{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:28:32Z","timestamp":1792268912866,"version":"4.4.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Science","doi-asserted-by":"publisher","award":["UL1TR000124"],"award-info":[{"award-number":["UL1TR000124"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["M01 RR00827"],"award-info":[{"award-number":["M01 RR00827"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2021,1]]},"abstract":"\n Background<\/jats:title>\n \n The ratio of\n \u0394<\/jats:italic>\n anion gap and\n \u0394<\/jats:italic>\n bicarbonate (\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n ) is used to detect coexisting acid-base disorders in patients with high anion gap metabolic acidosis. Classic teaching holds that, in lactic acidosis, the\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n is 1:1 within the first few hours of onset and subsequently rises to 1.8:1. However, this classic 1:1 stoichiometry in early lactic acidosis was derived primarily from animal models and only limited human data. The objective of this study was to examine the\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n within the first hours of the development of lactic acidosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Data were obtained prospectively from a convenience sample of adult (age >18 years) trauma-designated patients at a single level-1 trauma center. Venous samples, including a chemistry panel and serum lactate, were drawn before initiation of intravenous fluid resuscitation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 108 patients were included. Of these, 63 patients had normal serum lactate levels (\u22642.1 mmol\/L) with a mean AG of 7.1 mEq\/L, the value used to calculate subsequent\n \u0394<\/jats:italic>\n AG values.\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n was calculated for 45 patients who had elevated serum lactate levels (>2.1 mmol\/L). The mean\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n for all patients with elevated serum lactate levels was 1.86 (SD, 1.40).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The mean\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n was 1.86 within the first hours of the development of lactic acidosis due to hypovolemic shock, confirming a small prior human study. This contradicts the traditional belief that, in lactic acidosis, the\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n is 1:1 within the first several hours. The classic 1:1 stoichiometry was determined on the basis of animal models in which lactic acid is infused into the extracellular space, facilitating extracellular buffering of protons by bicarbonate. In contrast, our results demonstrate a higher initial\n \u0394<\/jats:italic>\n AG\/\n \u0394<\/jats:italic>\n HCO\n 3<\/jats:sub>\n ratio in early endogenous lactic acidosis in humans. Our analysis indicates this is likely due to unmeasured anions contributing to an elevation in AG.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000842019","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T18:40:14Z","timestamp":1605033614000},"page":"20-25","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["The \u0394 Anion Gap\/\u0394 Bicarbonate Ratio in Early Lactic Acidosis: Time for Another Delta?"],"prefix":"10.34067","volume":"2","author":[{"given":"Scott E.","family":"Rudkin","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of California, Irvine, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan R.","family":"Grogan","sequence":"additional","affiliation":[{"name":"Department of Medicine Statistics Core, University of California, Los Angeles, California"},{"name":"David Geffen School of Medicine, University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Treger","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California, Los Angeles, California"},{"name":"Division of Nephrology and Hypertension, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"B1-20250825","doi-asserted-by":"crossref","first-page":"162","DOI":"10.2215\/CJN.03020906","article-title":"Serum anion gap: Its uses and limitations in clinical medicine","volume":"2","author":"Kraut","year":"2007","journal-title":"Clin J Am Soc Nephrol"},{"key":"B2-20250825","first-page":"F345","article-title":"Relationship between blood pH and potassium and phosphorus during acute metabolic acidosis","volume":"235","author":"Oster","year":"1978","journal-title":"Am J Physiol"},{"key":"B3-20250825","first-page":"15","article-title":"Hypochloremia as a consequence of anion gap metabolic acidosis","volume":"104","author":"Madias","year":"1984","journal-title":"J Lab Clin Med"},{"key":"B4-20250825","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1056\/NEJM197710132971502","article-title":"Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia","volume":"297","author":"Orringer","year":"1977","journal-title":"N Engl J Med"},{"key":"B5-20250825","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/BF02425050","article-title":"Hyperchloremic acidosis during grand mal seizure lactic acidosis","volume":"20","author":"Brivet","year":"1994","journal-title":"Intensive Care Med"},{"key":"B6-20250825","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.ajem.2011.09.027","article-title":"Prospective correlation of arterial vs venous blood gas measurements in trauma patients","volume":"30","author":"Rudkin","year":"2012","journal-title":"Am J Emerg Med"},{"key":"B7-20250825","first-page":"448","article-title":"Clinical significance of the fractional excretion of anions in metabolic acidosis","volume":"55","author":"Kim","year":"2001","journal-title":"Clin Nephrol"},{"key":"B8-20250825","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/0002-9343(63)90240-7","article-title":"Spontaneous lactic acidosis. The nature of the acid-base disturbance and considerations in diagnosis and management","volume":"35","author":"Waters","year":"1963","journal-title":"Am J Med"},{"key":"B9-20250825","doi-asserted-by":"crossref","first-page":"925","DOI":"10.7326\/0003-4819-89-6-925","article-title":"Hyperchloremic acidosis during the recovery phase of diabetic ketosis","volume":"89","author":"Oh","year":"1978","journal-title":"Ann Intern Med"},{"key":"B10-20250825","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s001340050350","article-title":"Reliability of anion gap as an indicator of blood lactate in critically ill patients","volume":"23","author":"Levraut","year":"1997","journal-title":"Intensive Care Med"},{"key":"B11-20250825","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/00005373-199602000-00008","article-title":"Serum lactate is not predicted by anion gap or base excess after trauma resuscitation","volume":"40","author":"Mikulaschek","year":"1996","journal-title":"J Trauma"},{"key":"B12-20250825","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1097\/00003246-199105000-00018","article-title":"Unaccounted for anion in metabolic acidosis during severe sepsis in humans","volume":"19","author":"Mecher","year":"1991","journal-title":"Crit Care Med"},{"key":"B13-20250825","doi-asserted-by":"crossref","first-page":"R591","DOI":"10.1186\/cc3806","article-title":"Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis","volume":"9","author":"Forni","year":"2005","journal-title":"Crit Care"},{"key":"B14-20250825","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/cc4954","article-title":"Unmeasured anions in metabolic acidosis: Unravelling the mystery","volume":"10","author":"Forni","year":"2006","journal-title":"Crit Care"},{"key":"B15-20250825","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1097\/01.CCM.0000132901.86681.CA","article-title":"Unidentified acids of strong prognostic significance in severe malaria","volume":"32","author":"Dondorp","year":"2004","journal-title":"Crit Care Med"},{"key":"B16-20250825","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1097\/01.CCM.0000125517.28517.74","article-title":"Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury","volume":"32","author":"Kaplan","year":"2004","journal-title":"Crit Care Med"},{"key":"B17-20250825","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/00003246-199003000-00005","article-title":"Low sensitivity of the anion gap as a screen to detect hyperlactatemia in critically ill patients","volume":"18","author":"Iberti","year":"1990","journal-title":"Crit Care Med"},{"key":"B18-20250825","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.2215\/CJN.04040413","article-title":"The serum anion gap in the evaluation of acid-base disorders: What are its limitations and can its effectiveness be improved?","volume":"8","author":"Kraut","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"B19-20250825","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1097\/00007611-199807000-00004","article-title":"Low anion gap","volume":"91","author":"Jurado","year":"1998","journal-title":"South Med J"},{"key":"B20-20250825","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1001\/archinte.1990.00390140057012","article-title":"The fall of the serum anion gap","volume":"150","author":"Winter","year":"1990","journal-title":"Arch Intern Med"}],"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000842019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:02:29Z","timestamp":1786478549000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000842019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.34067\/kid.0000842019","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2019-12-03","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}