1. Hyperglycemic Crises

2. Hyperglycemic Crises Diabetic Ketoacidosis Hyperglycemia, Ketonemia, Metabolic Acidosis Mortality rate: <5% Hyperosmolar Hyperglycemic State Mortality rate: ~11%

4. Pathogenesis Reduction in net effective action of circulating insulin Elevation of counterregulatory hormones: glucagon, catecholamines, cortisol and growth hormone

5. Pathogenesis

6. Diagnostic Criteria

7. Diagnostic Criteria – DKA Serum glucose > 250 mg/dl Arterial pH < 7.3 Serum Bicarbonate < 18 mEq/L Moderate ketonuria or ketonemia

8. Diagnostic Criteria - HHS Serum glucose > 600 mg/dl Arterial pH > 7.3 Serum Bicarbonate > 15 mEq/L Minimal ketonuria or ketonemia

9. Diagnostic Criteria

10. Diagnostic Criteria

11. Precipitating Factors Inadequate/inappropriate insulin therapy Infection Pancreatitis Myocardial infarction Cerebrovascular accident Drugs (corticosteroids, thiazides, sympathomimetics, 2nd gen antipsychotics) New onset Type 1 DM Discontinuation of Insulin in Type 1 DM

12. Diagnosis

14. History Polyuria Polydipsia Weight loss Vomiting Abdominal pain Dehydration Weakness Mental status change Coma

15. Physical Findings Poor skin turgor Kussmaul respirations Tachycardia Hypotension Alteration in mental status Shock Coma

16. Laboratory Exams Plasma glucose Blood Urea Nitrogen Creatinine Serum ketones Electrolytes (with calculated anion gap) Urinalysis, urine ketones Arterial blood gases Complete blood count

17. Laboratory Exams – if indicated 12-L ECG Chest xray Urine, blood, or sputum cultures HBA1c

18. Laboratory Findings Hyperglycemia, ketonemia, metabolic acidosis Leukocytosis proportional to blood ketones Low serum sodium Elevated serum potassium Elevated amylase

19. Treatment

20. Treatment Correction of dehydration Correction of hyperglycemia Correction of electrolyte imbalances Identification of precipitating events Frequent patient monitoring

21. Fluid Therapy

24. If corrected serum Na⁺ is low, then start 0.9% NaCl at similar rateWhen serum glucose reaches 200 mg/dl, then change to 5% dextrose with 0.45% NaCl at 150-250 ml/hr

25. Serum Na in Hyperglycemia Translational hyponatremia in Hyperglycemia Corrected Sodium = Sodium + {[(glucose - 100)/100] x 1.6} = Sodium + 0.016 x (glucose - 100) *for every 100 mg/dl glucose > 100 mg/dl, add 1.6 mEq to Sodium value

28. Insulin Therapy (IV) When plasma glucose reaches 200 mg/dl in DKA or 300 mg/dl in HHS, decrease infusion to 0.05-0.1 u/kg/hr. Keep glucose level between 150-200 mg/dl (DKA) until resolution of DKA. In HHS, keep glucose level between 250-300 mg/dl until plasma osmolality is ≤ 315 mOsm/kg and patient is mentally alert.

29. Insulin Therapy (SC) Give rapid acting insulin 0.2 u/kg followed by 0.1 u/kg every hour OR 0.3 u /kg followed by 0.2 u/kg every 2 hours until glucose reaches < 250 mg/dl If serum glucose does not fall by 50-70 mg/dl in the first hour, then double SC bolus Decrease insulin to 0.05 or 0.1 u/kg given every 1-2 hours until resolution of DKA.

30. Fluid Therapy

31. Potassium Establish adequate renal function If K⁺ < 3.3 mEq/L, Hold insulin Give 20-30 mEq K⁺/hr until K⁺ > 3.3 mEq/L If K⁺ > 5.3 mEq/L, Do not give K⁺, check serum K⁺ every 2 hours If K⁺ is between 3.3 and 5.3 mEq/L, give 20-30 mEq per liter of IV fluid to keep K⁺ between 4-5 meq/L.

32. Fluid Therapy

33. Bicarbonate At pH > 7.0, insulin administration blocks lipolysis and resolves ketoacidosis. If pH< 6.9, Dilute NaHCO₃ (100 mmol/L) in 400 ml H2O with 20 mEqKCl and infuse for 2 hours Repeat NaHCO₃ administration every 2 hours until pH > 7.0 Monitor serum potassium

34. Bicarbonate If pH = 6.9 to 7.0, Dilute NaHCO₃ (50 mmol/L) in 200 ml H2O with 10 mEqKCl and infuse over 1 hour Repeat NaHCO₃ administration every 2 hours until pH > 7.0 Monitor serum potassium If pH > 7.0 = no NaHCO₃

35. Fluid Therapy

36. Phosphate Phosphate decreases with insulin therapy No beneficial effect in routine phosphate replacement Indicated in patients with cardiac dysfunction, anemia and respiratory depression or if serum PO₄ < 1.0 mg/dl, Add 20 – 30 mEq/L potassium phosphate

37. Monitoring Check electrolytes, BUN, creatinine, glucose, and venous pH (for DKA) every 2-4 hours until stable. After resolution of DKA/HHS and patient is able to eat, initiate SC multidose insulin regimen Continue IV insulin infusion for 1-2 hours after SC insulin to ensure adequate plasma levels Insulin-naïve patients, start at 0.5-0.8 u/kg/day Resume previous dose in patients already on insulin

38. Criteria for Resolution of DKA Glucose < 200 mg/dl Serum Bicarbonate ≥ 18 mEq/l Venous pH > 7.3

39. Complications Iatrogenic Hypoglycemia Iatrogenic Hypokalemia Hyperglycemia Hypochloremic Acidosis Cerebral edema (rare)

40. Prevention Proper patient education Blood glucose goals Use of short or rapid acting insulin during illness Importance of managing infections Initiation of easily digestable liquid diet containing carbohydrates and salt Importance of continuous insulin therapy