1. Presentation title SUB TITLE HERE A Nimalasuriya MD Maria Ureña RN, MHA Diabetic Ketoacidosis Management

2. Goals of Discussion Pathophysiology of DKA Biochemical criteria for DKA Treatment of DKA Prevention of DKA Hyperosmolar Nonketoic Syndrome

3. Epidemiology Annual incidence in U.S. 5-8 per 1000 diabetic subjects 2.8% of all diabetic admissions are due to DKA Overall mortality rate ranges from 2-10%  Higher is older patients

4. Diabetic Ketoacidosis Due to:  Severe insulin deficiency  Absolute type 1  Relative type 2  Associated with cocaine use  Atypical anti-psychotics

5. DKA Precipitating Factors Failure to take insulin  Psychological  Secondary gain  Weight concerns Failure to increase insulin  Illness/Infection  Pneumonia  MI  Stroke  Acute stress  Trauma  Emotional

6. Diabetic Ketoacidosis Also… Excess counterregulatory hormones Glucagon Epinephrine Cortisol Growth hormone

7. Role of Insulin Required for transport of glucose into:  Muscle  Adipose  Liver Inhibits lipolysis Absence of insulin  Glucose accumulates in the blood  Liver  Uses amino acids for gluconeogenesis  Converts fatty acids into ketone bodies  Acetone, Acetoacetate, β-hydroxybutyrate

8. Counterregulatory Hormones - DKA Increases insulin resistance Activates glycogenolysis and gluconeogenesis Activates lipolysis Inhibits insulin secretion Epinephrine XXXX Glucagon X Cortisol XX Growth Hormone XXX

9. Insulin Deficiency Glucose uptake Proteolysis Lipolysis Amino Acids Glycerol Free Fatty Acids Gluconeogenesis Glycogenolysis Hyperglycemia Ketogenesis Acidosis Osmotic diuresis Dehydration

10. Signs and Symptoms of DKA Polyuria, polydipsia  Enuresis Dehydration  Tachycardia  Orthostasis Abdominal pain  Nausea  Vomiting Fruity breath  Acetone Kussmaul breathing Mental status changes  Combative  Drunk  Coma

11. Signs and Symptoms of DKA (continued) DKA Pancreatitis Acute surgical Emergency Amylase Lipase Acute abdomen

12. Lab Findings Hyperglycemia blood sugar greater than 250 Anion gap acidosis  Bicarbonate <15 mEq/L  pH <7.3 Urine ketones and serum ketones Hyperosmolarity

13. Differential Diagnosis Anion Gap Acidosis Alcoholic ketoacidosis Lactic acidosis Renal failure Ethylene glycol or methyl alcohol poisoning Starvation in late pregnancy or lactation (rare)

14. Treatment of DKA Initial hospital management  Replace fluid and electrolytes  IV Insulin therapy  Glucose administration  Watch for complications  Treat causes  Disconnect insulin pump Once resolved  Convert to home insulin regimen  Prevent recurrence

15. Flow sheet STAT Arterial ABG CBC with differential urinalysis blood glucose blood urea nitrogen (BUN) Electrolytes chemistry profile creatinine levels electrocardiogram chest X-ray and cultures as needed. Serum Na should be corrected for hyperglycemia Follow up labs plasma glucose Lytes BUN/creatinine venous pH every 2 -4 hr

16. Treatment of DKA Fluids and Electrolytes Fluid replacement  Restores perfusion of the tissues  Average fluid deficit 3-5 liters Initial resuscitation  1-2 liters of normal saline over the first 2 hours  Slower rates of 500cc/hr x 4 hrs or 250 cc/hr x 4 hours When fluid overload is a concern After the first Liter consider ½ NS

17. Treatment of DKA Fluids and Electrolytes Sodium replacement  Calculate effective serum sodium  Serum sodium + 1.6 ( blood glucose-100)/100  isotonic saline (0.9% NaCl) is infused at a rate of 15–20 ml · kg−1 body wt · h−1 or greater during the 1st hour ( ∼ 1–1.5 l in the average adult). Subsequent choice for fluid replacement depends on the state of hydration, serum electrolyte levels, and urinary output.  In general, 0.45% NaCl infused at 4–14 ml · kg−1 · h−1 is appropriate if the corrected serum sodium is normal or elevated; 0.9% NaCl at a similar rate is appropriate if corrected serum sodium is low.

18. Treatment of DKA Fluids and Electrolytes Hyperkalemia initially present  Resolves quickly with insulin drip  Once urine output is present and K<5.5, add 20-40 meq KCL per liter. Phosphate deficit  May want to use Kphos Bicarbonate not given unless pH <7

19. Treatment of DKA Insulin Therapy IV bolus of 0.15 units/kg (~ 10 units) regular insulin IV infusion 0.1 units/kg /hr If blood glucose does not drop by 50 mg double the infusion rate Do not give if K is less than 3.3 mEq/L Hydrate first Follow with hourly regular insulin infusion Glucose levels  Decrease 75-100 mg/dl hour not more than this  Minimize rapid fluid shifts

20. Treatment of DKA Glucose Administration plasma glucose reaches 250 mg/dl in DKA or 300 mg/dl in HHS, decrease the insulin infusion rate to 0.05–0.1 unit · kg−1 · h−1 (3–6 units/h), Add dextrose (5–10%) to the intravenous fluids. maintain the above glucose values until acidosis in DKA or mental obtundation and hyperosmolarity in HHS are resolved

21. DKA Resolved Treatment Blood sugar less than 200 mg Bicarbonate greater than 18 mEq/L Venous pH greater than 7.3

22. Once DKA Resolved Treatment Most patients require 0.5-0.6 units/kg/day highly insulin resistant patients  0.8-1.0 units/kg/day Long acting insulin  1/2-2/3 daily requirement  NPH or Lantus Short acting insulin  1/3-1/2 given at meals  Regular, Humalog, Novolog Give insulin at least 2 hours prior to weaning insulin infusion.

23. Complications of DKA Infection  Precipitates DKA  Fever  Leukocytosis can be secondary to acidosis Shock  If not improving with fluids r/o MI Vascular thrombosis  Severe dehydration  Cerebral vessels  Occurs hours to days after DKA Pulmonary Edema  Result of aggressive fluid resuscitation Cerebral Edema  First 24 hours  Mental status changes  Tx: Mannitol  May require intubation with hyperventilation

24. Prevention of DKA Sick Day Rules Never omit insulin Cut long acting in half Prevent dehydration and hypoglycemia Monitor blood sugars frequently Monitor for ketosis Provide supplemental fast acting insulin Treat underlying triggers Maintain contact with medical team

25. Goals of Discussion Pathophysiology of DKA Biochemical criteria for DKA Treatment of DKA Prevention of DKA Hyperosmolar Nonketoic Syndrome

26. Hyperosmolar Nonketotic Syndrome Extreme hyperglycemia and dehydration  Unable to excrete glucose as quickly as it enters the extracellular space  Maximum hepatic glucose output results in a plateau of plasma glucose no higher than 300- 500 mg/dl  When sum of glucose excretion plus metabolism is less than the rate which glucose enters extracellular space.

27. Hyperosmolar Nonketotic Syndrome Extreme hyperglycemia and hyperosmolarity High mortality (12-46%) At risk  Older patients with intercurrent illness  Impaired ability to ingest fluids Urine volume falls  Decreased glucose excretion Elevated glucose causes CNS dysfunction and fluid intake impaired No ketones  Some insulin may be present  Extreme hyperglycemia inhibits lipolysis

28. Hyperosmolar Nonketotic Syndrome Presentation Extreme dehydration Supine or orthostatic hypotension Confusion coma Neurological findings  Seizures  Transient hemiparesis  Hyperreflexia  Generalized areflexia

29. Hyperosmolar Nonketotic Syndrome Presentation Glucose >600 mg/dl Sodium  Normal, elevated or low Potassium  Normal or elevated Bicarbonate >15 mEq/L Osmolality >320 mOsm/L

30. Hyperosmolar Nonketotic Syndrome Treatment Fluid repletion  NS 2-3 liters rapidly  Total deficit = 10 liters  Replete ½ in first 6 hours Insulin  Make sure perfusion is adequate  Insulin drip 0.1U/kg/hr Treat underlying precipitating illness

31. Clinical Errors Fluid shift and shock  Giving insulin without sufficient fluids  Using hypertonic glucose solutions Hyperkalemia  Premature potassium administration before insulin has begun to act Hypokalemia  Failure to administer potassium once levels falling Recurrent ketoacidosis  Premature discontinuation of insulin and fluids when ketones still present Hypoglycemia  Insufficient glucose administration

32. Successful management requires  Judicious use of fluids  Establish good perfusion  Insulin drip  Steady decline  Complete resolution of ketosis  Electrolyte replacement  Frequent neurological evaluations  High suspicion for complications Determine etiology to avoid recurrent episodes Successful Management

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