Therapy of Lactic Acidosis: Alternatives to Sodium Bicarbonate

  • Allen I. Arieff
Part of the Clinical Physiology Series book series (CLINPHY)


Lactic acidosis is the most common form of metabolic acidosis, and the current mortality from this condition is in excess of 50%. Because of its diverse pathophysiology, the clinical management of lactic acidosis is difficult. The mainstay of therapy has traditionally been the intravenous administration of sodium bicarbonate (NaHCO3), but recent clinical and experimental evidence strongly suggests that such therapy may in fact be detrimental. Lactic acidosis is generally defined as a metabolic acidosis due to the accumulation of lactic acid in the blood in excess of 5 mM, with an accompanying blood pH of less than 7.25. However, the mechanisms by which lactic acid accumulation occurs vary and include both the stimulation of lactate production and reductions of lactate metabolism. Clinically, the disorders of lactate metabolism are conveniently divided as either anaerobic (type A) or aerobic (type B) (16). The hallmark of type A lactic acidosis is tissue hypoxia, resulting in anaerobic lactic acid production. The most common causes of type A lactic acidosis are cardiopulmonary arrest and other states characterized by impaired cardiac performance, reduced tissue perfusion, and arterial hypoxemia. In these states, the hypoxia and circulatory insufficiency combine to reduce tissue oxygen availability, resulting in anaerobic metabolism and stimulation of lactic acid production. In type B lactic acidosis, on the other hand, tissue hypoxia appears not to be present, and lactic acid production is metabolically enhanced for other reasons in what is apparently an aerobic state. Examples of type B lactic acidosis include diabetes mellitus, certain malignancies, and congenital diseases of the liver that impair lactic acid metabolism. Of the two forms of lactic acidosis, type A is by far the more important clinical problem and is generally associated with a much higher morbidity and mortality. Cardiopulmonary arrest is probably the most common cause of type A lactic acidosis in the United States and Europe. Accordingly, the discussion of the therapy of lactic acidosis will focus primarily on the management of type A lactic acidosis.


Metabolic Acidosis Lactic Acidosis Sodium Bicarbonate Lactic Acid Production Tissue Oxygen Delivery 
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  1. 1.
    National Conference on Cardiopulmonary Resuscitation: Standards and guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). Part III: Adult advanced cardiac life support. JAMA 255: 2933–2954, 1986.Google Scholar
  2. 2.
    Stacpoole, P. W.: The design of a randomized, multicenter study of dichloroacetate (DCA) as a treatment for lactic acidosis. Soc. Clin. Trials 8: 291–292, 1987.Google Scholar
  3. 3.
    Arieff, A. I., E. W. Gertz, R. Park, W. Leach, and V. C. Lazarowitz: Lactic acidosis and the cardiovascular system in the dog. Clin. Sci. (Oxford) 64: 573–580, 1983.Google Scholar
  4. 4.
    Arieff, A. I., and H. Graf: Pathophysiology of type A hypoxic lactic acidosis in dogs. Am. J. Physiol. (Endocrine Metab.) 253: E271 - E276, 1987.Google Scholar
  5. 5.
    Arieff, A. I., and A. Kerian: Lactic acidosis: An experimental model. Metabolism 25: 307–312, 1976.CrossRefGoogle Scholar
  6. 6.
    Arieff, A. I., A. Kerian, S. G. Massry, and J. Delima: Intracellular pH of brain: Alterations in acute respiratory acidosis and alkalosis. Am. J. Physiol. 230: 804–812, 1976.PubMedGoogle Scholar
  7. 7.
    Arieff, A. I., R. Park, W. J. Leach, and V. C. Lazarowitz: Pathophysiology of experimental lactic acidosis in dogs. Am. J. Physiol. (Renal Fluid Electrolyte Physiol.) 239: F135 - F142, 1980.Google Scholar
  8. 8.
    Bersin, R. M., and A. I. Arieff: Improved hemodynamic function during hypoxia with carbicarb, a new agent for the management of acidosis. Circulation 77: 227–233, 1988.PubMedCrossRefGoogle Scholar
  9. 9.
    Bihari, D., M. Smithies, A. Gimson, and J. Tinker: The effects of vasodilation with prostacylin on oxygen delivery and uptake in critically ill patients. N. Engl. J. Med. 317: 397–403, 1987.PubMedCrossRefGoogle Scholar
  10. 10.
