Surviving DKA (as house staff)

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

2. ↑ counterregulatory hormones + = ↓ insulin DKA

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

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

5. ↑ Counterregulatory Hormones Relative Insulin Deficiency Absolute Insulin Deficiency Absent or minimal ketogenesis ↑ Ketoacidosis HHS DKA

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

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

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

9. Objectives • Diagnosis • Management • Common “Pitfalls” • Clinical cases

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

11. Diagnosis of DKA • Physical Exam • Tachycardia • Postural hypotension • Kussmaul respirations • Fruity breath • Altered sensorium • Abdominal tenderness • Clinical presentation • Polydipsia/polyuria • Constitutional symptoms • Nausea/vomiting • Abdominal pain (40-75%) • Altered sensorium

12. Diagnostic Criteria

13. DKA Severity

14. Electrolytes and Hydration

15. The Usual Suspects

16. Objectives • Diagnosis • Management • Common “Pitfalls” • Clinical cases

17. Management of DKA IV Fluids Potassium Insulin ? ? ? Assess need for bicarbonate ?

18. Management of DKA Severe dehydration Mild dehydration Shock IV Fluids Potassium Insulin Calculate corrected Na Pressors 0.9% NaCl 1L/hr Na high Na normal Na low Assess need for bicarbonate 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 Serum glucose ↓ to 200 mg/dL: decrease IV rate to 0.05-0.1 U/kg/hr If serum glucose does not fall by 50-70 mg/dL in first hour, double IV rate Target glucose: 150-200 mg/dL until DKA resolved

20. Potassium Establish adequate renal function (UOP ~50 cc/hr) Serum K+ ≥ 5.3 mEq/L: Do not give K+ but check serum K+ every 2 hrs Serum K+ ≤ 3.3 mEq/L: Hold insulin & give 20-30 mEq/hr K+ until serum K+ > 3.3 mEq/L 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

21. Assess need for bicarbonate pH < 6.9 pH 6.9 - 7 pH > 7.0 Dilute NaHCO3 (100 mmol) in 400 ml water with 20 mEqKCl. Infuse 2 hr Dilute NaHCO3 (50 mmol) in 200 ml water with 10 mEqKCl. Infuse 1 hr No HCO3 Repeat NaHCO3 infusion every 2 hr until pH > 7.0. Monitor K+

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

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

24. Objectives • Diagnosis • Management • Common “Pitfalls” • Clinical cases

25. Common Pitfalls • Hypoglycemia (10-25%) • Hypokalemia • Hyperchloremic (nongap) acidosis • NaCl treatment • Loss of substrate for bicarbonate regeneration • Recurrent DKA • Failure to overlap SQ insulin with IV insulin

26. (Less) Common Pitfalls • Cerebral edema • Associated with rapid correction of serum osmolality • 1% of children with DKA • Reported in young adults • Mortality 40-90% • Clinical manifestations: • Lethargy • Seizures • Bradycardia • Respiratory arrest

27. Objectives • Diagnosis • Management • Common “Pitfalls” • Clinical 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? • A) Lisinopril • B) HCTZ • C) Amlodipine • D) Losartan

29. Answer: B) HCTZ • Medications which may precipitate DKA: • HCTZ • Beta blockers • Steroids • Phenytoin

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: • Gluc 286 mg/dL • Creat 3.5 mg/dL • Bicarb 8mEq/L • Anion gap 20 • Serum ketonesneg

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

32. Answer: C) Metformin use • Differential diagnosis: • Starvation ketosis • Generally not hyperglycemic • Alcoholic ketoacidosis • Bicarb rarely < 18; generally not hyperglycemic • Anion gap acidosis • Lactic 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? • 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) • Lipase 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? • A) Serum potassium • B) Serum phosphate • C) Serum magnesium • D) Serum calcium

36. Answer: D) Serum calcium • Phosphate replacement: • Prospective randomized studies have failed to show benefit in DKA outcomes • Risk of severe hypocalcemia (younger patients) • Not 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”

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? • It is likely related to the DKA and should improve with treatment • B) It is unlikely to be related to the DKA • Both, A & B are correct • Answer A

38. Answer: B) Unlikely related • 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.”

39. Objectives • Diagnosis • Management • Common “Pitfalls” • Clinical cases

40. Questions?