Is Bicarbonate ever Indicated in DKA? – Dr. E. Sosa

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Diabetic ketoacidosis (DKA) is characterized by hyperglycemia, elevated serum ketones, and metabolic acidosis. To explain briefly, this disorder results from dysfunctional glucose metabolism in the context of insulin underproduction and/or insensitivity. Unable to utilize glucose, cells begin to consume fatty acids via anaerobic metabolism, leading to the buildup of acidic ketone bodies and other electrolyte abnormalities. Some common precipitants of this acutely life-threatening condition include infection and noncompliance with insulin therapy in known diabetics. DKA is often how new-onset diabetics initially present, but it can also be found in patients with acute pancreatitis, MI, and CVA. Nevertheless, the complexity of metabolic derangements that come with DKA can be formidable to manage, regardless of the precipitating insult.1

Resuscitation of a DKA patient involves aggressive fluid replacement and insulin administration, all while continuously managing sodium, potassium, chloride, phosphate, and bicarbonate shifts. For this review, we will focus on the management of low bicarbonate levels in metabolic acidosis. Since bicarbonate will be very low in severe cases, many physicians treat this metabolic acidosis with intravenous sodium bicarbonate, hoping to reverse the acidosis more quickly. However, this practice is controversial.2

There are three major adverse effects to consider when using bicarbonate:
1) When given continuously, the acidemic drive to blow off CO2 via hyperventilation is blunted. In the hypercapnic state that results, CO2 crosses the blood-brain barrier preferentially, leading to a paradoxical drop in cerebral pH and neurologic deterioration.3
2) It can actually slow ketone clearance by about 6 hours, causing a more refractory acidosis. Animal studies suggest that bicarbonate induces hepatic ketogenesis.4,5,6
3) The use of bicarbonate might help close the anion gap, but may simultaneously delay correction of the acidosis (low HCO3). This occurs because, while ketones are excreted in the urine, they are naturally excreted with an equal amount of protons when they are excreted with hydrogen or ammonium. Meanwhile, some of the ketoacids will be metabolized to regenerate some of the lost HCO3. This process both closes the anion gap and corrects the acidosis. On the other hand, when bicarbonate is used ketones are excreted with sodium and potassium, which are considered bicarbonate precursors. This process leads to a paradoxical loss of potential bicarbonate, as well as a hyperchloremic non-anion-gap metabolic acidosis. Interestingly, this does not happen in ESRD patients, since they cannot excrete excessive amounts of urinary ketones and bicarbonate precursors.7,8,9,10,11

Based on anecdotal evidence, the pH threshold for administration of bicarbonate had been as high as <7.2 for some physicians in the past.  In 2006 and 2009, the American Diabetes Association (ADA) lowered its pH threshold for IV bicarbonate in DKA from <7.0 to <6.9, respectively.  This was based on the facts that results were varied in studies on patients with a pH >7.0, that there is a paucity of data demonstrating its effect in patients with a pH <7.0, and that there is no published data on patients with a pH <6.85.1,12

In general, the literature supporting the use of bicarbonate in DKA is weak. The body of literature includes mostly case-control and retrospective cohort studies. There are a total of three single- or double-blinded randomized controlled trials (RCT), all of which had sample sizes in the double digits.4,6,13 Pediatric studies tend to look at the risk of cerebral edema, whereas adult studies have not.14,15,16,17 There have been no RCTs in pediatric populations.

A few studies showed an initial improvement in acidosis in the short-term when bicarbonate was used, but they did not demonstrate any sustained benefit beyond a couple of hours. These studies also showed paradoxical worsening of ketonemia in these patients.6,13 Other studies showed that patients who received bicarbonate also needed more potassium supplementation and gained no advantage in terms of hemodynamic stability.13,18,19 One study actually showed a slower rate of lactate clearance in patients who received bicarbonate, implying impaired tissue oxygenation.6 In studies where cerebrospinal fluid (CSF) was analyzed, the bicarbonate group actually demonstrated mild decreases in CSF pH and increases in CSF PCO2, reflecting the rapid transport and accumulation of CO2 across the blood brain barrier.4,20,21 And even in pediatrics, the trend leans toward an increased risk of cerebral edema in the bicarbonate groups.14,15,16

No studies have ever shown any significant difference in mortality, length of hospital stays, neurologic recovery, insulin requirements, or improvement of hyperglycemia. No difference has been shown between slow isotonic infusions vs. small concentrated intermittent boluses, with regard to risk of rapid pH/osmolality changes 4,6,13,18,19,22,23. What we do know is that giving bicarbonate can lead to harm in the form of refractory acidosis, worsened tissue hypoxia, paradoxical CNS acidosis and neurologic decline, and cerebral edema in children.

In summary, since patients routinely recover from DKA with fluids and insulin1,5,14,18, the use of bicarbonate in DKA remains controversial and is explicitly not recommended by some experts.2  The literature simply does not provide convincing evidence of its clinical benefit.  Still, the ADA guidelines say it should be applied in DKA when the pH is below 6.9, despite no evidence to support this recommendation.  But as with any medical debate, clinical equipoise comes into play, and there are a few circumstances in which giving bicarbonate may make theoretical sense.  Those include: 1) patients with a pH below 7.0, in whom decreased cardiac contractility and vasodilatation may be impairing tissue perfusion, and 2) patients with severe hyperkalemia, and 3) patients with coma.  In any case in which bicarbonate is used, it should be discontinued once the pH rises above 7.0.3,24,25  In these special cases, the answer lies with weighing the risks and benefits.

1. Kitabchi AE, Umpierrez GE, Miles JM, & Fisher JN. (2009). Hyperglycemic crises in adult patients with diabetes. Diabetes Care, 32(7), 1335-1343.
2. Chansky ME, Lubkin CL. Chapter 220. Diabetic Ketoacidosis. In: Tintinalli JE, Stapczynski JS, Cline DM, Ma OJ, Cydulka RK, Meckler GD, eds.Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 7th ed. New York: McGraw-Hill; 2011.
3. Narins RG, Cohen JJ. Bicarbonate therapy for organic acidosis: the case for its continued use. Ann Intern Med. 1987;106(4):615.
4. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med. 1986;105(6):836.
5. Okuda Y, Adrogue HJ, Field JB, Nohara H, Yamashita K. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab. 1996;81(1):314.
6. 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.
7. Adrogué HJ, Eknoyan G, Suki WK. Diabetic ketoacidosis: role of the kidney in the acid-base homeostasis re-evaluated. Kidney Int. 1984;25(4):591.
8. Adrogué HJ, Wilson H, Boyd AE 3rd, Suki WN, Eknoyan G. Plasma acid-base patterns in diabetic ketoacidosis. N Engl J Med. 1982;307(26):1603.
9. Owen OE, Licht JH, Sapir DG. Renal function and effects of partial rehydration during diabetic ketoacidosis. Diabetes. 1981;30(6):510.
10. Oh MS, Carroll HJ, Goldstein DA, Fein IA. Hyperchloremic acidosis during the recovery phase of diabetic ketosis. Ann Intern Med. 1978;89(6):925.
11. Oh MS, Carroll HJ, Uribarri J. Mechanism of normochloremic and hyperchloremic acidosis in diabetic ketoacidosis. Nephron. 1990;54(1):1.
12. Chua HR, Schneider A, and Bellomo R. Bicarbonate in diabetic ketoacidosis – a systematic review. Annals of Intensive Care 2011, 1:23.
13. Gamba G, Oseguera J, Castrejon M, Gomez-Perez FJ. Bicarbonate therapy in severe diabetic ketoacidosis. A double blind, randomized, placebo controlled trial. Revista de Investigacion Clinica 1991, 43:234-238.
14. Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, Kaufman F, Quayle K, Roback M, Malley R, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. New England Journal of Medicine 2001, 344:264-269.
15. Lawrence SE, Cummings EA, Gaboury I, Daneman D. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. Journal of Pediatrics 2005, 146:688-692.
16. Edge JA, Jakes RW, Roy Y, Hawkins M, Winter D, Ford-Adams ME, Murphy NP, Bergomi A, Widmer B, Dunger DB. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006, 49:2002-2009.
17. Edge JA, Roy Y, Bergomi A, Murphy NP, Ford-Adams ME, Ong KK, Dunger DB. Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration. Pediatric Diabetes 2006, 7:11-15.
18. Viallon A, Zeni F, Lafond P, Venet C, Tardy B, Page Y, Bertrand JC. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med. 1999;27(12):2690.
19. Lever E, Jaspan JB. Sodium bicarbonate therapy in severe diabetic ketoacidosis. Am J Med. 1983;75(2):263.
20. Assal JP, Aoki TT, Manzano FM, Kozak GP. Metabolic effects of sodium bicarbonate in management of diabetic ketoacidosis. Diabetes 1974, 23:405-411.
21. Ohman JL, Marliss EB, Aoki TT, Munichoodappa CS, Khanna VV, Kozak GP. The cerebrospinal fluid in diabetic ketoacidosis. N Engl J Med 1971, 284:283-290.
22. Duhon B, Attridge RL, Franco-Martinez AC, Maxwell PR, Hughes DW. Intravenous Sodium Bicarbonate Therapy in Severely Acidotic Diabetic Ketoacidosis. Ann Pharmacother 2013;47:970-5.
23. Lutterman JA, Adriaansen AA, van ‘t Laar A. Treatment of severe diabetic ketoacidosis. A comparative study of two methods. Diabetologia 1979;17:17-21.
24. DeFronzo RA, Matzuda M, Barret E. Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy. Diabetes Rev. 1994; 2:209.
25. Fraley DS, Adler S. Correction of hyperkalemia by bicarbonate despite constant blood pH. Kidney Int. 1977;12(5):354.

One Comment

  • Tonynap

    Bravo! Never use it except in clear cut cases of pH 6.9 where weight based insulin drip and 2-4 liters of fluid fails to improve VS.Also of note 70kg x 1.5= 105 meq. So 2 amps will raise the HCO3 content by 1.5meq/liter….not alot. In the end you are talking about temporarizing only.

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