The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial
Philipp Heinrich Baldia, Bernhard Wernly, Hans Flaatten, Jesper Fjølner, Antonio Artigas, Bernardo Bollen Pinto, Joerg C Schefold, Malte Kelm, Michael Beil, Raphael Romano Bruno, Stephan Binnebößel, Georg Wolff, Ralf Erkens, Sviri Sigal, Peter Vernon Van Heerden, Wojciech Szczeklik, Muhammed Elhadi, Michael Joannidis, Sandra Oeyen, Brian Marsh, Finn H Andersen, Rui Moreno, Susannah Leaver, Dylan W De Lange, Bertrand Guidet, Christian Jung, Philipp Eller, Michael Joannidis, Dieter Mesotten, Pascal Reper, Walter Swinnen, Nicolas Serck, Elisabeth Dewaele, Helene Brix, Jens Brushoej, Pritpal Kumar, Helene Korvenius Nedergaard, Ida Riise Balleby, Camilla Bundesen, Maria Aagaard Hansen, Stine Uhrenholt, Helle Bundgaard, Richard Innes, James Gooch, Lenka Cagova, Elizabeth Potter, Michael Reay, Miriam Davey, Mohammed Abdelshafy Abusayed, Sally Humphreys, Arnaud Galbois, 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, 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, Stefan Schaller, Muhammed Kurt, Andreas Faltlhauser, Stefan Schaller, Milena Milovanovic, Matthias Lutz, Gonxhe Shala, Hendrik Haake, Winfried Randerath, Anselm Kunstein, Patrick Meybohm, Stefan Schaller, 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, Antonios Papadogoulas, Francesk Mulita, Nikoletta Rovina, Zoi Aidoni, Evangelia Chrisanthopoulou, Eumorfia Kondili, Ioannis Andrianopoulos, Martijn Groenendijk, Mirjam Evers, Mirjam Evers, Lenneke Van Lelyveld-Haas, Iwan Meynaar, Alexander Daniel Cornet, Marieke Zegers, Willem Dieperink, Dylan W De Lange, Tom Dormans, Michael Hahn, Britt Sjøbøe, Hans Frank Strietzel, Theresa Olasveengen, Luis Romundstad, Anna Kluzik, Paweł Zatorski, Tomasz Drygalski, 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, Mjosé 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, Nawfel Ben-Hamouda, Andrea Roberti, Yvan Fleury, Nour Abidi, Alexander Dullenkopf, Richard Pugh, Sara Smuts
BMC Geriatrics, doi:10.1186/s12877-022-03709-w
Background: In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients.
Methods: This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day-and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression. Results: 44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p < 0.001), arterial hypertension (70% versus 65%, p = 0.006) and had a higher score on Clinical Frailty Scale (CFS; IQR 2-5 versus IQR 2-4, p < 0.001). Patients under prior paracetamol treatment were less often subjected to intubation and vasopressor use, compared to patients without paracetamol intake (65 versus 71%, p < 0.001; 63 versus 69%, p = 0.007). Paracetamol intake was not associated with ICU-, 30-day-and 3-month-mortality, remaining true after multivariate adjusted analysis.
Elisabeth-Krankenhaus Essen Essen
Declarations Ethics approval and consent to participate The primary competent ethics committee was the Ethics Committee of the University of Duesseldorf, Germany (application number 2020-892). Each participating center received a copy of the study protocol. Institutional research ethic board approval was obtained from each study site and was mandatory for study participation. Due to the observational nature of the study, participation in this study did not impact medical procedures, which were all executed in accordance with the relevant medical guidelines and regulations. No additional examinations, e.g., sampling and storage of biomaterials, such as blood or CT-scans and X-rays, were performed. The study was planned in adherence to the European Union General Data Privacy Regulation (GDPR) directive, which is implemented in most participating countries. Deceased patients were included within strict consideration of local requirements set up by the local ethics committees. However, in a few countries, recruitment was possible without informed consent in accordance with the respective local ethics committee (see above).
Consent for publication The manuscript does not contain any individual person's data in any form.
Competing interests The authors declare that they have no competing interests. JCS reports
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional..
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'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>In the early COVID-19 pandemic concerns about the correct choice of '
'analgesics in patients with COVID-19 were raised. Little data was available on potential '
'usefulness or harmfulness of prescription free analgesics, such as paracetamol. This '
'international multicentre study addresses that lack of evidence regarding the usefulness or '
'potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease '
'within a large, prospectively enrolled cohort of critically ill and frail intensive care unit '
'(ICU) patients.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>This prospective international observation study (The COVIP study) '
'recruited ICU patients\u2009≥\u200970\xa0years admitted with COVID-19. Data on Sequential '
'Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10\xa0days before '
'admission, ICU therapy, limitations of care and survival during the ICU stay, at 30\xa0days, '
'and 3\xa0months. Paracetamol intake was analysed for associations with ICU-, 30-day- and '
'3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to '
'stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic '
'regression.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>44% of the 2,646 patients with data recorded regarding paracetamol '
'intake within 10\xa0days prior to ICU admission took paracetamol. There was no difference in '
'age between patients with and without paracetamol intake. Patients taking paracetamol '
'suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, '
'<jats:italic>p</jats:italic>\u2009<\u20090.001), arterial hypertension (70% versus 65%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.006) and had a higher score on Clinical Frailty '
'Scale (CFS; IQR 2–5 versus IQR 2–4, <jats:italic>p</jats:italic>\u2009<\u20090.001). '
'Patients under prior paracetamol treatment were less often subjected to intubation and '
'vasopressor use, compared to patients without paracetamol intake (65 versus 71%, '
'<jats:italic>p</jats:italic>\u2009<\u20090.001; 63 versus 69%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.007). Paracetamol intake was not associated with '
'ICU-, 30-day- and 3-month-mortality, remaining true after multivariate adjusted '
'analysis.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Conclusion</jats:title>\n'
' <jats:p>Paracetamol intake prior to ICU admission was not associated with '
'short-term and 3-month mortality in old, critically ill intensive care patients suffering '
'from COVID-19.</jats:p>\n'
' <jats:p>Trial registration.</jats:p>\n'
' <jats:p>This prospective international multicentre study was registered on '
'ClinicalTrials.gov with the identifier “NCT04321265” on March 25, 2020.\n'
'</jats:p>\n'
' </jats:sec>',
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'title': 'The association of prior paracetamol intake with outcome of very old intensive care patients '
'with COVID-19: results from an international prospective multicentre trial',
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'end-of-life care on ICU outcome. Intensive Care Med. 2021;47(5):624–5.',
'journal-title': 'Intensive Care Med'}],
'container-title': 'BMC Geriatrics',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12877-022-03709-w.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
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'deposited': { 'date-parts': [[2022, 12, 27]],
'date-time': '2022-12-27T23:08:25Z',
'timestamp': 1672182505000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-03709-w'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 12, 27]]},
'references-count': 32,
'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2022, 12]]}},
'alternative-id': ['3709'],
'URL': 'http://dx.doi.org/10.1186/s12877-022-03709-w',
'relation': {},
'ISSN': ['1471-2318'],
'subject': ['Geriatrics and Gerontology'],
'container-title-short': 'BMC Geriatr',
'published': {'date-parts': [[2022, 12, 27]]},
'assertion': [ { 'value': '14 January 2022',
'order': 1,
'name': 'received',
'label': 'Received',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '19 December 2022',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '27 December 2022',
'order': 3,
'name': 'first_online',
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{'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}},
{ 'value': 'The primary competent ethics committee was the Ethics Committee of the '
'University of Duesseldorf, Germany (application number 2020–892). Each '
'participating center received a copy of the study protocol. Institutional '
'research ethic board approval was obtained from each study site and was '
'mandatory for study participation.Due to the observational nature of the study, '
'participation in this study did not impact medical procedures, which were all '
'executed in accordance with the relevant medical guidelines and regulations. No '
'additional examinations, e.g., sampling and storage of biomaterials, such as '
'blood or CT-scans and X-rays, were performed.The study was planned in adherence '
'to the European Union General Data Privacy Regulation (GDPR) directive, which '
'is implemented in most participating countries. Deceased patients were included '
'within strict consideration of local requirements set up by the local ethics '
'committees. However, in a few countries, recruitment was possible without '
'informed consent in accordance with the respective local ethics committee (see '
'above).',
'order': 2,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}},
{ 'value': 'The manuscript does not contain any individual person’s data in any form.',
'order': 3,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}},
{ 'value': '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.',
'order': 4,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}],
'article-number': '1000'}
