Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus

Overview

Journal Clin J Am Soc Nephrol

Specialty Nephrology

Date 2015 Mar 13

PMID 25762524

Citations 14

Authors

Lawrence S Weisberg

Affiliations

Soon will be listed here.

Abstract

Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin's role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested.

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References

Emmett M . Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): a tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle. Clin J Am Soc Nephrol. 2013; 9(1):191-200. PMC: 3878708. DOI: 10.2215/CJN.07730713. View

Levraut J, Bounatirou T, Ichai C, Ciais J, Jambou P, Hechema R . Reliability of anion gap as an indicator of blood lactate in critically ill patients. Intensive Care Med. 1997; 23(4):417-22. DOI: 10.1007/s001340050350. View

Moviat M, Terpstra A, Ruitenbeek W, Kluijtmans L, Pickkers P, van der Hoeven J . Contribution of various metabolites to the "unmeasured" anions in critically ill patients with metabolic acidosis. Crit Care Med. 2008; 36(3):752-8. DOI: 10.1097/CCM.0B013E31816443CB. View

Gabow P, Kaehny W, Fennessey P, Goodman S, Gross P, Schrier R . Diagnostic importance of an increased serum anion gap. N Engl J Med. 1980; 303(15):854-8. DOI: 10.1056/NEJM198010093031505. View

Moe O, Fuster D . Clinical acid-base pathophysiology: disorders of plasma anion gap. Best Pract Res Clin Endocrinol Metab. 2003; 17(4):559-74. DOI: 10.1016/s1521-690x(03)00054-x. View

Cooper D, Walley K, Wiggs B, Russell J . Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med. 1990; 112(7):492-8. DOI: 10.7326/0003-4819-112-7-492. View

Andersen L, Mackenhauer J, Roberts J, Berg K, Cocchi M, Donnino M . Etiology and therapeutic approach to elevated lactate levels. Mayo Clin Proc. 2013; 88(10):1127-40. PMC: 3975915. DOI: 10.1016/j.mayocp.2013.06.012. View

Levy B . Bench-to-bedside review: Is there a place for epinephrine in septic shock?. Crit Care. 2005; 9(6):561-5. PMC: 1414043. DOI: 10.1186/cc3901. View

Lalau J . Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf. 2010; 33(9):727-40. DOI: 10.2165/11536790-000000000-00000. View

10.

Vecchio S, Giampreti A, Petrolini V, Lonati D, Protti A, Papa P . Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol (Phila). 2013; 52(2):129-35. DOI: 10.3109/15563650.2013.860985. View

11.

Pedersen K . Binding of calcium to serum albumin. II. Effect of pH via competitive hydrogen and calcium ion binding to the imidazole groups of albumin. Scand J Clin Lab Invest. 1972; 29(1):75-83. DOI: 10.3109/00365517209081058. View

12.

Kirpichnikov D, McFarlane S, Sowers J . Metformin: an update. Ann Intern Med. 2002; 137(1):25-33. DOI: 10.7326/0003-4819-137-1-200207020-00009. View

13.

Rachoin J, Weisberg L, McFadden C . Treatment of lactic acidosis: appropriate confusion. J Hosp Med. 2010; 5(4):E1-7. DOI: 10.1002/jhm.600. View

14.

Arieff A, Leach W, Park R, Lazarowitz V . Systemic effects of NaHCO3 in experimental lactic acidosis in dogs. Am J Physiol. 1982; 242(6):F586-91. DOI: 10.1152/ajprenal.1982.242.6.F586. View

15.

Gray L, Tompkins S, Taylor E . Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci. 2013; 71(14):2577-604. PMC: 4059968. DOI: 10.1007/s00018-013-1539-2. View

16.

Scale T, Harvey J . Diabetes, metformin and lactic acidosis. Clin Endocrinol (Oxf). 2010; 74(2):191-6. DOI: 10.1111/j.1365-2265.2010.03891.x. View

17.

Zahler R, Barrett E, Majumdar S, Greene R, Gore J . Lactic acidosis: effect of treatment on intracellular pH and energetics in living rat heart. Am J Physiol. 1992; 262(5 Pt 2):H1572-8. DOI: 10.1152/ajpheart.1992.262.5.H1572. View

18.

De Corte W, Vuylsteke S, De Waele J, Dhondt A, Decruyenaere J, Vanholder R . Severe lactic acidosis in critically ill patients with acute kidney injury treated with renal replacement therapy. J Crit Care. 2014; 29(4):650-5. DOI: 10.1016/j.jcrc.2014.02.019. View

19.

Lalau J, Andrejak M, Moriniere P, Coevoet B, Debussche X, Westeel P . Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin: a study of metformin elimination. Int J Clin Pharmacol Ther Toxicol. 1989; 27(6):285-8. View

20.

Kraut J, Kurtz I . Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol. 2007; 3(1):208-25. DOI: 10.2215/CJN.03220807. View