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Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study | Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Full Text
<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <title>Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study | Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Full Text</title> <meta name="citation_abstract" content="Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. 59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0 mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, P < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs."/> <meta name="journal_id" content="13049"/> <meta name="dc.title" content="Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study"/> <meta name="dc.source" content="Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2023 31:1"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="BioMed Central"/> <meta name="dc.date" content="2023-06-20"/> <meta name="dc.type" content="OriginalPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2023 The Author(s)"/> <meta name="dc.rights" content="2023 The Author(s)"/> <meta name="dc.rightsAgent" content="reprints@biomedcentral.com"/> <meta name="dc.description" content="Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) &gt; 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24&nbsp;h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. 59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0&nbsp;mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9&nbsp;mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1&nbsp;mmHg vs. 6.8 ± 3.7&nbsp;mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23&nbsp;mmHg vs. 71.8 ± 14.1&nbsp;mmHg, P &lt; 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1&nbsp;mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9&nbsp;mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs."/> <meta name="prism.issn" content="1757-7241"/> <meta name="prism.publicationName" content="Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine"/> <meta name="prism.publicationDate" content="2023-06-20"/> <meta name="prism.volume" content="31"/> <meta name="prism.number" content="1"/> <meta name="prism.section" content="OriginalPaper"/> <meta name="prism.startingPage" content="1"/> <meta name="prism.endingPage" content="11"/> <meta name="prism.copyright" content="2023 The Author(s)"/> <meta name="prism.rightsAgent" content="reprints@biomedcentral.com"/> <meta name="prism.url" content="https://sjtrem.biomedcentral.com/articles/10.1186/s13049-023-01095-9"/> <meta name="prism.doi" content="doi:10.1186/s13049-023-01095-9"/> <meta name="citation_pdf_url" content="https://sjtrem.biomedcentral.com/counter/pdf/10.1186/s13049-023-01095-9"/> <meta name="citation_fulltext_html_url" content="https://sjtrem.biomedcentral.com/articles/10.1186/s13049-023-01095-9"/> <meta name="citation_journal_title" content="Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine"/> <meta name="citation_journal_abbrev" content="Scand J Trauma Resusc Emerg Med"/> <meta name="citation_publisher" content="BioMed Central"/> <meta name="citation_issn" content="1757-7241"/> <meta name="citation_title" content="Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study"/> <meta name="citation_volume" content="31"/> <meta name="citation_issue" content="1"/> <meta name="citation_publication_date" content="2023/12"/> <meta name="citation_online_date" content="2023/06/20"/> <meta name="citation_firstpage" content="1"/> <meta name="citation_lastpage" content="11"/> <meta name="citation_article_type" content="Original research"/> <meta name="citation_fulltext_world_readable" content=""/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1186/s13049-023-01095-9"/> <meta name="DOI" content="10.1186/s13049-023-01095-9"/> <meta name="size" content="175359"/> <meta name="citation_doi" content="10.1186/s13049-023-01095-9"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1186/s13049-023-01095-9&api_key="/> <meta name="description" content="Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) &gt; 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24&nbsp;h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. 59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0&nbsp;mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9&nbsp;mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1&nbsp;mmHg vs. 6.8 ± 3.7&nbsp;mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23&nbsp;mmHg vs. 71.8 ± 14.1&nbsp;mmHg, P &lt; 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1&nbsp;mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9&nbsp;mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs."/> <meta name="dc.creator" content="Werner, Marie"/> <meta name="dc.creator" content="Bergis, Benjamin"/> <meta name="dc.creator" content="Leblanc, Pierre-Etienne"/> <meta name="dc.creator" content="Wildenberg, Lucille"/> <meta name="dc.creator" content="Duranteau, Jacques"/> <meta name="dc.creator" content="Vigué, Bernard"/> <meta name="dc.creator" content="Harrois, Anatole"/> <meta name="dc.subject" content="Emergency Medicine"/> <meta name="dc.subject" content="Traumatic Surgery"/> <meta name="citation_reference" content="Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. 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However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. Methods We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. Results 59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0 mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, P < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. Conclusion In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs."/> <meta property="og:image" content="https://static-content.springer.com/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig1_HTML.png"/> <script type="application/ld+json">{"mainEntity":{"headline":"Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study","description":"Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. 59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0 mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, P < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs.","datePublished":"2023-06-20T00:00:00Z","dateModified":"2023-06-20T00:00:00Z","pageStart":"1","pageEnd":"11","license":"http://creativecommons.org/publicdomain/zero/1.0/","sameAs":"https://doi.org/10.1186/s13049-023-01095-9","keywords":["Veno-arterial carbon dioxide tension difference","Venous oxygen saturation","Lactate","Tissue hypoxia","Severe trauma","Hemorrhagic shock","Emergency Medicine","Traumatic Surgery"],"image":["https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig1_HTML.png","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig2_HTML.png","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig3_HTML.png"],"isPartOf":{"name":"Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine","issn":["1757-7241"],"volumeNumber":"31","@type":["Periodical","PublicationVolume"]},"publisher":{"name":"BioMed Central","logo":{"url":"https://www.springernature.com/app-sn/public/images/logo-springernature.png","@type":"ImageObject"},"@type":"Organization"},"author":[{"name":"Marie Werner","url":"http://orcid.org/0000-0001-9019-3122","affiliation":[{"name":"AP-HP, Université Paris-Saclay, Équipe DYNAMIC, Inserm UMR_S999","address":{"name":"Service d’Anesthésie Réanimation Chirurgicale, DMU 12 Anesthésie Réanimation Chirurgicale Médecine Péri-Opératoire et Douleur, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Équipe DYNAMIC, Inserm UMR_S999, Le Kremlin-Bicêtre, France","@type":"PostalAddress"},"@type":"Organization"}],"email":"marie.werner@aphp.fr","@type":"Person"},{"name":"Benjamin Bergis","affiliation":[{"name":"AP-HP, Université Paris-Saclay, Équipe DYNAMIC, Inserm UMR_S999","address":{"name":"Service d’Anesthésie Réanimation Chirurgicale, DMU 12 Anesthésie Réanimation Chirurgicale Médecine Péri-Opératoire et Douleur, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Équipe DYNAMIC, Inserm UMR_S999, Le Kremlin-Bicêtre, France","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Pierre-Etienne Leblanc","affiliation":[{"name":"AP-HP","address":{"name":"Service d’Anesthésie Réanimation Chirurgicale, DMU 12 Anesthésie Réanimation Chirurgicale Médecine Péri-Opératoire et Douleur, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Lucille Wildenberg","affiliation":[{"name":"AP-HP","address":{"name":"Service d’Anesthésie Réanimation Chirurgicale, DMU 12 Anesthésie Réanimation Chirurgicale Médecine Péri-Opératoire et Douleur, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Jacques Duranteau","affiliation":[{"name":"AP-HP, Université Paris-Saclay, Équipe DYNAMIC, Inserm UMR_S999","address":{"name":"Service d’Anesthésie Réanimation Chirurgicale, DMU 12 Anesthésie Réanimation Chirurgicale Médecine Péri-Opératoire et Douleur, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Équipe DYNAMIC, Inserm UMR_S999, Le