Metabolic acidosis is a frequently encountered acid-base disorder in critical care patients, demanding meticulous attention and effective management due to its potential for serious consequences.

It is characterized by a fall in plasma HCO3 and a fall in pH (below 7.35). The PaCO2 is reduced secondarily by hyperventilation, and this compensatory mechanism minimizes the fall in pH.

Metabolic acidosis can result from the loss of HCO3 via the gastrointestinal (GI) tract or kidneys, overproduction of endogenous nonvolatile acids, ingestion or infusion of acid or potential acids, and failure of H+ excretion by the kidney.

Calculation of anion gap (AG) is extremely helpful in narrowing etiological diagnosis:

Anion Gap (AG)

= Na+ - (Cl- + HCO3)

= 12 ± 2 (Normal Value)

Metabolic acidosis can be classified into two groups based on the anion gap: high anion gap acidosis (e.g., lactic acidosis, ketoacidosis, ingested toxins, and acute or chronic renal impairment) and normal anion gap acidosis (e.g., diarrhea, renal tubular acidosis, or large volume saline administration). Table 31.1 summarizes the causes of metabolic acidosis classified based on the anion gap, their mechanisms of development, and how acidosis occurs in each cause.

The mnemonic “GOLDMARK” is helpful for remembering the causes of high anion gap metabolic acidosis (Table 31.2) [1].

