Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study
Authors: Giabicani Mikhael , Le Terrier Christophe , Poncet Antoine , Guidet Bertrand , Rigaud Jean-Philippe , Quenot Jean-Pierre , Mamzer Marie-France , Pugin Jérôme , Weiss Emmanuel , Bourcier Simon ,   COVID-ICU study 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 , Déserts Marc Danguy des , Mathais Quentin , Rager Gwendoline , Pasquier Pierre , Reignier Jean , Seguin Amélie , Garret Charlotte , Canet Emmanuel , 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 , Beduneau Gaetan , 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 , 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 , Bouar Gurvan L. E. , Boukhanza Messabi , Demarest Elsa , Bajolet Marie-France , Charrier Nathanaël , Quenet Audrey , Zylberfajn Cécile , Dufour Nicolas , Mégarbane Buno , Voicu Sébastian , 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 , Le Terrier Christophe , Suh Noémie , Primmaz Steve , Pugin Jérome , Weiss Emmanuel , Gauss Tobias , Moyer Jean-Denis , Burtz Catherine Paugam , La Combe Béatrice , Smonig Rolland , Violleau Jade , Cailliez Pauline , Chelly Jonathan , 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 , Lamraoui Meriam , Alessandri Claire , de Roux Quentin , 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 , Ricard Jean-Damien , 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 , Terzi Nicolas , 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 , Bavozet Florent , Heron Anne , Carreira Serge , Emery Malo , Le Floch Anne Sophie , Giovannangeli Luana , Herzog Nicolas , Giacardi Christophe , Baudic Thibaut , Thill Chloé , Lebbah Said , Palmyre Jessica , Tubach Florence , Hajage David , 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: March 2023

Abstract
Background
Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients.

Methods
We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions.

Results
Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3–21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1–11) after LST limitations.

Conclusions
In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.