Lactate is associated with mortality in very old intensive care patients suffering from COVID-19: results from an international observational study of 2860 patients

Raphael Romano Bruno, Bernhard Wernly, Hans Flaatten, Jesper Fjølner, Antonio Artigas, Bernardo Bollen Pinto, Joerg C Schefold, Stephan Binnebössel, Philipp Heinrich Baldia, Malte Kelm, Michael Beil, Sivri Sigal, Peter Vernon van Heerden, Wojciech Szczeklik, Muhammed Elhadi, Michael Joannidis, Sandra Oeyen, Tilemachos Zafeiridis, Jakob Wollborn, Maria José Arche Banzo, Kristina Fuest, Brian Marsh, Finn H Andersen, Rui Moreno, Susannah Leaver, Ariane Boumendil, Dylan W De Lange, Bertrand Guidet, Christian Jung, COVIP Study Group, Philipp Eller, Michael Joannidis, Dieter Mesotten, Pascal Reper, Sandra Oeyen, Walter Swinnen, Nicolas Serck, Elisabeth Dewaele, Edwin Chapeta, Helene Brix, Jens Brushoej, Pritpal Kumar, Helene Korvenius Nedergaard, Tim Koch Johnsen, Camilla Bundesen, Maria Aagaard Hansen, Stine Uhrenholt, Helle Bundgaard, Jesper Fjølner, Richard Innes, James Gooch, Lenka Cagova, Elizabeth Potter, Michael Reay, Miriam Davey, Mohammed Abdelshafy Abusayed, Sally Humphreys, Amy Collins, Avinash Aujayeb, Susannah Leaver, Waqas Khaliq, Ayman Abdelmawgoad Habib, Mohammed A Azab, Kyrillos Wassim, Yumna A Elgazzar, Rehab Salah, Hazem Maarouf Abosheaishaa, Aliae A R Hussein Mohamed, Ahmed Y Azzam, Samar Tharwat, Yasmin Khairy Nasreldin Mohamed Ali, Omar Elmandouh, Islam Galal, Ahmed Abu-Elfatth, Karam Motawea, Mohammad Elbahnasawy, Mostafa Shehata, Mohamed Elbahnasawy, Mostafa Tayeb, Nermin Osman, Wafaa Abdel-Elsalam, Aliae Mohamed Hussein, Amer Aldhalia, Arnaud Galbois, Bertrand Guidet, Cyril Charron, Caroline Hauw Berlemont, Guillaume Besch, Jean-Philippe Rigaud, Julien Maizel, Michel Djibré, Philippe Burtin, Pierre Garcon, Saad Nseir, Xavier Valette, Nica Alexandru, Nathalie Marin, Marie Vaissiere, Gaëtan Plantefeve, Hervé Mentec, Thierry Vanderlinden, Igor Jurcisin, Buno Megarbane, Benjamin Glenn Chousterman, François Dépret, Marc Garnier, Sebastien Besset, Johanna Oziel, Alexis Ferre, Stéphane Dauger, Guillaume Dumas, Bruno Goncalves, Lucie Vettoretti, Didier Thevenin, Stefan Schaller, Muhammed Kurt, Andreas Faltlhauser, Christian Meyer, Milena Milovanovic, Matthias Lutz, Gonxhe Shala, Hendrik Haake, Winfried Randerath, Anselm Kunstein, Patrick Meybohm, Stephan Steiner, Eberhard Barth, Tudor Poerner, Philipp Simon, Marco Lorenz, Zouhir Dindane, Karl Friedrich Kuhn, Martin Welte, Ingo Voigt, Hans-Joachim Kabitz, Jakob Wollborn, Ulrich Goebel, Sandra Emily Stoll, Detlef Kindgen-Milles, Simon Dubler, Christian Jung, Kristina Fuest, Michael Schuster, Stephan Steiner, Antonios Papadogoulas, Francesk Mulita, Nikoletta Rovina, Zoi Aidoni, Evangelia Chrisanthopoulou, Eumorfia Kondili, Ioannis Andrianopoulos, Mohan Gurjar, Ata Mahmoodpoor, Rand Hussein, Maytham Aqeel Al-Juaifari, Abdullah Khudhur Ahmed Karantenachy, Sigal Sviri, Ahmed Elsaka, Brian Marsh, Vittoria Comellini, Farah Al-Ali, Sari Almani, Almu' Atasim Khamees, Khayry Al-Shami, Ibrahim Salah El Din, Taha Abubaker, Hazem Ahmed, Ahmed Rabha, Abdulmueti Alhadi, Marwa Emhamed, Saedah Abdeewi, Abdurraouf