    Bishop, R. L., and M. L. Weisfeldt: Sodium bicarbonate administration during cardiac arrest. Effect on arterial pH, pco2, and osmolality. JAMA 235: 506–509, 1976.PubMedCrossRefGoogle Scholar
  11. 11.
    Bureau, M. A., R. Begin, Y. Berthiaume, D. Shappcott, K. Khoury, and N. Gagnonn: Cerebral hypoxia from bicarbonate infusion in diabetic acidosis. J. Pediatr. 96: 968–973, 1980.PubMedCrossRefGoogle Scholar
  12. 12.
    Burns, A. H., M. E. Giaimo, and W. R. Summer: Dichoroacetate acid improves in vitro myocardial function following in vivo endotoxin administration. J. Crit. Care 1: 11–17, 1986.CrossRefGoogle Scholar
  13. 13.
    Burns, A. H., W. R. Summer, L. A. R. Burns, and L. E. R. Shepherd: Inotropic interactions of dichloroacetate with amrinone and ouabain in isolated hearts from endotoxinshocked rats. J. Cardiovasc. Pharmacol. 11: 379–386, 1988.PubMedCrossRefGoogle Scholar
  14. 14.
    Capparelli, E., M. Chow, J. Kluger, and A. Fieldman: Differences in arterial, venous and myocardial blood acid—base status during cardiopulmonary resuscitation. J. Am. Coll. Cardiol. 9: 201A, 1987.Google Scholar
  15. 15.
    Cohen, R. D., R. A. Iles, D. Barnett, M. E. O. Howell, and J. Strunin: The effect of changes in lactate uptake on the intracellular pH of the perfused rat liver. Clin. Sci. 41: 159–170, 1971.PubMedGoogle Scholar
  16. 16.
    Cohen, R. D., and H. F. Woods: In: The clinical presentations and classification of lactic acidosis. Clinical and Biochemical Aspects of Lactic Acidosis, edited by R. D. Cohen and H. F. Woods. Oxford: Blackwell Scientific Publications, 1976, p. 40–76.Google Scholar
  17. 17.
    Conant, J. S., and R. E. Hughs: The usefulness of THAM in metabolic acidosis. Ann. NY Acad. Sci. 92: 751–754, 1961.PubMedCrossRefGoogle Scholar
  18. 18.
    Cooper, D. J., and L. I. G. Worthley: Adverse haemodynamic effects of sodium bicarbonate in metabolic acidosis. Intensive Care Med. 13: 425–427, 1987.PubMedCrossRefGoogle Scholar
  19. 19.
    Cooper, J. D., K. R. Walley, B. R. Wiggs, and J. A. Russell: Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. Ann. intern. Med. 112: 492–498, 1980.CrossRefGoogle Scholar
  20. 20.
    Downing, S. E., N. S. Talner, and T. H. Gardner: Cardiovascular responses to metabolic acidosis. Am. J. Physiol. 208: 237–242, 1965.PubMedGoogle Scholar
  21. 21.
    Downing, S. E., N. S. Talner, and T. H. Gardner: Influences of arterial oxygen tension and pH on cardiac function in the newborn lamb. Am. J. Physiol. 211: 1203–1208, 1966.PubMedGoogle Scholar
  22. 22.
    Effron, M. B., T. Guarnieri, J. W. Frederiksen, H. L. Greene, and M. L. Weisfeldt: Effect of tris (hydroxymethyl)aminomethane on ischemic myocardium. Am. J. Physiol. (Heart Circ. Physiol.) 235: H167 - H174, 1978.Google Scholar
  23. 23.
    Filley, G. F., and N. B. Kindig: Carbicarb, an alkalinizing ion generating agent of possible clinical usefulness. Trans. Am. Clin. Climatol. Assoc. 96: 141–153, 1984.Google Scholar
  24. 24.
    Fulop, M., M. Horowitz, A. Aberman, and E. R. Jaffe: Lactic acidosis in pulmonary edema due to left ventricular failure. Ann. Intern. Med. 79: 180–186, 1973.PubMedCrossRefGoogle Scholar
  25. 25.
    Graf, H., and A. I. Arieff: The use of sodium bicarbonate in the therapy of organic acidosis. Intensive Care Med. 12: 1–4, 1986.CrossRefGoogle Scholar
  26. 26.
