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1. Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients

Author

Emilio Maseda, Santiago Grau, Sonia Luque, Maria-Pilar Castillo-Mafla, Alejandro Suárez-de-la-Rica, Ana Montero-Feijoo, Patricia Salgado, Maria-Jose Gimenez, Carlos A. García-Bernedo, Fernando Gilsanz, and Jason A. Roberts

Subjects
Morbid obesity, PK/PD, Monte-Carlo simulation, Intensive care unit, Candida spp., Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC0–24h)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. Methods Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100–150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC0–24/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (nonparapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%. Results Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m2 and 150 mg for morbidly obese patients with BMI > 45 kg/m2 (except two noncritically ill obese patients with BMI ~ 35 kg/m2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights

Published
2018
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2. Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials

Author

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, A. Serpa Neto, Sabrine NT. Hemmes, Paolo Severgnini, Markus W. Hollmann, Jan M. Binnekade, Hermann Wrigge, Jaume Canet, Michael Hiesmayr, Werner Schmid, Edda Tschernko, Samir Jaber, Göran Hedenstierna, Christian Putensen, 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, 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, Jan-Paul Mulier, Jeroen Vandenbrande, Johann Geib, Jonathan Yaqub, Jorge Florez, Juan F. Mayoral, Juraj Sprung, Jurgen Van Limmen, Lieuwe DJ. Bos, Luc de Baerdemaeker, Luc Jamaer, Luigi Spagnolo, Lydia Strys, Manuel Granell Gil, Marcos F. Vidal Melo, Maria Carmen Unzueta, Maria Victoria Moral, Marion Ferner, Martin Weiss, Massimo Vanoni, Maximilian S. Schaefer, Mercè Prieto, Michele Grio, Peter Markus Spieth, Philipp Simon, Phoebe Bodger, Pilar Sierra, Rita Laufenberg-Feldmann, Roberta Rusca, Rodolfo Proietti, Santi Maurizio Raineri, Santo Caroleo, Sergi Sabaté, Stefan De Hert, Stefano Pezzato, Tanja A. Treschan, Tatjana Goranovic, Thea Koch, Thomas Kiss, Valter Perilli, Virginia Cegarra, Javier Belda, Marina Soro, 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, 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, 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, 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, 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, Genaro Arbesú, Hanna Artsi, Caterina Aurilio, Omer Hilmi Ayanoglu, Harris Baig, Yolanda Baird, Konstantin Balonov, Samantha Banks, Xiaodong Bao, Mélanie Baumgartner, Isabel Belda Tortosa, Alice Bergamaschi, Lars Bergmann, Luca Bigatello, Elena Biosca Pérez, Katja Birr, 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, 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, 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, Najia Garofano, Luca Gregorio Giaccari, Fernando Gilsanz, Felix Girrbach, Luca Gobbi, Marc Bernard Godfried, Nicolai Goettel, Peter A. Goldstein, Or Goren, Andrew Gorlin, Juan Graterol, Pierre Guyon, Kevin Haire, Philippe Harou, Antonia Helf, Gunther Hempel, María José Hernández Cádiz, Björn Heyse, 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, Selin Kivrak, Vlasta Klarić, 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, Paolo Navalesi, 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, Sanja Peremin, Christoph Philipsenburg, Daniela Pinho, Silvia Pinho, Linda M. Posthuma, Vincenzo Pota, Benedikt Preckel, Paolo Priani, 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, Humberto S. Machado, Catarina S. Nunes, Giovanni Sabbatini, Jon D. Samuels, Josep Martí Sanahuja, Pasquale Sansone, Alice Santos, Mohamed Sayedalahl, Martin Scharffenberg, Eduardo Schiffer, Nadja Schliewe, Raoul Schorer, Roman Schumann, Gabriele Selmo, Mar Sendra, Mert Senturk, Kate Shaw, Mirjana Shosholcheva, Abdulrazak Sibai, Francesca Simonassi, Claudia Sinno, Nukhet Sivrikoz, Vasiliki Skandalou, Neil Smith, Maria Soares, Tania Socorro Artiles, Diogo Sousa Castro, Miguel Sousa, Savino Spadaro, 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, 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, Piet Wyffels, Julio Yagüe, David Yates, Ayşen Yavru, Lilach Zac, Jing Zhong, Anesthesiology, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, ACS - Microcirculation, Campos, Niklas S, Bluth, Thoma, Hemmes, Sabrine N T, Librero, Julian, Pozo, Natividad, Ferrando, Carlo, Ball, Lorenzo, Mazzinari, Guido, Pelosi, Paolo, Gama de Abreu, Marcelo, Schultz, Marcus J, Serpa Neto, A, investigators for the PROVHILO study including, Cortegiani, Andrea, Raineri, Santi Maurizio, and Giarratano, Antonino

