Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study

Type Journal Article Author Brenda T. Pun Author Rafael Badenes Author Gabriel Heras La Calle Author Onur M. Orun Author Wencong Chen Author Rameela Raman Author Beata-Gabriela K. Simpson Author Stephanie Wilson-Linville Author Borja Hinojal Olmedillo Author Ana Vallejo de la Cueva Author Mathieu van der Jagt Author Rosalía Navarro Casado Author Pilar Leal Sanz Author Günseli Orhun Author Carolina Ferrer Gómez Author Karla Núñez Vázquez Author Patricia Piñeiro Otero Author Fabio Silvio Taccone Author Elena Gallego Curto Author Anselmo Caricato Author Hilde Woien Author Guillaume Lacave Author Hollis R. O'Neal Author Sarah J. Peterson Author Nathan E. Brummel Author Timothy D. Girard Author E. Wesley Ely Author Pratik P. Pandharipande Author Jacques Creteur Author Elisa Govea Bogossian Author Lorenzo Peluso Author Felipe González-Seguel Author Viviane Hidalgo-Calibin Author Pablo Carreño-Montenegro Author Verónica Rojas Author Eduardo Tobar Author Antonio Ramírez-Palma Author Karen Herrera-Davis Author Alexis Ferré Author Stéphane Legriel Author Thomas Godet Author Ugo Fraisse Author Bruno Gonçalves Author Aurélien Mazeraud Author Myrto Tzimou Author Frank Rasulo Author Silvia Beretta Author Mattia Marchesi Author Chiara Robba Author Denise Battaglini Author Paolo Pelosi Author Anna Teresa Mazzeo Author Alberto Noto Author Giuseppe Servillo Author Annachiara Marra Author Salvatore Lucio Cutuli Author Gabriele Pintaudi Author Eleonora Stival Author Eloisa Sofia Tanzarella Author Erik Roman-Pognuz Author Chiara Maria Concetta Massaro Author Muhammed Elhadi Author Lisa Smit Author Theresa Olasveengen Author Isabel Jesus Pereira Author Carla Margarida Teixeira Author Alice Santos Author Miguel Valente Author Cristina Granja Author Rita Pereia Author João Silva Author Blanca Furquet Author Mónica García Simón Author Daniel A. Godoy Torres Author Berta Monleón Author Esteban Morcillo Author Nekane Romero Author Ainhoa Serrano Author Sara Torrico Sánchez Author Francisco Luis Pérez Caballero Author Isabel Peña Luna Author Ignacio Baeza Gómez Author Milagros Calizaya Vargas Author Jordi Morillas Pérez Author Genís Carrasco Gómez Author Ricard Molina Latorre Author Sheila Moya Gutiérrez Author Irene Patricia Barón Barrera Author Cristina Delgado Palacios Author Beatriz García Góngora Author Laura Labrador Romero Author Laura Galarza Author Ignacio Catalán-Monzón Author Enver Rodriguez-Martínez Author Cristina Murcia Gubianas Author Ariadna Bellès Author María Esther Rodriguez Delgado Author Jesús Caballero Author Dulce Morales Author Andrés Pujol Author Jorge Rubio Author Eva Álvarez Torres Author Estefanía Carvajal Revuelta Author Isabel de la Calle Gil Author Blanca Fernández Tomás Author Berta Gallego Rodríguez Author Matilde González Serrano Author Paloma LaTorre Andreu Author Aris Pérez Lucendo Author Elena Abril Palomares Author Elena González González Author María Cruz Martín Delgado Author Carlos Muñoz De Cabo Author Pablo T. Aznar Author Carlos A. Calvo Author Ignacio Garutti Author Fernando Higuero Author David Martínez-Gascueña Author Emilio Maseda Author Itziar Insausti Author Ana Montero Feijoo Author Alejandro Suarez-de-la-Rica Author Beatriz Del Moral Barbudo Author Yago García Blanco-Traba Author Maria Claudia Giménez Santamarina Author Alba Gonzalo Millán Author Sergio Llorente Damas Author David Pestaña Lagunas Author Isabel Reyes García Author Alejandro Ruiz Perea Author Álvaro Ortega Guerrero Author María Jesús Mármol Cubillo Author David Díaz Muñoz Author Silvia García de Castrillón i Ramal Author Xavier Andorrà Sunyer Author María de las Nieves Noci Moreno Author Rosa María Pérez Manrique Author Emilio del Campo Molina Author María Elena Martínez Quintana Author Sol Fernandez-Gonzalo Author Gemma Gomà Fernández Author Guillem Navarra-Ventura Author Anna Baró Serra Author Cristina Fuster Author Oriol Plans Galván Author Diana Gil-Castillejos Author Mario Dalorzo González Author Francisco Javier Morán Gallego Author Irene Paredes Borrachero Author Patricia Rodríguez Villamizar Author Juan Romeu Prieto Author María José Sánchez Carretero Author Susana Gallardo Sánchez Author Filadelfo Bustos Molina Author María Luisa García Pérez Author Paula Castello-Mora Author Jaume Puig Author María Rosa Sanchis-Martin Author Carmen Andrea Sanchis-Veryser Author María Pilar Vicente-Fernández Author Rafael Zaragoza Author Laura Lizama Author Irene Torres Author Cristina Álvarez Author Paula Ramírez Author Meri Martin Cerezuela Author María Jesús Montero Author Jose García Cantos Author Paola Valls Author Nerea Aretxabala Cortajarena Author Pablo García Domelo Author Laura González Cubillo Author Marta Martín Martínez Author Inés Pérez Francisco Author Yolanda Poveda Hernández Author Amaia Quintano Rodero Author César Rodriguez Nuñez Author Martin Siegemund Author Anna Estermann Author Núria Zellweger Author Imen Ben Saida Author Mohamed Boussarsar Author Figen Esen Author Perihan Ergin Özcan Author Christopher Berkey Author Christine Harb Author Morgan H. Tandy Author Ellis Morgan Author Karen Shephard Author Robert C. Hyzy Author Michael Kenes Author Kristine Nelson Author Robert E. Hosse Author Katie M. Vance Author C. Adrian Austin Author Aaron Lerner Author Emily Sanders Author Robert A. Balk Author David A. Bennett Author Andrew R. Vogel Author Lucia Chowdhury Author Kiran Devulapally Author Michelle Woodham Author Sarah Cohen Author Nihal Patel Author Catherine M. Kuza Author Mandeep Sing Author Spencer Roberson Author Kelly Drumright Author Sameep Sehgal Author Sara C. LaHue Author Vanja C. Douglas Author Aarti Sarwal URL https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30552-X/abstract Publication The Lancet Respiratory Medicine ISSN 2213-2600, 2213-2619 Date 08/01/2021 Extra Publisher: Elsevier PMID: 33428871 Journal Abbr The Lancet Respiratory Medicine DOI 10.1016/S2213-2600(20)30552-X Library Catalog www.thelancet.com Language English Abstract Summary Background To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. Methods This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. Findings Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU. Interpretation Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19. Short Title Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D)