Medicine, Critical Care and Intensive Care Medicine, Pulmonary and Respiratory Medicine, Internal Medicine
16
Scopus Publications
Scopus Publications
Contemporary validation of a SAPS 3 customized version in patients admitted to Brazilian and Uruguayan intensive care units: a multicenter cohort study Marcio Soares, Lunna Perdigão Borges, Gastón Burghi, Pedro Kurtz, José Raimundo Araújo de Azevedo, Carlos Eduardo Brandão, Aloysio Saulo Breves Beiler, Niklas Soderberg Campos, Liane Oliveira Cavalcante, Mario Diego Teles Correia, Victor de Souza Cravo, Pedro Henrique Barbosa D’Almeida, Flávio Geraldo Rezende de Freitas, Thais de Almeida Machado, Marcelo de Oliveira Maia, Edson Silva Marques, Gloria Adriana Rocha Martins, Ulisses de Oliveira Melo, Laura Herranz Prinz, Silvia Regina Ramos, Thiago Gomes Romano, Marcos Soares Tavares, Suzana Margareth Lobo, Jorge Ibrain Figueira Salluh, Ederlon Rezende Critical Care Science, 2026 OBJECTIVE: To compare the performance of the standard equation (SAPS 3-SE) and a customized version (SAPS 3-Custom) of the Simplified Acute Physiology Score 3 in a contemporary cohort of Brazilian and Uruguayan intensive care unit patients. METHODS: We conducted a retrospective cohort study of 262,198 adults admitted to 177 intensive care units between 2022 and 2023. Discrimination was assessed using the area under the Receiver Operating Characteristic curve (AUROC), and calibration by comparing predicted and observed mortality in calibration curves. RESULTS: Of patients 70% were medical, and 21% were scheduled for surgery; mean SAPS 3 was 46.6 ± 16.0. Median intensive care unit and hospital stays were 3 (1 - 5) and 8 (4 - 16) days, respectively. Intensive care unit mortality was 10.6% and hospital mortality was 16.4%. Predicted mortality was 19.0% for SAPS 3-SE and 16.6% for SAPS 3-Custom. Both models had excellent discrimination (AUROC = 0.841). SAPS 3-SE overestimated mortality across all risk deciles, whereas SAPS 3-Custom achieved uniform agreement between predicted and observed values. Standardized mortality rates were 0.86 (95%CI 0.85 - 0.87) for SAPS 3-SE and 0.98 (0.98 - 0.99) for SAPS 3-Custom; standardized resource use rates were 0.90 (0.90 - 0.91) and 0.98 (0.97 - 0.98), respectively. At the intensive care unit level, SAPS 3-Custom produced standardized mortality rates (0.95 [0.77 - 1.17]) and standardized resource use rates (0.97 [0.82 - 1.23]) distributions centered around 1.0, unlike SAPS 3-SE, which yielded lower values. Findings were consistent for medical and surgical subgroups. CONCLUSION: In this large, contemporary cohort, SAPS 3-Custom demonstrated superior calibration and accuracy over SAPS 3-SE, supporting its use for performance evaluation and benchmarking in intensive care units in Brazil and Uruguay.
Dapagliflozin in Acute Cardiovascular Conditions: Insights From the DEFENDER Trial Caio A.M. Tavares, Luciano C.P. Azevedo, Patrícia O. Guimarães, Álvaro Rea-Neto, Paula G. David-João, Niklas S. Campos, Cristina P. Amendola, Amanda C. Kozesinski-Nakatani, Thiago C. Filiponi, Guacyra M.B. Almeida, Ricardo R. Bergo, Suzana M. Lobo, Alexandre P. Tognon, Marcos S. Tavares, Fabio S. Silveira, Marianna D.A. Dracoulakis, Rodrigo S. Biondi, Frederico Monfardini, Josue Nieri, Vagner Madrini, Ary Serpa-Neto, Fernando Bacal, Pedro A. Lemos, Otavio Berwanger, Justin A. Ezekowitz, Fernando G. Zampieri Jacc Advances, 2026 BACKGROUND: Sodium-glucose cotransporter-2 inhibitors improve clinical outcomes across various settings, but their use in critically ill patients hospitalized for acute cardiovascular conditions remains unexplored. OBJECTIVES: Secondary analysis aimed to: 1) determine whether treatment effects of dapagliflozin differ between critically ill patients admitted for cardiovascular vs noncardiovascular reasons; and 2) to investigate acute effects of in-hospital dapagliflozin initiation in patients with acute cardiovascular conditions. METHODS: This secondary analysis of the DEFENDER (Dapagliflozin in Critically Ill Patients with Acute Organ Dysfunction) trial, which randomized 507 critically ill patients to dapagliflozin 10 mg daily or standard care alone, compared cardiovascular (n = 162) vs noncardiovascular (n = 345) admissions. The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay through 28 days, analyzed by win ratio; median in-hospital follow-up was 9 days (Q1-Q3: 5-17 days). Daily parameters were analyzed in 134 cardiovascular patients using Bayesian mixed models. RESULTS: The win ratio for the primary outcome was 0.94 (95% CI: 0.77-1.15) in the cardiovascular subgroup and 1.05 (95% CI: 0.91-1.21) in the noncardiovascular subgroup (interaction P = 0.69). Serious adverse events were similar between arms in both subgroups. In cardiovascular patients, dapagliflozin increased urine output by 212 mL/day (95% credible interval: 30-392) and decreased fluid balance by -237 mL/day (95% credible interval: -447 to -26) with minimal increases in norepinephrine (0.01 μg/kg/min) and dobutamine (0.43 μg/kg/min) requirements. CONCLUSIONS: No treatment effect heterogeneity was observed based on intensive care unit admission reason. Dapagliflozin use in critically ill cardiovascular patients appeared safe, demonstrating a modest diuretic effect with minimal vasoactive support increases, warranting further investigation. (Dapagliflozin in Patients With Critical Illness [DEFENDER]; NCT05558098).