Subjects
Adult, Lung Diseases, PEEP, postoperative pulmonary complications, mechanical ventilation, Positive-Pressure Respiration, surgery, Anesthesiology and Pain Medicine, Postoperative Complications, Tidal Volume, Humans, Postoperative Period, Lung, Randomized Controlled Trials as Topic
Abstract

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).

Published
2022

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

Author

Ana Vallejo de la Cueva, Pablo T. Aznar, Laura González Cubillo, Chiara Robba, Oriol Plans Galván, Nerea Aretxabala Cortajarena, Robert C. Hyzy, Imen Ben Saida, Jorge Rubio, María José Sánchez Carretero, Katie M. Vance, Blanca Furquet, Irene Patricia Barón Barrera, Sarah J. Peterson, Sara C. LaHue, Sergio Llorente Damas, Andrew R. Vogel, Nihal Patel, Alejandro Suarez-de-la-Rica, Cristina Álvarez, Ricard Molina Latorre, Günseli Orhun, Karen Shephard, Marta Martín Martínez, Paula Castello-Mora, Guillem Navarra-Ventura, Michelle Woodham, Carmen Andrea Sanchis-Veryser, Annachiara Marra, Kristine Nelson, Carolina Ferrer Gómez, Francisco Javier Morán Gallego, Muhammed Elhadi, Sarah Cohen, María Esther Rodriguez Delgado, Rafael Badenes, Isabel Reyes García, Christopher Berkey, Karla Núñez Vázquez, Beata-Gabriela K Simpson, Amaia Quintano Rodero, María Pilar Vicente-Fernández, María Luisa García Pérez, Vanja C. Douglas, María Elena Martínez Quintana, Silvia García de Castrillón i Ramal, Silvia Beretta, Mandeep Sing, Robert A Balk, Yolanda Poveda Hernández, Spencer Roberson, Martin Siegemund, Jordi Morillas Pérez, Rameela Raman, Giuseppe Servillo, João Manoel Silva, Brenda T. Pun, Aurélien Mazeraud, María Cruz Martín Delgado, Borja Hinojal Olmedillo, Gemma Gomà Fernández, Miguel Valente, Michael T. Kenes, Laura Galarza, Fabio Silvio Taccone, Wencong Chen, Rita Pereia, Álvaro Ortega Guerrero, Morgan H. Tandy, Alejandro Ruiz Perea, Stephanie Wilson-Linville, Meri Martin Cerezuela, Salvatore Lucio Cutuli, Carlos A. Calvo, María de las Nieves Noci Moreno, Ariadna Bellès, Elisa Govea Bogossian, Mario Dalorzo González, Eva Álvarez Torres, David Díaz Muñoz, Carla Margarida Teixeira, Emilio del Campo Molina, Sol Fernandez-Gonzalo, Christine Harb, Berta Monleón, Anna Teresa Mazzeo, Beatriz Del Moral Barbudo, Thomas Godet, Cristina Delgado Palacios, C. Adrian Austin, Hilde Wøien, Anselmo Caricato, Erik Roman-Pognuz, Bruno Gonçalves, Patricia Rodríguez Villamizar, Eloisa Sofia Tanzarella, Daniel A Godoy Torres, Robert E. Hosse, Lisa Smit, María Rosa Sanchis-Martin, Cristina Murcia Gubianas, Emily Sanders, Karen Herrera-Davis, Sara Torrico Sánchez, Isabel Peña Luna, David A Bennett, Irene Torres, Diana Gil-Castillejos, Laura Labrador Romero, Felipe González-Seguel, Carlos Muñoz De Cabo, Ellis Morgan, Itziar Insausti, Mónica García