Impact of intensive prone position therapy on outcomes in intubated patients with ARDS related to COVID-19
Authors: Le Terrier Christophe , Walter Thaïs , Lebbah Said , Hajage David , Sigaud Florian , Guérin Claude , Desmedt Luc , Primmaz Steve , Joussellin Vincent , Della Badia Chiara , Ricard Jean-Damien , Pugin Jérôme , Terzi Nicolas ,   COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators, Mercat Alain , Asfar Pierre , Beloncle François , Demiselle Julien , Pham Tài , Pavot Arthur , Monnet Xavier , Richard Christian , Demoule Alexandre , Dres Martin , Mayaux Julien , Beurton Alexandra , Daubin Cédric , Descamps Richard , Joret Aurélie , Du Cheyron Damien , Pene Frédéric , Chiche Jean-Daniel , Jozwiak Mathieu , Jaubert Paul , Voiriot Guillaume , Fartoukh Muriel , Teulier Marion , Blayau Clarisse , L’Her Erwen , Aubron Cécile , Bodenes Laetitia , Ferriere Nicolas , Auchabie Johann , Le Meur Anthony , Pignal Sylvain , Mazzoni Thierry , Quenot Jean-Pierre , Andreu Pascal , Roudau Jean-Baptiste , Labruyère Marie , Nseir Saad , Preau Sébastien , Poissy Julien , Mathieu Daniel , Benhamida Sarah , Paulet Rémi , Roucaud Nicolas , Thyrault Martial , Daviet Florence , Hraiech Sami , Parzy Gabriel , Sylvestre Aude , Jochmans Sébastien , Bouilland Anne-Laure , Monchi Mehran , des Déserts Marc Danguy , Mathais Quentin , Rager Gwendoline , Pasquier Pierre , Jean Reignier , Amélie Seguin , Charlotte Garret , Emmanuel Canet , Dellamonica Jean , Saccheri Clément , Lombardi Romain , Kouchit Yanis , Jacquier Sophie , Mathonnet Armelle , Nay Mai-Ahn , Runge Isabelle , Martino Frédéric , Flurin Laure , Rolle Amélie , Carles Michel , Coudroy Rémi , Thille Arnaud W. , Frat Jean-Pierre , Rodriguez Maeva , Beuret Pascal , Tientcheu Audrey , Vincent Arthur , Michelin Florian , Tamion Fabienne , Carpentier Dorothée , Boyer Déborah , Girault Christophe , Gissot Valérie , Ehrmann Stéphan , Gandonniere Charlotte Salmon , Elaroussi Djlali , Delbove Agathe , Fedun Yannick , Huntzinger Julien , Lebas Eddy , Kisoka Grâce , Grégoire Céline , Marchetta Stella , Lambermont Bernard , Argaud Laurent , Baudry Thomas , Bertrand Pierre-Jean , Dargent Auguste , Guitton Christophe , Chudeau Nicolas , Landais Mickaël , Darreau Cédric , Ferre Alexis , Gros Antoine , Lacave Guillaume , Bruneel Fabrice , Neuville Mathilde , Devaquet Jérôme , Tachon Guillaume , Gallot Richard , Chelha Riad , Galbois Arnaud , Jallot Anne , Lemoine Ludivine Chalumeau , Kuteifan Khaldoun , Pointurier Valentin , Jandeaux Louise-Marie , Mootien Joy , Damoisel Charles , Sztrymf Benjamin , Schmidt Matthieu , Combes Alain , Chommeloux Juliette , Luyt Charles Edouard , Schortgen Frédérique , Rusel Leon , Jung Camille , Gobert Florent , Vimpere Damien , Lamhaut Lionel , Sauneuf Bertrand , Charrrier Liliane , Calus Julien , Desmeules Isabelle , Painvin Benoît , Tadie Jean-Marc , Castelain Vincent , Michard Baptiste , Herbrecht Jean-Etienne , Baldacini Mathieu , Weiss Nicolas , Demeret Sophie , Marois Clémence , Rohaut Benjamin , Moury Pierre-Henri , Savida Anne-Charlotte , Couadau Emmanuel , Série Mathieu , Alexandru Nica , Bruel Cédric , Fontaine Candice , Garrigou Sonia , Mahler Juliette Courtiade , Leclerc Maxime , Ramakers Michel , Garçon Pierre , Massou Nicole , Van Vong Ly , Sen Juliane , Lucas Nolwenn , Chemouni Franck , Stoclin Annabelle , Avenel Alexandre , Faure Henri , Gentilhomme Angélie , Ricome Sylvie , Abraham Paul , Monard Céline , Textoris Julien , Rimmele Thomas , Montini Florent , Lejour Gabriel , Lazard Thierry , Etienney Isabelle , Kerroumi Younes , Dupuis Claire , Bereiziat Marine , Coupez Elisabeth , Thouy François , Hoffmann Clément , Donat Nicolas , Chrisment Anne , Blot Rose-Marie , Kimmoun Antoine , Jacquot Audrey , Mattei Matthieu , Levy Bruno , Ravan Ramin , Dopeux Loïc , Liteaudon Jean-Mathias , Roux Delphine , Rey Brice , Anghel Radu , Schenesse Deborah , Gevrey Vincent , Castanera Jermy , Petua Philippe , Madeux Benjamin , Hartman Otto , Piagnerelli Michael , Joosten Anne , Noel Cinderella , Biston Patrick , Noel Thibaut , Le Bouar Gurvan , Boukhanza Messabi , Demarest Elsa , Bajolet Marie-France , Charrier Nathanaël , Quenet Audrey , Zylberfajn Cécile , Dufour Nicolas , Mégarbane Buno , Voicu Sqébastian , Deye Nicolas , Malissin Isabelle , Legay François , Debarre Matthieu , Barbarot Nicolas , Fillatre Pierre , Delord Bertrand , Laterrade Thomas , Saghi Tahar , Pujol Wilfried , Cungi Pierre Julien , Esnault Pierre , Cardinale Mickael , Ha Vivien Hong Tuan , Fleury Grégory , Brou Marie-Ange , Zafimahazo Daniel , Tran-Van David , Avargues Patrick , Carenco Lisa , Robin Nicolas , Ouali Alexandre , Houdou Lucie , Suh Noémie , Weiss Emmanuel , Gauss Tobias , Moyer Jean-Denis , Burtz Catherine Paugam , La Combe Béatrice , Smonig Rolland , Violleau Jade , Cailliez Pauline , Marchalot Antoine , Saladin Cécile , Bigot Christelle , Fayolle Pierre-Marie , Fatséas Jules , Ibrahim Amr , Resiere Dabor , Hage Rabih , Cholet Clémentine , Cantier Marie , Trouiler Pierre , Montravers Philippe , Lortat-Jacob Brice , Tanaka Sebastien , Dinh Alexy Tran , Duranteau Jacques , Harrois Anatole , Dubreuil Guillaume , Werner Marie , Godier Anne , Hamada Sophie , Zlotnik Diane , Nougue Hélène , Mekontso-Dessap Armand , Carteaux Guillaume , Razazi Keyvan , De Prost Nicolas , Mongardon Nicolas , Langeron Olivier , Levesque Eric , Attias Arié , de Roquetaillade Charles , Chousterman Benjamin G. , Mebazaa Alexandre , Gayat Etienne , Garnier Marc , Pardo Emmanuel , Satre-Buisson Lea , Gutton Christophe , Yvin Elise , Marcault Clémence , Azoulay Elie , Darmon Michael , Oufella Hafid Ait , Hariri Geoffroy , Urbina Tomas , Mazerand Sandie , Heming Nicholas , Santi Francesca , Moine Pierre , Annane Djillali , Bouglé Adrien , Omar Edris , Lancelot Aymeric , Begot Emmanuelle , Plantefeve Gaétan , Contou Damien , Mentec Hervé , Pajot Olivier , Faguer Stanislas , Cointault Olivier , Lavayssiere Laurence , Nogier Marie-Béatrice , Jamme Matthieu , Pichereau Claire , Hayon Jan , Outin Hervé , Dépret François , Coutrot Maxime , Chaussard Maité , Guillemet Lucie , Goffin Pierre , Thouny Romain , Guntz Julien , Jadot Laurent , Persichini Romain , Jean-Michel Vanessa , Georges Hugues , Caulier Thomas , Pradel Gaël , Hausermann Marie-Hélène , Nguyen-Valat Thi My Hue , Boudinaud Michel , Vivier Emmanuel , Rosseli Sylvène , Bourdin Gaël , Pommier Christian , Vinclair Marc , Poignant Simon , Mons Sandrine , Bougouin Wulfran , Bruna Franklin , Maestraggi Quentin , Roth Christian , Bitker Laurent , Dhelft François , Bonnet-Chateau Justine , Filippelli Mathilde , Morichau-Beauchant Tristan , Thierry Stéphane , Le Roy Charlotte , Jouan Mélanie Saint , Goncalves Bruno , Mazeraud Aurélien , Daniel Matthieu , Sharshar Tarek , Cadoz Cyril , Gaci Rostane , Gette Sébastien , Louis Guillaune , Sacleux Sophe-Caroline , Ordan Marie-Amélie , Cravoisy Aurélie , Conrad Marie , Courte Guilhem , Gibot Sébastien , Benzidi Younès , Casella Claudia , Serpin Laurent , Setti Jean-Lou , Besse Marie-Catherine , Bourreau Anna , Pillot Jérôme , Rivera Caroline , Vinclair Camille , Robaux Marie-Aline , Achino Chloé , Delignette Marie-Charlotte , Mazard Tessa , Aubrun Frédéric , Bouchet Bruno , Frérou Aurélien , Muller Laura , Quentin Charlotte , Degoul Samuel , Stihle Xavier , Sumian Claude , Bergero Nicoletta , Lanaspre Bernard , Quintard Hervé , Maiziere Eve Marie , Egreteau Pierre-Yves , Leloup Guillaume , Berteau Florin , Cottrel Marjolaine , Bouteloup Marie , Jeannot Matthieu , Blanc Quentin , Saison Julien , Geneau Isabelle , Grenot Romaric , Ouchike Abdel , Hazera Pascal , Masse Anne-Lyse , Demiri Suela , Vezinet Corinne , Baron Elodie , Benchetrit Deborah , Monsel Antoine , Trebbia Grégoire , Schaack Emmanuelle , Lepecq Raphaël , Bobet Mathieu , Vinsonneau Christophe , Dekeyser Thibault , Delforge Quentin , Rahmani Imen , Vivet