Association of intraoperative end-tidal CO2 levels with postoperative outcomes: a patient-level analysis of two randomised clinical trials Prashant Nasa, David M.P. van Meenen, Frederique Paulus, Carlos Ferrando, Thomas Bluth, Marcelo Gama de Abreu, Lorenzo Ball, Sebastiaan M. Bossers, Patrick Schober, Marcus J. Schultz, Ary Serpa Neto, Sabrine N.T. Hemmes, Niklas S. Campos, Thomas Bluth, Sabrine N.T. Hemmes, Julian Librero, Natividad Pozo, Carlos Ferrando, Lorenzo Ball, Guido Mazzinari, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J. Schultz, Ary Serpa Neto, Sabrine N.T. Hemmes, Marcelo Gama de Abreu, Paolo Severgnini, Markus W. Hollmann, Jan M. Binnekade, Hermann Wrigge, Jaume Canet, Michael Hiesmayr, Werner Schmid, Edda Tschernko, Samir Jaber, Göran Hedenstierna, Christian Putensen, Paolo Pelosi, Marcus J. Schultz, Agnes Marti, Alessandro Bacuzzi, Alexander Brodhun, Alexandre Molin, Alfred Merten, Ana Parera, Andrea Brunelli, Andrea Cortegiani, Andreas Güldner, Andreas W. Reske, Angelo Gratarola, Antonino Giarratano, Bea Bastin, Bjorn Heyse, Branka Mazul-Sunko, Bruno Amantea, Bruno Barberis, Christian Putensen, Christopher Uhlig, Conrado Minguez Marín, Cristian Celentano, Daniela La Bella, David D’Antini, David Velghe, Demet Sulemanji, Edoardo De Robertis, Eric Hartmann, Francesca Montalto, Francesco Tropea, Gary H. Mills, Gilda Cinnella, Giorgio Della Rocca, Girolamo Caggianelli, Giulia Pellerano, Giuseppina Mollica, Guillermo Bugedo, Hermann Wrigge, Jan-Paul Mulier, Jeroen Vandenbrande, Johann Geib, Jonathan Yaqub, Jorge Florez, Juan F. Mayoral, Juraj Sprung, Jurgen Van Limmen, Lieuwe D.J. Bos, Luc de Baerdemaeker, Luc Jamaer, Luigi Spagnolo, Lydia Strys, Manuel Granell Gil, Marcelo Gama de Abreu, Marcos F. Vidal Melo, Marcus J. Schultz, Maria Carmen Unzueta, Maria Victoria Moral, Marion Ferner, Markus W. Hollmann, Martin Weiss, Massimo Vanoni, Maximilian S. Schaefer, Mercè Prieto, Michele Grio, Paolo Severgnini, Peter Markus Spieth, Philipp Simon, Phoebe Bodger, Pilar Sierra, Rita Laufenberg-Feldmann, Roberta Rusca, Rodolfo Proietti, Sabrine N.T. Hemmes, Santi Maurizio Raineri, Santo Caroleo, Sergi Sabaté, Stefan De Hert, Stefano Pezzato, Tanja A. Treschan, Tatjana Goranovic, Thea Koch, Thomas Bluth, Thomas Kiss, Valter Perilli, Virginia Cegarra, Werner Schmid, Thomas Bluth, Ary Serpa Neto, Ilona Bobek, Jaume Canet, Gilda Cinnella, Luc de Baerdemaeker, Cesare Gregoretti, Göran Hedenstierna, Sabrine N.T. Hemmes, Michael Hiesmayr, Markus W. Hollmann, Samir Jaber, John Laffey, Marc-Joseph Licker, Klaus Markstaller, Idit Matot, Gary H. Mills, Jan Paul Mulier, Christian Putensen, Rolf Rossaint, Jochen Schmitt, Mert Senturk, Paolo Severgnini, Juraj Sprung, Marcos F. Vidal Melo, Hermann Wrigge, Marcus J. Schultz, Paolo Pelosi, Marcelo Gama de Abreu, Fernando Abelha, Sühayla Abitağaoğlu, Marc Achilles, Afeez Adebesin, Ine Adriaensens, Charles Ahene. Fatima Akbar, Mohammed Al Harbi, Rita Al Khoury al Kallab, Xavier Albanel, Florence Aldenkortt, Rawan Abdullah Saleh Alfouzan, Reef Alruqaie, Fernando Altermatt, Bruno Luís de Castro Araujo, Arbesú Genaro, Hanna Artsi, Caterina Aurilio. Omer Hilmi Ayanoglu, Alessandro Bacuzzi, Harris Baig, Yolanda Baird, Konstantin Balonov. Jaume Balust, Samantha Banks, Xiaodong