Nothing to disclose. Disclosure

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1 Nothing to disclose. Disclosure

2 Inpatient Management of Diabetes Mellitus Cindy Chin, MD Pediatrics in the Red Rocks 2015

3 Objectives Name 3 diagnostic criteria for diabetes mellitus. Understand and apply the rule of 15s. Distinguish between type 1 & insulin-requiring type 2 diabetes mellitus. Discuss the significance of ketonuria.

4 Outline Yes Diabetes? No Diabetic ketoacidosis? Yes No Treat 1 condition New Onset? Yes No Type 1 or Type 2? T1DM T2DM

5 Outline Yes Diabetes? No Diabetic ketoacidosis? Yes No Treat 1 condition New Onset? Yes No Type 1 or Type 2? T1DM T2DM

6 Cases Case 1: 2 yo boy recently diagnosed with anemia with 2 week history of polyuria, polydipsia, and polyphagia. Serum glucose 767, bicarb 21 Urine glucose 500, ketones small Case 2: 8 yo boy with diagnosed with H1N1 2.5 weeks ago s/p Tamiflu who finished a course of oral steroid 10 days prior to presentation to PCP s office for 3 week history of polyuria, polydipsia, and polyphagia. Fasting POC glucose 201 Urine glucose 250 (2+), ketones large Case 3: 10 yo girl with no significant medical history presents to the ED with nausea and vomiting after breakfast. No history of polyuria or polydipsia. Serum glucose 220, bicarb 18 Urine ketones 3+.

7 Which of these patients meet diagnostic criteria for diabetes mellitus? Case 1: 2 yo boy with polyuria, polydipsia, and polyphagia. Serum glucose 767, bicarb 21; Urine glucose 500, ketones small Case 2: 8 yo boy with recent steroids and polys Fasting POC glucose 201; Urine glucose 250 (2+), ketones large Case 3: 10 yo girl with no history of polyuria or polydipsia. Serum glucose 220, bicarb 18; Urine ketones 3+. A: Case 1 only B: Case 2 only C: Case 3 only D: Case 1 and 2 E: Case 1 and 3

8 ADA Diagnostic criteria Diabetes Care, 2010, 33, Supplement 1

9 ADA Diagnostic criteria Diabetes Care, 2010, 33, Supplement 1

10 ADA Diagnostic criteria Diabetes Care, 2010, 33, Supplement 1

11 ADA Diagnostic criteria Diabetes Care, 2010, 33, Supplement 1

12 ADA Diagnostic criteria Diabetes Care, 2010, 33, Supplement 1

13 ADA Diagnostic criteria Diabetes Care, 2010, 33, Supplement 1

14 Does the case meet diagnostic criteria? Case 1: 2 yo boy recently diagnosed with anemia with 2 week history of polyuria, polydipsia, and polyphagia. Serum glucose 767, bicarb 21 Urine glucose 500, ketones small

15 Does the case meet diagnostic criteria? Case 1: 2 yo boy recently diagnosed with anemia with 2 week history of polyuria, polydipsia, and polyphagia. Serum glucose 767, bicarb 21 Urine glucose 500, ketones small

16 Does the case meet diagnostic criteria? Case 1: 2 yo boy recently diagnosed with anemia with 2 week history of polyuria, polydipsia, and polyphagia. Serum glucose 767, bicarb 21 Urine glucose 500, ketones small

17 Does the case meet diagnostic criteria? Case 1: 2 yo boy recently diagnosed with anemia with 2 week history of polyuria, polydipsia, and polyphagia. Serum glucose 767, bicarb 21 Urine glucose 500, ketones small

18 Does the case meet diagnostic criteria? Case 2: 8 yo boy with h/o H1N1 2.5 weeks ago s/p Tamiflu and oral steroid 10 days prior to presentation to PCP s office for 3 week history of polyuria, polydipsia, and polyphagia. Fasting POC glucose 201 Urine glucose 250 (2+), ketones large

19 Does the case meet diagnostic criteria? Case 2: 8 yo boy with h/o H1N1 2.5 weeks ago s/p Tamiflu and oral steroid 10 days prior to presentation to PCP s office for 3 week history of polyuria, polydipsia, and polyphagia. Fasting POC glucose 201 Urine glucose 250 (2+), ketones large

