DKA: Tripping on Acidosis

Transcription

1 DKA: Tripping on Acidosis Grace Chan Oei, MD, MA Attending Physician, Division of Pediatric Critical Care, Loma Linda University Children s Hospital Assistant Professor of Pediatrics, Loma Linda University School of Medicine

2 Objectives Explain the most common acid base disorders present in patients with diabetic ketoacidosis Analyze the pathophysiology of anion gap and non-anion gap metabolic acidosis Identify ways to improve current treatment practice of children with DKA

3 Do the best you can until you know better. Then when you know better, do better. -- Maya Angelou

4 Cassie Cassie is a 8 year old female with a history of diabetes mellitus type I. Diagnosed 3 years ago, presented in DKA No hospitalizations since diagnosis Follows up regularly with endocrinologist Last HgbA1c 8.7

5 Cassie 1 day prior to presentation goes to a birthday pool party after coming home glucometer reads High additional short acting insulin Overnight home glucometer continues to read high despite additional insulin This morning nausea, vomiting, abdominal pain Goes to ED at the nearest hospital POC glucose high Weight = 25 kg

6 Cassie Labs are drawn, NS bolus 250 ml is given BMP (drawn prior to bolus) Na 132 K 4.7 Cl 98 HCO3 5 BUN 38 Cr 0.8 Glucose

7 Cassie ABG (drawn prior to bolus) ph 7.08 PCO 2 18 PO HCO 3-5 Base deficit not available

8 Cassie Outside hospital starts NS at 1.5x maintenance (97 ml/hour), insulin drip at 2 units/hour, and is checking POC glucose hourly Outside hospital calls the PICU and requests transport, transport team drives out Outside hospital is ~ 1 hour away At outside hospital blood glucose has decreased < 100 mg/dl Treatment continued transport comes back

9 Cassie In the PICU labs are drawn, IVF is changed to NS with KCl 20 meq/l and Kphos 20 meq/l IVF rate continues to be 1.5x maintenance, insulin drip is increased to 2.5 units/hour IV fluids are managed by the following protocol: Glucose > 300 NS with KCl 20 meq/l and Kphos x maintenance Glucose NS with KCl 20 meq/l and Kphos maintenance and D10 NS with KCl 20 meq/l and Kphos maintenance Glucose < 200 D10 NS with KCl 20 meq/l and Kphos x maintenance

10 Question Do you support a patient s blood glucose during the ICU phase of DKA treatment by titrating fluids (such as the previously described protocol) or titrating insulin? Fluid titration Insulin titration

11 Question Does you routinely use intravenous fluids OTHER than normal saline (i.e. NS +/- other electrolytes) while the patient is receiving IV insulin? Yes No

12 Question In the PICU which of the following values demonstrates resolution of DKA? Increasing HCO - 3 Decreasing anion gap Decreasing BUN / creatinine Other

13 Cassie Outside hospital Admission 6 hours later 12 hours later Na K Cl HCO BUN Cr Glu hours later

14 Question Cassie is hungry and thirsty. She does not have any abdominal pain or nausea / vomiting. Are you comfortable with transitioning this patient from an insulin drip to SQ insulin? Yes No

15 Question If you answered that you would NOT transition Cassie which of the following comes closest to your reason why? Serum bicarbonate (HCO 3- ) is still too low Dehydration has not yet resolved (BUN/Cr still too high) Anion gap has not yet closed Unsure but she does not seem ready to be transitioned

16 Question Is Cassie s ICU course thus far similar to the patients with DKA that you have cared for? Very similar Somewhat similar Unsure Somewhat different Very different

17 DKA Management Doing Better What is the benefits / burdens of current therapy? Are we transitioning from IVF/IV insulin therapy to SQ insulin/po diet at the right time? Are there ways to help us better determine when to transition our patients to SQ insulin?

