Usage of Serum Anion Gap to Predict in-Hospital and 1-Year All-Cause Mortality in Cardiac Care Unit Patients


Authors: Thanapon Nilmoje, Saranyou Suwanugsorn, Wisanuwee Suriyaamorn, Ittipon Preechawettayakul, Veerapong Vattanavanit, and Ply Chichareon
Page Range: 117-182
Published in: World Heart Journal, 14#2 (2022)
ISSN: 1556-4002

ISBN: N/A Category:

Table of Contents


Background: Anion gap has been used as a prognostic indicator in critical care settings as well as cardiovascular fields. However, few studies have demonstrated the association between anion gap in cardiac care units (CCU) and mortality. Objective: To assess a prognostic value of anion gap for in-hospital and 1-year all-cause mortality in CCU patients. Subjects and methods: This is a retrospective cohort study in Songklanagarind Hospital, a tertiary center in Southern Thailand. Patients admitted from the emergency department and outpatient department to CCU from July 2015 to December 2019 were included. Anion gap was calculated from serum electrolytes obtained at the emergency department or within 1 hour of CCU admission by the following formula; Na(mmol/L)-(Cl(mmol/L)+HCO3(mmol/L)). The associations between anion gap and either in-hospital or 1-year all-cause mortality were assessed by logistic and Cox regression models, respectively. Results: This study included 1,271 patients. There was a higher prevalence of diabetes mellitus and chronic kidney disease in patients with a wide anion gap (≥12) than inpatients with a normal anion gap. Compared with the normal anion gap group, hemoglobin level, blood urea nitrogen and serum creatinine were higher in the wide anion gap group, whereas the mean Braden skin score was lower. The 1-year survival rate of patients with an anion gap  14 was significantly lower than that of those with an anion gap <14. The survival rate of patients with an anion gap < 12 was not different from that of those with an anion gap between 12 and 14. There were linear relationships between baseline anion gap and in-hospital and 1-year all-cause mortality risk. Anion gap was an independent predictor for both in-hospital (odds ratio 1.13, 95% CI 1.07-1.19, p < 0.0001) and 1-year all-cause mortality (hazard ratio 1.09, 95%CI 1.07-1.12, p < 0.0001) in the multivariate analysis. Conclusions: Anion gap was an independent predictor for in-hospital and 1-year all-cause mortality in CCU patients. Calculating anion gap from three routine basic electrolytes can be used as a quick and reliable marker to predict the risk of CCU patients without extra cost.