Simón, Patricia Piñeiro Otero, Genís Carrasco Gómez, M. Montero, Jose García Cantos, Ignacio Garutti, César Rodriguez Nuñez, Fernando Higuero, Sameep Sehgal, Catherine M. Kuza, Yago García Blanco-Traba, Juan Romeu Prieto, Ainhoa Serrano, Elena Abril Palomares, Perihan Ergin Özcan, Mathieu van der Jagt, Elena Gallego Curto, Berta Gallego Rodríguez, Rosalía Navarro Casado, Aaron Lerner, Myrto Tzimou, Sheila Moya Gutiérrez, Beatriz García Góngora, Eleonora Stival, Xavier Andorrà Sunyer, Susana Gallardo Sánchez, Anna Baró Serra, Filadelfo Bustos Molina, Rafael Zaragoza, Verónica Rojas, Paolo Pelosi, Aris Pérez Lucendo, Stéphane Legriel, Eduardo Tobar, Laura Lizama, Viviane Hidalgo-Calibin, Chiara Maria Concetta Massaro, Nekane Romero, Pablo García Domelo, Isabel Jesus Pereira, Kelly Drumright, Frank Rasulo, Mattia Marchesi, Jacques Creteur, Estefanía Carvajal Revuelta, Timothy D. Girard, Pablo Carreño-Montenegro, Ana Montero Feijoo, Ignacio Baeza Gómez, Alba Gonzalo Millán, Esteban Morcillo, Alice Santos, Pilar Leal Sanz, Dulce Morales, Gabriel Heras La Calle, Hollis R. O’Neal, Antonio Ramírez-Palma, Inés Pérez Francisco, Alberto Noto, Matilde González Serrano, Paola Valls, María Jesús Mármol Cubillo, Emilio Maseda, Anna Estermann, Andrés Pujol, E. Wesley Ely, Alexis Ferré, Lucia Chowdhury, Guillaume Lacave, Cristina Granja, Isabel de la Calle Gil, Onur M Orun, Mohamed Boussarsar, David Pestaña Lagunas, Denise Battaglini, Nathan E. Brummel, Rosa María Pérez Manrique, Núria Zellweger, Jaume Puig, Kiran Devulapally, Milagros Calizaya Vargas, Jesús Caballero, Theresa Olasveengen, Cristina Fuster, Aarti Sarwal, Pratik P. Pandharipande, Gabriele Pintaudi, Paula Ramirez, Blanca Fernández Tomás, Maria Claudia Giménez Santamarina, Francisco Luis Pérez Caballero, Enver Rodriguez-Martinez, David Martínez-Gascueña, Irene Paredes Borrachero, Ugo Fraisse, Paloma LaTorre Andreu, Ignacio Catalán-Monzón, Elena Gonzalez, Figen Esen, Lorenzo Peluso, Intensive Care, Pun, B. T., Badenes, R., Heras La Calle, G., Orun, O. M., Chen, W., Raman, R., Simpson, B. -G. K., Wilson-Linville, S., Hinojal Olmedillo, B., Vallejo de la Cueva, A., van der Jagt, M., Navarro Casado, R., Leal Sanz, P., Orhun, G., Ferrer Gomez, C., Nunez Vazquez, K., Pineiro Otero, P., Taccone, F. S., Gallego Curto, E., Caricato, A., Woien, H., Lacave, G., O'Neal, H. R., Peterson, S. J., Brummel, N. E., Girard, T. D., Ely, E. W., Pandharipande, P. P., Creteur, J., Bogossian, E. G., Peluso, L., Gonzalez-Seguel, F., Hidalgo-Cabalin, V., Carreno-Montenegro, P., Rojas, V., Tobar, E., Ramirez-Palma, A., Herrera-Davis, K., Ferre, A., Legriel, S., Godet, T., Fraisse, U., Goncalves, B., Mazeraud, A., Tzimou, M., Rasulo, F., Beretta, S., Marchesi, M., Robba, C., Battaglini, D., Pelosi, P., Mazzeo, A. T., Noto, A., Servillo, G., Marra, A., Cutuli, S. L., Pintaudi, G., Stival, E., Tanzarella, E. S., Roman-Pognuz, E., Concetta Massaro, C. M., Elhadi, M., Smit, L., Olasveengen, T., Pereira, I. J., Teixeira, C. M., Santos, A., Valente, M., Granja, C., Pereia, R., Silva, J., Furquet, B., Garcia Simon, M., Godoy Torres, D. A., Monleon, B., Morcillo, E., Romero, N., Serrano, A., Torrico Sanchez, S., Perez Caballero, F. L., Pena Luna, I., Baeza Gomez, I., Calizaya Vargas, M., Morillas Perez, J., Carrasco Gomez, G., Molina Latorre, R., Moya Gutierrez, S., Baron Barrera, I. P., Delgado Palacios, C., Garcia Gongora, B., Labrador Romero, L., Galarza, L., Catalan-Monzon, I., Rodriguez-Martinez, E., Murcia Gubianas, C., Belles, A., Rodriguez Delgado, M. E., Caballero, J., Morales, D., Pujol, A., Rubio, J., Alvarez Torres, E., Carvajal Revuelta, E., de la Calle Gil, I., Fernandez Tomas, B., Gallego Rodriguez, B., Gonzalez Serrano, M., LaTorre Andreu, P., Perez Lucendo, A., Abril Palomares, E., Gonzalez Gonzalez, E., Martin Delgado, M. C., Munoz De Cabo, C., Aznar, P. T., Calvo, C. A., Garutti, I., Higuero, F., Martinez-Gascuena, D., Maseda, E., Insausti, I., Montero Feijoo, A., Suarez-de-la-Rica, A., Del Moral Barbudo, B., Garcia Blanco-Traba, Y., Gimenez Santamarina, M. C., Gonzalo Millan, A., Llorente Damas, S., Pestana Lagunas, D., Reyes Garcia, I., Ruiz Perea, A., Ortega Guerrero, A., Marmol Cubillo, M. J., Diaz Munoz, D., Garcia de Castrillon i Ramal, S., Andorra Sunyer, X., Noci Moreno, M. D. L. N., Perez Manrique, R. M., del Campo Molina, E., Martinez Quintana, M. E., Fernandez-Gonzalo, S., Goma Fernandez, G., Navarra-Ventura, G., Baro Serra, A., Fuster, C., Plans Galvan, O., Gil-Castillejos, D., Dalorzo Gonzalez, M., Moran Gallego, F. J., Paredes Borrachero, I., Rodriguez Villamizar, P., Romeu Prieto, J., Sanchez Carretero, M. J., Gallardo Sanchez, S., Bustos Molina, F., Garcia Perez, M. L., Castello-Mora, P., Puig, J., Sanchis-Martin, M. R., Sanchis-Veryser, C. A., Vicente-Fernandez, M. P., Zaragoza, R., Lizama, L., Torres, I., Alvarez, C., Ramirez, P., Martin Cerezuela, M., Montero, M. J., Garcia Cantos, J., Valls, P., Aretxabala Cortajarena, N., Garcia Domelo, P., Gonzalez Cubillo, L., Martin Martinez, M., Perez Francisco, I., Poveda Hernandez, Y., Quintano Rodero, A., Rodriguez Nunez, C., Siegemund, M., Estermann, A., Zellweger, N., Ben Saida, I., Boussarsar, M., Esen, F., Ergin Ozcan, P., Berkey, C., Harb, C., Tandy, M. H., Morgan, E., Shephard, K., Hyzy, R. C., Kenes, M., Nelson, K., Hosse, R. E., Vance, K. M., Austin, C. A., Lerner, A., Sanders, E., Balk, R. A., Bennett, D. A., Vogel, A. R., Chowdhury, L., Devulapally, K., Woodham, M., Cohen, S., Patel, N., Kuza, C. M., Sing, M., Roberson, S., Drumright, K., Sehgal, S., Lahue, S. C., Douglas, V. C., and Sarwal, A.