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19 Acid / Base and the Anion Gap Your body must have electroneutrality positive ions = negative ions Cations Anions

20 Acid / Base and the Anion Gap Your body must have electroneutrality positive ions = negative ions Anion GAP HCO - 3 Na + Cl - Cations Anions

21 Acid / Base and the Anion Gap Electroneutrality Same number of positive ions and negative ions in solution Changes in concentration of positive or negative charge is the basis of cell conduction Unless the cell function is conduction, cells need electroneutral environment Acid / base Represented by ph

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23 Acid / Base and the Anion Gap Electroneutrality Same number of positive ions and negative ions in solution Changes in concentration of positive or negative charge is the basis of cell conduction Unless the cell function is conduction, cells need electroneutral environment Acid / base Represented by ph Cellular environment needs a neutral ph to work optimally ph is a measure of hydrogen ion [H + ] concentration in the fluid Strong acid is a compound that disassociates completely into H + and its component base in solution

24 Quick Acid / Base Facts Cl - H + H + H + H + Cl - Cl - H + Cl - Cl - Cl - Cl - Cl - Cl - Cl - H + H + H + H + H + HCl is a strong acid HCl in solution dissociates rapidly into H + + Cl - ph of solution is a measure of H + concentration This is a very acidic solution This solution is electroneutral

25 Acid / Base and the Anion Gap Anion GAP HCO - 3 Na + Cl - Plasma Electroneutral (equal numbers of positive and negative ions) ph is neutral (7.4) because of the bicarbonate buffer system Cations Anions

26 Bicarbonate Buffer System Acid CA H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - CA Carbonic acid Bicarbonate

27 Bicarbonate Buffer System Acid CA H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - CA Carbonic acid Bicarbonate

28 HCO 3 - H +

29 Bicarbonate Buffer System Acid CA H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - CA Carbonic acid Bicarbonate

30 Acid / Base and the Anion Gap Anion GAP HCO - 3 Na + Cl - Anion Gap Difference between measured cations and anions Formula is Na + - (Cl - + HCO 3- ) Unmeasured anions include: phosphate (PO 4 3- ), albumin, sulfates (SO 4 2- ), and other serum proteins Normal AG is 8 +/- 4 Cations Anions

31 Acid / Base and the Anion Gap Anion GAP HCO - 3 Na + Cl - What causes an increase in the anion gap? Production of strong acids from metabolism H + + anion HCO 3 - mops up with H + which keeps the ph neutral Anion is added to the anion gap Exchange of HCO 3 - with anion electroneutrality Cations Anions

32 Acid / Base and the Anion Gap Anion GAP HCO - 3 Na + Cl - Lactic acid Lactate acid CH 3 CH(OH)COOH CH 3 CH(OH)COO - + H + Cations Anions

33 Anion Gap Normal Anion GAP HCO - 3 Na + Cl - Anion gap metabolic acidosis Anion GAP HCO - 3 Na + Cl - Cations Anions Cations Anions

34 What Causes Anion Gap Metabolic Acidosis? M U D P I L E S

35 What Causes Anion Gap Metabolic Acidosis? Methanol Uremia Diabetic ketoacidosis Paraldehyde INH, iron, inborn errors of metabolism Lactic acid Ethylene glycol, ethanol Salicylates

36 Non-Anion Gap Metabolic Acidosis Normal Anion GAP HCO - 3 Na + Cl - Non-anion gap metabolic acidosis Anion GAP HCO - 3 Na + Cl - Cations Anions Cations Anions

37 Non-Anion Gap Metabolic Acidosis Normal Anion GAP HCO - 3 Na + Cl - Non-anion gap metabolic acidosis Anion GAP HCO - 3 Na + Cl - The same Decreased Increased Cations Anions Cations Anions

38 Non-Anion Gap Metabolic Acidosis U S E D C A R P

39 Non-Anion Gap Metabolic Acidosis Ureteroenterostomy Small bowel fistula Extra chloride Diarrhea Carbonic anhydrase inhibitors Adrenal insufficiency Renal tubular acidosis Pancreatic fistula

40 Non-Anion Gap Metabolic Acidosis Ureteroenterostomy Small bowel fistula Extra chloride Diarrhea Carbonic anhydrase inhibitors Adrenal insufficiency Renal tubular acidosis Pancreatic fistula

41 Non-Anion Gap Metabolic Acidosis Ureteroenterostomy Small bowel fistula Extra chloride Diarrhea Carbonic anhydrase inhibitors Adrenal insufficiency Renal tubular acidosis Pancreatic fistula

42 Non-Anion Gap Metabolic Acidosis Ureteroenterostomy Small bowel fistula Extra chloride Diarrhea Carbonic anhydrase inhibitors Adrenal insufficiency Renal tubular acidosis Pancreatic fistula

