{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:33:54Z","timestamp":1793817234120,"version":"4.6.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Whether lactate clearance (LC) influences outcomes differently depending on the infection site in sepsis cases is not fully elucidated. Herein, we analyzed LC\u2019s clinical utility as a predictor of patient outcomes according to infection site. This retrospective study, conducted at two tertiary emergency critical care medical centers in Japan, included patients with sepsis or septic shock. The associations between infection site (lungs vs. other organs) and in-hospital mortality and ventilator-free days (VFDs) were evaluated using univariable and multivariate analyses. We assessed LC\u2019s ability to predict in-hospital mortality using the area under the receiver operating characteristic curve. Among 369 patients with sepsis, infection sites were as follows: lungs, 186 (50.4%); urinary tract, 45 (12.2%); abdomen, 102 (27.6%); and other, 36 (9.8%). Patients were divided into a pneumonia group or non-pneumonia group depending on their infection site. The pneumonia group displayed a higher in-hospital mortality than the non-pneumonia group (24.2% vs. 15.8%, <jats:italic>p<\/jats:italic>\u2009=\u20090.051). In the multivariate analysis, lower LC was associated with higher in-hospital mortality [adjusted odds ratio (AOR), 0.97; 95% confidence interval (CI) 0.96\u20130.98; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001] and fewer VFD [adjusted difference <jats:italic>p<\/jats:italic> value (AD), \u2212\u20091.23; 95% CI \u2212\u20092.42 to \u2212\u20090.09; <jats:italic>p<\/jats:italic>\u2009=\u20090.025] in the non-pneumonia group. Conversely, LC did not affect in-hospital mortality (AOR 0.99; 95% CI 0.99\u20131.00; <jats:italic>p<\/jats:italic>\u2009=\u20090.134) and VFD (AD \u2212\u20090.08; 95% CI \u2212\u20092.06 to 1.91; <jats:italic>p<\/jats:italic>\u2009=\u20090.854) in the pneumonia group. Given the differences in the impact of LC on outcomes between the pneumonia and non-pneumonia groups, this study suggests that optimal treatment strategies might improve outcomes. Further studies are warranted to validate our results and develop optimal therapeutic strategies for sepsis patients.<\/jats:p>","DOI":"10.1038\/s41598-021-01856-5","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T11:03:51Z","timestamp":1637147031000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The impact of lactate clearance on outcomes according to infection sites in patients with sepsis: a retrospective observational study"],"prefix":"10.1038","volume":"11","author":[{"given":"Momoko","family":"Sugimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Takayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Otomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"1856_CR1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1007\/s00134-017-4683-6","volume":"43","author":"A Rhodes","year":"2017","unstructured":"Rhodes, A. et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 43, 304\u2013377 (2017).","journal-title":"Intensive Care Med."},{"key":"1856_CR2","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1056\/NEJMra1208943","volume":"369","author":"JL Vincent","year":"2013","unstructured":"Vincent, J. L. & De Backer, D. Circulatory shock. N. Engl. J. Med. 369, 1729\u20131734 (2013).","journal-title":"N. Engl. J. Med."},{"key":"1856_CR3","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1476-9255-7-6","volume":"7","author":"HB Nguyen","year":"2010","unstructured":"Nguyen, H. B. et al. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J. Inflamm. (Lond.) 7, 6 (2010).","journal-title":"J. Inflamm. (Lond.)"},{"key":"1856_CR4","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1097\/01.CCM.0000132904.35713.A7","volume":"32","author":"HB Nguyen","year":"2004","unstructured":"Nguyen, H. B. et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit. Care Med. 32, 1637\u20131642 (2004).","journal-title":"Crit. Care Med."},{"key":"1856_CR5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/2110-5820-3-3","volume":"3","author":"P Marty","year":"2013","unstructured":"Marty, P. et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann. Intensive Care 3, 3 (2013).","journal-title":"Ann. Intensive Care"},{"key":"1856_CR6","first-page":"357","volume":"21","author":"H Wang","year":"2009","unstructured":"Wang, H. et al. Relationship between blood lactic level, lactic clearance, duration of lacticemia and prognosis of critically ill patients in intensive care unit. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 21, 357\u2013360 (2009).","journal-title":"Zhongguo Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"1856_CR7","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/SHK.0000000000000260","volume":"43","author":"M Dettmer","year":"2015","unstructured":"Dettmer, M., Holthaus, C. V. & Fuller, B. M. The impact of serial lactate monitoring on emergency department resuscitation interventions and clinical outcomes in severe sepsis and septic shock: an observational cohort study. Shock 43, 55\u201361 (2015).","journal-title":"Shock"},{"key":"1856_CR8","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1164\/rccm.200912-1918OC","volume":"182","author":"TC Jansen","year":"2010","unstructured":"Jansen, T. C. et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized control trial. Am. J. Respir. Crit. Care Med. 182, 752\u2013761 (2010).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1856_CR9","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1097\/CCM.0000000000000742","volume":"43","author":"B Casserly","year":"2015","unstructured":"Casserly, B. et al. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit. Care Med. 43, 567\u2013573 (2015).","journal-title":"Crit. Care Med."},{"key":"1856_CR10","doi-asserted-by":"crossref","unstructured":"National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network et al. Comparison of two fluid-management strategies in acute lung injury. N. Engl. J. Med. 354, 2564\u20132575 (2006).","DOI":"10.1056\/NEJMoa062200"},{"key":"1856_CR11","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer, M. et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315, 801\u2013810 (2016).","journal-title":"JAMA"},{"key":"1856_CR12","doi-asserted-by":"crossref","unstructured":"Schoenfeld, D. A., Bernard, G. R. & ARDS Network. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit. Care Med. 30, 1772\u20131777 (2002).","DOI":"10.1097\/00003246-200208000-00016"},{"key":"1856_CR13","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/S0002-9610(97)89552-9","volume":"171","author":"J Bakker","year":"1996","unstructured":"Bakker, J., Gris, P., Coffernils, M., Kahn, R. J. & Vincent, J. L. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am. J. Surg. 171, 221\u2013226 (1996).","journal-title":"Am. J. Surg."},{"key":"1856_CR14","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1378\/chest.99.4.956","volume":"99","author":"J Bakker","year":"1991","unstructured":"Bakker, J., Coffernils, M., Leon, M., Gris, P. & Vincent, J. L. Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest 99, 956\u2013962 (1991).","journal-title":"Chest"},{"key":"1856_CR15","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/BF01728326","volume":"22","author":"G Bernardin","year":"1996","unstructured":"Bernardin, G., Pradier, C., Tiger, F., Deloffre, P. & Mattei, M. Blood pressure and arterial lactate level are early indicators of short-term survival in human septic shock. Intensive Care Med. 22, 17\u201325 (1996).","journal-title":"Intensive Care Med."},{"key":"1856_CR16","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1056\/NEJMoa1401602","volume":"370","author":"ProCESS Investigators","year":"2014","unstructured":"Investigators, ProCESS. et al. A randomized trial of protocol-based care for early septic shock. N. Engl. J. Med. 370, 1683\u20131693 (2014).","journal-title":"N. Engl. J. Med."},{"key":"1856_CR17","doi-asserted-by":"crossref","unstructured":"ARISE Investigators et al. Goal-directed resuscitation for patients with early septic shock. N. Engl. J. Med. 371, 1496\u20131506 (2014).","DOI":"10.1056\/NEJMoa1404380"},{"key":"1856_CR18","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1056\/NEJMoa1500896","volume":"372","author":"PR Mouncey","year":"2015","unstructured":"Mouncey, P. R. et al. Trial of early, goal-directed resuscitation for septic shock. N. Engl. J. Med. 372, 1301\u20131311 (2015).","journal-title":"N. Engl. J. Med."},{"key":"1856_CR19","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/j.1553-2712.2012.01292.x","volume":"19","author":"MA Puskarich","year":"2012","unstructured":"Puskarich, M. A. et al. Prognostic value and agreement of achieving lactate clearance or central venous oxygen saturation goals during early sepsis resuscitation. Acad. Emerg. Med. 19, 252\u2013258 (2012).","journal-title":"Acad. Emerg. Med."},{"key":"1856_CR20","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.jcrc.2013.02.004","volume":"28","author":"CA Walker","year":"2013","unstructured":"Walker, C. A., Griffith, D. M., Gray, A. J., Datta, D. & Hay, A. W. Early lactate clearance in septic patients with elevated lactate levels admitted from the emergency department to intensive care: time to aim higher?. J. Crit. Care. 28, 832\u2013837 (2013).","journal-title":"J. Crit. Care."},{"key":"1856_CR21","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1001\/jama.2010.158","volume":"303","author":"AE Jones","year":"2010","unstructured":"Jones, A. E. et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 303, 739\u2013746 (2010).","journal-title":"JAMA"},{"key":"1856_CR22","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1186\/s13054-016-1403-5","volume":"20","author":"JL Vincent","year":"2016","unstructured":"Vincent, J. L. et al. The value of blood lactate kinetics in critically ill patients: a systematic review. Crit. Care. 20, 257 (2016).","journal-title":"Crit. Care."},{"key":"1856_CR23","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1378\/chest.117.6.1749","volume":"117","author":"F Alsou","year":"2000","unstructured":"Alsou, F., Khamiees, M., DeGirolamo, A., Amoateng-Adjepong, Y. & Manthous, C. A. Negative fluid balance predicts survival in patients with septic shock: a retrospective pilot study. Chest 117, 1749\u20131754 (2000).","journal-title":"Chest"},{"key":"1856_CR24","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1056\/NEJMoa050333","volume":"353","author":"GD Rubenfeld","year":"2005","unstructured":"Rubenfeld, G. D. et al. Incidence and outcomes of acute lung injury. N. Engl. J. Med. 353, 1685\u20131693 (2005).","journal-title":"N. Engl. J. Med."},{"key":"1856_CR25","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/S0883-9441(96)90014-3","volume":"11","author":"SD Brown","year":"1996","unstructured":"Brown, S. D., Clark, C. & Gutierrez, G. Pulmonary lactate release in patients with sepsis and ARDS. J. Crit. Care. 11, 2\u20138 (1996).","journal-title":"J. Crit. Care."},{"key":"1856_CR26","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1164\/ajrccm.156.4.9701048","volume":"156","author":"D De Backer","year":"1997","unstructured":"De Backer, D., Creteur, J., Zhang, H., Norrenberg, M. & Vincent, J. L. Lactate production by the lungs in acute lung injury. Am. J. Respir. Crit. Care Med. 156, 1099\u20131104 (1997).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1856_CR27","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1378\/chest.111.5.1301","volume":"111","author":"JA Kellum","year":"1997","unstructured":"Kellum, J. A. et al. Release of lactate by the lung in acute lung injury. Chest 111, 1301\u20131305 (1997).","journal-title":"Chest"},{"key":"1856_CR28","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1186\/cc1519","volume":"6","author":"F Iscra","year":"2002","unstructured":"Iscra, F., Gullo, A. & Biolo, G. Bench-to-bedside review: Lactate and the lung. Crit. Care 6, 327\u2013329 (2002).","journal-title":"Crit. Care"},{"key":"1856_CR29","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1097\/SHK.0000000000000268","volume":"43","author":"DJ Kelm","year":"2015","unstructured":"Kelm, D. J. et al. Fluid overload in patients with severe sepsis and septic shock treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock 43, 68\u201373 (2015).","journal-title":"Shock"},{"issue":"Suppl","key":"1856_CR30","doi-asserted-by":"publisher","first-page":"48s","DOI":"10.1183\/09031936.03.00420803","volume":"42","author":"P Pelosi","year":"2003","unstructured":"Pelosi, P. et al. Pulmonary and extrapulmonary acute respiratory distress syndrome are different. Eur. Respir. J. 42(Suppl), 48s\u201356s (2003).","journal-title":"Eur. Respir. J."},{"key":"1856_CR31","doi-asserted-by":"publisher","first-page":"L953","DOI":"10.1152\/ajplung.00335.2014","volume":"308","author":"RG Lottes","year":"2015","unstructured":"Lottes, R. G. et al. Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells. Am. J. Physiol. Lung. Cell. Mol. Physiol. 308, L953\u2013L961 (2015).","journal-title":"Am. J. Physiol. Lung. Cell. Mol. Physiol."},{"key":"1856_CR32","doi-asserted-by":"publisher","first-page":"e489","DOI":"10.1097\/CCM.0000000000003030","volume":"46","author":"SM Ryoo","year":"2018","unstructured":"Ryoo, S. M. et al. Lactate level versus lactate clearance for predicting mortality in patients with septic shock defined by sepsis-3. Crit. Care Med. 46, e489-495 (2018).","journal-title":"Crit. Care Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01856-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01856-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01856-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T17:28:56Z","timestamp":1670088536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01856-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["1856"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-01856-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]},"assertion":[{"value":"10 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22394"}}