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, covid-19, delirium, Outcomes, Lower risk, Critical Ilness, Task-Force, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Intensive-Care-Unit, Intensive care, Settore MED/41 - ANESTESIOLOGIA, medicine, Survivors, 030212 general & internal medicine, Simplified Acute Physiology Score, Mechaniically Ventilated Patients, Epitiomology, Mechanical ventilation, Coma, Intensive-Care-Unit, Mechaniically Ventilated Patients, Clinical practice Guidelines, Critical Ilness, Task-Force, Sedation, ICU, Survivors, Outcomes, Epitiomology, business.industry, covid, Retrospective cohort study, Articles, Clinical practice Guidelines, covid, delirium, 030228 respiratory system, Sedation, ICU, Emergency medicine, Delirium, medicine.symptom, business, Cohort study
Abstract

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

Published
2021

4. Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients

Author

Sonia Luque, Jason A. Roberts, Emilio Maseda, Santiago Grau, Alejandro Suarez-de-la-Rica, Ana Montero-Feijoo, Patricia Salgado, Maria-Pilar Castillo-Mafla, Carlos A García-Bernedo, Fernando Gilsanz, and María-José Giménez

Subjects
Male, 0301 basic medicine, Letter, Antifungal Agents, Critical Care and Intensive Care Medicine, Body Mass Index, law.invention, Morbid obesity, Echinocandins, law, Candida spp, Candida, Aged, 80 and over, 2. Zero hunger, Candidiasis, Area under the curve, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, Intensive care unit, Obesity, Morbid, 3. Good health, Area Under Curve, Obesitat, Female, Monte Carlo Method, medicine.drug, Adult, medicine.medical_specialty, Critical Illness, 030106 microbiology, Microbial Sensitivity Tests, Monte-Carlo simulation, Lipopeptides, 03 medical and health sciences, Pharmacokinetics, Internal medicine, medicine, Humans, Obesity, Dosing, PK/PD models, Aged, Dose-Response Relationship, Drug, business.industry, Research, Micafungin, PK/PD, lcsh:RC86-88.9, ROC Curve, Spain, Pharmacodynamics, business, Body mass index
Abstract

Altres ajuts: This work was supported in part by an unrestricted grant from Astellas Pharma S.A. (Madrid, Spain). The funder had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. JAR is funded by a Career Development Fellowship from the National Health and Medical Research Council of Australia (APP1048652). Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100-150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (non parapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%. Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m 2 and 150 mg for morbidly obese patients with BMI > 45 kg/m 2 (except two noncritically ill obese patients with BMI ~ 35 kg/m 2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m 2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights < 115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115 kg. The lack of adequacy for the 100 mg/24 h dose suggested the need to increase the dose to 150 mg/24 h for C. albicans infections. Further pharmacokinetic/pharmacodynamic studies should address optimization of micafungin dosing for nonalbicans Candida infections.

Published
2018

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