43 Non-Anion Gap Metabolic Acidosis Normal Anion GAP HCO - 3 Na + Cl - Extra chloride Non-anion gap metabolic acidosis Anion GAP HCO - 3 Na + Cl - Cations Anions Cations Anions

44 Components of IVF Fluid Na (meq/l) Chloride (meq/l) Normal Saline (0.9%) Lactate (meq/l) ½ NS (0.45%) ¼ NS (0.2%) Lactacted Ringers

45 Review The body always needs to maintain electroneutrality (same number of positive ions as negative ions) ph is a measure of the plasma concentration of H + A strong acid in solution (plasma) produces H + + anion Bicarbonate buffer system mops up H + and maintains ph for optimal cellular function

46 Anion Gap Normal Anion GAP HCO - 3 Na + Cl - Anion gap metabolic acidosis Anion GAP HCO - 3 Na + Cl - Cations Anions Cations Anions

47 Review The body always needs to maintain electroneutrality (same number of positive ions as negative ions) ph is a measure of the concentration of H + An acid in solution (plasma) produces H + + anion Bicarbonate buffer system mops up H + and maintains ph for optimal cellular function A common cause for iatrogenic non-anion gap metabolic acidosis is administration of excess chloride

48 Anion Gap Normal Anion GAP HCO - 3 Na + Cl - Anion gap metabolic acidosis Na + Cl - Anion GAP HCO - 3 Non-anion gap metabolic acidosis Anion GAP HCO - 3 Na + Cl - Cations Anions Cations Anions Cations Anions

49 Cassie Outside hospital Admission 6 hours later 12 hours later Na K Cl HCO BUN Cr Glu hours later

50 Outside hospital Admission 6 hours later 12 hours later Na K Cl HCO AG BUN Cr Glu hours later

51 Outside hospital Admission 6 hours later 12 hours later Na K Cl HCO AG BUN Cr Glu hours later

52 Cassie Bolus NS 10 ml/kg 1.5 x maintenance of NS fluids Glucose > 300 NS with KCl 20 meq/l and Kphos x maintenance Glucose NS with KCl 20 meq/l and Kphos maintenance and D10 NS with KCl 20 meq/l and Kphos maintenance Glucose < 200 D10 NS with KCl 20 meq/l and Kphos x maintenance Total IVF received so far: 2300 ml or 2.3 liters

53 Cassie Total IVF received so far: 2300 ml or 2.3 liters or 109 ml/hour Total = ~340 meq Na + + Cl - Maintenance IVF with ½ NS over the same time period = 105 meq Na + + Cl -

54 Cassie Is she ready to transition from IV insulin to SQ insulin at 18 hours? Transition when AG closes ketoacids are gone and DKA has reversed

55 Outside hospital Admission 6 hours later 12 hours later Na K Cl HCO AG BUN Cr Glu hours later

56 Cassie Is she ready to transition from IV insulin to SQ insulin? Transition when AG closes ketoacids are gone and DKA has reversed What happens if she continues to get IV insulin and IVF for another 6 hours until another BMP is drawn? Additional chloride load ~90 meq Cl - Chloride load will inhibit the kidney s ability to regenerate bicarbonate continued or even worsening non-gap metabolic acidosis Another unnecessary 6 hours of NPO status Prolonged ICU care

57 Cassie How do we prevent non-gap metabolic acidosis from occurring or treat it once is happens? Stop giving chloride Replace bicarbonate

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59 Sodium Bicarbonate in Treatment of DKA Sodium bicarbonate administration does not routinely help patients in DKA

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62 Sodium Bicarbonate in Treatment of DKA Sodium bicarbonate administration does not routinely help patients in DKA Sodium bicarbonate can change serum (extracelluar) ph very quickly K shifting from extracellular to intracellular hypokalemia

63 Sodium Bicarbonate in Treatment of DKA Sodium bicarbonate administration does not routinely help patients in DKA Sodium bicarbonate can change serum (extracelluar) ph very quickly K shifting from extracellular to intracellular hypokalemia Sodium bicarbonate additional sodium load increase serum osmolality Sodium bicarbonate metabolic alkalosis after resolution of DKA

