This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

Conflict(s) of Interest

All authors have no conflict of interest to disclose.

References with DOI

1. Jung B, Rimmele T, Le Goff C, Chanques G, Corne P, Jonquet O, Muller L, Lefrant JY, Guervilly C, Papazian L, Allaouchiche B and Jaber S. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study. Crit Care. 2011;15:R238. https://doi.org/10.1186/cc10487

2. Kraut JA and Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010;6:274-85. https://doi.org/10.1038/nrneph.2010.33

3. Lee SW, Hong YS, Park DW, Choi SH, Moon SW, Park JS, Kim JY and Baek KJ. Lactic acidosis not hyperlactatemia as a predictor of in hospital mortality in septic emergency patients. Emerg Med J. 2008;25:659-65. https://doi.org/10.1136/emj.2007.055558

4. Gabow PA, Kaehny WD, Fennessey PV, Goodman SI, Gross PA and Schrier RW. Diagnostic importance of an increased serum anion gap. N Engl J Med. 1980;303:854-8. https://doi.org/10.1056/nejm198010093031505

5. Kraut JA and Madias NE. Lactic acidosis. N Engl J Med. 2014;371:2309-19. https://doi.org/10.1056/nejmra1309483

6. Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol. 2001;12 Suppl 17:S15-9.

7. Adeva-Andany M, Lopez-Ojen M, Funcasta-Calderon R, Ameneiros-Rodriguez E, Donapetry-Garcia C, Vila-Altesor M and Rodriguez-Seijas J. Comprehensive review on lactate metabolism in human health. Mitochondrion. 2014;17:76-100. https://doi.org/10.1016/j.mito.2014.05.007

8. Madias NE. Lactic acidosis. Kidney Int. 1986;29:752-74. https://doi.org/10.1038/ki.1986.62

9. Cingolani HE, Mattiazzi AR, Blesa ES and Gonzalez NC. Contractility in isolated mammalian heart muscle after acid-base changes. Circ Res. 1970;26:269-78. https://doi.org/10.1161/01.res.26.3.269

10. Fabiato A and Fabiato F. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. J Physiol. 1978;276:233-55. https://doi.org/10.1113/jphysiol.1978.sp012231

11. Solaro RJ, Lee JA, Kentish JC and Allen DG. Effects of acidosis on ventricular muscle from adult and neonatal rats. Circ Res. 1988;63:779-87. https://doi.org/10.1161/01.res.63.4.779

12. Shapiro JI. Functional and metabolic responses of isolated hearts to acidosis: effects of sodium bicarbonate and Carbicarb. The American journal of physiology. 1990;258:H1835-9.

13. Schotola H, Toischer K, Popov AF, Renner A, Schmitto JD, Gummert J, Quintel M, Bauer M, Maier LS and Sossalla S. Mild metabolic acidosis impairs the beta-adrenergic response in isolated human failing myocardium. Crit Care. 2012;16:R153. https://doi.org/10.1186/cc11468

14. Kimmoun A, Ducrocq N and Levy B. New conclusive data on human myocardial dysfunction induced by acidosis. Crit Care. 2012;16:160. https://doi.org/10.1186/cc11520

15. Shapiro JI. Pathogenesis of cardiac dysfunction during metabolic acidosis: therapeutic implications. Kidney international Supplement. 1997;61:S47-51.

16. Shapiro JI, Whalen M and Chan L. Hemodynamic and hepatic pH responses to sodium bicarbonate and Carbicarb during systemic acidosis. Magn Reson Med. 1990;16:403-10. https://doi.org/10.1002/mrm.1910160306

17. Suleymanlar G, Zhou HZ, McCormack M, Elkins N, Kucera R, Reiss OK and Shapiro JI. Mechanism of impaired energy metabolism during acidosis: role of oxidative metabolism. The American journal of physiology. 1992;262:H1818-22.

18. Harrison SM, Frampton JE, McCall E, Boyett MR and Orchard CH. Contraction and intracellular Ca2+, Na+, and H+ during acidosis in rat ventricular myocytes. The American journal of physiology. 1992;262:C348-57.

19. Choi HS, Trafford AW, Orchard CH and Eisner DA. The effect of acidosis on systolic Ca2+ and sarcoplasmic reticulum calcium content in isolated rat ventricular myocytes. The Journal of physiology. 2000;529 Pt 3:661-8.