20 Does the case meet diagnostic criteria? Case 2: 8 yo boy with h/o H1N1 2.5 weeks ago s/p Tamiflu and oral steroid 10 days prior to presentation to PCP s office for 3 week history of polyuria, polydipsia, and polyphagia. Fasting POC glucose 201 Urine glucose 250 (2+), ketones large

21 Does the case meet diagnostic criteria? Case 2: 8 yo boy with h/o H1N1 2.5 weeks ago s/p Tamiflu and oral steroid 10 days prior to presentation to PCP s office for 3 week history of polyuria, polydipsia, and polyphagia. Fasting POC glucose 201 Urine glucose 250 (2+), ketones large

22 Does the case meet diagnostic criteria? Case 3: 10 yo girl with no significant medical history presents to the ED with nausea and vomiting after breakfast. No history of polyuria or polydipsia. Serum glucose 220, bicarb 18 Urine ketones 3+

23 Does the case meet diagnostic criteria? Case 3: 10 yo girl with no significant medical history presents to the ED with nausea and vomiting after breakfast. No history of polyuria or polydipsia. Serum glucose 220, bicarb 18 Urine ketones 3+

24 Does the case meet diagnostic criteria? Case 3: 10 yo girl with no significant medical history presents to the ED with nausea and vomiting after breakfast. No history of polyuria or polydipsia. Serum glucose 220, bicarb 18 Urine ketones 3+

25 Does the case meet diagnostic criteria? Case 3: 10 yo girl with no significant medical history presents to the ED with nausea and vomiting after breakfast. No history of polyuria or polydipsia. Serum glucose 220, bicarb 18 Urine ketones 3+

26 Summary Diabetes Care, 2010, 33, Supplement 1

27 Which of these patients meet diagnostic criteria for diabetes mellitus? Case 1: 2 yo boy with polyuria, polydipsia, and polyphagia. Serum glucose 767, bicarb 21; Urine glucose 500, ketones small Case 2: 8 yo boy with recent steroids and polys Fasting POC glucose 201; Urine glucose 250 (2+), ketones large Case 3: 10 yo girl with no history of polyuria or polydipsia. Serum glucose 220, bicarb 18; Urine ketones 3+. A: Case 1 only B: Case 2 only C: Case 3 only D: Case 1 and 2 E: Case 1 and 3

28 Outline Yes Diabetes? No Diabetic ketoacidosis? Yes No Treat 1 condition New Onset? Yes No Type 1 or Type 2? T1DM T2DM

29 Diabetic ketoacidosis Definition Pathophysiology Management Epidemiology Cerebral edema

30 Case 4 11 yo boy with no significant past medical history seen at his PCP s office for ear pain. 2 week history of polyuria and polydipsia 26 lb in 2 months POC glucose elevated and ketonuric Per PCP, looks clinically well. Referred to the ED for possible new onset diabetes mellitus.

31 Case 4: Labs

32 Is he in diabetic ketoacidosis? Case 4: 11 yo boy with polyuria and polydipsia but looks well clinically. A: No, does not have diabetes B: No, DM but not in DKA C: Yes, mild DKA D: Yes, moderate DKA E: Yes, severe DKA

33 Diabetic ketoacidosis Definition Pathophysiology Management Epidemiology Cerebral edema

34 Diabetic ketoacidosis (DKA) Criteria Hyperglycemia: Glucose > 200 mg/dl Acidosis: ph < 7.3, bicarbonate < 15 mmol/l Severity Mild: Venous ph < 7.3, bicarbonate < 15 Moderate: Venous ph < 7.2, bicarbonate < 10 Severe: Venous ph < 7.1, bicarbonate < 5

35 Diabetic ketoacidosis (DKA) Criteria Hyperglycemia: Glucose > 200 mg/dl Acidosis: ph < 7.3, bicarbonate < 15 mmol/l Severity Mild: Venous ph < 7.3, bicarbonate < 15 Moderate: Venous ph < 7.2, bicarbonate < 10 Severe: Venous ph < 7.1, bicarbonate < 5

36 Diabetic ketoacidosis (DKA) Criteria Hyperglycemia: Glucose > 200 mg/dl Acidosis: ph < 7.3, bicarbonate < 15 mmol/l Severity Mild: Venous ph < 7.3, bicarbonate < 15 Moderate: Venous ph < 7.2, bicarbonate < 10 Severe: Venous ph < 7.1, bicarbonate < 5