Kremlin-Bicêtre, France","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Bernard Vigué","affiliation":[{"name":"AP-HP","address":{"name":"Service d’Anesthésie Réanimation Chirurgicale, DMU 12 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data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Marie-Werner-Aff1" data-author-popup="auth-Marie-Werner-Aff1" data-author-search="Werner, Marie" data-corresp-id="c1">Marie Werner<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0001-9019-3122"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0001-9019-3122</a></span><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Benjamin-Bergis-Aff1" data-author-popup="auth-Benjamin-Bergis-Aff1" data-author-search="Bergis, Benjamin">Benjamin Bergis</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Pierre_Etienne-Leblanc-Aff2" data-author-popup="auth-Pierre_Etienne-Leblanc-Aff2" data-author-search="Leblanc, Pierre-Etienne">Pierre-Etienne Leblanc</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Lucille-Wildenberg-Aff2" data-author-popup="auth-Lucille-Wildenberg-Aff2" data-author-search="Wildenberg, Lucille">Lucille Wildenberg</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Jacques-Duranteau-Aff1" data-author-popup="auth-Jacques-Duranteau-Aff1" data-author-search="Duranteau, Jacques">Jacques Duranteau</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Bernard-Vigu_-Aff2" data-author-popup="auth-Bernard-Vigu_-Aff2" data-author-search="Vigué, Bernard">Bernard Vigué</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup> & </li><li class="c-article-author-list__show-more" aria-label="Show all 7 authors for this article" title="Show all 7 authors for this article">…</li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Anatole-Harrois-Aff1" data-author-popup="auth-Anatole-Harrois-Aff1" data-author-search="Harrois, Anatole">Anatole Harrois</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup> </li></ul><button aria-expanded="false" class="c-article-author-list__button"><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-down-medium"></use></svg><span>Show authors</span></button> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine</i></a> <b data-test="journal-volume"><span class="u-visually-hidden">volume</span> 31</b>, Article number: <span data-test="article-number">31</span> (<span data-test="article-publication-year">2023</span>) <a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">1958 <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">11 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/10.1186/s13049-023-01095-9/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </div> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Background</h3><p>Veno-arterial carbon dioxide tension difference (ΔPCO<sub>2</sub>) and mixed venous oxygen saturation (SvO<sub>2</sub>) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO<sub>2</sub> (ΔPCO<sub>2 fem</sub>) and SvO<sub>2</sub> (SvO<sub>2 fem</sub>) could predict the need for red blood cell (RBC) transfusion following severe trauma.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Methods</h3><p>We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO<sub>2 fem,</sub> SvO<sub>2 fem</sub> and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBC<sub>H6</sub>) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Results</h3><p>59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBC<sub>H6</sub> and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO<sub>2 fem</sub> was 9.1 ± 6.0 mmHg, SvO<sub>2 fem</sub> 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO<sub>2 fem</sub> was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, <i>P</i> = 0.003) and SvO<sub>2 fem</sub> was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, <i>P</i> < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBC<sub>H6</sub> were 8.1 mmHg for ΔPCO<sub>2 fem</sub> and 63% for SvO<sub>2 fem</sub>. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO<sub>2 fem</sub> and 63% for SvO<sub>2 fem</sub>. Blood lactate was not predictive of pRBC<sub>H6</sub> or the need for a hemostatic procedure.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Conclusion</h3><p>In severe trauma patients, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs.</p></div></div></section> <section data-title="Background"><div class="c-article-section" id="Sec2-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec2">Background</h2><div class="c-article-section__content" id="Sec2-content"><p>Severe trauma remains the leading cause of death before the age of 50 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 201; 390(10100):1151–210." href="/articles/10.1186/s13049-023-01095-9#ref-CR1" id="ref-link-section-d341416928e891">1</a>]. Approximately 40% of trauma deaths involve hemorrhagic shock and are possibly preventable through damage control resuscitation and early bleeding control [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="Dutton RP, Stansbury LG, Leone S, Kramer E, Hess JR, Scalea TM. Trauma mortality in mature trauma systems: are we doing better? An analysis of trauma mortality patterns, 1997–2008. J Trauma. 2010;69(3):620–6." href="/articles/10.1186/s13049-023-01095-9#ref-CR2" id="ref-link-section-d341416928e894">2</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Drake SA, Holcomb JB, Yang Y, Thetford C, Myers L, Brock M, et al. Establishing a regional trauma preventable/potentially preventable death rate. Ann Surg. 2020;271(2):375–82." href="/articles/10.1186/s13049-023-01095-9#ref-CR3" id="ref-link-section-d341416928e897">3</a>]. Hemorrhage-induced hypovolemia leads to a drop in cardiac output (CO) responsible for tissue hypoperfusion and impaired oxygen delivery to the organs. When the adaptive mechanisms to hypovolemia are overwhelmed and can no longer compensate for the decrease in oxygen delivery, alterations of cellular homeostasis may ultimately lead to refractory shock and multiorgan dysfunction [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 4" title="Rixen D, Siegel JH. Bench-to-bedside review: oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock. Crit Care. 2005;9(5):441–53." href="/articles/10.1186/s13049-023-01095-9#ref-CR4" id="ref-link-section-d341416928e900">4</a>]. It is therefore necessary to identify patients with severe blood loss as early as possible in order to quickly start appropriate resuscitation.</p><p>At the initial phase of severe trauma management, CO monitoring is not readily available. Several biomarkers have been proposed to assess the adequacy between oxygen delivery and demand in these conditions. Thus, admission lactate has been shown to be predictive of severe hemorrhage associated with massive transfusion [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 5" title="Régnier MA, Raux M. Prognostic significance of blood lactate and lactate clearance in trauma patients. Anesthesiology. 2012;117(6):1276–88." href="/articles/10.1186/s13049-023-01095-9#ref-CR5" id="ref-link-section-d341416928e906">5</a>]. However, during hemorrhage, blood lactate increases only beyond a critical threshold of oxygen delivery when cell anaerobic metabolism is triggered to maintain ATP production. Lactate production therefore only rises when blood loss gets significant [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 6" title="Van der Linden P, Rausin I, Deltell A, Bekrar Y, Gilbart E, Bakker J, et al. Detection of tissue hypoxia by arteriovenous gradient for PCO2 and pH in anesthetized dogs during progressive hemorrhage. Anesth Analg. 1995;80(2):269–75." href="/articles/10.1186/s13049-023-01095-9#ref-CR6" id="ref-link-section-d341416928e909">6</a>]. Other metabolic parameters have been proposed to assess the adequacy between oxygen demand and supply in different critical conditions such as sepsis and major surgery. These parameters include the venous to arterial carbon dioxide gradient (ΔPCO<sub>2</sub>) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 7" title="Mallat J, Lazkani A, Lemyze M, Pepy F, Meddour M, Gasan G, et al. Repeatability of blood gas parameters, PCO2 gap, and PCO2 gap to arterial-to-venous oxygen content difference in critically ill adult patients. Medicine (Baltimore). 2015;94(3):e415." href="/articles/10.1186/s13049-023-01095-9#ref-CR7" id="ref-link-section-d341416928e914">7</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Futier E, Robin E, Jabaudon M, Guerin R, Petit A, Bazin JE, et al. Central venous O2 saturation and venous-to-arterial CO2 difference as complementary tools for goal-directed therapy during high-risk surgery. Crit Care. 2010;14(5):R193." href="/articles/10.1186/s13049-023-01095-9#ref-CR8" id="ref-link-section-d341416928e917">8</a>] and venous oxygen saturation (SvO<sub>2</sub>) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 9" title="Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED. Changes in central venous saturation after major surgery, and association with outcome. Crit Care. 2005;9(6):R694-699." href="/articles/10.1186/s13049-023-01095-9#ref-CR9" id="ref-link-section-d341416928e923">9</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 10" title="Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368–77." href="/articles/10.1186/s13049-023-01095-9#ref-CR10" id="ref-link-section-d341416928e926">10</a>] but none of them has been studied in severe trauma patients. A drop in CO is responsible for a decrease in tissue blood flow leading to venous carbon dioxide accumulation and an increase in the fraction of extracted oxygen that cause an increase in ΔPCO<sub>2</sub> [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 11" title="Cuschieri J, Rivers EP, Donnino MW, Katilius M, Jacobsen G, Nguyen HB, et al. Central venous-arterial carbon dioxide difference as an indicator of cardiac index. Intensive Care Med. 2005;31(6):818–22." href="/articles/10.1186/s13049-023-01095-9#ref-CR11" id="ref-link-section-d341416928e931">11</a>] and a decrease in SvO<sub>2</sub> respectively [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 12" title="Lee J, Wright F, Barber R, Stanley L. Central venous oxygen saturation in shock: a study in man. Anesthesiology. 1972;36(5):472–8." href="/articles/10.1186/s13049-023-01095-9#ref-CR12" id="ref-link-section-d341416928e937">12</a>].</p><p>Femoral arterial and central venous catheters are commonly inserted during initial management of severe trauma patients in the trauma bay [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 13" title="Hamada SR, Fromentin M, Ronot M, Gauss T, Harrois A, Duranteau J, et al. Femoral arterial and central venous catheters in the trauma resuscitation room. Injury. 2018;49(5):927–32." href="/articles/10.1186/s13049-023-01095-9#ref-CR13" id="ref-link-section-d341416928e943">13</a>]. They make venous and arterial blood gas available to appraise the venous to arterial difference in CO<sub>2</sub> (ΔPCO<sub>2 fem</sub>) as well as femoral venous oxygen saturation (SvO<sub>2 fem</sub>).</p><p>The aim of the present study was to assess the ability of ΔPCO<sub>2 fem</sub>, SvO<sub>2 fem</sub> and arterial blood lactate to predict transfusion of red blood cells (RBC) over the first hours following severe trauma.</p></div></div></section><section data-title="Methods"><div class="c-article-section" id="Sec3-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec3">Methods</h2><div class="c-article-section__content" id="Sec3-content"><h3 class="c-article__sub-heading" id="Sec4">Study design</h3><p>This observational, prospective and single-centre study was conducted in the surgical Intensive Care Unit of Bicêtre Hospital, an academic level-1 trauma center, from September 2015 to May 2020. This hospital provides 24-h availability of all essential trauma specialties, staff and equipment for trauma patient care. This study was approved by the ethics committee (“Comité de Protection des Personnes”) of the hospital (SC13-014 RCB: 2013-A01171-44) with waiver of participant consent. Patients or relatives were informed and we obtained confirmation of non-objection to data use.</p><h3 class="c-article__sub-heading" id="Sec5">Study population</h3><p>Patients over 18, admitted from the trauma scene, with an Injury Severity Score (ISS) greater than 15, and for whom initial management in the trauma room required the insertion of an arterial and a venous catheter at the femoral site, were included.</p><p>Pregnant women, patients with NYHA III or IV heart failure or chronic kidney disease (clearance < 30 ml/min) and patients with lower limb amputation or severe crush injury on the same side the femoral catheters were inserted were not included in the study.</p><h3 class="c-article__sub-heading" id="Sec6">Clinical management</h3><p>Following the emergency call, a physician-staffed mobile intensive care unit was sent to the trauma scene. After clinical assessment and medical care adjusted to trauma severity, patients were transported to the study center. Upon arrival in the trauma room, the insertion of femoral catheters was decided based on the patient’s history, clinical examination, and FAST ultrasound results, at the discretion of the clinician in charge as detailed elsewhere [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 13" title="Hamada SR, Fromentin M, Ronot M, Gauss T, Harrois A, Duranteau J, et al. Femoral arterial and central venous catheters in the trauma resuscitation room. Injury. 2018;49(5):927–32." href="/articles/10.1186/s13049-023-01095-9#ref-CR13" id="ref-link-section-d341416928e990">13</a>]. Briefly, the catheter lines were prepared in a sterile manner before patients’ arrival. Arterial (5 Fr, 11 cm) and venous femoral catheters (7 Fr, 20 cm) were simultaneously inserted by a trained resident under supervision of the trauma leader (consultant). The decision to transfuse was made by the physician in charge, based on his evaluation of the patient’s clinical situation using standard parameters (including clinical signs of shock, positive FAST ultrasound or obvious external hemorrhage and bed-side measurement of hemoglobin level) and blinded to the ΔPCO<sub>2 fem</sub>, SvO<sub>2 fem</sub> results.</p><h3 class="c-article__sub-heading" id="Sec7">Data collection</h3><p>For each patient, demographics, past medical history, trauma characteristics, pre-hospital management data such as time to hospital admission, initial Glasgow Coma Scale (GCS) score, minimum systolic blood pressure, peripheral oxygen saturation, maximum heart rate, need for mechanical ventilation, volume of fluid resuscitation, catecholamines use were collected. We also reported the following scores: Injury Severity Score (ISS) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 14" title="Baker SP, O’Neill B, Haddon W, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974;14(3):187–96." href="/articles/10.1186/s13049-023-01095-9#ref-CR14" id="ref-link-section-d341416928e1005">14</a>], details of injuries for each organ (Abbreviated Injury Scale 2015, AIS) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 15" title="Association for the Advancement of Automotive Medicine. The Abbreviated Injury Scale 2015 revision. 2015." href="/articles/10.1186/s13049-023-01095-9#ref-CR15" id="ref-link-section-d341416928e1008">15</a>] and simplified acute physiology score (SAPS II) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 16" title="Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270(24):2957–63." href="/articles/10.1186/s13049-023-01095-9#ref-CR16" id="ref-link-section-d341416928e1011">16</a>]. Severe organ injury was defined by an AIS for the correspondent organ over 2. On hospital admission, mean arterial blood pressure, heart rate, peripheral oxygen saturation, laboratory parameters (hemoglobin, prothrombin time, fibrinogen, myoglobin) were reported. Fluid administration, dose of catecholamines, transfusion therapy (type of product and amount) and hemostatic procedures were collected during the first 6 h of admission. The following outcome variables were also reported: length of mechanical ventilation, length of intensive care unit (ICU) stay and hospital mortality.</p><h3 class="c-article__sub-heading" id="Sec8">Blood gas measurement</h3><p>Venous and arterial blood gas were sampled from femoral catheters at insertion and regularly during the first 24 h, between 4 and 8 h from ICU admission (H6), 10 and 14 h from ICU admission (H12) 20 and 26 h from ICU admission (H24). pH, arterial (PaCO<sub>2fem</sub>) and femoral venous carbon dioxide partial pressure (PvCO<sub>2fem</sub>), arterial oxygen partial pressure (PaO<sub>2</sub>), venous oxygen saturation (SvO<sub>2fem</sub>), arterial oxygen saturation (SaO<sub>2</sub>)<sub>,</sub> hemoglobin concentration and blood lactate were measured on both samples using a point-of-care blood gases analyzer (ABL 800, Radiometer). The femoral venous to arterial difference in carbon dioxide pressure (ΔPCO<sub>2 fem</sub>) was calculated as femoral PvCO<sub>2</sub>–PaCO<sub>2</sub>.</p><h3 class="c-article__sub-heading" id="Sec9">Outcome</h3><p>The primary outcome of interest was the transfusion of at least one pack of RBC during the first six hours of admission (pRBC<sub>H6</sub>). The secondary outcome was the need for an emergency hemostatic procedure. It was defined as performing angioembolization or hemostatic surgery within the first six hours of management from admission. Orthopedic surgery for fracture osteosynthesis was not considered as a hemostatic procedure.</p><p>There is no data regarding ΔPCO<sub>2 fem</sub> and SvO<sub>2fem</sub> in trauma patients. Since trauma patients present a wide variety of traumatic injuries, we considered that a sample of 60 patients would be representative for this exploratory study.</p><h3 class="c-article__sub-heading" id="Sec10">Statistical analysis</h3><p>Qualitative variables were expressed as counts (proportions). Quantitative variables were expressed as mean (SD) or median (25th–75th interquartile range) according to their distributions. Correlations between blood lactate, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> at admission were analyzed by Pearson correlation.</p><p>In the overall population, volumes of pRBC<sub>H6</sub> transfused were reported according to quartile distribution of blood lactate, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub>. Then, patients were separated into two groups according to whether they had been transfused with pRBC<sub>H6</sub> or not. Their characteristics were compared by a Student t-test or a Mann–Whitney test for quantitative variables (according to data distribution) and by a Chi-square test for qualitative variables. Evolution of lactate, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> during the 24 first hours of admission were compared over time and between the two groups with a mixed-effect model. Time, group (transfusion, no transfusion) and interaction (time x group) were set as fixed effect and patient as random effect.</p><p>To evaluate the ability of admission lactate, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> to predict the need for pRBC<sub>H6</sub> transfusion or an emergency hemostatic procedure, receiver operating characteristic curves (ROCs) were built and their areas under the curve (AUC) were calculated. The best threshold for the prediction of pRBC<sub>H6</sub> transfusion or to predict the need for an emergency hemostatic procedure was defined as the value maximizing the Youden index (Y = Sensitivity + Specificity-1). Sensitivity, specificity, positive and negative predictive values (PPV and NPV), were reported for each variable. Two-sided level of significance was fixed at <i>P</i> = 0.05. Data were analyzed using Prism (GraphPad Software, San Diego, California, USA).</p></div></div></section><section data-title="Results"><div class="c-article-section" id="Sec11-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec11">Results</h2><div class="c-article-section__content" id="Sec11-content"><h3 class="c-article__sub-heading" id="Sec12">Population characteristics</h3><p>Seventy patients were enrolled in the study. Eleven patients were secondarily excluded because their ISS was less than 15, leaving 59 patients in the final analysis (Additional file <a data-track="click" data-track-label="link" data-track-action="supplementary material anchor" href="/articles/10.1186/s13049-023-01095-9#MOESM1">1</a>). Patients were 46 ± 20 years old and one third were women (17(29%)). Patients experienced predominantly blunt trauma (87%) with a median ISS of 26 (22–32). Median ICU length of stay was 10 (5–15.5) days and the overall hospital mortality was 26%. Two patients died in the first 24 h. The main characteristics of the population are presented in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/s13049-023-01095-9#Tab1">1</a>.</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-1"><figure><figcaption class="c-article-table__figcaption"><b id="Tab1" data-test="table-caption">Table 1 General characteristics in the overall population and in both transfused and non-transfused patients</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/articles/10.1186/s13049-023-01095-9/tables/1" aria-label="Full size table 1"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec13">Incidence of transfusion</h3><p>Over the first six hours of admission, 28 patients (47%) received at least one pack of RBC. The characteristics of transfused and non-transfused patients are shown in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/s13049-023-01095-9#Tab1">1</a>. Transfused and non-transfused patients were similar with regard to age, gender, SAPSII, type of trauma and on-scene hemodynamic parameters. Transfused patients presented more severe abdominal (43% vs. 10%, <i>P</i> = 0.006) and pelvic trauma (54% vs. 29%, <i>P</i> = 0.020), but they had significantly less traumatic head injuries (28.6% vs. 64.5%, <i>P</i> = 0.006) than non-transfused patients.</p><p>Mean blood pressure at hospital admission was significantly lower in the transfused group (<i>P</i> = 0.020). The given volume of crystalloids (<i>P</i> < 0.001) and colloids (<i>P</i> = 0.020) over the first six hours of management were significantly greater in patients who got transfused. Nineteen patients (67.8%) required an emergency hemostatic procedure in the transfused group and only 2 (6.5%) in the non-transfused group (<i>P</i> < 0.001). Mortality was not different between the two groups (<i>P</i> = 0.060) (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/s13049-023-01095-9#Tab1">1</a>).</p><h3 class="c-article__sub-heading" id="Sec14">Blood gas analysis</h3><p>In the whole cohort, blood lactate was 2.7 ± 1.9 mmol/l, ΔPCO<sub>2 fem</sub> was 9.1 ± 6.0 mmHg and SvO<sub>2 fem</sub> was 61.5 ± 21.6% on admission. As shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/s13049-023-01095-9#Fig1">1</a>, volume of pRBC<sub>H6</sub> was associated with a greater ΔPCO<sub>2 fem</sub> or blood lactate level and a lower SvO<sub>2 fem</sub>. Volume of pRBC<sub>H6</sub> transfused was larger when ΔPCO<sub>2 fem</sub> was greater than 13 mmHg, SvO<sub>2 fem</sub> was less than 50% or blood lactate was greater than 3.5 mmol/l (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/s13049-023-01095-9#Fig1">1</a>).</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-1" data-title="Fig. 1"><figure><figcaption><b id="Fig1" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 1</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/articles/10.1186/s13049-023-01095-9/figures/1" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig1_HTML.png?as=webp"><img aria-describedby="Fig1" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig1_HTML.png" alt="figure 1" loading="lazy" width="685" height="507"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-1-desc"><p>Volumes of red blood cells transfused during the first six hours of admission. Volumes are shown according to quartile distribution of <b>A</b> ΔPCO<sub>2 fem</sub>. <b>B</b> SvO<sub>2 fem</sub> and <b>C</b> lactate. All data are reported as mean ± SD. ΔPCO<sub>2 fem</sub> femoral venous-arterial difference in carbon dioxide pressure. SvO<sub>2 fem</sub> femoral venous oxygen saturation</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/articles/10.1186/s13049-023-01095-9/figures/1" data-track-dest="link:Figure1 Full size image" aria-label="Full size image figure 1" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>At admission, in the overall population ΔPCO<sub>2 fem</sub> was at its highest level and then decreased to a mean minimal value at H24 of 5.4 ± 3.5 mmHg. SvO<sub>2 fem</sub> was the lowest at admission and then plateaued from H6 with a mean value of 68.5 ± 16.8%. Maximum lactate was reached at H6 (2.8 ± 2.1 mmol/) and then decreased with a mean value of 2.0 ± 1.9 mmol/l at H24 (Additional file <a data-track="click" data-track-label="link" data-track-action="supplementary material anchor" href="/articles/10.1186/s13049-023-01095-9#MOESM1">1</a>). At admission, ΔPCO<sub>2 fem</sub> (r = 0.48; <i>P</i> < 0.001) and SvO<sub>2 fem</sub> (r = 0.40; <i>P</i> < 0.004) were correlated with lactate and they were correlated together (r = 0.63; <i>P</i> < 0.001).</p><p>At admission, ΔPCO<sub>2 fem</sub> (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg; <i>P</i> = 0.003), SvO<sub>2 fem</sub> (50.0 ± 23.0% vs. 71.8 ± 14.1%; <i>P</i> < 0.001) and lactate (3.3 ± 2.4 mmol/l vs. 2.2 ± 1.3 mmol/l; <i>P</i> = 0.04) were significantly different in transfused compared to non-transfused patients (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/s13049-023-01095-9#Tab2">2</a>).</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-2"><figure><figcaption class="c-article-table__figcaption"><b id="Tab2" data-test="table-caption">Table 2 Hemodynamic variables in the overall population and in transfused and non-transfused patients</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/articles/10.1186/s13049-023-01095-9/tables/2" aria-label="Full size table 2"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Over the first 24 h, ΔPCO<sub>2 fem</sub> decreased significantly and was statistically different between transfused and non-transfused groups without interaction between time and groups (time effect, <i>P</i> = 0.002; transfusion effect, <i>P</i> = 0.008; time x transfusion effect, <i>P</i> = 0.1). SvO<sub>2 fem</sub> remained stable in the non-transfused group, over the first 24 h, while it significantly increased over time in the transfused group (time effect, <i>P</i> = 0.04; transfusion effect, <i>P</i> = 0.02; time x transfusion effect, <i>P</i> < 0.001). In the transfused group, blood lactate peaked at H6 and then decreased over the first 24 h while it decreased, from admission to H24, in the non-transfused group. Blood lactate was different between non-transfused and transfused patients without interaction between time and groups (time effect, <i>P</i> = 0.01; transfusion effect, <i>P</i> = 0.007; time x transfusion effect, <i>P</i> = 0.7) (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/s13049-023-01095-9#Fig2">2</a> and Additional files <a data-track="click" data-track-label="link" data-track-action="supplementary material anchor" href="/articles/10.1186/s13049-023-01095-9#MOESM2">2</a> and <a data-track="click" data-track-label="link" data-track-action="supplementary material anchor" href="/articles/10.1186/s13049-023-01095-9#MOESM3">3</a>).</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-2" data-title="Fig. 2"><figure><figcaption><b id="Fig2" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 2</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/articles/10.1186/s13049-023-01095-9/figures/2" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig2_HTML.png?as=webp"><img aria-describedby="Fig2" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig2_HTML.png" alt="figure 2" loading="lazy" width="685" height="456"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-2-desc"><p>Evolution during the first 24 h of hemodynamic variables in transfused and non-transfused patients. <b>A</b> ΔPCO<sub>2 fem</sub>. <b>B</b> SvO<sub>2 fem</sub> and <b>C</b> lactate. All data are reported as mean ± SD. *<i>P</i> < 0.05; **<i>P</i> < 0.005; ***<i>P</i> < 0.001. Parameters were measured at hospital admission and over the first 24 h. ΔPCO<sub>2 fem</sub> femoral venous-arterial difference in carbon dioxide pressure. SvO<sub>2 fem</sub> femoral venous oxygen saturation</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/articles/10.1186/s13049-023-01095-9/figures/2" data-track-dest="link:Figure2 Full size image" aria-label="Full size image figure 2" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec15">Transfusion prediction</h3><p>The abilities of admission ΔPCO<sub>2 fem</sub>, SvO<sub>2 fem</sub> and blood lactate to predict the need for pRBC<sub>H6</sub> transfusion and the need for a hemostatic procedure during the first six hours of admission are presented in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/s13049-023-01095-9#Fig3">3</a> and Additional file <a data-track="click" data-track-label="link" data-track-action="supplementary material anchor" href="/articles/10.1186/s13049-023-01095-9#MOESM4">4</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-3" data-title="Fig. 3"><figure><figcaption><b id="Fig3" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 3</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/articles/10.1186/s13049-023-01095-9/figures/3" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig3_HTML.png?as=webp"><img aria-describedby="Fig3" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_Fig3_HTML.png" alt="figure 3" loading="lazy" width="685" height="618"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-3-desc"><p>ROC curves for prediction of RBC transfusion and hemostatic procedure by ΔPCO<sub>2fem</sub> and SvO<sub>2fem</sub>. <b>A</b> ROC curve for prediction of pRBC<sub>H6</sub> by ΔPCO<sub>2 fem</sub> at admission. <b>B</b> ROC curve for prediction of pRBC<sub>H6</sub> by SvO<sub>2 fem</sub> at admission. <b>C</b> ROC curve for prediction of hemostatic procedure during the first 6 h of admission by ΔPCO<sub>2 fem</sub> at admission. <b>D</b> ROC curve for prediction of hemostatic procedure during the first 6 h of admission by SvO<sub>2 fem</sub> at admission. AUC area under the curve. ΔPCO<sub>2 fem</sub> femoral venous-arterial difference in carbon dioxide pressure. pRBC<sub>H6</sub> transfusion of at least 1 pack of red blood cell during the first 6 h of admission. ROC Receiver operating characteristics. SvO<sub>2 fem</sub> femoral venous oxygen saturation</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/articles/10.1186/s13049-023-01095-9/figures/3" data-track-dest="link:Figure3 Full size image" aria-label="Full size image figure 3" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Admission ΔPCO<sub>2 fem</sub> significantly predicted pRBC<sub>H6</sub> transfusion with an AUC of 0.71 (CI95% 0.57–0.86; <i>P</i> = 0.008) and SvO<sub>2 fem</sub> significantly predicted pRBC<sub>H6</sub> transfusion with an AUC of 0.77 (CI95% 0.64–0.91; <i>P</i> < 0.001). At admission, the optimal thresholds of ΔPCO<sub>2 fem</sub> to predict the need for pRBC<sub>H6</sub> transfusion was 8.1 mmHg and the optimal threshold of SvO<sub>2 fem</sub> to predict the need for pRBC<sub>H6</sub> transfusion was 63%. The predictive performances of ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> are given in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/s13049-023-01095-9#Tab3">3</a>.</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-3"><figure><figcaption class="c-article-table__figcaption"><b id="Tab3" data-test="table-caption">Table 3 Predictive performances of hemodynamic variables for transfusion of red blood cells during the first six hours of admission</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/articles/10.1186/s13049-023-01095-9/tables/3" aria-label="Full size table 3"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Admission ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> significantly predicted the need for an emergency hemostatic procedure with respective AUCs of 0.74 (CI95% 0.58–0.90, <i>P</i> = 0.02) and 0.72 (CI95% 0.57–0.87, <i>P</i> = 0.01). A threshold of 5.9 mmHg for ΔPCO<sub>2 fem</sub> and 63% for SvO<sub>2 fem</sub> at admission were the optimal values to predict the need for an emergency hemostatic procedure.</p><p>Admission blood lactate did not significantly predict the need for pRBC<sub>H6</sub> transfusion (AUC = 0.64 CI95% 0.49–0.79; <i>P</i> = 0.07) or the need for a hemostatic procedure (AUC = 0.60 CI95% 0.42–0.78; <i>P</i> = 0.3) in the first six hours of admission.</p></div></div></section><section data-title="Discussion"><div class="c-article-section" id="Sec16-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec16">Discussion</h2><div class="c-article-section__content" id="Sec16-content"><p>We performed this prospective and observational study to assess the ability of ΔPCO<sub>2 fem</sub>, SvO<sub>2 fem</sub> and arterial blood lactate to predict transfusion of red blood cells over the first six hours (pRBC<sub>H6</sub>) following severe trauma. We found that the difference in femoral venous to arterial PCO<sub>2</sub> (ΔPCO<sub>2 fem</sub>) and venous oxygen saturation (SvO<sub>2 fem</sub>) at admission were predictive of RBC transfusion within the first six hours of admission, with respective optimal thresholds of 8.1 mmHg and 63%. Second, we also found that ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> were predictive of an emergency hemostatic procedure. Third, though admission blood lactate correlated with the volume of transfused RBC over the first 6 h, it was neither predictive of pRBC<sub>H6</sub> transfusion nor predictive of an emergency hemostatic procedure. Fourth, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> normalized earlier than lactate after transfusion.</p><h3 class="c-article__sub-heading" id="Sec17">Relationship with previous studies</h3><p>Venous to arterial PCO<sub>2</sub> difference and venous O<sub>2</sub> saturation have hardly been studied in the setting of severe trauma. We found that admission ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> were predictive of pRBC<sub>H6</sub> transfusion. These results are consistent with studies carried out on animal models of hemorrhagic shock [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 17" title="Dubin A, Ferrara G, Kanoore Edul VS, Martins E, Canales HS, Canullán C, et al. Venoarterial PCO2-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study. Ann Intensive Care. 2017;7(1):65." href="/articles/10.1186/s13049-023-01095-9#ref-CR17" id="ref-link-section-d341416928e3143">17</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Williams KB, Christmas AB, Heniford BT, Sing RF, Messick J. Arterial versus venous blood gas differences during hemorrhagic shock. World J Crit Care Med. 2014;3(2):55–60." href="/articles/10.1186/s13049-023-01095-9#ref-CR18" id="ref-link-section-d341416928e3146">18</a>] where incremental blood loss led to a progressive increase in ΔPCO<sub>2</sub> and decrease in SvO<sub>2</sub>. According to Fick equation, generated CO<sub>2</sub> (VCO<sub>2</sub>) equals the product of CO by the difference between mixed venous and arterial CO<sub>2</sub> contents (Cv-aCO<sub>2</sub>) and is constant in aerobic and anaerobic conditions. ΔPCO<sub>2</sub> has been shown to be linearly related to Cv-aCO<sub>2</sub>. Thus, increase in ΔPCO<sub>2</sub> during hemorrhage results from a drop in CO leading to CO<sub>2</sub> stagnation at tissue level with an increase in venous CO<sub>2</sub>. During hemorrhage, an increase in ΔPCO<sub>2</sub> thus reflects the inadequacy between CO and metabolic activity. Hemorrhage also results in a decrease in oxygen transport to tissues responsible for an increase in oxygen extraction ratio and therefore a decrease in SvO<sub>2</sub>. Thus, increased ΔPCO<sub>2 fem</sub> and decreased SvO<sub>2 fem</sub> likely reflect the decrease in tissue blood flow to the lower limbs related to the magnitude of blood loss in trauma patients.</p><p>We measured femoral ΔPCO<sub>2</sub> and SvO<sub>2</sub> (ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub>) while most clinical and experimental studies reported about central ΔPCO<sub>2</sub> and ScvO<sub>2</sub>. Normal central ΔPCO<sub>2</sub> ranges from 2 to 5 mmHg [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 19" title="Groeneveld AB. Interpreting the venous-arterial PCO2 difference. Crit Care Med. 1998;26(6):979–80." href="/articles/10.1186/s13049-023-01095-9#ref-CR19" id="ref-link-section-d341416928e3199">19</a>]. In a study conducted in 14 healthy volunteers, ΔPCO<sub>2 fem</sub> ranged from 2 to 4 mmHg while volunteers were passively cycling [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Gojda J, Waldauf P, Hrušková N, Blahutová B, Krajčová A, Urban T, et al. Lactate production without hypoxia in skeletal muscle during electrical cycling: Crossover study of femoral venous-arterial differences in healthy volunteers. PLoS ONE. 2019;14(3):e0200228." href="/articles/10.1186/s13049-023-01095-9#ref-CR20" id="ref-link-section-d341416928e3204">20</a>]. Several studies reported conflicting differences between ScvO<sub>2</sub> and SvO<sub>2 fem</sub> with bias of 2.7 ± 7.9% in patients undergoing elective right heart catheterization [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 21" title="van Beest PA, van der Schors A, Liefers H, Coenen LGJ, Braam RL, Habib N, et al. Femoral venous oxygen saturation is no surrogate for central venous oxygen saturation. Crit Care Med. 2012;40(12):3196–201." href="/articles/10.1186/s13049-023-01095-9#ref-CR21" id="ref-link-section-d341416928e3212">21</a>] to bias of 2 to 8% in critical care patients [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 22" title="Marti YN, de Freitas FGR, de Azevedo RP, Leão M, Bafi AT, Machado FR. Is venous blood drawn from femoral access adequate to estimate the central venous oxygen saturation and arterial lactate levels in critically ill patients? Rev Bras Ter Intensiva. 2015;27(4):340–6." href="/articles/10.1186/s13049-023-01095-9#ref-CR22" id="ref-link-section-d341416928e3215">22</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 23" title="Davison DL, Chawla LS, Selassie L, Jones EM, McHone KC, Vota AR, et al. Femoral-based central venous oxygen saturation is not a reliable substitute for subclavian/internal jugular-based central venous oxygen saturation in patients who are critically ill. Chest. 2010;138(1):76–83." href="/articles/10.1186/s13049-023-01095-9#ref-CR23" id="ref-link-section-d341416928e3218">23</a>]. However, though SvO<sub>2 fem</sub> is not a reliable surrogate of ScvO<sub>2</sub>, we found it to be more predictive of pRBC<sub>H6</sub> transfusion than admission ΔPCO<sub>2 fem</sub> or blood lactate.</p><p>Although there is a significant correlation between blood lactate, ΔPCO<sub>2 fem</sub>, SvO<sub>2 fem</sub>, these measurements are not interchangeable. Unlike what Régnier et al. reported, admission lactate was not found as a predictive marker of pRBC<sub>H6</sub> transfusion [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 5" title="Régnier MA, Raux M. Prognostic significance of blood lactate and lactate clearance in trauma patients. Anesthesiology. 2012;117(6):1276–88." href="/articles/10.1186/s13049-023-01095-9#ref-CR5" id="ref-link-section-d341416928e3239">5</a>]. However, we used a lower threshold (one pRBC<sub>H6</sub> as compared to massive transfusion defined by 6 pack of RBC in 24 h). ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> appeared thus to be more sensitive than blood lactate to predict hemorrhage requiring RBC transfusion. A hypothesis is that these two parameters are a direct reflection of tissue blood flow to the lower limbs while aerobic metabolism is still present [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 24" title="Vallet B, Teboul JL, Cain S, Curtis S. Venoarterial CO2 difference during regional ischemic or hypoxic hypoxia. J Appl Physiol. 2000;89(4):1317–21." href="/articles/10.1186/s13049-023-01095-9#ref-CR24" id="ref-link-section-d341416928e3249">24</a>], whereas blood lactate increases at a later stage of hemorrhage, when patient blood loss is more pronounced with concomitant triggering of anaerobic metabolism [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 6" title="Van der Linden P, Rausin I, Deltell A, Bekrar Y, Gilbart E, Bakker J, et al. Detection of tissue hypoxia by arteriovenous gradient for PCO2 and pH in anesthetized dogs during progressive hemorrhage. Anesth Analg. 1995;80(2):269–75." href="/articles/10.1186/s13049-023-01095-9#ref-CR6" id="ref-link-section-d341416928e3252">6</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 25" title="Cohen IL, Sheikh FM, Perkins RJ, Feustel PJ, Foster ED. Effect of hemorrhagic shock and reperfusion on the respiratory quotient in swine. Crit Care Med. 1995;23(3):545." href="/articles/10.1186/s13049-023-01095-9#ref-CR25" id="ref-link-section-d341416928e3255">25</a>]. Consistently with what has been shown in animals [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 6" title="Van der Linden P, Rausin I, Deltell A, Bekrar Y, Gilbart E, Bakker J, et al. Detection of tissue hypoxia by arteriovenous gradient for PCO2 and pH in anesthetized dogs during progressive hemorrhage. Anesth Analg. 1995;80(2):269–75." href="/articles/10.1186/s13049-023-01095-9#ref-CR6" id="ref-link-section-d341416928e3258">6</a>], following an active hemorrhage, it would seem that the drop in CO, responsible for peripheral vasoconstriction and a drop in blood flow to the lower limbs can be more rapidly detected by an elevation of ΔPCO<sub>2 fem</sub> and a decrease of SvO<sub>2 fem</sub> than using blood lactate level. Blood flow is indeed early reduced in musculo-cutaneous tissue (i.e. lower limbs) to preserve flow to the noble organs (i.e. heart, brain) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 26" title="Forsyth RP, Hoffbrand BI, Melmon KL. Redistribution of cardiac output during hemorrhage in the unanesthetized monkey. Circ Res. 1970;27(3):311–20." href="/articles/10.1186/s13049-023-01095-9#ref-CR26" id="ref-link-section-d341416928e3266">26</a>], which may explain the early increase in ΔPCO<sub>2 fem</sub> and decrease in SvO<sub>2fem</sub>.</p><p>It is interesting to note that patients did not present with the same injuries in the two groups. The transfused group presented mainly abdominal and pelvic injuries, more often responsible for hemorrhage, while the non-transfused group presented mainly intracranial injuries. Although mean ΔPCO<sub>2 fem</sub> was higher in the transfused group compared to the non-transfused group (11.6 vs. 6.8 mmHg), some patients had a high ΔPCO<sub>2 fem</sub> in the non-transfused group. These patients presented a severe head injury with an AIS head greater than 3, or had bowel perforation without hemorrhage and others had severe thoracic injuries with a hemo- or pneumothorax. In patients with no clinical or CT evidence of hemorrhage, the presence of a high ΔPCO<sub>2 fem</sub> should therefore lead to the search for another cause of cardiovascular dysfunction. Severely injured trauma patients can indeed present causes of shock other than hemorrhage like tamponade, peritonitis associated with bowel perforation, spinal cord injury but also neurogenic cardiovascular dysfunction reported in several studies in patients with severe head injury [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 27" title="Prathep S, Sharma D, Hallman M, Joffe A, Krishnamoorthy V, Mackensen GB, et al. Preliminary report on cardiac dysfunction after isolated traumatic brain injury. Crit Care Med. 2014;42(1):142–7." href="/articles/10.1186/s13049-023-01095-9#ref-CR27" id="ref-link-section-d341416928e3282">27</a>].</p><p>Consistent with what has been observed in animals, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> corrected more rapidly than lactate, which increased until H6 in the transfused group [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 25" title="Cohen IL, Sheikh FM, Perkins RJ, Feustel PJ, Foster ED. Effect of hemorrhagic shock and reperfusion on the respiratory quotient in swine. Crit Care Med. 1995;23(3):545." href="/articles/10.1186/s13049-023-01095-9#ref-CR25" id="ref-link-section-d341416928e3293">25</a>]. ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> are likely corrected in parallel with the improvement of tissue blood flow following transfusion, whereas hyperlactatemia is an unreliable marker of hypoxia and hypoperfusion. Indeed, lactate production is also a consequence of cellular dysoxia secondary to injury-induced inflammation and microcirculation alterations, frequently observed after severe trauma, despite tissue perfusion improvement [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 28" title="Tachon G, Harrois A, Tanaka S, Kato H, Huet O, Pottecher J, et al. Microcirculatory alterations in traumatic hemorrhagic shock. Crit Care Med. 2014;42(6):1433–41." href="/articles/10.1186/s13049-023-01095-9#ref-CR28" id="ref-link-section-d341416928e3301">28</a>]. Unrelated to tissue dysoxia, hyperlactatemia is also frequently observed in shock state, following aerobic glycolysis activation through catecholamine-dependent ß2-receptor stimulation [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 29" title="Levy B, Desebbe O, Montemont C, Gibot S. Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states. Shock. 2008;30(4):417–21." href="/articles/10.1186/s13049-023-01095-9#ref-CR29" id="ref-link-section-d341416928e3304">29</a>].</p><h3 class="c-article__sub-heading" id="Sec18">Implication of study findings</h3><p>Our findings imply that ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> are more sensitive than blood lactate to predict the need for early blood transfusion or hemostatic procedure, on admission of severe trauma patients. Seven patients (25%) who were transfused with RBC during the first six hours of management had indeed a high ΔPCO<sub>2 fem</sub> and/or a low SvO<sub>2 fem</sub> but a normal blood lactate. Moreover, the evolution of ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> over time may help to assess transfusion effectiveness to restore adequate tissue perfusion. Cardiac output monitoring using standard tools such as cardiac ultrasound or thermodilution are not available in the trauma bay during the initial phase, and macro-hemodynamic parameters such as heart rate and mean blood pressure are poorly correlated with CO during hemorrhagic shock states. Thus, in this study, we showed that ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> could be easily used to assess the adequation of tissue blood flow (i.e. to the lower limbs) with metabolic needs following severe trauma.</p><h3 class="c-article__sub-heading" id="Sec19">Strengths and limitations</h3><p>This study has several strengths. To our knowledge, this is the first study evaluating ΔPCO<sub>2</sub> and SvO<sub>2 fem</sub> in severe trauma patients and their capacities to predict early transfusion. Moreover, we provided new data on the level of ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> values in such patients. These results allowed us to propose alternative markers to assess the adequacy between tissue blood flow and metabolic needs in trauma patients.</p><p>This study also has several limitations. First, it is a single-centre study with a small sample-size, in patients who required the insertion of an arterial and a venous catheter at the femoral site which prevents generalization of these results. Indeed, only patients which ICU clinician judged, severe at hospital admission [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 13" title="Hamada SR, Fromentin M, Ronot M, Gauss T, Harrois A, Duranteau J, et al. Femoral arterial and central venous catheters in the trauma resuscitation room. Injury. 2018;49(5):927–32." href="/articles/10.1186/s13049-023-01095-9#ref-CR13" id="ref-link-section-d341416928e3351">13</a>], were included which make this study applicable only to these patients. Second, we studied ΔPCO<sub>2</sub> and SvO<sub>2</sub> at the femoral site which are not good surrogates of central ΔPCO<sub>2</sub> and ScvO<sub>2</sub>, considered as standards. However, we were able to report cut-off values for these markers at femoral site for transfusion prediction. Third we do not know the normal values for ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> at baseline but we highlighted significant differences in ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> according to the need for transfusion, reflecting the hemorrhage-induced drop in tissue blood flow and allowing to assess resuscitation efficacy over time. Nevertheless, additional studies will be necessary to determine the range of normal value of ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> at the femoral level. Finally, since SvO<sub>2</sub> is dependent on hemoglobin, its predictive value for red blood cell transfusion may have been overestimated by the effect of anemia in patients with severe hemorrage [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 30" title="Jain A, Shroff SG, Janicki JS, Reddy HK, Weber KT. Relation between mixed venous oxygen saturation and cardiac index. Nonlinearity and normalization for oxygen uptake and hemoglobin. Chest. 1991;99(6):1403–9." href="/articles/10.1186/s13049-023-01095-9#ref-CR30" id="ref-link-section-d341416928e3378">30</a>]. Moreover, due to the Haldane effect, it is possible that in the most severe patients with low hemoglobin level and significant metabolic acidosis, the ΔPCO<sub>2 fem</sub> may have been overestimated compared to veno-arterial CO<sub>2</sub> content (Cv-aCO<sub>2</sub>). Indeed, for the same level of Cv-aCO<sub>2</sub>, ΔPCO<sub>2</sub> increases in case of metabolic acidosis and anemia [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 31" title="Teboul JL, Scheeren T. Understanding the Haldane effect. Intensive Care Med. 2017;43(1):91–3." href="/articles/10.1186/s13049-023-01095-9#ref-CR31" id="ref-link-section-d341416928e3392">31</a>] making the relationship between the two values no longer linear. This was however observed at the late phase of hemorrhage, when bloodloss was major [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 17" title="Dubin A, Ferrara G, Kanoore Edul VS, Martins E, Canales HS, Canullán C, et al. Venoarterial PCO2-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study. Ann Intensive Care. 2017;7(1):65." href="/articles/10.1186/s13049-023-01095-9#ref-CR17" id="ref-link-section-d341416928e3395">17</a>] and, in a way, reflect the seriousness of hemorrhage which is consistent with what we expected to predict.</p></div></div></section><section data-title="Conclusion"><div class="c-article-section" id="Sec20-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec20">Conclusion</h2><div class="c-article-section__content" id="Sec20-content"><p>In severe trauma patients, ΔPCO<sub>2</sub> and SvO<sub>2</sub> measured at the femoral level at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. In this study, ΔPCO<sub>2 fem</sub> and SvO<sub>2 fem</sub> appear thus to be more sensitive to blood loss than lactate in patients requiring femoral venous and arterial catheters insertion, which might be of importance to assess the adequation of tissue blood flow with metabolic needs following severe trauma.</p></div></div></section> <section data-title="Availability of data and materials"><div class="c-article-section" id="availability-of-data-and-materials-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="availability-of-data-and-materials">Availability of data and materials</h2><div class="c-article-section__content" id="availability-of-data-and-materials-content"> <p>After publication, the data will be made available upon reasonable request from the corresponding author.</p> </div></div></section><section data-title="Abbreviations"><div class="c-article-section" id="abbreviations-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="abbreviations">Abbreviations</h2><div class="c-article-section__content" id="abbreviations-content"><dl class="c-abbreviation_list"><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>ΔPCO<sub>2</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Veno-arterial carbon dioxide tension difference</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>ΔPCO<sub>2 fem</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Femoral veno-arterial carbon dioxide tension difference</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>AIS:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Abbreviated Injury Scale 2015</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>CO:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Cardiac output</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>GCS:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Glasgow Coma Scale</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>Hb:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Hemoglobin</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>HR:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Heart rate</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>Ht:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Hematocrit</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>ICU:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Intensive care unit</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>ISS:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Injury severity score</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>MBP:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Mean blood pressure</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>PaCO<sub>2</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Arterial carbon dioxide partial pressure</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>PaO<sub>2</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Arterial oxygen partial pressure (PaO<sub>2</sub>)</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>pRBC<sub>H6</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Pack of red blood cell transfused over the first 6 h of admission</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>PvCO<sub>2</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Venous carbon dioxide partial pressure</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>PT:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Prothrombin time</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>RBC:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Red blood cells</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>ROC:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Receiver operating characteristics</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>SAPS:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Simplified Acute Physiology Score</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>SD:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Standard deviation</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>SBP:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Systolic blood pressure</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>SaO<sub>2</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Arterial oxygen saturation</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>SpO<sub>2</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Pulse oximeter oxygen saturation</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>SvO<sub>2</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Venous oxygen saturation</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>SvO<sub>2 fem</sub> :</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Femoral venous oxygen saturation</p> </dd></dl></div></div></section><div id="MagazineFulltextArticleBodySuffix"><section aria-labelledby="Bib1" data-title="References"><div class="c-article-section" id="Bib1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Bib1">References</h2><div 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MW performed the statistical data analysis, designed the figures and wrote the manuscript. MW and AH interpreted the data. AH revised the article critically. All authors were involved in collection of data, revised the article for important intellectual content and approved the version to be published.</p><h3 class="c-article__sub-heading" id="corresponding-author">Corresponding author</h3><p id="corresponding-author-list">Correspondence to <a id="corresp-c1" href="mailto:marie.werner@aphp.fr">Marie Werner</a>.</p></div></div></section><section data-title="Ethics declarations"><div class="c-article-section" id="ethics-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="ethics">Ethics declarations</h2><div class="c-article-section__content" id="ethics-content"> <h3 class="c-article__sub-heading" id="FPar1">Ethic approval and consent to participate</h3> <p>This study was approved by the ethics committee (“Comité de Protection des Personnes”) of the hospital (SC13-014 RCB: 2013-A01171-44) with waiver of participant consent. Patients or relatives were informed and we obtained confirmation of non-objection to data use.</p> <h3 class="c-article__sub-heading" id="FPar2">Consent for publication</h3> <p>All authors read and approved the manuscript for publication.</p> <h3 class="c-article__sub-heading" id="FPar3">Competing interests</h3> <p>The authors declare that they have no competing interests.</p> </div></div></section><section data-title="Additional information"><div class="c-article-section" id="additional-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="additional-information">Additional information</h2><div class="c-article-section__content" id="additional-information-content"><h3 class="c-article__sub-heading">Publisher's Note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></div></div></section><section data-title="Supplementary Information"><div class="c-article-section" id="Sec21-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec21">Supplementary Information</h2><div class="c-article-section__content" id="Sec21-content"><div data-test="supplementary-info"><div id="figshareContainer" class="c-article-figshare-container" data-test="figshare-container"></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM1"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="additional file 1" href="https://static-content.springer.com/esm/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_MOESM1_ESM.pdf" data-supp-info-image=""><b>Additional file 1</b></a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>. Flow-chart of study participants.</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM2"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="additional file 2." href="https://static-content.springer.com/esm/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_MOESM2_ESM.pdf" data-supp-info-image=""><b>Additional file 2.</b></a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p> Evolution of ΔPCO<sub>2 fem</sub>, SvO<sub>2 fem</sub> and lactate during the first 24 hours in the overall population. All data are reported as mean ± SD. Parameters were measured at hospital admission and over the first 24 hours. ΔPCO<sub>2 fem</sub> femoral venous-arterial difference in carbon dioxide pressure. SvO<sub>2 fem</sub> femoral venous oxygen saturation.</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM3"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="additional file 3" href="https://static-content.springer.com/esm/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_MOESM3_ESM.xlsx" data-supp-info-image=""><b>Additional file 3</b></a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>. Evolution of blood gas parameters during the 24 first hours of admission. Data are shown in the overall population in non-transfused and transfused patients. All data are reported as mean ± SD. Art pH arterial pH. H0 measurement at admission. H<sub>6</sub> measurement 6 hours after admission. H12 measurement 12 hours after admission. H<sub>2</sub>4 measurement 24 hours after admission. ΔPCO<sub>2</sub> fem femoral venous-arterial difference in carbon dioxide pressure. SvO<sub>2</sub> fem femoral venous oxygen saturation.</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM4"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="additional file 4" href="https://static-content.springer.com/esm/art%3A10.1186%2Fs13049-023-01095-9/MediaObjects/13049_2023_1095_MOESM4_ESM.pdf" data-supp-info-image=""><b>Additional file 4</b></a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>. ROC curves for prediction of red blood cell transfusion and hemostatic procedure by lactate. <b>a</b> ROC curve for prediction of pRBCH6 by lactate at admission. <b>b</b> ROC curve for prediction of hemostatic procedure during the first 6 hours of admission by lactate at admission. AUC area under the curve. pRBCH6 transfusion of at least 1 pack of red blood cell during the first 6 hours of admission. ROC Receiver operating characteristics.</p></div></div></div></div></div></section><section data-title="Rights and permissions"><div class="c-article-section" id="rightslink-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="rightslink">Rights and permissions</h2><div class="c-article-section__content" id="rightslink-content"> <p><b>Open Access</b> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. 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id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Werner, M., Bergis, B., Leblanc, PE. <i>et al.</i> Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study. <i>Scand J Trauma Resusc Emerg Med</i> <b>31</b>, 31 (2023). https://doi.org/10.1186/s13049-023-01095-9</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1186/s13049-023-01095-9?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" 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saturation</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Lactate&facet-discipline="Medicine%20%26%20Public%20Health"" data-track="click" data-track-action="view keyword" data-track-label="link">Lactate</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Tissue%20hypoxia&facet-discipline="Medicine%20%26%20Public%20Health"" data-track="click" data-track-action="view keyword" data-track-label="link">Tissue hypoxia</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Severe%20trauma&facet-discipline="Medicine%20%26%20Public%20Health"" data-track="click" data-track-action="view keyword" data-track-label="link">Severe trauma</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Hemorrhagic%20shock&facet-discipline="Medicine%20%26%20Public%20Health"" data-track="click" data-track-action="view keyword" data-track-label="link">Hemorrhagic 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