20. Sikes PJ, Zhao P, Maass DL, White J and Horton JW. Sodium/hydrogen exchange activity in sepsis and in sepsis complicated by previous injury: 31P and 23Na NMR study. Crit Care Med. 2005;33:605-15. https://doi.org/10.1097/01.ccm.0000155910.89252.fe

21. DeSantiago J, Maier LS and Bers DM. Phospholamban is required for CaMKII-dependent recovery of Ca transients and SR Ca reuptake during acidosis in cardiac myocytes. J Mol Cell Cardiol. 2004;36:67-74. https://doi.org/10.1016/j.yjmcc.2003.10.012

22. Wu LL, Tang C, Dong LW and Liu MS. Altered phospholamban-calcium ATPase interaction in cardiac sarcoplasmic reticulum during the progression of sepsis. Shock. 2002;17:389-93. https://doi.org/10.1097/00024382-200205000-00008

23. Dong LW, Wu LL, Ji Y and Liu MS. Impairment of the ryanodine-sensitive calcium release channels in the cardiac sarcoplasmic reticulum and its underlying mechanism during the hypodynamic phase of sepsis. Shock. 2001;16:33-9. https://doi.org/10.1097/00024382-200116010-00007

24. Katz AM and Hecht HH. Editorial: the early "pump" failure of the ischemic heart. Am J Med. 1969;47:497- 502. https://doi.org/10.1016/0002-9343(69)90180-6

25. Miller RG, Boska MD, Moussavi RS, Carson PJ and Weiner MW. 31P nuclear magnetic resonance studies of high energy phosphates and pH in human muscle fatigue. Comparison of aerobic and anaerobic exercise. J Clin Invest. 1988;81:1190-6. https://doi.org/10.1172/jci113434

26. Kimmoun A, Novy E, Auchet T, Ducrocq N and Levy B. Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside. Crit Care. 2015;19:175. https://doi.org/10.1186/s13054-015-0896-7

27. Mitchell JH, Wildenthal K and Johnson RL, Jr. The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney international. 1972;1:375-89. https://doi.org/10.1038/ki.1972.48

28. Darby TD and Watts DT. ACIDOSIS AND BLOOD EPINEPHRINE LEVELS IN HEMORRHAGIC HYPOTENSION. The American journal of physiology. 1964;206:1281-4.

29. Nahas GG, Zagury D, Milhaud A, Manger WM and Pappas GD. Acidemia and catecholamine output of the isolated canine adrenal gland. The American journal of physiology. 1967;213:1186-92.

30. Nahas GG, Ligou JC and Mehlman B. Effects of pH changes on oxygen uptake and plasma catecholamine levels in the dog. The American journal of physiology. 1960;198:60-6.

31. Campbell GS. Cardiac arrest: further studies on the effect of pH changes on vagal inhibition of the heart. Surgery. 1955;38:615-34.

32. Cooper DJ, Walley KR, Wiggs BR and Russell JA. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Annals of internal medicine. 1990;112:492-8. https://doi.org/10.1097/00132586-199012000-00067

33. Teplinsky K, O'Toole M, Olman M, Walley KR and Wood LD. Effect of lactic acidosis on canine hemodynamics and left ventricular function. The American journal of physiology. 1990;258:H1193-9.

34. Davies AO. Rapid desensitization and uncoupling of human beta-adrenergic receptors in an in vitro model of lactic acidosis. J Clin Endocrinol Metab. 1984;59:398-405. https://doi.org/10.1210/jcem-59-3-398

35. Kellum JA, Song M and Venkataraman R. Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis. Chest. 2004;125:243-8. https://doi.org/10.1378/chest.125.1.243

26. Orchard CH and Cingolani HE. Acidosis and arrhythmias in cardiac muscle. Cardiovasc Res. 1994;28:1312-9. https://doi.org/10.1093/cvr/28.9.1312

37. Arieff AI, Leach W, Park R and Lazarowitz VC. Systemic effects of NaHCO3 in experimental lactic acidosis in dogs. The American journal of physiology. 1982;242:F586-91.

38. Graf H, Leach W and Arieff AI. Evidence for a detrimental effect of bicarbonate therapy in hypoxic lactic acidosis. Science. 1985;227:754-6. https://doi.org/10.1126/science.3969564

39. Adler S, Roy A and Relman AS. Intracellular Acid-Base Regulation. I. The Response of Muscle Cells to Changes in Co2 Tension or Extracellular Bicarbonate Concentration. J Clin Invest. 1965;44:8-20.

40. Kraut JA and Madias NE. Treatment of acute metabolic acidosis: a pathophysiologic approach. Nat Rev Nephrol. 2012;8:589-601. https://doi.org/10.1038/nrneph.2012.186

41. Shapiro JI, Whalen M, Kucera R, Kindig N, Filley G and Chan L. Brain pH responses to sodium bicarbonate and Carbicarb during systemic acidosis. The American journal of physiology. 1989;256:H1316-21.

42. Kindig NB, Sherrill DS, Shapiro JI and Filley GF. Extracorporeal bicarbonate space after bicarbonate or a bicarbonate-carbonate mixture in acidotic dogs. J Appl Physiol (1985). 1989;67:2331-4.

43. Shapiro JI, Mathew A, Whalen M, Honigman B, Kaehny WD, Petty TL and Chan L. Different effects of sodium bicarbonate and an alternate buffer (Carbicarb) in normal volunteers. Journal of Critical Care. 1990;5:157-160. https://doi.org/10.1016/0883-9441(90)90036-9

44. Olson DE, Dart GA and Filley GF. Pressure drop and fluid flow regime of air inspired into the human lung. J Appl Physiol. 1970;28:482-94.