Keywords: Anion gap, cardiac care unit (CCU), mortality predictors


[1] Mendis S, Davis S, Norrving B. Organizational update: the world health organization global status report on noncommunicable diseases 2014; one more landmark step in the combat against stroke and vascular disease. Stroke 2015; 46 (5): e121-2.
[2] 2017 Global Burden of Disease Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392 (10159): 1736-1788.
[3] Chen Q, Chen Q, Li L, Lin X, Chang SI, Li Y, Tian Z, Liu W, Huang K. Serum anion gap on admission predicts intensive care unit mortality in patients with aortic aneurysm. Exp Ther Med 2018; 16 (3): 1766-1777.
[4] Oh YK. Acid-base disorders in ICU patients. Electrolyte Blood Press. 2010; 8 (2): 66-71.
[5] Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol 2007; 2 (1): 162-174.
[6] Forman JP, Rifas-Shiman SL, Taylor EN, Lane K, Gillman MW. Association between the serum anion gap and blood pressure among patients at Harvard Vanguard Medical Associates. J Hum Hypertens 2008; 22 (2): 122-125.
[7] Kraut JA, Nagami GT. The serum anion gap in the evaluation of acid-base disorders: what are its limitations and can its effectiveness be improved? Clin J Am Soc Nephrol 2013; 8 (11): 2018-2024.
[8] Yang SW, Zhou YJ, Zhao YX, Liu YY, Tian XF, Wang ZJ, Jia DA, Han HY, Hu B, Shen H, Gao F, Wang LY, Lin J, Pan GZ, Zhang J, Guo ZF, Du J, Hu DY. The serum anion gap is associated with disease severity and all-cause mortality in coronary artery disease. J Geriatr Cardiol 2017; 14 (6): 392-400.
[9] Sahu A, Cooper HA, Panza JA. The initial anion gap is a predictor of mortality in acute myocardial infarction. Coron Artery Dis 2006; 7 (5): 409-412.
[10] Kim MJ, Kim YH, Sol IS, Kim SY, Kim JD, Kim HY, Kim KW, Sohn MH, Kim KE. Serum anion gap at admission as a predictor of mortality in the pediatric intensive care unit. Sci Rep 2017; 7 (1): 1456.
[11] Cheng B, Li D, Gong Y, Ying B, Wang B. Serum anion gap predicts all-cause mortality in critically ill patients with acute kidney injury: analysis of the MIMIC-III database. Dis Markers 2020; 2020: 6501272.
[12] Sun T, Cai C, Shen H, Yang J, Guo Q, Zhang J, Zhang B, Ding Y, Zhou Y. Anion gap was associated with inhospital mortality and adverse clinical outcomes of coronary care unit patients. Biomed Res Int 2020; 2020: 4598462.
[13] Labeau SO, Afonso E, Benbenishty J, Blackwood B, Boulanger C, Brett SJ, Calvino-Gunther S, Chaboyer W, Coyer F, Deschepper M, François G, Honore PM, Jankovic R, Khanna AK, Llaurado-Serra M, Lin F, Rose L, Rubulotta F, Saager L, Williams G, Blot SI; DecubICUs Study Team; European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators. Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study. Intens Care Med 2021; 47 (4): 503-520.
[14] Mojto V, Singh RB, Gvozdjakova A, Pella D, Fedacko J, Pella D. Molecular hydrogen: a new approach for the management of cardiovascular diseases. World Heart Journal 2018; 10( 1): 83-93.
[15] Singh RB, Fedacko J, Sharma JP, Vargova V, Sharma MM, De Meester F, Otsuka K. Association of inflammation, heavy meals, magnesium, nitrite, and coenzyme Q10 deficiency and circadian rhythms with risk of acute coronary syndromes. World Heart J 2010; 2: 219-28.
[16] Singh RB. Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. Magnes Trace Elem 1990; 9 (3): 143-151.
[17] Neligan P. How should acid-base disorders be diagnosed? In: Deutschman CS, Neligan PJ, eds. Evidence-Based Practice of Critical Care, 3rd ed. Elsevier, 2020. p. 408-418.e1.
[18] Chawla LS, Jagasia D, Abell LM, Seneff MG, Egan M, Danino N, et al. Anion gap, anion gap corrected for albumin, and base deficit fail to accurately diagnose clinically significant hyperlactatemia in critically ill patients. J Intensive Care Med 2008; 23 (2): 122-127.
[19] Wigger O, Bloechlinger S, Berger D, Haner J, Zanchin T, Windecker S, et al. Baseline serum bicarbonate levels independently predict short-term mortality in critically ill patients with ischaemic cardiogenic shock. Eur Heart J Acute Cardiovasc Care 2018; 7 (1): 45-52.
[20] Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore) 1977; 56 (1): 38-54.
[21] Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, et al. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatric Critical Care Medicine 2020; 21 (2): e52-e106.