Abusalama, Abdulmueti Alhadi, Mohammed Huwaysh, Esraa Abdalqader Alghati, Abdelilah Ghannam, Silvio A Namendys-Sylva, Martijn Groenendijk, Mirjam Evers, Lenneke Van Lelyveld-Haas, Iwan Meynaar, Alexander Daniel Cornet, Marieke Zegers, Willem Dieperink, Dylan De Lange, Tom Dormans, Michael Hahn, Britt Sjøbøe, Hans Frank Strietzel, Theresa Olasveengen, Luis Romundstad, Finn H Andersen, John George Grace Massoud, Aamir Ghafoor Khan, Shahd Al-Qasrawi, Sarah Amro, Anna Kluzik, Paweł Zatorski, Tomasz Drygalski, Wojciech Szczeklik, Jakub Klimkiewicz, Joanna Solek-Pastuszka, Dariusz Onichimowski, Miroslaw Czuczwar, Ryszard Gawda, Jan Stefaniak, Karina Stefanska-Wronka, Ewa Zabul, Ana Isabel Pinho Oliveira, Rui Assis, Maria De Lurdes Campos Santos, Henrique Santos, Filipe Sousa Cardoso, André Gordinho, Ioana Marina Grintescu, Dana Tomescu, Mohamed Raafat Badawy, M José Arche Banzo, Begoña Zalba-Etayo, Patricia Jimeno Cubero, Jesús Priego, Gemma Gomà, Teresa Maria Tomasa-Irriguible, Susana Sancho, Aida Fernández Ferreira, Eric Mayor Vázquez, Ángela Prado Mira, Mercedes Ibarz, David Iglesias, Susana Arias-Rivera, Fernando Frutos-Vivar, Sonia Lopez-Cuenca, Cesar Aldecoa, David Perez-Torres, Isabel Canas-Perez, Luis Tamayo-Lomas, Cristina Diaz-Rodriguez, Pablo Ruiz De Gopegui, Mahmoud Saleh, Momin Majed Yousuf Hilles, Enas M Y Abualqumboz, Nawfel Ben-Hamouda, Andrea Roberti, Yvan Fleury, Nour Abidi, Joerg C Schefold, Ivan Chau, Alexander Dullenkopf, Mohammad Karam Chaaban, Mohammed Mouaz Shebani, Ahmad Hmaideh, Aymen Shaher, Ayca Sultan Sahin, Kemal Tolga Saracoglu, Mohammed Al-Sadawi, Richard Pugh, Sara Smuts, Rafat Ameen Mohammed Al-Saban, Raphael Romano Bruno, Bernhard Wernly, Hans Flaatten, Jesper Fjølner, Antonio Artigas, Bernardo Bollen Pinto, Joerg C Schefold, Stephan Binnebössel, Philipp Heinrich Baldia, Malte Kelm, Michael Beil, Sivri Sigal, Peter Vernon van Heerden, Wojciech Szczeklik, Muhammed Elhadi, Michael Joannidis, Sandra Oeyen, Tilemachos Zafeiridis, Jakob Wollborn, Maria José Arche Banzo, Kristina Fuest, Brian Marsh, Finn H Andersen, Rui Moreno, Susannah Leaver, Ariane Boumendil, Dylan W De Lange, Bertrand Guidet, Christian Jung, COVIP Study Group, Philipp Eller, Michael Joannidis, Dieter Mesotten, Pascal Reper, Sandra Oeyen, Walter Swinnen, Nicolas Serck, Elisabeth Dewaele, Edwin Chapeta, Helene Brix, Jens Brushoej, Pritpal Kumar, Helene Korvenius Nedergaard, Tim Koch Johnsen, Camilla Bundesen, Maria Aagaard Hansen, Stine Uhrenholt, Helle Bundgaard, Jesper Fjølner, Richard Innes, James Gooch, Lenka Cagova, Elizabeth Potter, Michael Reay, Miriam Davey, Mohammed Abdelshafy Abusayed, Sally Humphreys, Amy Collins, Avinash Aujayeb, Susannah Leaver, Waqas Khaliq, Ayman Abdelmawgoad Habib, Mohammed A Azab, Kyrillos Wassim, Yumna A Elgazzar, Rehab Salah, Hazem Maarouf Abosheaishaa, Aliae A R Hussein Mohamed, Ahmed Y Azzam, Samar Tharwat, Yasmin Khairy Nasreldin Mohamed Ali, Omar Elmandouh, Islam Galal, Ahmed Abu-Elfatth, Karam Motawea, Mohammad Elbahnasawy, Mostafa Shehata, Mohamed Elbahnasawy, Mostafa Tayeb, Nermin Osman, Wafaa Abdel-Elsalam, Aliae Mohamed Hussein, Amer Aldhalia, Arnaud Galbois, Bertrand Guidet, Cyril Charron, Caroline Hauw Berlemont, Guillaume Besch, Jean-Philippe Rigaud, Julien Maizel, Michel Djibré, Philippe Burtin, Pierre Garcon, Saad Nseir, Xavier Valette, Nica Alexandru, Nathalie Marin, Marie Vaissiere, Gaëtan Plantefeve, Hervé Mentec, Thierry Vanderlinden, Igor Jurcisin, Buno Megarbane, Benjamin Glenn Chousterman, François Dépret, Marc Garnier, Sebastien Besset, Johanna Oziel, Alexis Ferre, Stéphane Dauger, Guillaume Dumas, Bruno Goncalves, Lucie Vettoretti, Didier Thevenin, Stefan Schaller, Muhammed Kurt, Andreas Faltlhauser, Christian Meyer, Milena Milovanovic, Matthias Lutz, Gonxhe Shala, Hendrik Haake, Winfried Randerath, Anselm Kunstein, Patrick Meybohm, Stephan Steiner, Eberhard Barth, Tudor Poerner, Philipp Simon, Marco Lorenz, Zouhir Dindane, Karl Friedrich Kuhn, Martin Welte, Ingo Voigt, Hans-Joachim Kabitz, Jakob Wollborn, Ulrich Goebel, Sandra Emily Stoll, Detlef Kindgen-Milles, Simon Dubler, Christian Jung, Kristina Fuest, Michael Schuster, Stephan Steiner, Antonios Papadogoulas, Francesk Mulita, Nikoletta Rovina, Zoi Aidoni, Evangelia Chrisanthopoulou, Eumorfia Kondili, Ioannis Andrianopoulos, Mohan Gurjar, Ata Mahmoodpoor, Rand Hussein, Maytham Aqeel Al-Juaifari, Abdullah Khudhur Ahmed Karantenachy, Sigal Sviri, Ahmed Elsaka, Brian Marsh, Vittoria Comellini, Farah Al-Ali, Sari Almani, Almu' Atasim Khamees, Khayry Al-Shami, Ibrahim Salah El Din, Taha Abubaker, Hazem Ahmed, Ahmed Rabha, Abdulmueti Alhadi, Marwa Emhamed, Saedah Abdeewi, Abdurraouf Abusalama, Abdulmueti Alhadi, Mohammed Huwaysh, Esraa Abdalqader Alghati, Abdelilah Ghannam, Silvio A Namendys-Sylva, Martijn Groenendijk, Mirjam Evers, Lenneke Van Lelyveld-Haas, Iwan Meynaar, Alexander Daniel Cornet, Marieke Zegers, Willem Dieperink, Dylan De Lange, Tom Dormans, Michael Hahn, Britt Sjøbøe, Hans Frank Strietzel, Theresa Olasveengen, Luis Romundstad, Finn H Andersen, John George Grace Massoud, Aamir Ghafoor Khan, Shahd Al-Qasrawi, Sarah Amro, Anna Kluzik, Paweł Zatorski, Tomasz Drygalski, Wojciech Szczeklik, Jakub Klimkiewicz, Joanna Solek-Pastuszka, Dariusz Onichimowski, Miroslaw Czuczwar, Ryszard Gawda, Jan Stefaniak, Karina Stefanska-Wronka, Ewa Zabul, Ana Isabel Pinho Oliveira, Rui Assis, Maria De Lurdes Campos Santos, Henrique Santos, Filipe Sousa Cardoso, André Gordinho, Ioana Marina Grintescu, Dana Tomescu, Mohamed Raafat Badawy, M José Arche Banzo, Begoña Zalba-Etayo, Patricia Jimeno Cubero, Jesús Priego, Gemma Gomà, Teresa Maria Tomasa-Irriguible, Susana Sancho, Aida Fernández Ferreira, Eric Mayor Vázquez, Ángela Prado Mira, Mercedes Ibarz, David Iglesias, Susana Arias-Rivera, Fernando Frutos-Vivar, Sonia Lopez-Cuenca, Cesar Aldecoa, David Perez-Torres, Isabel Canas-Perez, Luis Tamayo-Lomas, Cristina Diaz-Rodriguez, Pablo Ruiz De Gopegui, Mahmoud Saleh, Momin Majed Yousuf Hilles, Enas M Y Abualqumboz, Nawfel Ben-Hamouda, Andrea Roberti, Yvan Fleury, Nour Abidi, Joerg C Schefold, Ivan Chau, Alexander Dullenkopf, Mohammad Karam Chaaban, Mohammed Mouaz Shebani, Ahmad Hmaideh, Aymen Shaher, Ayca Sultan Sahin, Kemal Tolga Saracoglu, Mohammed Al-Sadawi, Richard Pugh, Sara Smuts, Rafat Ameen Mohammed Al-Saban

