Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study
Authors: Amado-Rodríguez Laura , Rodríguez-Garcia Raquel , Bellani Giacomo , Pham Tài , Fan Eddy , Madotto Fabiana , Laffey John G. , Albaiceta Guillermo M. ,   LUNG SAFE investigators, Pesenti Antonio , Brochard Laurent , Esteban Andres , Gattinoni Luciano , van Haren Frank , Larsson Anders , McAuley DanielF , Ranieri Marco , Rubenfeld Gordon , Taylor Thompson B. , Wrigge Hermann , Slutsky Arthur S. , Rios Fernando , Van Haren Frank , Sottiaux Thierry , Depuydt Pieter , Lora Fredy S. , Azevedo Luciano Cesar , Bugedo Guillermo , Qiu Haibo , Gonzalez Marcos , Silesky Juan , Cerny Vladimir , Nielsen Jonas , Jibaja Manuel , Wrigge Hermann , Matamis Dimitrios , Ranero Jorge Luis , Amin Pravin , Hashemian S. M. , Clarkson Kevin , Kurahashi Kiyoyasu , Villagomez Asisclo , Zeggwagh Amine Ali , Heunks Leo M. , Laake Jon Henrik , Palo Jose Emmanuel , do Vale Fernandes Antero , Sandesc Dorel , Arabi Yaasen , Bumbasierevic Vesna , Nin Nicolas , Lorente Jose A. , Larsson Anders , Piquilloud Lise , Abroug Fekri , McAuley DanielF , McNamee Lia , Hurtado Javier , Bajwa Ed , Démpaire Gabriel , Sula Hektor , Nunci Lordian , Cani Alma , Zazu Alan , Dellera Christian , Insaurralde Carolina S. , Las Lomas Sanatorio , Isidro San , Alejandro Risso V. , Daldin Julio , Vinzio Mauricio , Fernandez Ruben O. , Cardonnet Luis P. , Bettini Lisandro R. , Bisso Mariano Carboni , Osman Emilio M. , Setten Mariano G. , Lovazzano Pablo , Alvarez Javier , Villar Veronica , Pozo Norberto C. , Grubissich Nicolas , Plotnikow Gustavo A. , Vasquez Daniela N. , Ilutovich Santiago , Tiribelli Norberto , Chena Ariel , Pellegrini Carlos A. , Saenz María G. , Estenssoro Elisa , Brizuela Matias , Gianinetto Hernan , Gomez Pablo E. , Cerrato Valeria I. , Bezzi Marco G. , Borello Silvina A. , Loiacono Flavia A. , Fernandez Adriana M. , Knowles Serena , Reynolds Claire , Inskip Deborah M. , Miller Jennene J. , Kong Jing , Whitehead Christina , Bihari Shailesh , Seven Aylin , Krstevski Amanda , Rodgers Helen J. , Millar Rebecca T. , McKenna Toni E. , Bailey Irene M. , Hanlon Gabrielle C. , Aneman Anders , Lynch Joan M. , Azad Raman , Neal John , Woods Paul W. , Roberts Brigit L. , Kol Mark R. , Wong Helen S. , Riss Katharina C. , Staudinger Thomas , Wittebole Xavier , Berghe Caroline , Bulpa Pierre A. , Dive Alain M. , Verstraete Rik , Lebbinck Herve , Depuydt Pieter , Vermassen Joris , Meersseman Philippe , Ceunen Helga , Rosa JonasI , Beraldo Daniel O. , Piras Claudio , Rampinelli Adenilton M. , Nassar Jr Antonio P. , Mataloun Sergio , Moock Marcelo , Thompson MarlusM , Gonçalves Claudio H. , Antônio Ana Carolina P. , Ascoli Aline , Biondi Rodrigo S. , Fontenele Danielle C. , Nobrega Danielle , Sales Vanessa M. , BinHJAbul Wahab Ahmad Yazid , Ismail Maizatul , Shindhe Suresh , Laffey John , Beloncle Francois , Davies Kyle G. , Cirone Rob , Manoharan Venika , Ismail Mehvish , Goligher Ewan C. , Jassal Mandeep , Nishikawa Erin , Javeed Areej , Curley Gerard , Rittayamai Nuttapol , Parotto Matteo , Ferguson Niall D. , Mehta Sangeeta , Knoll Jenny , Pronovost Antoine , Canestrini Sergio , Bruhn Alejandro R. , Garcia Patricio H. , Aliaga Felipe A. , Farías Pamela A. , Yumha Jacob S. , Ortiz Claudia A. , Salas Javier E. , Saez Alejandro A. , Vega Luis D. , Labarca Eduardo F. , Martinez Felipe T. , Carreño Nicolás G. , Lora Pilar , Liu Haitao , Qiu Haibo , Liu Ling , Tang Rui , Luo Xiaoming , An Youzhong , Zhao Huiying , Gao Yan , Zhai Zhe , Ye Zheng L. , Wang Wei , Li Wenwen , Li Qingdong , Zheng Ruiqiang , Yu Wenkui , Shen Juanhong , Li Xinyu , Yu Tao , Lu Weihua , Wu Ya Q. , Huang Xiao B. , He Zhenyang , Lu Yuanhua , Han Hui , Zhang Fan , Sun Renhua , Wang Hua X. , Qin Shu H. , Zhu Bao H. , Zhao Jun , Liu Jian , Li Bin , Liu Jing L. , Zhou Fa C. , Li Qiong J. , Zhang Xing Y , Li-Xin Zhou , Xin-Hua Qiang , Jiang Liangyan , Gao Yuan N. , Zhao Xian Y. , Li Yuan Y. , Li Xiao L. , Wang Chunting , Yao Qingchun , Yu Rongguo , Chen Kai , Shao Huanzhang , Qin Bingyu , Huang Qing Q. , Zhu Wei H. , Hang Ai Y. , Hua Ma X. , Li Yimin , Xu Yonghao , Di Yu D. , Ling Long L. , Qin Tie H. , Wang ShouH , Qin Junping , Han Yi , Zhou Suming , Vargas Monica P. , Jimenez Juan I. Silesky , Rojas Manuel A. González , SolisQuesada Jaime E. , Ramirez-Alfaro ChristianM , Máca Jan , Sklienka Peter , Gjedsted Jakob , Christiansen Aage , Nielsen Jonas , Villamagua BorisG , Llano Iguel , Burtin Philippe , Buzancais Gautier , Beuret Pascal , Pelletier Nicolas , Mortaza Satar , Mercat Alain , Chelly Jonathan , Jochmans Sébastien , Terzi Nicolas , Daubin Cédric , Carteaux Guillaume , de Prost Nicolas , Chiche Jean-Daniel , Daviaud Fabrice , Fartoukh Muriel , Barberet Guillaume , Biehler Jerome , Dellamonica Jean , Doyen Denis , Arnal Jean-Michel , Briquet Anais , Hraiech Sami , Papazian Laurent , Follin Arnaud , Roux Damien , Messika Jonathan , Kalaitzis Evangelos , Dangers Laurence , Combes Alain , Béduneau Gaetan , Carpentier Dorothée , Zogheib Elie H. , Dupont Herve , Ricome Sylvie , Santoli FrancescoL , Besset Sebastien L. , Michel Philippe , Gelée Bruno , Danin Pierre-Eric , Goubaux Bernard , Crova Philippe J. , Phan Nga T. , Berkelmans Frantz , Badie Julio C. , Tapponnier Romain , Gally Josette , Khebbeb Samy , Herbrecht Jean-Etienne , Schneider Francis , Declercq PierreLouis M. , Rigaud Jean-Philippe , Duranteau Jacques , Harrois Anatole , Chabanne Russell , Marin Julien , Bigot Charlene , Thibault Sandrine , Ghazi Mohammed , Boukhazna Messabi , Zein Salem Ould , Richecoeur Jack R. , Combaux DanieleM , Grelon Fabien , Le Moal Charlene , Sauvadet EliseP , Robine Adrien , Lemiale Virginie , Reuter Danielle , Dres Martin , Demoule Alexandre , Goldgran-Toledano