Diabetic Ketoacidosis Management

1. Diabetic Ketoacidosis Management Heidi Chamberlain Shea, MD Endocrine Associates of Dallas

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. Failure to take insulin Failure to increase insulin Illness/Infection Pneumonia MI Stroke Acute stress Trauma Emotional Medical Stress Counterregulatory hormones Oppose insulin Stimulate glucagon release Hypovolmemia Increases glucagon and catecholamines Decreased renal blood flow Decreases glucagon degradation by the kidney DKAPrecipitating Factors

5. Diabetic Ketoacidosis Due to: Severe insulin deficiency Excess counterregulatory hormones Glucagon Epinephrine Cortisol Growth hormone

6. 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 • Increased counterregulatory hormones

7. Counterregulatory Hormones - DKA

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

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

10. Lab Findings • Hyperglycemia • Anion gap acidosis • (Na + K) – (Cl + Bicarb) >12 • Bicarbonate <15 mEq/L • pH <7.3 • Urine ketones and serum ketones • Hyperosmolarity

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

12. Atypical Presentations • DKA can be present with BS <300 • Impaired gluconeogenesis • Liver disease • Acute alcohol ingestion • Prolonged fasting • Insulin-independent glucose is high (pregnancy) • Chronic poor control but taking insulin • Bedside urine ketones false negatives • Measure acetoacetate not β-hydroxybutyrate • Send blood to lab

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

14. Treatment of DKAFluids and Electrolytes • Fluid replacement • Restores perfusion of the tissues • Lowers counterregulatory hormones • 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 • If hypernatremia develops ½ NS can be used

15. Treatment of DKAFluids and Electrolytes • Hyperkalemia initially present • Resolves quickly with insulin drip • Once urine output is present and K<5.0, add 20-40 meq KCL per liter. • Normo/Hypokalemia • Malnourished individuals (alcoholics) • Start K replacement and have K > 3.0 prior to start of insulin • Remember to check magnesium • Phosphate deficit • May want to use Kphos • Bicarbonate not given unless pH <7 or bicarbonate <5 mmol/L

16. Treatment of DKAInsulin Therapy • IV bolus of 0.1-0.2 units/kg (~ 10 units) regular insulin • Follow with hourly regular insulin infusion • Glucose levels • Decrease 75-100 mg/dl hour • Minimize rapid fluid shifts • Continue IV insulin until urine is free of ketones

17. Treatment of DKAGlucose Administration • Supplemental glucose • Hypoglycemia occurs • Insulin has restored glucose uptake • Suppressed glucagon • Prevents rapid decline in plasma osmolality • Rapid decrease in insulin could lead to cerebral edema • Glucose decreases before ketone levels decrease • Start glucose when plasma glucose <300 mg/dl

18. Insulin-Glucose Infusion for DKA

19. 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 Complications of DKA

20. Once DKA ResolvedTreatment • Most patients require 0.5-0.6 units/kg/day • Pubertal or highly insulin resistant patients • 0.8-1.0 units/kg/day • Long acting insulin • 1/2-2/3 daily requirement • NPH, Levemir or Lantus • Short acting insulin • 1/3-1/2 given at meals • Regular, Humalog, Novolog or Apidra

21. Once DKA ResolvedTreatment • Give SQ insulin at least 2 hours prior to stopping insulin infusion. • Lantus or Levemir • Steady state at 2-4 hrs • Short acting analogs for meal times • If transitioning to the pump • Restart the pump and after 30 minutes stop insulin infusion • May still be more insulin resistant so will need more than usual dose • Check blood sugars in 2 hrs • Offer supplemental

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23. Insulin Types and Action

24. Prevention of DKASick 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. Preventing DKA • Education • Sick days or NPO • Do not stop insulin but adjust • Continue basal insulin • NPH insulin- decrease by 30-50% • Use short acting • Q2-3 hrs with Novolog, Humalog and Apidra • Q4 hrs with regular insulin • Hyperglycemia • If > 300 mg/dl, then check urine ketones • If ketones positive • Increase fluids • Take supplemental insulin Q2 hrs • Insulin temperature sensitive • < 77 degrees • Teenagers, homeless, pen and pump users • Do not store insulin in the car • Traveling and summer outdoor activities • May need to replace more frequently

26. Pump patients • If blood sugars are increasing (>200 mg/dl) • Bolus • Check 2 hrs later, if climbing • Give SQ correction • Change site • Make sure pump is working • Change insulin • Pump patients need long acting back up at home and when traveling

27. Pump patients • If in DKA • Disconnect the pump • Transitioning back to pump • Start pump with basal x 2 hrs, then stop insulin drip • Check blood sugars every 2 hrs to make sure they are in range

28. Clinical Trials • Immune modulating studies • www.jdrf.org • www.ClinicalTrials.gov • Anti CD3- monoclonal AB • Phase 3 trials • Newly diagnosed Type 1 Diabetes • Call Research Institute of Dallas 214-363-5535 • Immune modulating vaccines • Stem cell and pancreas transplants

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

30. 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.

31. 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

32. Hyperosmolar Nonketotic SyndromePresentation • Extreme dehydration • Supine or orthostatic hypotension • Confusion coma • Neurological findings • Seizures • Transient hemiparesis • Hyperreflexia • Generalized areflexia

33. Hyperosmolar Nonketotic SyndromePresentation • Glucose >600 mg/dl • Sodium • Normal, elevated or low • Potassium • Normal or elevated • Bicarbonate >15 mEq/L • Osmolality >320 mOsm/L

34. Hyperosmolar Nonketotic SyndromeTreatment • 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

35. 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

36. Conclusion • 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