    Graf, H., W. Leach, and A. I. Arieff: Effects of dichloroacetate in the treatment of hypoxic lactic acidosis in dogs. J. Clin. Invest. 76: 919–923, 1985.PubMedCrossRefGoogle Scholar
  27. 27.
    Graf, H., W. Leach, and A. I. Arieff: Evidence for a detrimental effect of bicarbonate therapy in hypoxic lactic acidosis. Science 227: 754–756, 1985.PubMedCrossRefGoogle Scholar
  28. 28.
    Graf, H., W. Leach, and A. I. Arieff: Metabolic effects of sodium bicarbonate in hypoxic lactic acidosis in dogs. Am. J. Physiol. (Renal Fluid Electrolyte Physiol.) 249: F630 - F635, 1985.Google Scholar
  29. 29.
    Harvey, R. M., Y. Enson, M. L. Lewis, W. B. Greenough, K. M. Ally, and R. A. Panno: Hemodynamic effects of dehydration and metabolic acidosis in Asiatic cholera. Trans. Assoc. Am. Physicians 79: 177–186, 1966.PubMedGoogle Scholar
  30. 30.
    Hope, P. L., E. B. Cady, D. T. Delpy, N. K. Ives, R. M. Gardiner, and E. O. Reynolds: Brain metabolism and intracellular pH during ischaemia: Effects of systemic glucose and bicarbonate administration studied by 31P and ‘H nuclear magnetic resonance spectroscopy in vivo in the lamb. J. Neurochem. 50: 1394–1402, 1988.PubMedCrossRefGoogle Scholar
  31. 31.
    Huckabee, W. E.: Abnormal blood lactate II. Lactic acidosis. Am. J. Med. 30: 840–848, 1961.PubMedCrossRefGoogle Scholar
  32. 32.
    Ichihara, K., N. Haga, and A. Yasushi: Is ischemia-induced pH decrease of dog myocardium respiratory or metabolic acidosis? Am. J. Physiol. (Heart Circ. Physiol.) 246: H652 - H657, 1984.Google Scholar
  33. 33.
    Iles, R. A., P. G. Baron, and R. D. Cohen: Mechanism of the effect of varying pc02 on gluconeogenesis from lactate in the perfused rat liver. Clin. Sci. Mol. Med. 55: 183–188, 1978.PubMedGoogle Scholar
  34. 34.
    Khuri, S. F., R. A. Loner, S. A. Karaffa, W. Marston, A. D. Taylor, N. C. J. Lai, D. E. Tow, and E. M. Barasmian: The significance of the late fall in myocardial pco2 and its relationship to myocardial pH after regional occlusion in the dog. Circ. Res. 56: 537–547, 1985.PubMedCrossRefGoogle Scholar
  35. 35.
    Kindig, N. B., L. V. Owens, and G. F. Filley: Carbicarb as a replacement for NaHCO3: Theory and in vitro experiments. Appl. Cardiopulm. Pathophysiol. 2: 231–240, 1987.Google Scholar
  36. 36.
    Kreisberg, R. A.: Lactate homeostasis and lactic acidosis. Ann. Intern. Med. 92: 227–237, 1980.PubMedCrossRefGoogle Scholar
  37. 37.
    Kubo, S. H., B. A. Walter, D. H. A. John, M. Clark, and R. J. Cody: Liver function abnormalities in chronic heart failure. Arch. Intern. Med. 147: 1227–1230, 1987.PubMedCrossRefGoogle Scholar
  38. 38.
    Lloyd, M. H., R. A. Iles, B. Walton, C. A. Hamilton, and R. D. Cohen: Effect of phenformin on gluconeogenesis from lactate and intracellular pH in the isolated perfused guinea pig liver. Diabetes 24: 618–624, 1975.PubMedCrossRefGoogle Scholar
  39. 39.
    Lloyd, M. N., R. A. Iles, B. R. Simpson, J. M. Strunin, J. M. Layton, and R. D. Cohen: The effect of simulated metabolic acidosis in intracellular pH and lactate metabolism in the isolated perfused rat liver. Clin. Sci. Mol. Med. 45: 543–549, 1973.PubMedGoogle Scholar
  40. 40.
    Luchsinger, P. C.: The use of 2-amino-2-hydroxymethyl-1,3-propanediol in the management of respiratory acidosis. Ann. NYAcad. Sci. 92: 743–750, 1961.Google Scholar
  41. 41.