REFERENCES

1. Mehta AN, Emmett JB, Emmett M. GOLD MARK: an anion gap mnemonic for the 21st century. Lancet. 2008;372(9642):892.
2. Achanti A, Szerlip HM. Acid-Base Disorders in the Critically Ill Patient. Clin J Am Soc Nephrol. 2023;18(1):102–112.
3. Kraut JA, Madias NE. Treatment of acute metabolic acidosis: a pathophysiologic approach. Nat Rev Nephrol. 2012;8(10):589–601.
4. Forni LG, Hodgson LE, Se lby NM. The Janus faces of bicarbonate therapy in the ICU: not sure! Intensive Care Med. 2020;46(3):522–524.
5. Farkas J. Non-anion-gap metabolic acidosis (NAGMA) PulmCrit September 19, 2019 https://emcrit.org/ibcc/nagma/#treatment.
6. Sabatini S, Kurtzman NA. Bicarbonate therapy in severe metabolic acidosis. J. Am. Soc. Nephrol. 2009;20(4):692–695.
7. Adeva-Andany MM, Fernández-Fernández C, Mouriño-Bayolo D, et al. Sodium bicarbonate therapy in patients with metabolic acidosis. ScientificWorldJournal. 2014;2014:627673.
8. Boyd JH, Walley KR. Is there a role for sodium bicarbonate in treating lactic acidosis from shock? Curr Opin Crit Care. 2008;14(4):379–83.
9. Velissaris D, Karamouzos V, Ktenopoulos N, et al. The use of sodium bicarbonate in the treatment of acidosis in sepsis: a literature update on a long term debate. Crit Care Res Pract. 2015;2015:605830.
10. Ghauri S, Javaeed A, Mustafa K, et al. Bicarbonate therapy for critically ill patients with metabolic acidosis: a systematic review. Cureus 2019;11(3):e4297.
11. Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet. 2018;392(10141):31–40.
12. Zhang Z, Zhu C, Mo L, et al. Effectiveness of sodium bicarbonate infusion on mortality in septic patients with metabolic acidosis. Intensive Care Med 2018;44(11):1888–1895.
13. Jung B, Martinez M, Claessens YE, et al. Diagnosis and management of metabolic acidosis: guidelines from a French expert panel. Ann Intensive Care. 2019;9(1):92.
14. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med 2021;49(11):e1063–143.
15. Matyukhin I, Patschan S, Ritter O, et al. Etiology and management of acute metabolic acidosis: An Update. Kidney Blood Press Res. 2020;45(4):523–531.
16. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009;32(7):1335–43.
17. Duhon B, Attridge RL, Franco-Martinez AC, et al. Intravenous sodium bicarbonate therapy in severely acidotic diabetic ketoacidosis. Ann Pharmacother. 2013;47(7–8):970–5.
18. Patel MP, Ahmed A, Gunapalan T, et al. Use of sodium bicarbonate and blood gas monitoring in diabetic ketoacidosis: A review. World J Diabetes. 2018;9(11):199–205.
19. Wildenthal K, Mierzwiak DS, Myers RW, et al. Effects of acute lactic acidosis on left ventricular performance. Am J Physiol 1968;214(6):1352–1359.
20. Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010;6(5):274–85.
21. Fujii T, Udy AA, Nichol A, et al. Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study. Crit Care. 2021;25(1):45.
22. Rudnick MR, Blair GJ, Kuschner WG, Barr J. Lactic Acidosis and the Role of Sodium Bicarbonate: A Narrative Opinion. Shock. 2020;53(5):528–536.
23. Rachoin JS, Weisberg LS, McFadden CB. Treatment of lactic acidosis: appropriate confusion. J Hosp Med 2010;5(4):E1–7.
24. Kraut JA, Kurtz I. Treatment of acute non-anion gap metabolic acidosis. Clin Kidney J. 2015;8(1):93–9.
25. Kimmoun A, Novy E, Auchet T, et al. Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside. Crit Care. 2015;19(1):175.
26. Sing RF, Branas CA, Sing RF. Bicarbonate therapy in the treatment of lactic acidosis: medicine or toxin? J Am Osteopath Assoc. 1995;95(1):52–7.
27. Abeysekara S, Zello GA, Lohmann KL, et al. Infusion of sodium bicarbonate in experimentally induced metabolic acidosis does not provoke cerebrospinal fluid (CSF) acidosis in calves. Can J Vet Res. 2012;76(1):16–22.
28. Cooper DJ, Walley KR, Wiggs BR, et al. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis: a prospective, controlled clinical study. Ann Intern Med 1990;112(7):492–498.
29. Gehlbach BK, Schmidt GA. Bench-to-bedside review: treating acid-base abnormalities in the intensive care unit-the role of buffers. Crit Care. 2004;8(4):259–65.
30. Handy JM, Soni N. Physiological effects of hyperchloraemia and acidosis. Br J Anaesth 2008;101(2):141–150.
31. Al Alawi AM, Al Flaiti A, Falhammar H. Lactation Ketoacidosis: A systematic review of case reports. Medicina (Kaunas). 2020;56(6):299.
32. Kraut JA, Kurtz I. Use of base in the treatment of severe acidemic states. Am. J. Kidney Dis. 2001;38(4):703–727.
33. Jung B, Rimmele T, Le Goff C, et al. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study. Crit Care Lond Engl. 2011;15(5):R238.
34. Kraut JA, Madias NE. Lactic Acidosis: Current treatments and future directions. Am J Kidney Dis. 2016;68(3):473–82.
35. Mathieu D, Neviere R, Billard V, et al. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med 1991;19(11):1352–6.
36. Stacpoole PW, Wright EC, Baumgartner TG, et al. Natural history and course of acquired lactic acidosis in adults. Am J Med. 1994;97(1):47–54.
37. Kim HJ, Son YK, An WS. Effect of sodium bicarbonate administration on mortality in patients with lactic acidosis: a retrospective analysis. PLoS One 2013;8(6):e65283.
38. Ahn S, Kim YJ, Sohn CH, et al. Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study. J Thorac Dis. 2018;10(4):2295–2302.
39. Fang ZX, Li YF, Zhou XQ, et al. Effects of resuscitation with crystalloid fluids on cardiac function in patients with severe sepsis. BMC Infect Dis. 2008;8:50.
40. El-Solh AA, Abou Jaoude P, Porhomayon J. Bicarbonate therapy in the treatment of septic shock: a second look. Intern Emerg Med 2010;5(4):341–47.
41. Chen XF, Ye JL, Zhu ZY. The use of sodium bicarbonate in stages in treating hypoperfusion induced lactic acidemia in septic shock [Article in Chinese]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2013;25(1):24–7.
42. Fujii T, Udy A, Licari E, et al. Sodium bicarbonate therapy for critically ill patients with metabolic acidosis: a scoping and a systematic review. J Crit Care 2019;51:184–191.
43. Lo KB, Garvia V, Stempel JM, et al. Bicarbonate use and mortality outcome among critically ill patients with metabolic acidosis: A meta analysis. Heart Lung. 2020;49(2):167–174.
44. Huang S, Yang B, Peng Y, et al. Clinical effectiveness of sodium bicarbonate therapy on mortality for septic patients with acute moderate lactic acidosis. Front Pharmacol. 2023;13:1059285.
45. Wiederkehr M, Emmett M, Sterns RH, et al. Bicarbonate therapy in lactic acidosis. In: UpToDate, Post TW (Ed), Wolters Kluwer. https://www.uptodate.com (Accessed on November 12, 2023).
46. Australian Product Information - Sodium Bicarbonate 8.4% (Sodium Bicarbonate) Injection BP.” [Internet]. Date of Revision: 09 February 2021. Available from: https://medsinfo.com.au/api/documents/Sodium_Bicarbonate_PI?format=pdf.
47. Melamed ML, Raphael KL. Metabolic Acidosis in CKD: A Review of Recent Findings. Kidney Med. 2021;3(2):267–277.
48. Wang XH, Mitch WE, Price SR. Pathophysiological mechanisms leading to muscle loss in chronic kidney disease. Nat Rev Nephrol. 2022;18(3):138–152.
49. Bushinsky DA, Krieger NS. Effects of acid on bone. Kidney Int. 2022;101(6):1160–1170.
50. Levy RV, McMahon DJ, Agarwal S, et al. Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease. J Am Soc Nephrol 2023;34(4):668–681.
51. Kraut JA, Madias NE. Adverse Effects of the Metabolic Acidosis of Chronic Kidney Disease. Adv Chronic Kidney Dis. 2017;24(5):289–297.
52. Di Iorio BR, Bellasi A, Raphael KL, et al. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study. J Nephrol. 2019;32(6):989–1001.
53. Hultin S, Hood C, Campbell KL, et al. A Systematic Review and Meta-Analysis on Effects of Bicarbonate Therapy on Kidney Outcomes. Kidney Int Rep. 2020;6(3):695–705.
54. Kim HJ, Ryu H, Kang E, et al. Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results. Front Med (Lausanne). 2021;8:707588.
55. Asahina Y, Sakaguchi Y, Kajimoto S, et al. Association of Time-Updated Anion Gap With Risk of Kidney Failure in Advanced CKD: A Cohort Study. Am J Kidney Dis. 2022;79(3):374–382.
56. Vincent-Johnson A, Scialla JJ. Importance of Metabolic Acidosis as a Health Risk in Chronic Kidney Disease. Adv Chronic Kidney Dis. 2022;29(4):329–336.
57. Beynon-Cobb B, Louca P, Hoorn EJ, et al. Effect of Sodium Bicarbonate on Systolic Blood Pressure in CKD: A Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol. 2023;18(4):435–445.
58. Hu MK, Witham MD, Soiza RL. Oral bicarbonate therapy in non-haemodialysis dependent chronic kidney disease patients: a systematic review and meta-analysis of randomised controlled trials. J Clin Med. 2019;8(2):208.
59. BiCARB study group. Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial. BMC Med. 2020;18(1):91.
60. Alexander RT, Cordat E, Chambrey R, et al. Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders. J Am Soc Nephrol. 2016;27(12):3511–3520.
61. Hale PJ, Crase J, Nattrass M. Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis. Br Med J (Clin Res Ed). 1984;289(6451):1035–8.
62. Okuda Y, Adrogue HJ, Field JB, et al. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab. 1996;81(1):314–20.
63. Viallon A, Zeni F, Lafond P, et al. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med. 1999;27(12):2690–3.
64. Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis – a systematic review. Ann Intensive Care 2011;1(1):23.
65. Gil-Olivares F, Manrique H, Castillo-Bravo, et al. Management of glycemic crises in adult patients With diabetes mellitus: evidence-based clinical Practice guideline clinical Rev. Fac Med. Hum. January 2021;21(1):50–64.
66. Palmer BF, Clegg DJ. Electrolyte Disturbances in Patients with Chronic Alcohol-Use Disorder. N Engl J Med 2017;377(14):1368–1377.
67. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med. 2018;378(3):270–280.
68. Long B, Lentz S, Gottlieb M. Alcoholic Ketoacidosis: Etiologies, Evaluation, and Management. J Emerg Med. 2021;61(6):658–665.
69. American College of Medical Toxicology. Guidance document: management priorities in salicylate toxicity. J Med Toxicol. 2015;11(1):149–52.
70. Shively RM, Hoffman RS, Manini AF. Acute salicylate poisoning: risk factors for severe outcome. Clin Toxicol (Phila). 2017;55(3):175–180.
71. Palmer BF, Clegg DJ. Salicylate Toxicity. N Engl J Med 2020;382(26):2544–2555.
72. Thurston JH, Pollock PG, Warren SK, et al. Reduced brain glucose with normal plasma glucose in salicylate poisoning. J Clin Invest 1970;49(11):2139–45.
73. Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal Treatment for Salicylate Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup. Ann Emerg Med. 2015;66(2):165–81.
74. Palmer BF, Kelepouris E, Clegg DJ. Renal Tubular Acidosis and Management Strategies: A Narrative Review. Adv Ther. 2021;38(2):949–968.
75. Reddy S, Kamath N. Clinical approach to renal tubular acidosis in children. Karnataka Paediatr J 2020;35(2):88–94.
76. Watanabe T. Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead. Pediatric Health Med Ther. 2018;9:181–190.
77. Lopez-Garcia SC, Emma F, Walsh SB, et al. Treatment and long-term outcome in primary distal renal tubular acidosis. Nephrol Dial Transplant 2019;34(6):981–991.
78. Giglio S, Montini G, Trepiccione F, et al. Distal renal tubular acidosis: a systematic approach from diagnosis to treatment. J Nephrol. 2021;34(6):2073–2083.