Risk factors associated with mortality among elderly patients with COVID-19: Data from 55 intensive care units in Spain

On behalf of CIBERESUCICOVID Project (COV20/00110ISCIII).Introduction and objectives: Critically-ill elderly ICU patients with COVID-19 have poor outcomes. We aimed to compare the rates of in-hospital mortality between non-elderly and elderly critically-ill COVID-19 ventilated patients, as well as to analyze the characteristics, secondary outcomes and independent risk factors associated with in-hospital mortality of elderly ventilated patients. Patients and Methods: We conducted a multicentre, observational cohort study including consecutive critically-ill patients admitted to 55 Spanish ICUs due to severe COVID-19 requiring mechanical ventilation (non-invasive respiratory support [NIRS; include non-invasive mechanical ventilation and high-flow nasal cannula] and invasive mechanical ventilation [IMV]) between February 2020 and October 2021. Results: Out of 5,090 critically-ill ventilated patients, 1,525 (27%) were aged =70 years (554 [36%] received NIRS and 971 [64%] received IMV. In the elderly group, median age was 74 years (interquartile range 72–77) and 68% were male. Overall in-hospital mortality was 31% (23% in patients <70 years and 50% in those =70 years; p<0.001). In-hospital mortality in the group =70 years significantly varied according to the modality of ventilation (40% in NIRS vs. 55% in IMV group; p<0.001). Factors independently associated with in-hospital mortality in elderly ventilated patients were age (sHR 1.07 [95%CI 1.05–1.10], p<0.001); previous admission within the last 30 days (sHR 1.40 [95%CI 1.04–1.89], p = 0.027); chronic heart disease (sHR 1.21 [95%CI 1.01–1.44], p = 0.041); chronic renal failure (sHR 1.43 [95%CI 1.12- 1.82], p = 0.005); platelet count (sHR 0.98 [95% CI 0.98–0.99], p<0.001); IMV at ICU admission (sHR 1.41 [95% CI 1.16- 1.73], p<0.001); and systemic steroids (sHR 0.61 [95%CI 0.48- 0.77], p<0.001). Conclusions: Amongst critically-ill COVID-19 ventilated patients, those aged =70 years presented significantly higher rates of in-hospital mortality than younger patients. Increasing age, previous admission within the last 30 days, chronic heart disease, chronic renal failure, platelet count, IMV at ICU admission and systemic steroids (protective) all comprised independent factors for in-hospital mortality in elderly patientsThis study was supported by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII); Fondo Europeo de Desarrollo Regional (FEDER); "Una manera de hacer Europa"; and Centro de Investigacion Biomédica En Red - Enfermedades Respiratorias (CIBERES). DdGC has received financial support from the Instituto de Salud Carlos III (Miguel Servet 2020:CP20/00041), co-funded by European Social Fund (ESF)/ “Investing in your future”. CC received a grant from the Fondo de Investigacion Sanitaria ( PI19/00207), Instituto de Salud Carlos III, co-funded by the European Union.Peer ReviewedCIBERESUCICOVID Project Investigators: Víctor D. Gumucio- Sanguino, Rafael Manez: Hospital Universitario de Bellvitge, Barcelona. Jordi Sole-Violan, Felipe Rodríguez de Castro: Hospital Dr. Negrín, Las Palmas. Fernando SuarezSipmann: Hospital Universitario La Princesa, Madrid. Ruth Noemí Jorge García, María Mora Aznar: Hospital Nuestra Senora de Gracia, Zaragoza. Mateu Torres, María Martinez, Cynthia Alegre, Jordi Riera, Sofía Contreras: Hospital Universitari Vall d’Hebron, Barcelona. Jesus Caballero, Javier Trujillano, Montse Vallverdu, Miguel