Bao, Mélanie Baumgartner, Isabel Belda Tortosa, Alice Bergamaschi, Lars Bergmann, Luca Bigatello, Elena Biosca Pérez, Katja Birr, Thomas Bluth, Elird Bojaxhi, Chiara Bonenti, Iwona Bonney, Elke M.E. Bos, Sara Bowman, Leandro Gobbo Braz, Elisa Brugnoni, Sorin J. Brull, Iole Brunetti, Andrea Bruni, Shonie L. Buenvenida, Cornelius Johannes Busch, Giovanni Camerini, Jaume Canet, Beatrice Capatti, Javiera Carmona, Jaime Carungcong, Marta Carvalho, Anat Cattan, Carla Cavaleiro, Davide Chiumello, Stefano Ciardo, Mark Coburn, Umberto Colella, Victor Contreras, Pelin Corman Dincer, Elizabeth Cotter, Marcia Crovetto, William Darrah, Simon Davies, Luc de Baerdemaeker, Stefan De Hert, Enrique Del Cojo Peces, Ellise Delphin, John Diaper, Paulo do Nascimento Junior, Valerio Donatiello, Jing Dong, Maria do Socorro Dourado, Alexander Dullenkopf, Felix Ebner, Hamed Elgendy, Christoph Ellenberger, Dilek Erdoğan Arı, Thomas Ermert, Fadi Farah, Ana Fernandez-Bustamante, Cristina Ferreira, Marco Fiore, Ana Fonte, Christina Fortià Palahí, Andrea Galimberti, Marcelo Gama de Abreu, Najia Garofano, Luca Gregorio Giaccari, Fernando Gilsanz, Felix Girrbach, Luca Gobbi, Marc Bernard Godfried, Nicolai Goettel, Peter A. Goldstein, Or Goren, Andrew Gorlin, Granell Gil Manuel, Angelo Gratarola, Juan Graterol, Pierre Guyon, Kevin Haire, Philippe Harou, Antonia Helf, Sabrine N.T. Hemmes, Gunther Hempel, María José Hernández Cádiz, Björn Heyse, Markus W. Hollmann, Ivan Huercio, Jasmina Ilievska, Lien Jakus, Vijay Jeganath, Yvonne Jelting, Minoa Jung, Barbara Kabon, Aalok Kacha, Maja Karaman Ilić, Arunthevaraja Karuppiah, Ayse Duygu Kavas, Gleicy Keli Barcelos, Todd A. Kellogg, Johann Kemper, Romain Kerbrat, Suraya Khodr, Peter Kienbaum, Bunyamin Kir, Thomas Kiss, Selin Kivrak, Vlasta Klarić, Thea Koch, Ceren Köksal, Ana Kowark, Peter Kranke, Bahar Kuvaki, Biljana Kuzmanovska, John Laffey, Mirko Lange, Marília Freitas de Lemos, Marc-Joseph Licker, Manuel López-Baamonde, Antonio López-Hernández, Mercedes Lopez-Martinez, Stéphane Luise, Mark MacGregor, Danielle Magalhães, Julien Maillard, Patrizia Malerbi, Natesan Manimekalai, Michael Margarson, Klaus Markstaller, Archer K. Martin, David P. Martin, Yvette N. Martin, Julia Martínez-Ocon, Ignacio Martin-Loeches, Emilio Maseda, Idit Matot, Niamh McAuliffe, Travis J. McKenzie, Paulina Medina, Melanie Meersch, Angelika Menzen. Els Mertens. Bernd Meurer, Tanja Meyer-Treschan. Changhong Miao. Camilla Micalizzi, Morena Milić, Norma Sueli Pinheiro Módolo, Pierre Moine, Patrick Mölders, Ana Montero-Feijoo, Enrique Moret, Markus K. Muller, Zoe Murphy, Pramod Nalwaya, Filip Naumovski. Navalesi Paolo, Lais Helena Navarro e Lima, Višnja Nesek Adam, Claudia Neumann, Christopher Newell, Zoulfira Nisnevitch, Junaid Nizamuddin, Cecilia Novazzi, Michael O'Connor, Günther Oprea, Mukadder Orhan Sungur, Şule Özbilgin, Maria Caterina Pace, Marcos Pacheco, Balaji Packianathaswamy, Estefania Palma Gonzalez, Fotios Papaspyros. Sebastián Paredes, Maria Beatrice Passavanti, Juan Cristobal Pedemonte, Paolo Pelosi. Sanja Peremin, Christoph Philipsenburg, Daniela Pinho, Silvia Pinho, Linda M. Posthuma, Vincenzo Pota, Benedikt Preckel, Paolo Priani, Christian Putensen, Mohamed Aymen Rached, Aleksandar Radoeshki, Riccardo