Diabetic Ketoacidosis

An overview on DKA management

1. DR SYED FAISAL TAHA CONSULTANT PHYSICIAN/NEPHROLOGIST

2. INTRODUCTION

3. UNDERSTANDING DIABETES Diabetes mellitus, often referred to simply as DIABETES. Diabetes is a condition in which the body: Does not produce enough insulin, and/or Does not properly respond to insulin Insulin is a hormone produced in the pancreas. Insulin enables cells to absorb glucose in order to turn it into energy. 3

4. Type 1 vs. Type 2 Type 1 diabetes Type 2 diabetes Diagnosed in children and young adults Typically diagnosed in adulthood Previously known as Juvenile Diabetes Also found in overweight children Insulin-dependent Non-insulin-dependent Body does not produce insulin Body fails to produce and properly use insulin

5. Complications of blood glucose alterations Hypoglycemia Hyperglycemia Ketosis Acidosis DKA (Hyperglycemia + Ketosis + Acidosis) Blood Glucose Alterations Normal fasting blood glucose level 4-6 mmol /L

6. DEFINI TION

7. DIABETIC KETOACIDOSIS (DKA) Hyperosmolar Hyperglycemic State (HHS)

8. DIABETIC KETOACIDOSIS (DKA) A state of absolute or relative insulin deficiency aggravated by ensuing hyperglycemia, dehydration, and acidosis-producing derangements in intermediary metabolism, including production of serum acetone. Can occur in both Type I Diabetes and Type II Diabetes In type II diabetics with insulin deficiency/dependence The presenting symptom for ~ 25% of Type I Diabetics.

9. Diabetic KetoAcidosis (DKA) 160,000 Admissions to private hospitals/year Cost = over 1 billion $ annually 65% = <19 years old Main cause of death in children with diabetes (approximately 85%) Cerebral edema in 69%

10. Hyperosmolar Hyperglycemic State (HHS) An acute metabolic complication of diabetes mellitus characterized by impaired mental status and elevated plasma osmolality in a patient with hyperglycemia. Occurs predominately in Type II Diabetics A few reports of cases in type I diabetics. The presenting symptom for 30-40% of Type II diabetics . Not commonly associated with ketonaemia and acidosis

11. CLASSIFICA TION

12. The biochemical criteria for the diagnosis of DKA 3,4 Hyperglycemia - blood glucose greater than 11.1 mmol /L Ketosis - ketones present in blood and/or urine Acidosis - pH less than 7.3 and/or bicarbonate less than 15 mmol /L Classic Triad of DKA

13. DKA is generally categorized by the severity of the acidosis. MILD – Venous pH less than 7.3 and/or bicarbonate concentration less than 15 mmol /L MODERATE – Venous pH less than 7.2 and/or bicarbonate concentration less than 10 mmol /L SEVERE – Venous pH less than 7.1 and/or bicarbonate concentration less than 5 mmol /L CLASSIFICATION OF DKA

14. RISK FACTOR

15. Risk factors for DKA at onset Age <12 yrs No first degree diabetic relative Lower socioeconomic status High dose glucocorticoids, atypical antipsychotics, diazoxide and some immunosuppresive drugs Poor access to medical care Uninsured Usage of SGLT-2 inhibitor – euglycaemic DKA SGLT2 inhibitors blunt insulin production in the face of stress hormones leading to increased ketotic metabolism

16. ETIOLOGY

17. Why do ketones develop? No carbohydrate intake fasting gastroenteritis Atkins diet, neonates fed high-fat milk Prolonged exercise, pregnancy Lack of insulin activity onset of diabetes (insufficient secretion) interruption of insulin delivery in established pt Increase in insulin resistance infection, illness, surgery, stress Alcohol, salicylate ingestion, inborn metabolic errors

18. Causes of DKA/HHS Stressful precipitating event that results in increased catecholamines, cortisol, glucagon. Infection (pneumonia, UTI) Alcohol, drugs Stroke Myocardial Infarction Pancreatitis Trauma Medications (steroids, thiazide diuretics) Non-compliance with insulin

19. PATHOPHYSIOLOGY

20. PATHOPHYSIOLOGY OF DKA Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(5):1150-1159. Reprinted with permission from The American Diabetes Association.