[22] Brenner BE. Clinical significance of the elevated anion gap. Am J Med 1985; 79 (3): 289-296.
[23] Berkman M, Ufberg J, Nathanson LA, Shapiro NI. Anion gap as a screening tool for elevated lactate in patients with an increased risk of developing sepsis in the Emergency Department. J Emerg Med 2009; 36 (4): 391-394.
[24] MacDonald L, Kruse JA, Levy DB, Marulendra S, Sweeny PJ. Lactic acidosis and acute ethanol intoxication. The American Journal of Emergency Medicine 1994; 12 (1): 32-35.
[25] Agoro EY, Wankasi M, Ileimokumo O. Relationship between serum anion gap and diabetes mellitus. J Diab Mell 2015; 5 (4): 199-205.
[26] Abramowitz MK, Hostetter TH, Melamed ML. The serum anion gap is altered in early kidney disease and associates with mortality. Kidney Int 2012; 82 (6): 701-709.
[27] Shashaty MG, Stapleton RD. Physiological and management implications of obesity in critical illness. Ann Am Thorac Soc 2014; 11 (8): 1286-1297.
[28] Han DC, Isono M, Chen S, Casaretto A, Hong SW, Wolf G, Ziyadeh FN. Leptin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF-β type II receptor expression. Kidney Int 2001; 59 (4): 1315-1323.
[29] Shashaty MG, Stapleton RD. Physiological and management implications of obesity in critical illness. Ann Am Thorac Soc 2014; 11 (8): 1286-1297.
[30] Bergstrom N, Braden BJ, Laguzza A, Holman V. The Braden Scale for Predicting Pressure Sore Risk. Nurs Res 1987; 36 (4): 205-210.
[31] Jentzer JC, Anavekar NS, Brenes-Salazar JA, Wiley B, Murphree DH, Bennett C, Murphy JG, Keegan MT, Barsness GW. Admission Braden Skin Score independently predicts mortality in cardiac intensive care patients. Mayo Clin Proc 2019; 94 (10): 1994-2003.
[32] Rogenski NM, Kurcgant P. The incidence of pressure ulcers after the implementation of a prevention protocol. Rev Lat Am Enfermagem 2012; 20 (2): 333-339.
[33] Abdel-Qadir H, Austin PC, Lee DS, Amir E, Tu JV, Thavendiranathan P, Fung K, Anderson GM. A population-based study of cardiovascular mortality following early-stage breast cancer. JAMA Cardiol 2017; 2 (1): 88-93.
[34] van Leeuwen FE, Ng AK. Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment. Hematology Am Soc Hematol Educ Program 2016; 2016 (1): 323-330.
[35] Hatherill M, Waggie Z, Purves L, Reynolds L, Argent A. Correction of the anion gap for albumin in order to detect occult tissue anions in shock. Arch Dis Child 2002; 87 (6): 526-529.
[36] Dinh CH, Ng R, Grandinetti A, Joffe A, Chow DC. Correcting the anion gap for hypoalbuminaemia does not improve detection of hyperlactataemia. Emerg Med J 2006; 23 (8): 627-629.
[37] Higgins C. Clinical aspects of the anion gap. URL: www acutecaretesting org. 2009.
[38] Tamion F. [Albumin in sepsis]. Ann Fr Anesth Reanim 2010; 29 (9): 629-634.
[39] Pongmanee W, Vattanavanit V. Can base excess and anion gap predict lactate level in diagnosis of septic shock? Open Access Emergency Medicine: OAEM 2018; 10: 1.
[40] Tang Y, Lin W, Zha L, Zeng X, Zeng X, Li G, Liu Z, Yu Z. Serum anion gap is associated with all-cause mortality among critically ill patients with congestive heart failure. Dis Markers 2020; 2020: 8833637.
[41] Xu C, Sun L, Dong M, Ullah H, Ullah H, Zhou J, Yuan Z. Serum anion gap is associated with risk of all-cause mortality in critically ill patients with acute myocardial infarction. Int J Gen Med 2022; 15: 223.
[42] Zhang T, Wang J, Li X. Association between anion gap and mortality in critically ill patients with cardiogenic shock. Int J Gen Med 2021; 14: 4765.
[43] Hassan MM. Acidosis and anion gap. new insights into metabolic syndrome: IntechOpen; 2020.
[44] Claeys MJ, Roubille F, Casella G, Zukermann R, Nikolaou N, De Luca L, Gierlotka M, Iakobishvili Z, Thiele H, Koutouzis M, Sionis A. Organization of intensive cardiac care units in Europe: Results of a multinational survey. European Heart Journal: Acute Cardiovascular Care 2020; 9 (8): 993-1001.
[45] Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Critical Care Medicine 1985; 13 (10): 818-829.
[46] Le Gall J-R, Lemeshow S, Saulnier F. A new simplified acute physiology score (SAPS II) based on a European /North American multicenter study. JAMA 1993; 270 (24): 2957-2963.