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. 2002 Dec;87(6):526–529. doi: 10.1136/adc.87.6.526

Correction of the anion gap for albumin in order to detect occult tissue anions in shock

M Hatherill 1, Z Waggie 1, L Purves 1, L Reynolds 1, A Argent 1
PMCID: PMC1755806  PMID: 12456555

Abstract

Background: It is believed that hypoalbuminaemia confounds interpretation of the anion gap (AG) unless corrected for serum albumin in critically ill children with shock.

Aim: To compare the ability of the AG and the albumin corrected anion gap (CAG) to detect the presence of occult tissue anions.

Methods: Prospective observational study in children with shock in a 22 bed multidisciplinary paediatric intensive care unit of a university childrenrsquo;s hospital. Blood was sampled at admission and at 24 hours, for acid-base parameters, serum albumin, and electrolytes. Occult tissue anions (lactate + truly "unmeasured" anions) were calculated from the strong ion gap. The anion gap ((Na + K) - (Cl + bicarbonate)) was corrected for serum albumin using the equation of Figge: AG + (0.25 x (44 - albumin)). Occult tissue anions (TA) predicted by the anion gap were calculated by (anion gap - 15 mEq/l). Optimal cut off values of anion gap were compared by means of receiver operating characteristic (ROC) curves. Ninety three sets of data from 55 children (median age 7 months, median weight 4.9 kg) were analysed. Data are expressed as mean (SD), and mean bias (limits of agreement).

Results: The incidence of hypoalbuminaemia was 76% (n = 42/55). Mean serum albumin was 25 g/l (SD 8). Mean AG was 15.0 mEq/l (SD 6.1), compared to the CAG of 19.9 mEq/l (SD 6.6). Mean TA was 10.2 mmol/l (SD 6.3). The AG underestimated TA with mean bias 10.2 mmol/l (4.1–16.1), compared to the CAG, mean bias 5.3 mmol/l (0.4–10.2). A clinically significant increase of TA >5 mmol/l was present in 83% (n = 77/93) of samples, of which the AG detected 48% (n = 36/77), and the CAG 87% (n = 67/77). Post hoc ROC analysis revealed optimal cut off values for detection of TA >5 mmol/l to be AG >10 mEq/l, and CAG >15.5 mEq/l.

Conclusion: Hypoalbuminaemia is common in critically ill children with shock, and is associated with a low observed anion gap that may fail to detect clinically significant amounts of lactate and other occult tissue anions. We suggest that the albumin corrected anion gap should be calculated to screen for occult tissue anions in these children.