21. PATHOPHYSIOLOGY OF DKA

22. CLINICAL MANIFESTATION

23. What are the presenting complaints? “Gastro-enteritis” Vomiting - but no diarrhea Dehydration - but excessive urine output ! “Respiratory distress” But no lung findings

24. DKA is a complex metabolic state of: hyperglycemia, ketosis, and acidosis Symptoms include: Deep, rapid breathing Fruity breath odor Very dry mouth Nausea and vomiting Lethargy/drowsiness DKA is life-threatening and needs immediate treatment

25. Symptoms of DKA/HHS Polyuria Polydypsia Blurred vision Nausea/Vomiting Abdominal Pain Fatigue Confusion Obtundation

26. Physical Examination in DKA/HHS Hypotension, tachycardia Kussmaul breathing (deep, labored breaths) Fruity odor to breath (due to acetone) Dry mucus membranes Confusion Abdominal tenderness

27. DIAGNOSTIC INVESTIGATION

28. Diagnostic Criteria for DKA and HHS Mild DKA Moderate DKA Severe DKA HHS Plasma glucose mmol /L > 14 > 14 > 14 > 33.3 Arterial pH 7.25-7.30 7.00-7.24 < 7.00 > 7.30 Sodium Bicarbonate (mEq/L) 15 – 18 10 - <15 < 10 > 15 Urine Ketones Positive Positive Positive Small Serum Ketones Positive Positive Positive Small Serum Osmolality (mOsm/kg) Variable Variable Variable > 320 Anion Gap > 10 > 12 > 12 variable Mental Status Alert Alert/Drowsy Stupor/Coma Stupor/Coma Serum ketones positive if > 1mg/dl or < 0.1 mmol /L Anion gap Na + K – Cl – Hco3 target < 10

29. TREATMENT

30. Identify and Treat the Precipitating Factor Insulin omission – MOST COMMON CAUSE of DKA New diagnosis of diabetes Infection / Sepsis Myocardial infarction Small rise in troponin may occur without overt ischemia ECG changes may reflect hyperkalemia Thyrotoxicosis Drugs

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

32. Treatment of DKA Fluids and Electrolytes Fluid replacement Restores perfusion of the tissues Lowers counterregulatory hormones Increase insulin sensitivity Average fluid deficit 3-5 liters

33. Initial fluid resuscitation 15 to 20 mL/kg lean body weight per hour (approximately 1000 mL/hour in an average-sized person) for the first couple of hours M aximum of <50 mL/kg in the first four hours 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

34. Treatment of DKA Fluids 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. Phosphate deficit May want to use Kphos Bicarbonate not given unless pH <7 or bicarbonate <5 mmol/L

35. Treatment of DKA Insulin Therapy IV bolus of 0.1-0.2 units/kg ( ~ 10 units) regular insulin Follow with hourly regular insulin infusion Glucose levels Decrease 4 to 5.5 mmol /L per hour Minimize rapid fluid shifts

36. Treatment of DKA Glucose 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 < 16.6 mmol /L

37. Insulin-Glucose Infusion for DKA Blood glucose Insulin Infusion D5W Infusion <70 0.5 units/hr 150 cc/hr 70-100 1.0 125 101-150 2.0 100 151-200 3.0 100 201-250 4.0 75 251-300 6.0 50 301-350 8.0 351-400 10.0 401-450 12.0 451-500 15.0 >500 20.0

38. Treatment of HHS Hydration!!! Even more important than in DKA Find underlying cause and treat! Insulin drip Should be started only once aggressive hydration has taken place. Switch to subcutaneous regimen once glucose < 11mmol/L and patient eating. Serial Electrolytes Potassium replacement.

39. Pottasium Replacement If the initial K is below 3.3 mmol /L, IV potassium chloride ( KCl ; 20 to 40 mmol /hour , before insulin therapy till raise the serum potassium concentration into the normal range of 4 to 5 mmol /L 3.3 to 5.3 given iv K with insulin infusion If above 5.3 not to given iv K till level less than than

40. Resolution of ketoacidosis in DKA ● N ormalization of the serum anion gap (less than 12 mEq /L) and blood beta- hydroxybutyrate levels ●Patients with HHS are mentally alert and the effective plasma osmolality has fallen below 315 mOsmol /kg ●The patient is able to eat

41. Caveat U rinary ketones by the nitroprusside method can be used for the initial diagnosis of ketoacidosis I t should not be used for monitoring resolution of DKA . Nitroprusside reacts mainly with acetoacetate, to a much lesser degree with acetone (which is not an acid), and not with beta- hydroxybutyrate . A positive nitroprusside test may persist for up to 36 hours after resolution of the ketoacidosis due to a positive reaction with acetone, which is slowly eliminated,

42. Once DKA Resolved Treatment 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, Lente, Ultralente 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.

43. COMPLICATION

44. 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

45. PREVEN TION

46. Prevention of DKA / HHS Type 1 diabetes Education around sick day management Continuation of insulin even when not eating Frequent monitoring when ill Type 2 diabetes Education around sick day management Frequent monitoring when ill

47. 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

48. SUMMARY

49. 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