1. Surviving DKA (as house staff) Matt Bouchonville Endocrinology Division Thursday School July 25, 2013

2. ↓ insulin ↑ counterregulatory hormones DKA +=

3. Hyperglycemia Ketosis Acidosis DKA ↓ insulin ↑ glucagon ↑ gluconeogenesis ↓ glucose utilization ↑ lipolysis ↑ ketone bodies

4. ↓ insulin ↑ glucagon ↑ GH ↑ cortisol ↑ catecholamines ↑ lipase Adipocytes ↑ glycerol↑ FFA gluconeogenesisketoacids (acetoacetic acid, betahydroxy butyrate) Liver

5. DKADKA HHSHHS Absolute Insulin Deficiency Deficiency Relative Insulin Deficiency Deficiency ↑ Counterregulatory Hormones Hormones ↑ Ketoacidosis Absent or minimal ketogenesis ketogenesis

6. DKA on the rise http://www.cdc.gov/diabetes 2009: 140,000 admissions for DKA ~10% of all diabetes-related admissions Discharges (in Thousands) Year

7. DKA: Mortality rates stable http://www.cdc.gov/diabetes Year Number Rate (per 100,000)

8. DKA: Mortality rates stable http://www.cdc.gov/diabetes Mortality (%) Age group (yrs) 2006 – Overall mortality rate for DKA: 0.41% Mortality:Mortality: –Precipitating event-related –DKA-related Hyperglycemia  osmotic diuresis  dehydration  shockHyperglycemia  osmotic diuresis  dehydration  shock Acidosis  electrolyte imbalance  arrhythmiasAcidosis  electrolyte imbalance  arrhythmias  impaired cardiac contractility  shock  impaired cardiac contractility  shock  vasodilation  shock  vasodilation  shock

9. Objectives DiagnosisDiagnosis ManagementManagement Common “Pitfalls”Common “Pitfalls” Clinical casesClinical cases

10. Diabetes Care, Vol 32 (7)1335-1343, 2009

11. Diagnosis of DKA Physical ExamPhysical Exam TachycardiaTachycardia Postural hypotensionPostural hypotension Kussmaul respirationsKussmaul respirations Fruity breathFruity breath Altered sensoriumAltered sensorium Abdominal tendernessAbdominal tenderness Clinical presentationClinical presentation Polydipsia/polyuriaPolydipsia/polyuria Constitutional symptomsConstitutional symptoms Nausea/vomitingNausea/vomiting Abdominal pain (40-75%)Abdominal pain (40-75%) Altered sensoriumAltered sensorium

12. Diagnostic Criteria Diagnostic criteria Laboratory Parameters Serum glucose, mg/dL> 250 Arterial pH< 7.3 Bicarbonate, mEq/L<18 Ketones (urine, serum)+

13. DKA Severity

14. Electrolytes and Hydration

15. The Usual Suspects

16. Objectives DiagnosisDiagnosis ManagementManagement Common “Pitfalls”Common “Pitfalls” Clinical casesClinical cases

17. Management of DKA IV Fluids Assess need for bicarbonate bicarbonate InsulinInsulin PotassiumPotassium ?????? ??

18. Management of DKA IV Fluids Assess need for bicarbonate Assess need for bicarbonate Insulin Potassium Severe dehydration Shock Mild dehydration 0.9% NaCl 1L/hr Pressors Calculate corrected Na Na low Na high Na normal 0.9% NaCl 250- 500 cc/hr 0.45% NaCl 250-500 cc/hr Change to D5 0.45% NaCl 150-250 cc/hr when glucose reaches 200 mg/dL

19. Insulin IV Bolus: 0.1 U/kg regular IV Continuous infusion: 0.1 U/kg/hr If serum glucose does not fall by 50-70 mg/dL in first hour, double IV rate Serum glucose ↓ to 200 mg/dL: decrease IV rate to 0.05-0.1 U/kg/hr Target glucose: 150-200 mg/dL until DKA resolved +/-

20. Potassium Establish adequate renal function (UOP ~50 cc/hr) Serum K+ 3.4- 5.2 mEq/L: Give 20-30 mEq K+ in each liter of IV fluid to maintain serum K+ 4-5 mEq/L Serum K+ ≤ 3.3 mEq/L: Hold insulin & give 20-30 mEq/hr K+ until serum K+ > 3.3 mEq/L Serum K+ ≥ 5.3 mEq/L: Do not give K+ but check serum K+ every 2 hrs

21. Assess need for bicarbonate pH < 6.9 pH 6.9 - 7 pH > 7.0 No HCO 3 Dilute NaHCO 3 (50 mmol) in 200 ml water with 10 mEq KCl. Infuse 1 hr Dilute NaHCO 3 (100 mmol) in 400 ml water with 20 mEq KCl. Infuse 2 hr Repeat NaHCO 3 infusion every 2 hr until pH > 7.0. Monitor K+

22. Criteria for resolution of DKA Serum glucose < 200 mg/dLSerum glucose < 200 mg/dL pH < 7.3pH < 7.3 Anion gap < 14Anion gap < 14 Serum bicarbonate ≥ 18 mEq/LSerum bicarbonate ≥ 18 mEq/L Ready for transition to SQ insulin?Ready for transition to SQ insulin? Eating >50% meal?Eating >50% meal?

23. Transition from IV to SQ insulin Total daily dose:Total daily dose: Resume previous outpatient doseResume previous outpatient dose Insulin naïve (new diagnosis of T1D)Insulin naïve (new diagnosis of T1D) Total daily dose:Total daily dose: Resume previous outpatient doseResume previous outpatient dose Insulin naïve (new diagnosis of T1D)Insulin naïve (new diagnosis of T1D) Weight based or infusion rate derived?Weight based or infusion rate derived? 0.5-0.8 units/kg/day0.5-0.8 units/kg/day ½ basal ½ bolus Timing of SQ insulin dose?Timing of SQ insulin dose? 1-2 hours before stopping IV insulin

24. Objectives DiagnosisDiagnosis ManagementManagement Common “Pitfalls”Common “Pitfalls” Clinical casesClinical cases

25. Hypoglycemia (10-25%)Hypoglycemia (10-25%) HypokalemiaHypokalemia Hyperchloremic (nongap) acidosisHyperchloremic (nongap) acidosis NaCl treatmentNaCl treatment Loss of substrate for bicarbonate regenerationLoss of substrate for bicarbonate regeneration Recurrent DKARecurrent DKA Failure to overlap SQ insulin with IV insulinFailure to overlap SQ insulin with IV insulin Common Pitfalls

26. (Less) Common Pitfalls Cerebral edemaCerebral edema Associated with rapid correction of serum osmolalityAssociated with rapid correction of serum osmolality 1% of children with DKA1% of children with DKA Reported in young adultsReported in young adults Mortality 40-90%Mortality 40-90% Clinical manifestations:Clinical manifestations: LethargyLethargy SeizuresSeizures BradycardiaBradycardia Respiratory arrestRespiratory arrest

27. Objectives DiagnosisDiagnosis ManagementManagement Common “Pitfalls”Common “Pitfalls” Clinical casesClinical cases

28. Case #1 34 yo F with T1D treated with glargine and humalog presents to ER in DKA. Which of the following antihypertensive medications may be precipitating her current presentation?34 yo F with T1D treated with glargine and humalog presents to ER in DKA. Which of the following antihypertensive medications may be precipitating her current presentation? A) Lisinopril B) HCTZ C) Amlodipine D) Losartan

29. Answer: B) HCTZ Medications which may precipitate DKA:Medications which may precipitate DKA: HCTZHCTZ Beta blockersBeta blockers SteroidsSteroids PhenytoinPhenytoin

30. Case #2 56 yo obese M with T2D treated with metformin, HTN treated with HCTZ, lisinopril brought in by EMS. Obtunded and found to have the following labs:56 yo obese M with T2D treated with metformin, HTN treated with HCTZ, lisinopril brought in by EMS. Obtunded and found to have the following labs: Gluc 286 mg/dLGluc 286 mg/dL Creat 3.5 mg/dLCreat 3.5 mg/dL Bicarb 8 mEq/LBicarb 8 mEq/L Anion gap 20Anion gap 20 Serum ketones negSerum ketones neg

31. Case #2 What is the most likely cause of this patient’s presentation?What is the most likely cause of this patient’s presentation? A)DKA B) HCTZ use C) Metformin use D) Vitamin D deficiency

32. Answer: C) Metformin use Differential diagnosis:Differential diagnosis: Starvation ketosisStarvation ketosis Generally not hyperglycemicGenerally not hyperglycemic Alcoholic ketoacidosisAlcoholic ketoacidosis Bicarb rarely < 18; generally not hyperglycemicBicarb rarely < 18; generally not hyperglycemic Anion gap acidosisAnion gap acidosis Lactic acidosis, salicylates, toxic alcoholsLactic acidosis, salicylates, toxic alcohols

33. Case #3 29 yo M presents to ER with abdominal pain, nausea, vomiting, weight loss, and polyuria. Found to be in DKA with likely new dx T1D. Hemodynamically stable. Exam remarkable for abdominal tenderness, no peritoneal signs. Labs remarkable for an elevated serum amylase. What next step would be most appropriate to determine whether the patient has acute pancreatitis?29 yo M presents to ER with abdominal pain, nausea, vomiting, weight loss, and polyuria. Found to be in DKA with likely new dx T1D. Hemodynamically stable. Exam remarkable for abdominal tenderness, no peritoneal signs. Labs remarkable for an elevated serum amylase. What next step would be most appropriate to determine whether the patient has acute pancreatitis? A) CT abdomen B) Abdominal ultrasound C) Serum lipase D) Whipple procedure

34. Answer: C) Serum lipase Serum amylase levels commonly elevated in patients with DKA (up to 80% cases)Serum amylase levels commonly elevated in patients with DKA (up to 80% cases) Lipase much less commonly elevatedLipase much less commonly elevated

35. Case #4 17 yo F with T1D, poor compliance, admitted with DKA. Treated with aggressive IV fluids, IV insulin. Receives supplemental potassium, phosphate, and magnesium overnight. Presents with tetany in the morning. Which laboratory abnormality could explain this finding?17 yo F with T1D, poor compliance, admitted with DKA. Treated with aggressive IV fluids, IV insulin. Receives supplemental potassium, phosphate, and magnesium overnight. Presents with tetany in the morning. Which laboratory abnormality could explain this finding? A) Serum potassium B) Serum phosphate C) Serum magnesium D) Serum calcium

36. Answer: D) Serum calcium Phosphate replacement:Phosphate replacement: Prospective randomized studies have failed to show benefit in DKA outcomesProspective randomized studies have failed to show benefit in DKA outcomes Risk of severe hypocalcemia (younger patients)Risk of severe hypocalcemia (younger patients) Not routinely recommendedNot routinely recommended ADA: “Careful phosphate replacement may sometimes be indicated in patients with cardiac dysfunction, anemia, or respiratory depression and in those with a serum phosphate concentration of < 1.0 mg/dL”ADA: “Careful phosphate replacement may sometimes be indicated in patients with cardiac dysfunction, anemia, or respiratory depression and in those with a serum phosphate concentration of < 1.0 mg/dL”

37. Case #5 28 yo M with unknown medical history is brought in by EMS after being found down. The patient is obtunded and found to be in DKA. Serum glucose is 400 mg/dL, serum bicarbonate is 10 mEq/L, anion gap is 20, serum osmolality is 298, serum ketones are positive. Which answer most accurately describes his mental status?28 yo M with unknown medical history is brought in by EMS after being found down. The patient is obtunded and found to be in DKA. Serum glucose is 400 mg/dL, serum bicarbonate is 10 mEq/L, anion gap is 20, serum osmolality is 298, serum ketones are positive. Which answer most accurately describes his mental status? A)It is likely related to the DKA and should improve with treatment B) It is unlikely to be related to the DKA C)Both, A & B are correct D)Answer A

38. Answer: B) Unlikely related ADA :ADA : “The occurrence of stupor or coma in diabetic patients in the absence of definitive elevation of effective osmolality (320 mOsm/kg) demands immediate consideration of other causes of mental status change.”“The occurrence of stupor or coma in diabetic patients in the absence of definitive elevation of effective osmolality (320 mOsm/kg) demands immediate consideration of other causes of mental status change.”

39. Objectives DiagnosisDiagnosis ManagementManagement Common “Pitfalls”Common “Pitfalls” Clinical casesClinical cases

40. Questions?