    Madias, N. E.: Lactic acidosis. Kidney Int. 29: 752–774, 1986.PubMedCrossRefGoogle Scholar
  42. 42.
    Mark, N. H., J. M. Leung, A. I. Arieff, and D. T. Mangano: Evidence for a detrimental metabolic effect of sodium bicarbonate in operative patients with metabolic acidosis. Kidney Int. 37: 267, 1990.Google Scholar
  43. 43.
    Matsuoka, S., D. Toshima, E. Naito, T. Nakatsu, Y. Miyauchi, Y. Kuroda, and M. Miayo: Effects of dichloroacetate on the mechanical function of the isolated ischemic heart. Jpn. Heart J. 28: 531–537, 1987.PubMedCrossRefGoogle Scholar
  44. 44.
    Mattar, J. A., M. H. Weil, H. Shubin, and L. Stein: Cardiac arrest in the critically ill. II. Hyperosmolar states following cardiac arrest. Am. J. Med. 56: 162–168, 1974.PubMedCrossRefGoogle Scholar
  45. 45.
    Minot, A. S., K. Dodd, and J. M. Saunders: The acidosis of guanidine intoxication. J. Clin. Invest. 13: 917–932, 1934.PubMedCrossRefGoogle Scholar
  46. 46.
    Mitchell, J. H., K. Wildenthal, and R. L. Johnson: The effects of acid—base disturbances on cardiovascular function. Kidney Int. 1: 375–389, 1972.PubMedCrossRefGoogle Scholar
  47. 47.
    Maos, O. D., N. E. Miller, R. A. Riemersma, and M. F. Oliver: Effects of dichloroacetate on myocardial substrate extraction, epicardial ST-segment elevation, and ventricular blood flow following coronary occlusion in dogs. Cardiovasc. Res. 10: 427–436, 1976.CrossRefGoogle Scholar
  48. 48.
    Narins, R. G., E. R. Jones, R. Townsend, D. A. Goodkin, and R. J. Shay: Metabolic acid base disorders; pathophysiology, classification and treatment. In: Fluid, Electrolyte and Acid Base Disorders,edited by A. I. Arieff and R. A. DeFronzo. New York: Churchill Livingstone, 1985, p. 281–335.Google Scholar
  49. 49.
    Ng, M. L., M. N. Levy, and H. A. Zieske: Effects of changes of pH and of carbon dioxide tension on left ventricular performance. Am. J. Physiol. 213: 115–120, 1967.PubMedGoogle Scholar
  50. 50.
    Ostrea, E. M., and G. B. Odell: The influence of bicarbonate administration on blood pH in a “closed system”: Clinical implications. Fetal Neonat. Med. 80: 671–680, 1972.Google Scholar
  51. 51.
    Park, R., and A. I. Arieff: Pathogenesis and treatment of lactic acidosis. In: Schade, D. S., ed. Clinics in Endocrinology and Metabolism, Philadelphia: W. B. Saunders, vol. 12, 1983, p. 339–358.Google Scholar
  52. 52.
    Park, R., A. I. Arieff, W. Leach, and V. C. Lazarowitz: Treatment of lactic acidosis with dichloroacetate in dogs. J. Clin. Invest. 70: 853–862, 1982.PubMedCrossRefGoogle Scholar
  53. 53.
    Park, R., W. J. Leach, and A. I. Arieff: Determination of liver intracellular pH in vivo and its homeostasis in acute acidosis and alkalosis. Am. J. Physiol. (Renal Fluid Electrolyte Physiol.) 236: F240 - F245, 1979.Google Scholar
  54. 54.
    Park, R., P. R. Radosevich, W. J. Leach, P. Seto, and A. I. Arieff: Metabolic effects of dichloroacetate in diabetic dogs. Am. J. Physiol. (Endocrine Metab.) 245: E94 - E101, 1983.Google Scholar
  55. 55.
    Rees, S. B., M. D. Younger, and A. E. Freedlender: Some in vivo and in vitro observations on the effects of Tris in diabetic acidosis. Ann. NYAcad. Sci. 92: 755–764, 1961.CrossRefGoogle Scholar
  56. 56.
    Robin, E. D., R. J. Wilson, and P. A. Bromberg: Intracellular acid—base relations and intracellular buffers. Ann. NYAcad. Sci. 92 539–546, 1961.CrossRefGoogle Scholar
  57. 57.