Ragazzi, Tamilselvan Rajamanickam, Arthi Rajamohan, Harish Ramakrishna. Desikan Rangarajan. Christian Reiterer, J.Ross Renew, Thomas Reynaud, Rhidian Rhys, Eva Rivas. Luisa Robitzky, Rolf Rossaint. Francesca Rubulotta. S. Machado Humberto, S.Nunes Catarina, Giovanni Sabbatini, Jon D. Samuels, Josep Martí Sanahuja, Pasquale Sansone, Alice Santos, Mohamed Sayedalahl, Maximilian S. Schaefer, Martin Scharffenberg, Eduardom Schiffer, Nadja Schliewe, Raoul Schorer, Marcus J. Schultz, Roman Schumann, Gabriele Selmo, Mar Sendra, Mert Senturk, Paolo Severgnini. Kate Shaw, Mirjana Shosholcheva. Abdulrazak Sibai. Philipp Simon, Francesca Simonassi, Claudia Sinno, Nukhet Sivrikoz, Vasiliki Skandalou. Neil Smith, Maria Soares, Tania Socorro Artiles, Diogo Sousa Castro. Miguel Sousa, Savino Spadaro. Juraj Sprung, Emmanouil Stamatakis, Luzius A. Steiner, Andrea Stevenazzi, Alejandro Suarez-de-la-Rica. Mélanie Suppan, Robert Teichmann, José Maria Tena Guerrero. Bram Thiel, Raquel Tolós, Gulbin Tore Altun, Michelle Tucci, Zachary A. Turnbull, Žana Turudić, Matthias Unterberg, Jurgen Van Limmen, Yves Van Nieuwenhove, Julia Van Waesberghe, Marcos Francisco Vidal Melo. Bibiana Vitković, Luigi Vivona, Marcela Vizcaychipi. Carlo Alberto Volta, Anne Weber, Toby N. Weingarten, Jakob Wittenstein, Hermann Wrigge, Piet Wyffels, Julio Yagüe, David Yates, Ayşen Yavru, Lilach Zac, Jing Zhong, Carlos Ferrando, Javier Belda, Marina Soro, Jaume Canet, Carmen Unzueta, Fernando Suarez-Sipmann, Julián Librero, Alicia Llombart, Lucas Rovira, Manuel Granell, César Aldecoa, Oscar Diaz-Cambronero, Jaume Balust, Ignacio Garutti, Rafael Gonzalez, Lucia Gallego, Santiago Garcia del Valle, Javier Redondo, David Pestaña, Aurelio Rodríguez, Javier García, Manuel de la Matta, Maite Ibáñez, Francisco Barrios, Samuel Hernández, Vicente Torres, Salvador Peiró, Natividad Pozo, Abigail Villena, Albert Carramiñana, Alberto Gallego-Casilda, Alejandro Duca, Amalia Alcón, Amanda Miñana, Ana Asensio, Ana Colás, Ana Isabel Galve, Ana Izquierdo, Ana Jurado, Ana María Pérez, Ana Mugarra, Ana Parera, Andrea Brunelli, Andrea Gutierrez, Ángeles De Miguel, Angels Lozano, Antonio Katime, Antonio Romero, Beatriz Garrigues, Begoña Ayas, Blanca Arocas, Carlos Delgado, Carmen Fernández, Carolina Romero, Clara Gallego, Cristina Garcés, Cristina Lisbona, Cristina Parrilla, Daniel López-Herrera, Domingo González, Eduardo Llamazares, Elena Del Rio, Elena Lozano, Ernesto Pastor, Estefanía Chamorro, Estefanía Gracia, Ester Sánchez, Esther Romero, Fernando Díez, Ferran Serralta, Francisco Daviu, Francisco Sandín, Gerardo Aguilar, Gerardo Tusman, Gonzalo Azparren, Graciela Martínez-Pallí, Guido Mazzinari, Inmaculada Benítez, Inmaculada Hernandéz, Inmaculada India, Irene León, Isabel Fuentes, Isabel Ruiz, Jaume Puig, Javie Ignacio Román, Jesús Acosta, Jesús Rico-Feijoo, Jonathan Olmedo, Jose A. Carbonell, Jose M. Alonso, Jose María Pérez, Jose Miguel Marcos, Jose Navarro, Jose Valdivia, Juan Carrizo, Laura Piqueras, Laura Soriano, Laura Vaquero, Lisset Miguel, Lorena Muñoz, Lucia Valencia, Luis Olmedilla, Ma Justina Etulain, Manuel Tisner, María Barrio, María Dolores Alonso, María García, María J. Hernández, María José Alberola, María Parra, María Pilar Argente, María Vila, Mario De Fez, Marta Agilaga, Marta Gine, Mercedes Ayuso, Mercedes García, Natalia Bejarano, Natalia Peña, Nazario Ojeda, Nilda Martínez, Nuria García, Oto Padrón, Pablo García, Paola Valls, Patricia Cruz, Patricia Piñeiro, Pedro Charco, Rafael Anaya, Ramiro López, Rayco Rodríguez, Rocío Martínez, Roger Pujol, Rosa Dosdá, Rosa Lardies, Ruben Díaz, Rubén Villazala, Sara Zapatero, Sergio Cabrera, Sergio Sánchez, Silvia Martin, Suzana Diaz, Tania Franco, Tania Moreno, Tania Socorro, Vicente Gilabert, Victor Balandrón, Victoria Moral, Virgina Cegarra, Viviana Varón British Journal of Anaesthesia, 2025 BACKGROUND: ) levels and postoperative outcomes remains unclear. We conducted a post hoc analysis of two randomised trials in adults undergoing major surgery under general anaesthesia. METHODS: analysis and propensity score matching were also performed to adjust for confounding. RESULTS: and postoperative pulmonary complications, which was also confirmed by propensity matching. CONCLUSIONS: level has an inverse dose-dependent relationship with postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT05550181.
Win Ratio approach for the composite outcome of postoperative pulmonary complications: Secondary analysis of a harmonised and pooled database of three randomised clinical trials Ary Serpa Neto, Niklas S. Campos, Thomas Bluth, Sabrine N.T. Hemmes, Carlos Ferrando, Julian Librero, Marina Soro, Lorenzo Ball, Guido Mazzinari, Marcelo Gama de Abreu, Marcus J. Schultz, and European Journal of Anaesthesiology, 2025 BACKGROUND The win ratio analysis method might provide new insight on the impact of positive end-expiratory pressure (PEEP) on clinical outcomes. OBJECTIVE The aim is to re-analyse the results of the ’Re-evaluation of the effects of high PEEP with recruitment manoeuvres vs. low PEEP without recruitment manoeuvres during general anaesthesia for surgery’ (REPEAT) study using the win ratio analysis. DESIGN Individual patient data meta-analysis. SETTING Three international multicentre randomised trials. PARTICIPANTS Patients undergoing general anaesthesia for surgery. INTERVENTION High vs. low PEEP. MAIN OUTCOME MEASURE Hierarchical composite endpoint of: all-cause hospital mortality; hospital length of stay; need for postoperative mechanical ventilation; severe pulmonary complications; and mild pulmonary complications. RESULTS A total of 3774 patients undergoing general anaesthesia for surgery were included in this analysis. The median (interquartile range [IQR]) age was 57 [45 to 68] years and 2077 (55%) were women. A total of 3 560 720 comparison pairs were produced. The high PEEP group had a higher percentage of losses than wins in hospital mortality (1.1 vs. 0.9%) and hospital length of stay (33.8 vs. 33.2%), comparable percentages of losses and wins in postoperative invasive mechanical ventilation (0.2 vs. 0.2%), a higher percentage of wins in severe complications (2.5 vs. 2.1%) and a higher percentage of ties in mild complications (18.7 vs. 3.9% wins vs. 3.3% losses). The win ratio for high PEEP compared with low PEEP group was 1.00 (95% CI 0.92 to 1.09). CONCLUSION No beneficial effects of high PEEP compared with low PEEP were found in this win ratio analysis. REGISTRATION Clinicaltrials.gov (study identifier NCT03937375).
Assessment of mortality due to severe SARS-CoV-2 infection in public and private intensive care units in Brazil: a multicenter retrospective cohort study Thiago Domingos Corrêa, Thais Dias Midega, Ricardo Kenji Nawa, Ricardo Luiz Cordioli, Adriano José Pereira, Moacyr Silva, Bruno de Arruda Bravim, Niklas Soderberg Campos, Amanda Pascoal Valle Felicio, Angelo Antônio Gomes de Carvalho, Andreia Pardini, Raquel Afonso Caserta Eid, Rodrigo Dias Rodrigues, Marcele Liliane Pesavento, Leonardo Van de Wiel Barros Urbano Andari, Bento Fortunato Cardoso dos Santos, Claudia Regina Laselva, Felipe Maia de Toledo Piza, Miguel Cendoroglo, Guilherme de Paula Pinto Schettino, Sidney Klajner, Leonardo José Rolim Ferraz Einstein Sao Paulo Brazil, 2025 BACKGROUND: This retrospective multicenter cohort study compared characteristics and outcomes of 5,790 critically ill patients with COVID-19 in Brazil's public and private intensive care units. Patients in public intensive care units exhibited greater disease severity, more frequent use of organ support, and higher mortality rates compared to those in private intensive care units. The risk of in-hospital death was more than twice as high in public intensive care units. ■ Public intensive care unit COVID-19 patients presented with more comorbidities and higher severity at admission. ■ Public intensive care units required more invasive organ support (e.g., mechanical ventilation, vasopressors, and renal replacement therapy) but less non-invasive ventilation and high-flow nasal cannula than private intensive care units. ■ In-hospital mortality was higher in public intensive care units, with an increased risk of death even after adjusting for patient characteristics and illness severity at intensive care unit admission. OBJECTIVE: To compare the clinical characteristics, use of organ support, and outcomes of critically ill patients with COVID-19 admitted to public and private intensive care units. METHODS: This multicenter retrospective cohort study included patients admitted to four intensive care units from March 1, 2020, to December 31, 2021. Patients with COVID-19 admitted to public and private intensive care units were compared. The primary outcome of interest, in-hospital mortality, was assessed using a hierarchical logistic regression (multilevel) model adjusted for study site and patient characteristics. RESULTS: A total of 5,790 patients with COVID-19 were admitted to the participating intensive care units, with 3,321 (57.3%) admitted to private hospitals and 2,469 (42.6%) admitted to public hospitals. Patients in public intensive care units were less likely to be male and had higher median SAPS III scores, Charlson Comorbidity Index values, and SOFA scores. They also required mechanical ventilation (53.1% versus 40.0%, p<0.001), vasopressors (43.1% versus 33.9%, p<0.001), and renal replacement therapy (20.3% versus. 14.5%, p<0.001) more frequently than those in private intensive care units. In contrast, patients in private intensive care units were more frequently managed with non-invasive ventilation (38.0% versus 66.8%; p<0.001) and high-flow nasal cannulas (18.3% versus 48.1%; p<0.001). The in-hospital mortality rate was significantly higher in public intensive care units (40.3%) compared to private intensive care units (16.4%) (adjusted OR=2.96; 95%CI=1.94-4.51; p<0.001). CONCLUSION: We observed significant differences in resource utilization and mortality rates between patients with COVID-19 admitted to public and private intensive care units. Patients with COVID-19 in public care units face a higher risk of in-hospital mortality compared to those in private care units.
High Positive End-expiratory Pressure (PEEP) with Recruitment Maneuvers versus Low PEEP during General Anesthesia for Surgery: A Bayesian Individual Patient Data Meta-analysis of Three Randomized Clinical Trials Guido Mazzinari, Fernando G. Zampieri, Lorenzo Ball, Niklas S. Campos, Thomas Bluth, Sabrine N. T. Hemmes, Carlos Ferrando, Julian Librero, Marina Soro, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J. Schultz, Ary Serpa Neto, and Anesthesiology, 2025 Background: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. The objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. Methods: Multilevel Bayesian logistic regression analysis was performed on individual patient data from three randomized clinical trials carried out on surgical patients at intermediate to high risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. This study examined the effect of high PEEP with recruitment maneuvers versus low PEEP ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect. Results: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio for high PEEP with recruitment maneuvers compared to low PEEP was 0.85 (95% credible interval, 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (odds ratio, 0.67 [0.50 to 0.87]) and those at high risk for postoperative pulmonary complications (odds ratio, 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results. Conclusions: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of postoperative pulmonary complication occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy.
Dapagliflozin for Critically Ill Patients with Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial Caio A. M. Tavares, Luciano C. P. Azevedo, Álvaro Rea-Neto, Niklas S. Campos, Cristina P. Amendola, Amanda C. Kozesinski-Nakatani, Paula G. David-João, Suzana M. Lobo, Thiago C. Filiponi, Guacyra M. B. Almeida, Ricardo R. Bergo, Mário R. R. Guimarães-Júnior, Rodrigo C. Figueiredo, Joan R. Castro, Clewer J. Schuler, Glauco A. Westphal, Ana C. R. Carioca, Frederico Monfradini, Josue Nieri, Flavia M. O. Neves, Jaqueline A. Paulo, Camila S. N. Albuquerque, Mariana C. R. Silva, Mikhail N. Kosiborod, Adriano J. Pereira, Lucas P. Damiani, Thiago D. Corrêa, Ary Serpa-Neto, Otavio Berwanger, Fernando G. Zampieri, , Juliano Souza, Luciana Sanches, Maisa Castro, Mariana Cunha, Flávia Fagundes, Juan Siqueira, Glauco Westphal, Cristian Ospina, Evelin Silva, Juliano Ramos, Miriam Machado, Ruthy Fermamdes, Camila Lunardi, Luana Radun, Andervan Moura, Evanio Silva, Livia Dantas, Livia Gomes, Maria Luzia Silva, Yolanda Nunes, Ana Beatriz Lino, Gabrielly Barros, João Pedro Nunes, Marivalda Barbosa, Guilherme Souza, Hugo Duarte, Hannah Mota, Joan Castro, Mayler Olambrada, Rafael Borges, Luciana Barros, Nelson Pereira, Marcos Tavares, Gabriela Joia, Gabriella Cordeiro, Natalia Mattos, Vinicius Lanza, Victoria Silva, Marianna A Dracoulakis, Natalia Alvaia, Camilla Vieira, Izabela Freitas, Beatriz Conceição, Jaqueline Borges, Aline Silva, Thais Caroline, Josiane Jesus, Allan Santos, Bruno Vieira, Isabelle Guerreiro, Luciana Oliveira, Luiz Esteves, Rodrigo Bolini, Edmilson Carvalho, Adilson Lacerda, Aline Ferreira, Gustavo Sica, Lara Oliveira, Maria das Vitórias Guedes, Otavio Gebara, Ana Paula Espirito Santo, Ana Tarina Lopes, Hevelton Ribeiro, Pablo Tomba, Vislaine Morete, Joyce Almeida, Claudia Silva, Luana Gato, Leticia Inada, Claire Dias, Frederico Dall’Orto, Graziela Melo, Ana Roberta Silva, Gislayne Ribeiro, Kemilys Ferreira, Rodrigo Biondi, Sergio Ramalho, Derick Silva, Eduardo Garbin, Ingrid Pereira, Luana Nunes, Rayane Lacourt, Cintia Loss, Jackelyne Silva, Claudio Jorge, Graziela Denerdin, Karla Millani, Luana Machado, Ana Carolina Affonso, Juliane Garcia, Tatiane Oiafuso, Luana Camargo, Kaio Morais, Aline Angeli, Cassia Pradela, Gustava Marques, Joelma Silva, Maria Fernanda Santos, Marina Zini, Keulle Candido, Tamires Silva, Verônica Barros, Mariana Pool, Fabio Serra, Alef Coelho, Lea Vieira, Tamyres Galvao, Alexandre Tognon, Marcos Dozza, Sabrina Henrich, Andressa Giordani, Aloma Menegasso, Murillo Antunes, Nicoli Gosmano, Stefany Moura, Tiberio Costa, Vitoria Canato, Gabriela Queiroz, Mariana Gonçalvez, Mariana Zanona, Hellen Dias, Eduardo Bazanelli Junqueira Ferraz, Caroline Rossi, Leandro Pozzo, Diogo Moia, Ronaldo Vicente Pereira Soares, Ramy Machado Marino, Bruna Ladeira Moreno, Arthur Serapião, Roberta Momesso, Bárbara Gomes da Silva, Cintia Selles Santos, Elaine de Jesus Santos, Bruna dos Santos Sampaio, Luciana Pereira Almeida de Piano JAMA, 2024 ImportanceSodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown.ObjectiveTo determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023.InterventionParticipants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first.Main Outcomes and MeasuresThe primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support–free days, ICU, and hospital stay, assessed using bayesian regression models.ResultsAmong 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group.Conclusion and RelevanceThe addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin.Trial RegistrationClinicalTrials.gov Identifier: NCT05558098
Effect of intraoperative PEEP with recruitment maneuvers on the occurrence of postoperative pulmonary complications during general anesthesia––protocol for Bayesian analysis of three randomized clinical trials of intraoperative ventilation Guido Mazzinari, Fernando G. Zampieri, Lorenzo Ball, Niklas S. Campos, Thomas Bluth, Sabrine N.T. Hemmes, Carlos Ferrando, Julian Librero, Marina Soro, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J. Schultz, Ary Serpa Neto, , , , and F1000research, 2023 Background: Using the frequentist approach, a recent meta–analysis of three randomized clinical trials in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high positive end–expiratory pressure with recruitment maneuvers when compared to ventilation that uses low positive end–expiratory pressure without recruitment maneuvers. Methods: We designed a protocol for a Bayesian analysis using the pooled dataset. The multilevel Bayesian logistic model will use the individual patient data. Prior distributions will be prespecified to represent a varying level of skepticism for the effect estimate. The primary endpoint will be a composite of postoperative pulmonary complications (PPC) within the first seven postoperative days, which reflects the primary endpoint of the original studies. We preset a range of practical equivalence to assess the futility of the intervention with an interval of odds ratio (OR) between 0.9 and 1.1 and assess how much of the 95% of highest density interval (HDI) falls between the region of practical equivalence. Ethics and dissemination: The used data derive from approved studies that were published in recent years. The findings of this current analysis will be reported in a new manuscript, drafted by the writing committee on behalf of the three research groups. All investigators listed in the original trials will serve as collaborative authors.