Leon, Mariona Badía, Begona Balsera, Lluís Servia, Judit Vilanova, Silvia Rodríguez, Neus Montserrat, Silvia Iglesias, Javier Prados, Sula Carvalho, Mar Miralbes, Josman Monclou, Gabriel Jimenez, Jordi Codina, Estela Val, Pablo Pagliarani, Jorge Rubio, Dulce Morales, Andres Pujol, Angels Furro, Beatriz García, Gerard Torres, Javier Vengoechea, David de Gonzalo-Calvo, Jessica Gonzalez, Silvia Gomez: Hospital Universitari Arnau de Vilanova, Lleida. Jose M. Gomez: Hospital General Universitario Gregorio Marañon, Madrid. Nieves Franco: Hospital Universitario de Mostoles, Madrid. Jose Barberan: Hospital Universitario HM Montepríncipe. Guillermo M Albaiceta, Lorena Forcelledo Espina, Emilio García Prieto, Paula Martín Vicente, Cecilia del Busto Martínez: Hospital Universitario Central de Asturias, Oviedo. Pablo Vidal: Complexo Hospitalario Universitario de Ourense, Ourense. Jose Luis García Garmendia, María Aguilar Cabello, Carmen Eulalia Martínez Fernandez: Hospital San Juan de Dios del Aljarafe, Sevilla. Nieves Carbonell, María Luisa Blasco Cortes, Ainhoa Serrano Lazaro, Mar Juan Díaz: Hospital Clínic Universitari de Valencia, Valencia. Aaron Blandino Ortiz:Hospital Universitario Ramon y Cajal, Madrid. Rosario Menendez: Hospital La Fe de Valencia. Luis Jorge Valdivia: Hospital Universitario de Leon, Leon. María Victoria Boado: Hospital Universitario de Cruces, Barakaldo. Susana Sancho Chinesta: Hospital Universitario y Politecnico La Fe, Valencia. Maria del Carmen de la Torre: Hospital de Mataro. Ignacio Martínez Varela, María Teresa Bouza Vieiro, Ines Esmorís Arij on: Hospital Universitario Lucus Augusti, Lugo. David Campi Hermoso., Rafaela Nogueras Salinas., Teresa Farre Monjo., Ramon Nogue Bou., Gregorio Marco Naya., Carme Barbera, Nuria Ramon Coll: Hospital Universitari de Santa Maria, Lleida. Mercedes Catalan-Gonzalez, Juan Carlos Montejo-Gonzalez: Hospital Universitario 12 de Octubre, Madrid. Gloria Renedo SanchezGiron, Juan Bustamante-Munguira, Elena Bustamante-Munguira, Ramon Cicuendez Avila, Nuria Mamolar Herrera: Hospital Clínico Universitario, Valladolid. Raquel Almansa: Instituto de Investigacion Biomedica de Salamanca (IBSAL). Víctor Sagredo: Hospital Universitario de Salamanca, Salamanca. Jose Anon, Alexander Agrifoglio, Lucia Cachafeiro, Emilio Maseda: Hospital Universitario La Paz-Carlos III, Madrid. Lorenzo Socias, Mariana Andrea Novo, Albert Figueras, Maria Teresa Janer, Laura Soliva, Marta Ocon, Luisa Clar, J Ignacio Ayestaran: Hospital Universitario Son Espases, Palma de Mallorca. Yhivian Penasco, Sandra Campos Fernandez: Hospital Universitario Marques de Valdecilla, Santander. Mireia Serra-Fortuny, Eva Forcadell-Ferreres, Immaculada Salvador-Adell, Neus Bofill, Berta Adell-Serrano, Josep Pedregosa Díaz, Nuria Casacuberta-Barbera, Luis Urrelo-Cerron, Angels Piñol-Tena, Ferran Roche-Campo: Hospital Verge de la Cinta de Tortosa, Tortosa. Amalia Martínez de la Gandara, Pablo Ryan Murua, Covadonga Rodríguez Ruíz, Laura Carrion García, Juan I Lazo Alvarez: Hospital Universitario Infanta Leonor, Madrid. Jose Angel Lorente: Hospital Universitario de Getafe. Ana Loza-Vazquez, Desire Macias Guerrero: Hospital Universitario Virgen de Valme, Sevilla. Arturo Huerta, Daniel Tognetti: Clinica Sagrada Familia, Barcelona. Carlos García Redruello, David Mosquera Rodríguez, Eva María Menor Fernandez, Sabela Vara Adrio, Vanesa Gomez Casal, Marta Segura Pensado, María Digna Rivas Vilas, Amaia García Sagastume: Hospital de Vigo, Vigo. Raul de Pablo Sanchez, David Pesta na Laguna, Tommaso