    Samiy, A. H., A. G. Ramsay, S. B. Rees, and J. P. Merrill: The use of 2-amino-w-hydroxymethyl-1,3-propanediol in the management of renal acidosis. Ann. NY Acad. Sci. 92: 802–812, 1961.PubMedCrossRefGoogle Scholar
  58. 58.
    Schaffer, W. T., and M. S. Olson: The regulation of pyruvate oxidation during membrane depolarization of rat brain synaptosomes. Biochem. J. 192 741–751, 1980.PubMedGoogle Scholar
  59. 59.
    Shapiro, J. I., A. Mathew, M. Whalen, B. Honigman, W. D. Kaehny, T. L. Petty, and L. Chan: Different effects of sodium bicarbonate and an alternate buffer (Carbicarb) in normal volunteers. J. Crit. Care (in press).Google Scholar
  60. 60.
    Shapiro, J. I., M. Whalen, R. Kucera, N. Kindig, G. Filley, and L. Chan: Brain pH responses to sodium bicarbonate and Carbicarb during systemic acidosis. Am. J. Physiol. (Heart Circ. Physiol.) 256: H1316 - H1321, 1989.Google Scholar
  61. 61.
    Stacpoole, P. W.: Effect of dichloroacetate on gluconeogenesis in isolated rat hepatocytes. Metabolism 26: 107–116, 1976.CrossRefGoogle Scholar
  62. 62.
    Stacpoole, P. W.: Lactic acidosis: The case against bicarbonate therapy. Ann. Intern. Med. 105: 276–279, 1986.PubMedCrossRefGoogle Scholar
  63. 63.
    Stacpoole, P. W.: The pharmacology of dichloroacetate. Metabolism 38: 1124–1144, 1989.PubMedCrossRefGoogle Scholar
  64. 64.
    Stacpoole, P. W., E. M. Harman, S. H. Curry, T. G. Baumgartner, and R. I. Misbin: Treatment of lactic acidosis with dichloroacetate. N. Engl. J. Med. 309: 390–396, 1983.PubMedCrossRefGoogle Scholar
  65. 65.
    Steenbergen, C., G. Deleuw, T. Rich, and J. R. Williamson: Effects of acidosis and ischemia on contractility and intracellualr pH of rat heart. Circ. Res. 41: 849–858, 1981.CrossRefGoogle Scholar
  66. 66.
    Sun, J. H., G. F. Filley, K. Hord, N. B. Kindig, and E. J. Bartle: Carbicarb: An effective substitute for NaHCO3 for the treatment of acidosis. Surgery 102: 835–839, 1987.PubMedGoogle Scholar
  67. 67.
    Taradash, M. R., and L. B. Jacobson: Vasodilator therapy of idiopathic lactic acidosis. N. Engl. J. Med. 293: 468–471, 1975.PubMedCrossRefGoogle Scholar
  68. 68.
    Tranquada, R. E., S. Bernstein, and W. J. Grant: Intravenous methylene blue in the therapy of lactic acidosis. Arch. Intern. Med. 114: 13–25, 1964.PubMedCrossRefGoogle Scholar
  69. 69.
    Waters, W. C., J. D. Hall, and W. B. Schwartz: Spontaneous lactic acidosis. Am. J. Med. 35: 781–793, 1963.PubMedCrossRefGoogle Scholar
  70. 70.
    Weil, M. H., E. C. Rackow, R. Trevino, W. Grundler, J. L. Falk, and M. I. Griffel: Difference in acid—base state between venous and arterial blood during cardiopulmonary resuscitation. N. Engl. J. Med. 315: 153–156, 1986.PubMedCrossRefGoogle Scholar
  71. 71.
    Weinberger, S. E., R. M. Schwartzstein, and J. W. Weiss: Hypercapnia. N. Engl. J. Med. 321: 1223–1231, 1989.PubMedCrossRefGoogle Scholar
  72. 72.
    Weisfeldt, M. L., R. L. Bishop, and H. L. Greene: Effects of pH and pco2 on performance of ischemic myocardium. In: Recent Advances in Studies on Cardiac Structure and Metabolism, edited by P. E. Roy and P. Harris. Baltimore: University Park Press, 1975, p. 355–364.Google Scholar
  73. 73.
    Williams, E. M. V.: The individual effects of CO„ bicarbonate and pH on the electrical and mechanical activity of isolated rabbit auricles. J. Physiol. 129: 90–110, 1955.Google Scholar

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  • Allen I. Arieff

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