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Selected References

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  1. Balasubramanyan N., Havens P. L., Hoffman G. M. Unmeasured anions identified by the Fencl-Stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric intensive care unit. Crit Care Med. 1999 Aug;27(8):1577–1581. doi: 10.1097/00003246-199908000-00030. [DOI] [PubMed] [Google Scholar]
  2. Carvounis C. P., Feinfeld D. A. A simple estimate of the effect of the serum albumin level on the anion Gap. Am J Nephrol. 2000 Sep-Oct;20(5):369–372. doi: 10.1159/000013618. [DOI] [PubMed] [Google Scholar]
  3. Constable P. D. Clinical assessment of acid-base status. Strong ion difference theory. Vet Clin North Am Food Anim Pract. 1999 Nov;15(3):447–471. doi: 10.1016/s0749-0720(15)30158-4. [DOI] [PubMed] [Google Scholar]
  4. Durward A., Skellett S., Mayer A., Taylor D., Tibby S. M., Murdoch I. A. The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis. Intensive Care Med. 2001 May;27(5):828–835. doi: 10.1007/s001340100915. [DOI] [PubMed] [Google Scholar]
  5. Emmett M., Narins R. G. Clinical use of the anion gap. Medicine (Baltimore) 1977 Jan;56(1):38–54. [PubMed] [Google Scholar]
  6. Fencl V., Jabor A., Kazda A., Figge J. Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med. 2000 Dec;162(6):2246–2251. doi: 10.1164/ajrccm.162.6.9904099. [DOI] [PubMed] [Google Scholar]
  7. Figge J., Jabor A., Kazda A., Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998 Nov;26(11):1807–1810. doi: 10.1097/00003246-199811000-00019. [DOI] [PubMed] [Google Scholar]
  8. Figge J., Mydosh T., Fencl V. Serum proteins and acid-base equilibria: a follow-up. J Lab Clin Med. 1992 Nov;120(5):713–719. [PubMed] [Google Scholar]
  9. Figge J., Rossing T. H., Fencl V. The role of serum proteins in acid-base equilibria. J Lab Clin Med. 1991 Jun;117(6):453–467. [PubMed] [Google Scholar]
  10. Frohlich J., Adam W., Golbey M. J., Bernstein M. Decreased anion gap associated with monoclonal and pseudomonoclonal gammopathy. Can Med Assoc J. 1976 Feb 7;114(3):231–232. [PMC free article] [PubMed] [Google Scholar]
  11. Hatherill M., McIntyre A. G., Wattie M., Murdoch I. A. Early hyperlactataemia in critically ill children. Intensive Care Med. 2000 Mar;26(3):314–318. doi: 10.1007/s001340051155. [DOI] [PubMed] [Google Scholar]
  12. Jurado R. L., del Rio C., Nassar G., Navarette J., Pimentel J. L., Jr Low anion gap. South Med J. 1998 Jul;91(7):624–629. doi: 10.1097/00007611-199807000-00004. [DOI] [PubMed] [Google Scholar]
  13. Kellum J. A., Kramer D. J., Pinsky M. R. Strong ion gap: a methodology for exploring unexplained anions. J Crit Care. 1995 Jun;10(2):51–55. doi: 10.1016/0883-9441(95)90016-0. [DOI] [PubMed] [Google Scholar]
  14. Lolekha P. H., Lolekha S. Value of the anion gap in clinical diagnosis and laboratory evaluation. Clin Chem. 1983 Feb;29(2):279–283. [PubMed] [Google Scholar]
  15. Lolekha P. H., Vanavanan S., Teerakarnjana N., Chaichanajarernkul U. Reference ranges of electrolyte and anion gap on the Beckman E4A, Beckman Synchron CX5, Nova CRT, and Nova Stat Profile Ultra. Clin Chim Acta. 2001 May;307(1-2):87–93. doi: 10.1016/s0009-8981(01)00437-5. [DOI] [PubMed] [Google Scholar]
  16. McAuliffe J. J., Lind L. J., Leith D. E., Fencl V. Hypoproteinemic alkalosis. Am J Med. 1986 Jul;81(1):86–90. doi: 10.1016/0002-9343(86)90187-7. [DOI] [PubMed] [Google Scholar]
  17. Mizock B. A., Falk J. L. Lactic acidosis in critical illness. Crit Care Med. 1992 Jan;20(1):80–93. doi: 10.1097/00003246-199201000-00020. [DOI] [PubMed] [Google Scholar]
  18. Nanji A. A., Campbell D. J., Pudek M. R. Decreased anion gap associated with hypoalbuminemia and polyclonal gammopathy. JAMA. 1981 Aug 21;246(8):859–860. [PubMed] [Google Scholar]
  19. Oh M. S., Carroll H. J. The anion gap. N Engl J Med. 1977 Oct 13;297(15):814–817. doi: 10.1056/NEJM197710132971507. [DOI] [PubMed] [Google Scholar]
  20. Roberts W. L., Johnson R. D. The serum anion gap. Has the reference interval really fallen? Arch Pathol Lab Med. 1997 Jun;121(6):568–572. [PubMed] [Google Scholar]
  21. Sheth K. J., Kher K. K. Anion gap in nephrotic syndrome. Int J Pediatr Nephrol. 1984 Jun;5(2):89–92. [PubMed] [Google Scholar]
  22. Singh R. N., Singh N. C., Hutchison J., Moses G. C. Lower anion gap increases sensitivity in predicting elevated lactate. Clin Intensive Care. 1994;5(5):221–224. [PubMed] [Google Scholar]
  23. Stewart P. A. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983 Dec;61(12):1444–1461. doi: 10.1139/y83-207. [DOI] [PubMed] [Google Scholar]
  24. Thomas D. W., Pain R. W., Duncan B. M. Letter: The anion gap. Lancet. 1973 Oct 13;2(7833):848–849. doi: 10.1016/s0140-6736(73)90893-3. [DOI] [PubMed] [Google Scholar]
  25. Weil M. H., Afifi A. A. Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation. 1970 Jun;41(6):989–1001. doi: 10.1161/01.cir.41.6.989. [DOI] [PubMed] [Google Scholar]
  26. Wilkes P. Hypoproteinemia, strong-ion difference, and acid-base status in critically ill patients. J Appl Physiol (1985) 1998 May;84(5):1740–1748. doi: 10.1152/jappl.1998.84.5.1740. [DOI] [PubMed] [Google Scholar]
  27. Winter S. D., Pearson J. R., Gabow P. A., Schultz A. L., Lepoff R. B. The fall of the serum anion gap. Arch Intern Med. 1990 Feb;150(2):311–313. [PubMed] [Google Scholar]
  28. Witte D. L., Rodgers J. L., Barrett D. A., 2nd The anion gap: its use in quality control. Clin Chem. 1976 May;22(5):643–646. [PubMed] [Google Scholar]

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