Bardi: Hospital Universitario Ramon y Cajal, Madrid. Rosario Amaya Villar, Carmen Gomez Gonzalez, Maria Luisa Gascon Castillo: Hospital Universitario Virgen del Rocio, Sevilla. Jose Garnacho-Montero, María Luisa Canton-Bulnes: Hospital Universitario Virgen Macarena, Sevilla. Judith Marin-Corral, Cristina Carbajales Perez: Hospital Alvaro Cunqueiro, Vigo. Joan Ramon Masclans, Ana Salazar Degracia, Judit Bigas, Rosana Munoz-Bermudez, Clara Vila-Vilardel, Francisco Parrilla, Irene Dot, Ana Zapatero, Yolanda Díaz, María Pilar Gracia, Purificacion Perez, Andrea Castellví, Cristina Climent: Hospital del Mar, Barcelona. Lidia Serra, Laura Barbena, Iosune Cano: Consorci Sanitari del Maresme, Barcelona. Pilar Ricart, Alba Herraiz, Pilar Marcos, Laura Rodríguez, Maria Teresa Sarinena, Ana Sanchez: Hospital Universitari Germans Trias i Pujol, Badalona. Alejandro Ubeda: Hospital Punta de Europa, Algeciras. María Cruz Martin Delgado: Hospital Universitario Torrejon-Universidad Francisco de Vitoria, Madrid. Elena Gallego, Juan Fernando Masa Jimenez: Hospital Universitario San Pedro de Alcantara, Caceres. Gemma Goma, Emi Díaz: Hospital Parc Taulí, Sabadell. Mercedes Ibarz, Diego De Mendoza: Hospital Universitari Sagrat Cor, Bacelona. Enric Barbeta, Victoria Alcaraz-Serrano, Joan Ramon Badia, Manuel Castella, Leticia Bueno, Adrian Ceccato, Andrea Palomeque, Laia Fernandez Barat, Catia Cilloniz, Pamela Conde, Javier Fernandez, Albert Gabarrus, Karsa Kiarostami, Alexandre Lopez- Gavín, Cecilia L Mantellini, Carla Speziale, Nil Vazquez, Hua Yang, Minlan Yang, Carlos Ferrando, Pedro Castro, Marta Arrieta, Jose Maria Nicolas, Rut Andrea: Hospital Clinic, Barcelona. Marta Barroso, Raquel Perez, Sergio Alvarez, Dario Garcia-Gasulla, Adrian Tormos: Barcelona supercomputing Center, Barcelona. Luis Tamayo Lomas, Cesar Aldecoa, Ruben Herran-Monge, Jose Angel Berezo García, Pedro Enríquez Giraudo: Hospital Rio Hortega, Valladolid. Pablo Cardinal Fernandez, Alberto Rubio Lopez, Orville Baez Pravia: Hospitales HM, Madrid. Juan Lopez Messa, Leire Perez Bastida, Antonjo Alvarez Ruiz: Complejo Asistencial Universitario de Palencia, Palencia. Jose Trenado, Anna Parera Pous: Hospital Universitari MutuaTerrassa, Terrassa. Cristobal Galban, Ana Lopez Lago, Eva Saborido Paz, Patricia Barral Segade: Hospital de Santiago de Compostela, Santiago. Ana Balan Marino, Manuel Valledor Mendez: Hospital San Agustin, Aviles. Raul de Frutos, Luciano Aguilera: Hospital Basurto, Basurto. Felipe Perez-García, Esther Lopez-Ramos, Angela Leonor Ruiz-García, Belen Betere: Hospital Universitario Principe Asturias, Alcala de Henares. Rafael Blancas: Hospital Universitario del Tajo, Aranjuez. Cristina Dolera, Gloria Perez Planelles, Enrique Marmol Peis, Maria Dolores Martinez Juan, Miriam Ruiz Miralles, Eva Perez Rubio, Maria Van der Hofstadt MartinMontalvo, Angel Sanchez-Miralles, Tatiana Villada Warrington: Hospital Universitario Sant Joan d’Alacant, Alicante. Juan Carlos Pozo-Laderas: Hospital Universitario Reina Sofia. Angel Estella, Sara Guadalupe Moreno Cano: Hospital de Jerez, Jerez. Federico Gordo: Hospital Universitario del Henares, Coslada. Basilisa Martinez Palacios: Hospital Universitario Infanta Cristina, Parla. Maite Nieto, Maria Teresa Nieto: Hospital de Segovia, Segovia. Sergio Ossa: Hospital de Burgos, Burgos. Ana Ortega: Hospital Montecelo, Pontevedra. Miguel Sanchez: Hospital Clinico, Madrid. Bitor Santacoloma: Hospital Galdakao, Galdakao.Postprint (published version

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation