{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:32:49Z","timestamp":1790026369939,"version":"4.0.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>CO<jats:sub>2<\/jats:sub>-derived parameters are increasingly used to identify either low-flow status or anaerobic metabolism in shock resuscitation. However, the performance of CO<jats:sub>2<\/jats:sub>-derived parameters in cardiac surgical patients is poorly understood. This study aims to compare the performance of lactate and CO<jats:sub>2<\/jats:sub>-derived parameters in predicting major postoperative complications after cardiac surgery with cardiopulmonary bypass.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>This is a prospective, single-center, diagnostic accuracy study. All patients who receive elective cardiac surgery involving cardiopulmonary bypass will be screened for study eligibility. Blood samples will be taken for the calculation of CO<jats:sub>2<\/jats:sub>-derived parameters, including the venous-arterial difference in CO<jats:sub>2<\/jats:sub>partial pressure (PCO<jats:sub>2<\/jats:sub>gap), venous-arterial difference in CO<jats:sub>2<\/jats:sub>content to arterial-venous O<jats:sub>2<\/jats:sub>content ratio (Cv-aCO<jats:sub>2<\/jats:sub>\/Ca-vO<jats:sub>2<\/jats:sub>), and venous-arterial difference in CO<jats:sub>2<\/jats:sub>partial pressure to arterial-venous O<jats:sub>2<\/jats:sub>content ratio (Pv-aCO<jats:sub>2<\/jats:sub>\/Ca-vO<jats:sub>2<\/jats:sub>) at ICU admission, and 3, 6, and 12 h later. Baseline, perioperative data will be collected daily for 7 days; patients will be followed up for 28 days to collect outcome data. The primary endpoint is the occurrence of major postoperative complications. Receiver-operating characteristics (ROC) curve analysis will be carried out to assess the predictive performance of lactate and CO<jats:sub>2<\/jats:sub>-derived parameters. The performance of the ROC curves will be compared.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold>The performance of lactate and CO<jats:sub>2<\/jats:sub>-derived parameters in predicting major postoperative complications will be investigated in the non-sepsis population, which has not been extensively investigated. Our study will compare the two surrogates of respiratory quotient directly, which is an important strength.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold>ChiCTR, ChiCTR2000029365. Registered January 26th, 2020,<jats:ext-link>http:\/\/www.chictr.org.cn\/showproj.aspx?proj=48744<\/jats:ext-link>.<\/jats:p>","DOI":"10.3389\/fcvm.2021.724713","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T06:17:46Z","timestamp":1633069066000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Performance of Lactate and CO2-Derived Parameters in Predicting Major Postoperative Complications After Cardiac Surgery With Cardiopulmonary Bypass: Protocol of a Diagnostic Accuracy Study"],"prefix":"10.3389","volume":"8","author":[{"given":"Xiao-Fen","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Guo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Min","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.bja.2019.09.012","article-title":"2019 EACTS\/EACTA\/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery","volume":"123","author":"Kunst","year":"2019","journal-title":"Br J Anaesth."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0205950","DOI":"10.1371\/journal.pone.0205950","article-title":"The ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content are not associated with overall anaerobic metabolism in postoperative cardiac surgery patients","volume":"13","author":"Abou-Arab","year":"2018","journal-title":"PLoS ONE."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1016\/j.athoracsur.2018.03.003","article-title":"The society of thoracic surgeons 2018 adult cardiac surgery risk models: part 2-statistical methods and results","volume":"105","author":"O'Brien","year":"2018","journal-title":"Ann Thorac Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.athoracsur.2018.08.085","article-title":"Impact of cardiopulmonary bypass flow on renal oxygenation in patients undergoing cardiac operations","volume":"107","author":"Lannemyr","year":"2019","journal-title":"Ann Thorac Surg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.athoracsur.2005.06.042","article-title":"Cardiac output augmentation during hypoxemia improves cerebral metabolism after hypothermic cardiopulmonary bypass","volume":"81","author":"Schultz","year":"2006","journal-title":"Ann Thorac Surg."},{"key":"B6","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s12630-018-1140-0","article-title":"Potential biomarkers of tissue hypoxia during acute hemodilutional anemia in cardiac surgery: a prospective study to assess tissue hypoxia as a mechanism of organ injury","volume":"65","author":"Hare","year":"2018","journal-title":"Can J Anaesth."},{"key":"B7","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1213\/ANE.0000000000001928","article-title":"Lactate elevation during and after major cardiac surgery in adults: a review of etiology, prognostic value, and management","volume":"125","author":"Andersen","year":"2017","journal-title":"Anesth Analg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12967-020-02210-5","article-title":"Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass","volume":"18","author":"Raggi","year":"2020","journal-title":"J Transl Med."},{"key":"B9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1051\/ject\/201749007","article-title":"Hyperlactatemia and cardiac surgery","volume":"49","author":"Minton","year":"2017","journal-title":"J Extra Corpor Technol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1177\/0310057X1204000404","article-title":"The interpretation of perioperative lactate abnormalities in patients undergoing cardiac surgery","volume":"40","author":"O'Connor","year":"2012","journal-title":"Anaesth Intensive Care."},{"key":"B11","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.jtcvs.2015.10.063","article-title":"Frequency and outcomes of severe hyperlactatemia after elective cardiac surgery","volume":"151","author":"Renew","year":"2016","journal-title":"J Thorac Cardiovasc Surg."},{"key":"B12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1097\/EJA.0000000000000949","article-title":"Central venous-to-arterial pCO2 difference, arteriovenous oxygen content and outcome after adult cardiac surgery with cardiopulmonary bypass: a prospective observational study","volume":"36","author":"Moussa","year":"2019","journal-title":"Eur J Anaesthesiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"S1551","DOI":"10.21037\/jtd.2019.01.109","article-title":"Venous-to-arterial pCO2 difference in high-risk surgical patients","volume":"11","author":"Huette","year":"2019","journal-title":"J Thorac Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1097\/SHK.0000000000000893","article-title":"The prognostic value of central venous-to-arterial CO2 difference\/arterial-central venous O2 difference ratio in septic shock patients with central venous O2 saturation \u226580","volume":"48","author":"He","year":"2017","journal-title":"Shock."},{"key":"B15","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13613-016-0110-3","article-title":"Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients","volume":"6","author":"Mallat","year":"2016","journal-title":"Ann Intensive Care."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1097\/00003246-199907000-00031","article-title":"Microcirculatory oxygenation and shunting in sepsis and shock","volume":"27","author":"Ince","year":"1999","journal-title":"Crit Care Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1164\/rccm.200109-016OC","article-title":"Microvascular blood flow is altered in patients with sepsis","volume":"166","author":"De Backer","year":"2002","journal-title":"Am J Respir Crit Care Med."},{"key":"B18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/978-3-319-43130-7_8","article-title":"Central venous-to-arterial carbon dioxide partial pressure difference:","volume-title":"Monitoring Tissue Perfusion in Shock: From Physiology to the Bedside","author":"Monnet","year":"2018"},{"key":"B19","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1378\/chest.101.2.509","article-title":"Veno-arterial carbon dioxide gradient in human septic shock","volume":"101","author":"Bakker","year":"1992","journal-title":"Chest."},{"key":"B20","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1007\/s00134-015-3720-6","article-title":"Combination of arterial lactate levels and venous-arterial CO2 to arterial-venous O2 content difference ratio as markers of resuscitation in patients with septic shock","volume":"41","author":"Ospina-Tascon","year":"2015","journal-title":"Intensive Care Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1007\/s00134-013-2998-5","article-title":"Resuscitation of patients with septic shock: please \u201cmind the gap\u201d!","volume":"39","author":"Vallet","year":"2013","journal-title":"Intensive Care Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.medine.2017.06.008","article-title":"Venous-to-arterial carbon dioxide difference in the resuscitation of patients with severe sepsis and septic shock: a systematic review","volume":"41","author":"Diaztagle Fernandez","year":"2017","journal-title":"Med Intensiva."},{"key":"B23","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/aas.13480","article-title":"Prospective, observational study of carbon dioxide gaps and free energy change and their association with fluid therapy following cardiac surgery","volume":"64","author":"Mahendran","year":"2020","journal-title":"Acta Anaesthesiol Scand."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1053\/j.jvca.2017.02.015","article-title":"Central venous-to-arterial carbon dioxide partial pressure difference in patients undergoing cardiac surgery is not related to postoperative outcomes","volume":"31","author":"Guinot","year":"2017","journal-title":"J Cardiothorac Vasc Anesth."},{"key":"B25","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1053\/j.jvca.2014.09.006","article-title":"Central venous-arterial PCO2 difference identifies microcirculatory hypoperfusion in cardiac surgical patients with normal central venous oxygen saturation: a retrospective analysis","volume":"29","author":"Habicher","year":"2015","journal-title":"J Cardiothorac Vasc Anesth."},{"key":"B26","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.hrtlng.2019.05.015","article-title":"Increased admission central venous-arterial CO(2) difference predicts ICU-mortality in adult cardiac surgery patients","volume":"48","author":"Zante","year":"2019","journal-title":"Heart Lung."},{"key":"B27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s10877-019-00286-z","article-title":"Comparison of the venous-arterial CO(2) to arterial-venous O(2) content difference ratio with the venous-arterial CO(2) gradient for the predictability of adverse outcomes after cardiac surgery","volume":"34","author":"Mukai","year":"2020","journal-title":"J Clin Monit Comput."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.4103\/0366-6999.156770","article-title":"The use of the ratio between the veno-arterial carbon dioxide difference and the arterial-venous oxygen difference to guide resuscitation in cardiac surgery patients with hyperlactatemia and normal central venous oxygen saturation","volume":"128","author":"Du","year":"2015","journal-title":"Chin Med J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1152\/jappl.1988.65.1.473","article-title":"Calculation of whole blood CO2 content","volume":"65","author":"Douglas","year":"1988","journal-title":"J Appl Physiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e006344","DOI":"10.1136\/bmjopen-2014-006344","article-title":"Procalcitonin as a predictor of moderate to severe acute respiratory distress syndrome after cardiac surgery with cardiopulmonary bypass: a study protocol for a prospective cohort study","volume":"4","author":"Chen","year":"2014","journal-title":"BMJ Open."},{"key":"B31","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1097\/EJA.0000000000000118","article-title":"Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European perioperative clinical outcome (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on perioperative outcome measures","volume":"32","author":"Jammer","year":"2015","journal-title":"Eur J Anaesthesiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.athoracsur.2009.05.053","article-title":"The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 1-coronary artery bypass grafting surgery","volume":"88","author":"Shahian","year":"2009","journal-title":"Ann Thorac Surg."},{"key":"B33","doi-asserted-by":"publisher","first-page":"S23","DOI":"10.1016\/j.athoracsur.2009.05.056","article-title":"The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2-isolated valve surgery","volume":"88","author":"O'Brien","year":"2009","journal-title":"Ann Thorac Surg."},{"key":"B34","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.1016\/j.athoracsur.2009.05.055","article-title":"The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 3-valve plus coronary artery bypass grafting surgery","volume":"88","author":"Shahian","year":"2009","journal-title":"Ann Thorac Surg."},{"key":"B35","doi-asserted-by":"publisher","first-page":"R31","DOI":"10.1186\/cc5713","article-title":"Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury","volume":"11","author":"Mehta","year":"2007","journal-title":"Crit Care."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1001\/jama.2012.5669","article-title":"Acute respiratory distress syndrome: the Berlin Definition","volume":"307","author":"Ranieri","year":"2012","journal-title":"JAMA."},{"key":"B37","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s001340100909","article-title":"Intensive care delirium screening checklist: evaluation of a new screening tool","volume":"27","author":"Bergeron","year":"2001","journal-title":"Intensive Care Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1161\/CIR.0b013e31826e1058","article-title":"Third universal definition of myocardial infarction","volume":"126","author":"Thygesen","year":"2012","journal-title":"Circulation."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1056\/NEJMra1208943","article-title":"Circulatory shock","volume":"369","author":"Vincent","year":"2013","journal-title":"N Engl J Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1007\/s00134-017-4683-6","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016","volume":"43","author":"Rhodes","year":"2017","journal-title":"Intensive Care Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics."},{"key":"B42","first-page":"299","article-title":"The relationship between the differences in pressure and content of carbon dioxide in arterial and venous blood","volume":"32","author":"McHardy","year":"1967","journal-title":"Clin Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1242\/jeb.204.11.2029","article-title":"Comparative analysis of autoxidation of haemoglobin","volume":"204","author":"Jensen","year":"2001","journal-title":"J Exp Biol."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.724713\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T19:57:56Z","timestamp":1699559876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.724713\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":43,"alternative-id":["10.3389\/fcvm.2021.724713"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.724713","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]},"article-number":"724713"}}