Bérengère , Paillot Jonathan , Hierle Lucie , Chaignat Claire , Valette Sarah , Her Benoït , Brunet Jennifier , Page Mathieu , Boiste Fabienne , Collin Anthony , Bavozet Florent , Garin Aude , Dlala Mohamed , Mhamdi Kais , Beilouny Bassem , Lavalard Alexandra , Perez Severine , Veber Benoit , Guitard Pierre-Gildas , Gouin Philippe , Lamacz Anna , Plouvier Fabienne , Delaborde Bertrand P. , Kherchache Aïssa , Chaalal Amina , Amouretti Marc , Freita-Ramos Santiago , Roux Damien , Constantin Jean-Michel , Assefi Mona , Lecore Marine , Selves Agathe , Prevost Florian , Lamer Christian , Shi Ruiying , Knani Lyes , Floury Sébastien Pili , Vettoretti Lucie , Levy Michael , Marsac Lucile , Dauger Stéphane , Guilmin-Crépon Sophie , Winiszewski Hadrien , Piton Gael , Soumagne Thibaud , Capellier Gilles , Putegnat Jean-Baptiste , Bayle Frédérique , Perrou Maya , Thao Ghyslaine , Géri Guillaume , Charron Cyril , Repessé Xavier , Vieillard-Baron Antoine , Guilbart Mathieu , Roger Pierre-Alexandre , Hinard Sébastien , Macq Pierre-Yves , Chaulier Kevin , Goutte Sylvie , Chillet Patrick , Pitta Anaïs , Darjent Barbara , Bruneau Amandine , Lasocki Sigismond , Leger Maxime , Gergaud Soizic , Lemarie Pierre , Schwebel Carole , Dartevel Anaïs , Galerneau Louis-Marie , Diehl Jean-Luc , Hauw-Berlemont Caroline , Péron Nicolas , Guérot Emmanuel , Amoli Abolfazl Mohebbi , Benhamou Michel , Deyme Jean-Pierre , Andremont Olivier , Lena Diane , Cady Julien , Causeret Arnaud , De La Chapelle Arnaud , Cracco Christophe , Rouleau Stéphane , Schnell David , Foucault Camille , Lory Cécile , Chapelle Thibault , Bruckert Vincent , Garcia Julie , Sahraoui Abdlazize , Abbosh Nathalie , Bornstain Caroline , Pernet Pierre , Poirson Florent , Pasem Ahmed , Karoubi Philippe , Poupinel Virginie , Gauthier Caroline , Bouniol François , Feuchere Philippe , Heron Anne , Carreira Serge , Emery Malo , Le Floch Anne Sophie , Giovannangeli Luana , Herzog Nicolas , Giacardi Christophe , Baudic Thibaut , Thill Chloé , Palmyre Jessica , Tubach Florence , Bonnet Nicolas , Ebstein Nathan , Gaudry Stéphane , Cohen Yves , Noublanche Julie , Lesieur Olivier , Sément Arnaud , Roca-Cerezo Isabel , Pascal Michel , Sma Nesrine , Colin Gwenhaël , Lacherade Jean-Claude , Bionz Gauthier , Maquigneau Natacha , Bouzat Pierre , Durand Michel , Hérault Marie-Christine , Payen Jean-Francois 
Published: June 2024

Abstract
Background
Previous retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less.

Methods
This study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland. Given that PP is recommended for a 16-h daily duration, intensive PP was defined as a cumulated duration of more than 32 h during the first 48 h, whereas standard PP was defined as a duration equal to or less than 32 h. Patients were followed-up for 90 days. The primary outcome was mortality at day 60. An Inverse Probability Censoring Weighting (IPCW) Cox model including a target emulation trial method was used to analyze the data.

Results
Out of 2137 intubated patients, 753 were placed in PP during the first 48 h of ICU admission. The intensive PP group (n = 79) had a median PP duration of 36 h, while standard PP group (n = 674) had a median of 16 h during the first 48 h. Sixty-day mortality rate in the intensive PP group was 39.2% compared to 38.7% in the standard PP group (p = 0.93). Twenty-eight-day and 90-day mortality as well as the ventilator-free days until day 28 were similar in both groups. After IPCW, there was no significant difference in mortality at day 60 between the two-study groups (HR 0.95 [0.52–1.74], p = 0.87 and HR 1.1 [0.77–1.57], p = 0.61 in complete case analysis or in multiple imputation analysis, respectively).

Conclusions
This secondary analysis of a large multicenter European cohort of intubated patients with ARDS due to COVID-19 found that intensive PP during the first 48 h did not provide a survival benefit compared to standard PP.