Dany , Baboi Loredana , Guérin Claude , Lohner Ralph , Kraßler Jens , Schäfer Susanne , Zacharowski Kai D. , Meybohm Patrick , Reske Andreas W. , Simon Philipp , Hopf HansBernd F. , Schuetz Michael , Baltus Thomas , Papanikolaou Metaxia N. , Papavasilopoulou Theonymfi G. , Zacharas Giannis A. , Ourailogloy Vasilis , Mouloudi Eleni K. , Massa Eleni V. , Nagy Eva O. , Stamou Electra E. , Kiourtzieva Ellada V. , Oikonomou Marina A. , Avila Luis E. , Cortez Cesar A. , Citalán Johanna E. , Jog Sameer A. , Sable Safal D. , Shah Bhagyesh , Gurjar Mohan , Baronia Arvind K. , Memon Mohammedfaruk , Muthuchellappan Radhakrishnan , Ramesh Venkatapura J. , Shenoy Anitha , Unnikrishnan Ramesh , Dixit Subhal B. , Rhayakar RachanaV , Ramakrishnan Nagarajan , Bhardwaj VallishK , Mahto HeeraL , Sagar Sudha V. , Palaniswamy Vijayanand , Ganesan Deeban , Hashemian Seyed Mohammadreza , Jamaati Hamidreza , Heidari Farshad , Meaney Edel A. , Nichol Alistair , Knapman Karl M. , O’Croinin Donall , Dunne EimhinS , Breen Dorothy M. , Clarkson Kevin P. , Jaafar Rola F. , Dwyer Rory , Amir Fahd , Ajetunmobi Olaitan O. , O’Muircheartaigh Aogan C. , Black ColinS , Treanor Nuala , Collins Daniel V. , Altaf Wahid , Zani Gianluca , Fusari Maurizio , Spadaro Savino , Volta Carlo A. , Graziani Romano , Brunettini Barbara , Palmese Salvatore , Formenti Paolo , Umbrello Michele , Lombardo Andrea , Pecci Elisabetta , Botteri Marco , Savioli Monica , Protti Alessandro , Mattei Alessia , Schiavoni Lorenzo , Tinnirello Andrea , Todeschini Manuel , Giarratano Antonino , Cortegiani Andrea , Sher Sara , Rossi Anna , Antonelli Massimo M. , Montini Luca M. , Casalena Paolo , Scafetti Sergio , Panarello Giovanna , Occhipinti Giovanna , Patroniti Nicolò , Pozzi Matteo , Biscione RobertoR , Poli Michela M. , Raimondi Ferdinando , Albiero Daniela , Crapelli Giulia , Beck Eduardo , Pota Vincenzo , Schiavone Vincenzo , Molin Alexandre , Tarantino Fabio , Monti Giacomo , Frati Elena , Mirabella Lucia , Cinnella Gilda , Fossali Tommaso , Colombo Riccardo , Terragni Pierpaolo , Pattarino Ilaria , Mojoli Francesco , Braschi Antonio , Borotto Erika E. , Cracchiolo Andrea N. , Palma Daniela M. , Raponi Francesco , Foti Giuseppe , Vascotto EttoreR , Coppadoro Andrea , Brazzi Luca , Floris Leda , Iotti Giorgio A. , Venti Aaron , Yamaguchi Osamu , Takagi Shunsuke , Maeyama Hiroki N. , Watanabe Eizo , Yamaji Yoshihiro , Shimizu Kazuyoshi , Shiozaki Kyoko , Futami Satoru , Ryosuke Sekine , Saito Koji , Kameyama Yoshinobu , Ueno Keiko , Izawa Masayo , Okuda Nao , Suzuki Hiroyuki , Harasawa Tomofumi , Nasu Michitaka , Takada Tadaaki , Ito Fumihito , Nunomiya Shin , Koyama Kansuke , Abe Toshikazu , Andoh Kohkichi , Kusumoto Kohei , Hirata Akira , Takaba Akihiro , Kimura Hiroyasu , Matsumoto Shuhei , Higashijima Ushio , Honda Hiroyuki , Aoki Nobumasa , Imai Hiroshi , Ogino Yasuaki , Mizuguchi Ichiko , Ichikado Kazuya , Nitta Kenichi , Mochizuki Katsunori , Hashida Tomoaki , Tanaka Hiroyuki , Nakamura Tomoyuki , Niimi Daisuke , Ueda Takeshi , Kashiwa Yozo , Uchiyama Akinori , Sabelnikovs Olegs , Oss Peteris , Haddad Youssef , Liew Kong Y. , Ñamendys-Silva Silvio A. , Jarquin-Badiola YvesD , Sanchez-Hurtado Luis A. , Gomez-Flores Saira S. , Marin Maria C. , Villagomez AsiscloJ , Lemus Jordana S. , Fierro Jonathan M. , Cervantes Mavy Ramirez , Mejia Francisco Javier Flores , Dector Dulce , Rojas Alejandro , Gonzalez Daniel R. , Estrella Claudia R. , Sanchez-Medina Jorge R. , Ramirez-Gutierrez Alvaro , George Fernando G. , Aguirre Janet S. , Buensuseso Juan A. , Poblano Manuel , Dendane Tarek , Zeggwagh Amine Ali , Balkhi Hicham , Elkhayari Mina , Samkaoui Nacer , Ezzouine Hanane , Benslama Abdellatif , Amor Mourad , Maazouzi Wajdi , Cimic Nedim , Beck Oliver , Bruns Monique M. , Schouten Jeroen A. , Rinia Myra , Raaijmakers Monique , Heunks Leo M. , Van Wezel Hellen M. , Heines Serge J , Strauch Ulrich , Buise Marc P. , Simonis Fabienne D. , Schultz Marcus J. , Goodson Jennifer C. , Browne Troy S. , Navarra Leanlove , Hunt Anna , Hutchison Robyn A. , Bailey Mathew B. , Newby Lynette , McArthur Colin , Kalkoff Michael , Mcleod Alex , Casement Jonathan , Hacking DanielleJ , Andersen Finn H. , Dolva Merete S. , Laake Jon H. , Barratt-Due Andreas , Noremark Kim Andre L. , Søreide Eldar , Sjøbø BritÅ , Guttormsen AnneB , LeonYoshido Hector H. , Aguilar Ronald Zumaran , Oscanoa Fredy A. Montes , Alisasis Alain U. , Robles Joanne B. , Pasanting-Lim Rossini Abbie B. , Tan Beatriz C. , Andruszkiewicz Pawel , Jakubowska Karina , Coxo Cristina M. , Alvarez António M. , Oliveira Bruno S. , Montanha Gustavo M. , Barros Nelson C. , Pereira Carlos S. , Messias António M. , Monteiro Jorge M. , Araujo AnaM , Catorze NunoT , Marum Susan M. , Bouw Maria J. , Gomes Rui M. , Brito Vania A. , Castro Silvia , Estilita Joana M. , Barros Filipa M. , Serra IsabelM , Martinho Aurelia M. , Tomescu Dana R. , Marcu Alexandra , Bedreag Ovidiu H. , Papurica Marius , Corneci Dan E. , Negoita Silvius Ioan , Grigoriev Evgeny , Gritsan Alexey I. , Gazenkampf Andrey A. , Almekhlafi Ghaleb , Albarrak Mohamad M. , Mustafa Ghanem M. , Maghrabi Khalid A. , Salahuddin Nawal , Aisa Tharwat M. , AlJabbary AhmedS , Tabhan Edgardo , Arabi YaseenM , Arabi Yaseen M. , Trinidad Olivia A. , Al Dorzi Hasan M. , Tabhan Edgardo E. , Bumbasirevic Vesna , Jovanovic Bojan , Bolon Stefan , Smith Oliver , Mancebo Jordi , Aguirre-Bermeo Hernan , Lopez-Delgado JuanC , Esteve Francisco , Rialp Gemma , Forteza Catalina , De Haro Candelaria , Artigas Antonio , Albaiceta GuillermoM , De Cima-Iglesias Sara , Seoane-Quiroga Leticia , Ceniceros-Barros Alexandra , RuizAguilar AntonioL , Claraco-Vega LuisM , Soler Juan Alfonso , del CarmenLorente Maria , Hermosa Cecilia , Gordo Federico , PrietoGonzález Miryam , López-Messa JuanB , Perez ManuelP , Perez CesarP , Allue Raquel Montoiro , RocheCampo Ferran , Ibañez-Santacruz Marcos , Temprano Susana , Pintado Maria C. , De Pablo Raul , Gómez Pilar Ricart Aroa , Ruiz Silvia Rodriguez , Moles Silvia Iglesias , Jurado M. Teresa , Arizmendi Alfons , Piacentini Enrique A. , Franco Nieves , Honrubia Teresa , Cheng Meisy Perez , Losada Elena Perez , Blanco Javier , Yuste Luis J. , Carbayo-Gorriz Cecilia , Cazorla-Barranquero Francisca G. , Alonso Javier G. , Alda Rosa S. , Algaba Ángela , Navarro Gonzalo , Cereijo Enrique , Diaz-Rodriguez Esther , Marcos Diego Pastor , Montero Laura Alvarez , Para Luis Herrera , Sanchez Roberto Jimenez , Navalpotro Miguel Angel Blasco , Abad Ricardo Diaz , González Raquel Montiel , Toribio Dácil Parrilla , Castro Alejandro G. , Artiga Maria Jose D. , Penuelas Oscar , Roser Tomas P. , Olga Moreno F. , Curto Elena Gallego , Sánchez Rocío Manzano , Imma Vallverdu P. , Elisabet Garcia M. , Claverias Laura , Magret Monica , Pellicer Ana M. , Rodriguez Lucia L. , Sánchez-Ballesteros Jesús , González-Salamanca Ángela , Jimenez AntonioG , Huerta FranciscoP , Diaz Juan Carlos J. Sotillo , Lopez Esther Bermejo , Moya David D. Llinares , Alfonso Alec A. Tallet , Luis Palazon Sanchez Eugenio , Cesar Palazon Sanchez , Rafael Sánchez I. , Virgilio CorcolesG , Recio NoeliaN , Adamsson Richard O. , Rylander Christian C. , Holzgraefe Bernhard , Broman Lars M , Wessbergh Joanna , Persson Linnea , Schiöler Fredrik , Kedelv Hans , Tibblin Anna Oscarsson , Appelberg Henrik , Hedlund Lars , Helleberg Johan , Eriksson KarinE , Glietsch Rita , Larsson Niklas , Nygren Ingela , Nunes SilviaL , Morin Anna-Karin , Kander Thomas , Adolfsson Anne , Zender HervéO , Leemann-Refondini Corinne , Elatrous Souheil , Bouchoucha Slaheddine , Chouchene Imed , Ouanes Islem , Souissi Asma Ben , Kamoun Salma , Demirkiran Oktay , Aker Mustafa , Erbabacan Emre , Ceylan Ilkay , Girgin Nermin Kelebek , Ozcelik Menekse , Ünal Necmettin , Meco Basak Ceyda , Akyol OnatO , Derman SuleymanS , Kennedy Barry , Parhar Ken , Srinivasa Latha , McNamee Lia , McAuley Danny , Hopkins Phil , Mellis Clare , Kakar Vivek , Hadfield Dan , Vercueil Andre , Bhowmick Kaushik , Humphreys Sally K. , Ferguson Andrew , Mckee Raymond , Raj Ashok S. , Fawkes Danielle A. , Watt Philip , Twohey Linda , Jha Rajeev R. , Thomas Matthew , Morton Alex , Kadaba Varsha , Smith Mark J. , Hormis Anil P. , Kannan Santhana G. , Namih Miriam , Reschreiter Henrik , Camsooksai Julie , Kumar Alek , Rugonfalvi Szabolcs , Nutt Christopher , Oneill Orla , Seasman Colette , Dempsey Ged , Scott ChristopherJ , Ellis HelenE , Mckechnie Stuart , Hutton PaulaJ , Di Tomasso Nora N. , Vitale Michela N. , Griffin Ruth O. , Dean MichaelN , Cranshaw JuliusH , Willett EmmaL , Ioannou Nicholas , Gillis Sarah , Csabi Peter , Macfadyen Rosaleen , Dawson Heidi , Preez PieterD , Williams Alexandra J , Boyd Owen , de Gordoa Laura Ortiz-Ruiz , Bramall Jon , Symmonds Sophie , Chau SimonK , Wenham Tim , Szakmany Tamas , Toth-Tarsoly Piroska , McCalman KatieH , Alexander Peter , Stephenson Lorraine , Collyer Thomas , Chapman Rhiannon , Cooper Raphael , Allan Russell M , Sim Malcolm , Wrathall David W , Irvine DonaldA , Zantua Charing Kim S. , Adams John C. , Burtenshaw Andrew J. , Sellors Gareth P. , Welters Ingeborg D. , Williams Karen E. , Hessell Robert J. , Oldroyd Matthew G. , Battle Ceri E. , Pillai Suresh , Kajtor Istvan , Sivashanmugavel Mageswaran , Okane Sinead C. , Donnelly Adrian , Frigyik Aniko D. , Careless Jon P. , May Martin M , Stewart Richard , Trinder T. John , Hagan SamanthaJ , Cole JadeM , MacFie Caroline C. , Dowling AnnaT , Hurtado Javier , Nin Nicolás , Hurtado Javier , Nuñez Edgardo , Pittini Gustavo , Rodriguez Ruben , Imperio María C. , Santos Cristina , França Ana G , Ebeid Alejandro , Deicas Alberto , Serra Carolina , Uppalapati Aditya , Kamel Ghassan , BannerGoodspeed Valerie M. , Beitler Jeremy R. , Mukkera Satyanarayana Reddy , Kulkarni Shreedhar , Shinn III John O. , Gomaa Dina , Tainter Christopher , Lee Jarone , Mesar Tomaz , Yeatts DaleJ , Warren Jessica , Lanspa MichaelJ , Miller Russel R. , Grissom ColinK , Brown SamuelM , Bauer Philippe R. , Gosselin Ryan J. , Kitch Barrett T. , Cohen Jason E. , Beegle Scott H. , Choudry Shazia , Gueret Renaud M. , Tulaimat Aiman , Stigler William , Batra Hitesh , Huff Nidhi G. , Lamb Keith D. , Oetting Trevor W. , Mohr Nicholas M. , Judy Claine , Saito Shigeki , Kheir Fayez M. , Kheir Fayez , Schlichting Adam B. , Delsing Angela , Crouch Daniel R. , Elmasri Mary , Crouch Daniel R. , Ismail Dina , Dreyer Kyle R. , Blakeman Thomas C. , Gomaa Dina , Baro Rebecca M. , Hou Peter C. , Seethala Raghu , Aisiku Imo , Henderson Galen , Frendl Gyorgy , Hou Sen-Kuang , Owens RobertL , Schomer Ashley 
Published: December 2022

Abstract
Background
Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality.

Methods
Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model.

Results
From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59–78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57–77] vs 74 [64–80] years, p < 0.001) and had lower driving (12 [8–16] vs 15 [11–17] cmH2O, p < 0.001), plateau (20 [15–23] vs 22 [19–26] cmH2O, p < 0.001) and peak (21 [17–27] vs 26 [20–32] cmH2O, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60–1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16–2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06–1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52–0.93], p = 0.015) were related to survival.

Conclusions
Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury.
Trial registration Clinicaltrials.gov NCT02010073