Abstract

Purpose: Lactate is an established prognosticator in critical care. However, there still is insufficient evidence about its role in predicting outcome in COVID-19. This is of particular concern in older patients who have been mostly affected during the initial surge in 2020.

Methods: This prospective international observation study (The COVIP study) recruited patients aged 70 years or older (ClinicalTrials.gov ID: NCT04321265) admitted to an intensive care unit (ICU) with COVID-19 disease from March 2020 to February 2021. In addition to serial lactate values (arterial blood gas analysis), we recorded several parameters, including SOFA score, ICU procedures, limitation of care, ICU- and 3-month mortality. A lactate concentration ≥ 2.0 mmol/L on the day of ICU admission (baseline) was defined as abnormal. The primary outcome was ICU-mortality. The secondary outcomes 30-day and 3-month mortality.

Results: In total, data from 2860 patients were analyzed. In most patients (68%), serum lactate was lower than 2 mmol/L. Elevated baseline serum lactate was associated with significantly higher ICU- and 3-month mortality (53% vs. 43%, and 71% vs. 57%, respectively, p < 0.001). In the multivariable analysis, the maximum lactate concentration on day 1 was independently associated with ICU mortality (aOR 1.06 95% CI 1.02-1.11; p = 0.007), 30-day mortality (aOR 1.07 95% CI 1.02-1.13; p = 0.005) and 3-month mortality (aOR 1.15 95% CI 1.08-1.24; p < 0.001) after adjustment for age, gender, SOFA score, and frailty. In 826 patients with baseline lactate ≥ 2 mmol/L sufficient data to calculate the difference between maximal levels on days 1 and 2 (∆ serum lactate) were available. A decreasing lactate concentration over time was inversely associated with ICU mortality after multivariate adjustment for SOFA score, age, Clinical Frailty Scale, and gender (aOR 0.60 95% CI 0.42-0.85; p = 0.004).

Conclusion: In critically ill old intensive care patients suffering from COVID-19, lactate and its kinetics are valuable tools for outcome prediction.

Trial registration number: NCT04321265.

Conflict of interest statement

The authors declare that they have no competing interests. JCS reports grants (full departmental disclosure) from Orion Pharma, Abbott Nutrition International, B. Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, Pierre Fabre Pharma AG, Pfizer, Bard Medica S.A., Abbott AG, Anandic Medical Systems, Pan Gas AG Healthcare, Bracco, Hamilton Medical AG, Fresenius Kabi, Getinge Group Maquet AG, Dräger AG, Teleflex Medical GmbH, Glaxo Smith Kline, Merck Sharp and Dohme AG, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Philips Medical, Phagenesis Ltd, Prolong Pharmaceuticals and Nycomed outside the submitted work. The money went into departmental funds. No personal financial gain applied.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
Distribution of maximum serum lactate values on day 1 (= day of ICU-admission), [mmol/L]
Fig. 3
Fig. 3
Kaplan–Meier for patients with a baseline lactate ≥ 2 mmol/L (red line) compared to patients with a baseline lactate

Fig. 4

Kaplan–Meier for patients with a…

Fig. 4

Kaplan–Meier for patients with a ∆ lactate 24 h > 0% (red line) compared…

Fig. 4
Kaplan–Meier for patients with a ∆ lactate 24 h > 0% (red line) compared to patients with a ∆ lactate 24 h ≤ 0% (blue line) (3-month mortality, ± standard deviation)
Fig. 4
Fig. 4
Kaplan–Meier for patients with a ∆ lactate 24 h > 0% (red line) compared to patients with a ∆ lactate 24 h ≤ 0% (blue line) (3-month mortality, ± standard deviation)

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Source: PubMed

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