64 Sodium Bicarbonate in Treatment of DKA Sodium bicarbonate administration does not routinely help patients in DKA Sodium bicarbonate can change serum (extracelluar) ph very quickly K shifting from extracellular to intracellular hypokalemia Sodium bicarbonate additional sodium load increase serum osmolality Sodium bicarbonate metabolic alkalosis after resolution of DKA Sodium bicarbonate administration is a risk factor for development of cerebral edema

65 Sodium Bicarbonate and Cerebral Edema Cerebral edema in DKA up to 1% of patients Mortality rate of 21-24% Association of lab abnormalities at presentation and development of cerebral edema include: Higher BUN at presentation Increased severity of acidosis and respiratory compensation at presentation

66 Sodium Bicarbonate and Cerebral Edema Cerebral edema in DKA up to 1% of patients Mortality rate of 21-24% Association of lab abnormalities at presentation and development of cerebral edema include: Higher BUN Increased severity of acidosis and respiratory compensation The only treatment variable shown to be associated with development of cerebral edema: Bicarbonate administration

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68 Proposed Pathophysiology H 2 O + CO 2 H 2 CO 3 H + + HCO 3 -

69 Proposed Pathophysiology H 2 O + CO 2 H 2 CO 3 H + + HCO 3 -

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72 Outside hospital Admission 6 hours later 12 hours later Na K Cl HCO AG BUN Cr Glu hours later

73 Preventing Non-gap Metabolic Acidosis in DKA Transition patients from IVF / IV insulin to SQ insulin when ketoacids disappear Measuring the anion gap is good but measuring beta-hydroxybutyrate and acetoacetate is more precise Decrease chloride load Replace some of the chloride in IVF with acetate Use ½ NS instead of NS

74 Electroneutral IVF Normal Saline Isotonic mix of NaCl and NaAcetate Na meq/l Cl meq/l Na meq/l Acetate - 54 meq/l Cl meq/l

75 Preventing Non-gap Metabolic Acidosis in DKA Transition patients from IVF / IV insulin to SQ insulin when ketoacids disappear Measuring the anion gap is good but measuring beta-hydroxybutyrate and acetoacetate is more precise Replace some of the chloride in IVF with acetate IVF must be electroneutral Acetate is metabolized in the liver and in other tissues including the muscles into bicarbonate Much slower metabolism ability to control PaCO 2 through adequate ventilation

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78 Conclusions Exclusive use of NaCl in management of patients in DKA can lead to morbidity Unnecessary delay to transitioning off of IVF in a timely manner because of inadequate recognition of non-gap metabolic acidosis Perhaps unnecessary development of non-gap metabolic acidosis that may be prevented by using mixed anion IV solutions

79 How to Do Better Study whether delays exist in transitioning patients with resolved DKA off of IVF in our patient population Add in more accurate tests to determine resolution of DKA in treatment protocols Study the use of balanced IVF solutions in patients with DKA

80 Thank You Questions?

81 References Brown TB. Cerebral oedema in childhood diabetic ketoacidosis: is treatment a factor? Emerg Med J. 2004;21(2): Dunger DB, Sperling MA, Acerini CL, Bohn DJ, Daneman D, Danne TP, et al. European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics. 2004;113(2):e Emrath ET, Fortenberry JD, Travers C, McCracken CE, Hebbar KB. Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis. Crit Care Med. 2017;45(7): Ferreira JP, Hamui M, Torrents M, Carrano R, Ferraro M, Toledo I. The Influence of Chloride for the Interpretation of Plasma Bicarbonate During the Treatment of Diabetic Ketoacidosis. Pediatr Emerg Care Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, 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. N Engl J Med. 2001;344(4):264-9.

82 References Green SM, Rothrock SG, Ho JD, Gallant RD, Borger R, Thomas TL, et al. Failure of adjunctive bicarbonate to improve outcome in severe pediatric diabetic ketoacidosis. Ann Emerg Med. 1998;31(1):41-8. 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): Kraut JA, Kurtz I. Treatment of acute non-anion gap metabolic acidosis. Clin Kidney J. 2015;8(1):93-9. Marcin JP, Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr. 2002;141(6): 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): Wolfsdorf JI, Allgrove J, Craig ME, Edge J, Glaser N, Jain V, et al. ISPAD Clinical Practice Consensus Guidelines Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 2014;15 Suppl 20: