 (31·3%) of 974 patients in the low PEEP group (absolute risk difference 18·09 percentage points [95% CI 14·41–21·77]), among which hypotension (360 [37·3%] of 966 patients in the high PEEP group vs 140 [14·3%] of 978 in the low PEEP group) and new arrhythmias (89 [9·9%] of 899 vs 37 [3·9%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [3·3%] of 888 vs 86 [8·8%] of 982). The proportions of patients with extrapulmonary postoperative complications (110 [10·6%] of 1036 vs 107 [10·2%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups. Interpretation: In patients with a BMI of less than 35 kg/m2 undergoing thoracic surgery, one-lung ventilation using higher PEEP with recruitment manoeuvres, compared with lower PEEP without recruitment manoeuvres, did not reduce PPCs. The choice for intraoperative lung expansion or permissive atelectasis should take the individual gas-exchange and haemodynamic conditions into account, which might vary during the intraoperative period. Funding: Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care; Department of Anaesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Technische Universität Dresden (Dresden, Germany); Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasília, Brazil); and the Association of Anaesthetists of GB and Ireland.
UR - https://www.scopus.com/pages/publications/105025885130
UR - https://www.scopus.com/pages/publications/105025885130#tab=citedBy
U2 - 10.1016/S2213-2600(25)00330-3
DO - 10.1016/S2213-2600(25)00330-3
M3 - Article
C2 - 41240959
AN - SCOPUS:105025885130
SN - 2213-2600
VL - 14
SP - 17
EP - 28
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 1
ER -