45. Shapiro JI, Elkins N, Logan J, Ferstenberg LB and Repine JE. Effects of sodium bicarbonate, disodium carbonate, and a sodium bicarbonate/carbonate mixture on the PCO2 of blood in a closed system. J Lab Clin Med. 1995;126:65-9.

46. Kimmoun A, Ducrocq N, Sennoun N, Issa K, Strub C, Escanye JM, Leclerc S and Levy B. Efficient extra- and intracellular alkalinization improves cardiovascular functions in severe lactic acidosis induced by hemorrhagic shock. Anesthesiology. 2014;120:926-34. https://doi.org/10.1097/01.sa.0000459223.08417.bf

47. Allegretti AS, Flythe JE, Benda V, Robinson ES and Charytan DM. The effect of bicarbonate administration via continuous venovenous hemofiltration on acid-base parameters in ventilated patients. BioMed research international. 2015;2015:901590. https://doi.org/10.1155/2015/901590

48. Rocktaschel J, Morimatsu H, Uchino S, Ronco C and Bellomo R. Impact of continuous veno-venous hemofiltration on acid-base balance. Int J Artif Organs. 2003;26:19-25.

49. Nahas GG, Sutin KM, Fermon C, Streat S, Wiklund L, Wahlander S, Yellin P, Brasch H, Kanchuger M, Capan L, Manne J, Helwig H, Gaab M, Pfenninger E, Wetterberg T, Holmdahl M and Turndorf H. Guidelines for the treatment of acidaemia with THAM. Drugs. 1998;55:191-224. https://doi.org/10.1007/bf03259987

50. Moon PF, Gabor L, Gleed RD and Erb HN. Acid-base, metabolic, and hemodynamic effects of sodium bicarbonate or tromethamine administration in anesthetized dogs with experimentally induced metabolic acidosis. American journal of veterinary research. 1997;58:771-6.

51. Wildenthal K, Mierzwiak DS, Myers RW and Mitchell JH. Effects of acute lactic acidosis on left ventricular performance. The American journal of physiology. 1968;214:1352-9.

52. Sirieix D, Delayance S, Paris M, Massonnet-Castel S, Carpentier A and Baron JF. Tris-hydroxymethyl aminomethane and sodium bicarbonate to buffer metabolic acidosis in an isolated heart model. American journal of respiratory and critical care medicine. 1997;155:957-63. https://doi.org/10.1164/ajrccm.155.3.9117032

53. Hoste EA, Colpaert K, Vanholder RC, Lameire NH, De Waele JJ, Blot SI and Colardyn FA. Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis. Journal of nephrology. 2005;18:303-7. https://doi.org/10.1203/00006450-197605000-00018

54. Stacpoole PW. The pharmacology of dichloroacetate. Metabolism: clinical and experimental. 1989;38:1124-44.

55. Wilkerson DP, Campbell IT, Blackwell JR, Berger NJ and Jones AM. Influence of dichloroacetate on pulmonary gas exchange and ventilation during incremental exercise in healthy humans. Respiratory physiology & neurobiology. 2009;168:224-9. https://doi.org/10.1016/j.resp.2009.07.004

56. Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH, Duncan CA, Harman EM, Henderson GN, Jenkinson S and et al. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. N Engl J Med. 1992;327:1564- 9. https://doi.org/10.1056/nejm199211263272204

57. Filley GF and Kindig NB. Carbicarb, an alkalinizing ion-generating agent of possible clinical usefulness. Trans Am Clin Climatol Assoc. 1985;96:141-53.

58. Li YC, Wiklund L and Bjerneroth G. Influence of alkaline buffers on cytoplasmic pH in myocardial cells exposed to hypoxia. Resuscitation. 1997;34:71-7. https://doi.org/10.1016/s0300-9572(96)01047-7

59. Li YC, Wiklund L, Tarkkila P and Bjerneroth G.Influence of alkaline buffers on cytoplasmic pH in myocardial cells exposed to metabolic acidosis. Resuscitation. 1996;32:33-44. https://doi.org/10.1016/0300-9572(95)00939-6

60. Bersin RM and Arieff AI. Improved hemodynamic function during hypoxia with Carbicarb, a new agent for the management of acidosis. Circulation. 1988;77:227-33. https://doi.org/10.1161/01.cir.77.1.227

61. Leung JM, Landow L, Franks M, Soja-Strzepa D, Heard SO, Arieff AI and Mangano DT. Safety and efficacy of intravenous Carbicarb in patients undergoing surgery: comparison with sodium bicarbonate in the treatment of mild metabolic acidosis. SPI Research Group. Study of Perioperative Ischemia. Critical care medicine. 1994;22:1540-9. https://doi.org/10.1097/00003246-199422100-00007

62. Kolloffel WJ, de Vroom TE, Weekers LE and Woittiez AJ. Severe cutaneous side effects of peripheral infusions with carbicarb half strength. Intensive Care Med. 1994;20:531. https://doi.org/10.1007/bf01711912