COVID-19-associated coagulopathy and acute kidney injury in critically ill patients Bruno Caldin da Silva, Ricardo Luiz Cordioli, Bento Fortunato Cardoso dos Santos, João Carlos de Campos Guerra, Roseny dos Reis Rodrigues, Guilherme Martins de Souza, Carolina Ashihara, Thais Dias Midega, Niklas Söderberg Campos, Bárbara Vieira Carneiro, Flávia Nunes Dias Campos, Hélio Penna Guimarães, Gustavo Faissol Janot de Matos, Valdir Fernandes de Aranda, Leonardo José Rolim Ferraz, Thiago Domingos Corrêa Einstein Sao Paulo Brazil, 2023 OBJECTIVE: The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. METHODS: Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. RESULTS: Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. CONCLUSION: Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.
Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study Caio de Assis Moura Tavares, Luciano César Pontes de Azevedo, Álvaro Rea-Neto, Niklas Söderberg Campos, Cristina Prata Amendola, Ricardo Reinaldo Bergo, Amanda Christina Kozesinski-Nakatani, Paula Geraldes David-João, Glauco Adrieno Westphal, Mário Roberto Rezende Guimarães Júnior, Suzana Margareth Ajeje Lobo, Marcos Soares Tavares, Marianna Deway Andrade Dracoulakis, Guilherme Martins de Souza, Guacyra Margarita Batista de Almeida, Otavio Celso Eluf Gebara, Pablo Oscar Tomba, Camila Santos N Albuquerque, Mariana Castaldi Ramalho Silva, Adriano José Pereira, Lucas Petri Damiani, Thiago Domingos Corrêa, Ary Serpa-Neto, Otavio Berwanger, Fernando Godinho Zampieri Critical Care Science, 2023 BACKGROUND: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. METHODS: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. CONCLUSION: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. CLINICALTRIALS.GOV REGISTRY: NCT05558098.
Emerging from the COVID-19 pandemic: the numbers and lessons that will stay with us forever Luiza Helena Degani-Costa, Fabiana Rolla, Raphael Augusto Gomes Oliveira, Guilherme de Paula Pinto Schettino, Ricardo Luiz Cordioli, Fábio Barlem Hohmann, Niklas Söderberg Campos, Roger Monteiro Alencar, Leonardo José Rolim Ferraz, Felipe Maia de Toledo Piza Einstein Sao Paulo Brazil, 2021
Coagulation profile of COVID-19 patients admitted to the ICU: An exploratory study Thiago Domingos Corrêa, Ricardo Luiz Cordioli, João Carlos Campos Guerra, Bruno Caldin da Silva, Roseny dos Reis Rodrigues, Guilherme Martins de Souza, Thais Dias Midega, Niklas Söderberg Campos, Bárbara Vieira Carneiro, Flávia Nunes Dias Campos, Hélio Penna Guimarães, Gustavo Faissol Janot de Matos, Valdir Fernandes de Aranda, Leonardo José Rolim Ferraz Plos One, 2020
Intensive care unit patients' opinion on enrollment in clinical research: A multicenter survey Flavia Julie do Amaral Pfeilsticker, Carolina Aguiar Sant Anna Siqueri, Niklas Soderberg Campos, Fernanda Guimarães Aguiar, Maria Laura Romagnoli, Renato Carneiro de Freitas Chaves, Carolina Scoqui Guimarães, Adriano José Pereira, Ricardo Luiz Cordioli, Ary Serpa Neto, Murillo Santucci Cesar Assuncão, Thiago Domingos Corrêa Plos One, 2020