37 Is he in diabetic ketoacidosis? Case 4: 11 yo boy with polyuria and polydipsia but looks well clinically. A: No, does not have diabetes B: No, DM but not in DKA C: Yes, mild DKA D: Yes, moderate DKA E: Yes, severe DKA

38 Is he in diabetic ketoacidosis? Case 4: 11 yo boy with polyuria and polydipsia but looks well clinically. A: No, does not have diabetes B: No, DM but not in DKA C: Yes, mild DKA D: Yes, moderate DKA E: Yes, severe DKA

39 Is he in diabetic ketoacidosis? Case 4: 11 yo boy with polyuria and polydipsia but looks well clinically. A: No, does not have diabetes B: No, DM but not in DKA C: Yes, mild DKA D: Yes, moderate DKA E: Yes, severe DKA

40 Is he in diabetic ketoacidosis? Case 4: 11 yo boy with polyuria and polydipsia but looks well clinically. Corrected Na

41 Is he in diabetic ketoacidosis? Case 4: 11 yo boy with polyuria and polydipsia but looks well clinically. Corrected Na = Measured Na (Glc 100/100)

42 Is he in diabetic ketoacidosis? Case 4: 11 yo boy with polyuria and polydipsia but looks well clinically. Corrected Na = Measured Na (Glc 100/100) = [( )/100] = 139.6

43 Diabetic ketoacidosis Definition Pathophysiology Management Epidemiology Cerebral edema

44 Insulin Action

45 Insulin Action: Signal of fed state

46 Insulin Action: Signal of fed state

47 Insulin Action: Signal of fed state

48 Insulin Action Insulin

49 Insulin Action Hypothalamus: Food intake Insulin

50 Insulin Action Insulin Skeletal muscle: Glucose uptake

51 Insulin Action Insulin White adipose tissue: Lipogenesis

52 Insulin Action Insulin Brown adipose tissue: Thermogenesis

53 Insulin Action Insulin Liver: Glucose production

54 Type 1 Diabetes Mellitus: Insulin deficiency Insulin

55 Type 1 Diabetes Mellitus: Insulin deficiency Insulin Skeletal muscle: Glucose uptake Liver: Glucose production

56 Pathophysiology Absolute insulin deficiency or Stress, infection, or insufficient insulin intake Wolfsdorf J et al. Diabetes Care, 2006, 29:

57 Pathophysiology compensatory response Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Wolfsdorf J et al. Diabetes Care, 2006, 29:

58 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Wolfsdorf J et al. Diabetes Care, 2006, 29:

59 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Hyperglycemia Wolfsdorf J et al. Diabetes Care, 2006, 29:

60 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Glucosuria (osmotic diuresis) Polyuria, weight loss, polyphagia, sticky urine Wolfsdorf J et al. Diabetes Care, 2006, 29:

61 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Loss of H 2 O & lytes electrolyte abnl Wolfsdorf J et al. Diabetes Care, 2006, 29:

62 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Dehydration Polydipsia, - unable to keep up hyperosmolarity Wolfsdorf J et al. Diabetes Care, 2006, 29:

63 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Dehydration Wolfsdorf J et al. Diabetes Care, 2006, 29:

64 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Lactic acidosis Wolfsdorf J et al. Diabetes Care, 2006, 29:

65 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Ketoacidosis Wolfsdorf J et al. Diabetes Care, 2006, 29:

66 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Impaired Renal Function Cr Wolfsdorf J et al. Diabetes Care, 2006, 29:

67 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Impaired Renal Function Wolfsdorf J et al. Diabetes Care, 2006, 29:

68 Type 1 Diabetes Mellitus: Insulin deficiency Insulin White adipose tissue: Lipogenesis

69 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis Wolfsdorf J et al. Diabetes Care, 2006, 29:

70 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis FFA to liver Gluconeogenesis Wolfsdorf J et al. Diabetes Care, 2006, 29:

71 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis FFA to liver Gluconeogenesis Hyperglycemia Wolfsdorf J et al. Diabetes Care, 2006, 29:

72 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis FFA to liver Ketogenesis Wolfsdorf J et al. Diabetes Care, 2006, 29:

73 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis FFA to liver ketonuria Ketogenesis Wolfsdorf J et al. Diabetes Care, 2006, 29:

74 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis FFA to liver Alkali reserve Wolfsdorf J et al. Diabetes Care, 2006, 29:

75 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis FFA to liver Ketoacidosis Blow off CO 2 (acid) Kussmaul breathing Wolfsdorf J et al. Diabetes Care, 2006, 29:

76 Pathophysiology Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis FFA to liver Nausea Emesis Ketoacidosis Wolfsdorf J et al. Diabetes Care, 2006, 29:

77 Pathophysiology: Summary Counterregulatory Hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis ketonuria Kussmaul breathing, nausea, emesis Ketoacidosis Hyperglycemia Polyuria, weight loss, polyphagia, sticky urine Electrolyte abnl Polydipsia, osm creatinine Wolfsdorf J et al. Diabetes Care, 2006, 29:

78 Diabetic ketoacidosis Definition Pathophysiology Management Epidemiology Cerebral edema

79 Diabetic ketoacidosis (DKA): Management Fluids Electrolytes Insulin Monitoring Adapted from: Dunger DB et al. Pediatrics, 2004, 113: e133-e140 Mark T. Harriet Lane, 20 th Edition, Table 10-1 Wolfsdorf J et al. Diabetes Care, 2006, 29: Wolfsdorf JI. Pediatric Diabetes, 2014, 15: Wolfsdorf JI et al. Pediatric Diabetes 2014, 15 (Suppl. 20):

80 Diabetic ketoacidosis (DKA): Management Fluids Electrolytes Insulin Monitoring Adapted from: Dunger DB et al. Pediatrics, 2004, 113: e133-e140 Mark T. Harriet Lane, 20 th Edition, Table 10-1 Wolfsdorf J et al. Diabetes Care, 2006, 29: Wolfsdorf JI. Pediatric Diabetes, 2014, 15: Wolfsdorf JI et al. Pediatric Diabetes 2014, 15 (Suppl. 20):

81 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Dehydration Wolfsdorf J et al. Diabetes Care, 2006, 29:

82 Diabetic ketoacidosis (DKA): Management we Fluids Assume 5-10% dehydration Total fluid deficit = 10 ml/kg q1% dehydration ml/kg bolus NS or LR over 1 hour Replace remaining fluid deficit equally over 48h + maintenance - Usually run IV fluids at times maintenance - Do not replace urinary loss

83 Diabetic ketoacidosis (DKA): Management we Fluids Assume 5-10% dehydration Total fluid deficit = 10 ml/kg q1% dehydration ml/kg bolus NS or LR over 1 hour Replace remaining fluid deficit equally over 48h + maintenance - Usually run IV fluids at times maintenance - Do not replace urinary loss

84 Diabetic ketoacidosis (DKA): Management we Fluids Assume 5-10% dehydration Total fluid deficit = 10 ml/kg q1% dehydration ml/kg bolus NS or LR over 1 hour Replace remaining fluid deficit equally over 48h + maintenance - Usually run IV fluids at times maintenance - Do not replace urinary loss

85 Diabetic ketoacidosis (DKA): Management we Fluids Assume 5-10% dehydration Total fluid deficit = 10 ml/kg q1% dehydration ml/kg bolus NS or LR over 1 hour Replace remaining fluid deficit equally over 48h + maintenance - Usually run IV fluids at times maintenance - Do not replace urinary loss

86 Diabetic ketoacidosis (DKA): Management we Fluids Assume 5-10% dehydration Total fluid deficit = 10 ml/kg q1% dehydration ml/kg bolus NS or LR over 1 hour Replace remaining fluid deficit equally over 48h + maintenance - Usually run IV fluids at times maintenance - Do not replace urinary loss

87 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Dehydration Wolfsdorf J et al. Diabetes Care, 2006, 29:

88 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Dehydration Wolfsdorf J et al. Diabetes Care, 2006, 29:

89 Diabetic ketoacidosis (DKA): Management Fluids Electrolytes Insulin Monitoring Adapted from: Dunger DB et al. Pediatrics, 2004, 113: e133-e140 Mark T. Harriet Lane, 20 th Edition, Table 10-1 Wolfsdorf J et al. Diabetes Care, 2006, 29: Wolfsdorf JI. Pediatric Diabetes, 2014, 15: Wolfsdorf JI et al. Pediatric Diabetes 2014, 15 (Suppl. 20):

90 Pathophysiology compensatory response Glucose utilization Proteolysis Protein Synthesis Glycogenolysis Loss of H 2 O & lytes electrolyte abnl Wolfsdorf J et al. Diabetes Care, 2006, 29:

91 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: Type of fluid: ½ NS NS/LR - Some use NS to risk of cerebral edema - Prolonged use of NS Hyperchloremic metabolic acidosis - Not to discourage use, but to consider if acidosis not improving - As glc, expect Na - If Na does not as expected, risk factor for cerebral edema

92 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: Type of fluid: ½ NS NS/LR - Some use NS to risk of cerebral edema - Prolonged use of NS Hyperchloremic metabolic acidosis - Not to discourage use, but to consider if acidosis not improving - As glc, expect Na - If Na does not as expected, risk factor for cerebral edema

93 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: Type of fluid: ½ NS NS/LR - Some use NS to risk of cerebral edema - Prolonged use of NS Hyperchloremic metabolic acidosis - Not to discourage use, but to consider if acidosis not improving - As glc, expect Na - If Na does not as expected, risk factor for cerebral edema

94 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: Type of fluid: ½ NS NS/LR - Some use NS to risk of cerebral edema - Prolonged use of NS Hyperchloremic metabolic acidosis - Not to discourage use, but to consider if acidosis not improving - As glc, expect Na - If Na does not as expected, risk factor for cerebral edema

95 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: Type of fluid: ½ NS NS/LR - Some use NS to risk of cerebral edema - Prolonged use of NS Hyperchloremic metabolic acidosis - Not to discourage use, but to consider if acidosis not improving - As glc, expect Na - If Na does not as expected, risk factor for cerebral edema

96 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: ½ NS NS/LR K: Patients are whole body K + depleted - Causes - Hyperosmolarity Transcellular K + shifts - Glycogenolysis, proteolysis - Acidosis (minor role) - Losses - Emesis - Osmotic diuresis - Volume depletion aldosterone urinary K + excretion

97 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: ½ NS NS/LR K: Patients are whole body K + depleted - Causes - Hyperosmolarity Transcellular K + shifts - Glycogenolysis, proteolysis - Acidosis (minor role) - Losses - Emesis - Osmotic diuresis - Volume depletion aldosterone urinary K + excretion

98 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: ½ NS NS/LR K: Patients are whole body K + depleted - Causes - Hyperosmolarity Transcellular K + shifts - Glycogenolysis, proteolysis - Acidosis (minor role) - Losses - Emesis - Osmotic diuresis - Volume depletion aldosterone urinary K + excretion

99 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: ½ NS NS/LR K: Patients are whole body K + depleted - With insulin treatment - serum K + risk of cardiac arrhythmia - K + treatment ½ KCl or K acetate + ½ KPO 4 (Avoid PO 4 if Ca 2+ low or dropping) K > 6: No K initially (Wait for documented urine output) K 4-6: 40 meq/l K < 4: Start K+ supplementation immediately (even before insulin therapy), consider supplementation (60 meq/l)

100 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: ½ NS NS/LR K: Patients are whole body K + depleted - With insulin treatment - serum K + risk of cardiac arrhythmia - K + treatment ½ KCl or K acetate + ½ KPO 4 (Avoid PO 4 if Ca 2+ low or dropping) K > 6: No K initially (Wait for documented urine output) K 4-6: 40 meq/l K < 4: Start K+ supplementation immediately (even before insulin therapy), consider supplementation (60 meq/l)

101 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: ½ NS NS/LR K: Patients are whole body K + depleted Replace (after documented urine) Phos: Patients often lose phosphorus with osmotic diuresis. Insulin therapy intracellular Phos serum Phos Do not replace unless Phos < 1 mg/dl. No clinical benefit. Be aware that Phos therapy Ca 2+ Stop Phos therapy

102 Diabetic ketoacidosis (DKA): Management we Electrolytes Na: ½ NS NS/LR K: Patients are whole body K + depleted Replace (after documented urine) Phos: Do not replace unless < 1 mg/dl. Phos therapy Ca 2+ Bicarbonate: Rarely used. Potential uses - Severe acidemia (ph < 7.00) + cardiac contractility, peripheral vasodilation - Life-threatening K Potential adverse effects - Paradoxical CNS acidosis - Rapid correction of acidosis K, Na tonicity - hepatic ketone production Slow recovery from ketosis

103 Diabetic ketoacidosis (DKA): Management Fluids Electrolytes Insulin Monitoring Adapted from: Dunger DB et al. Pediatrics, 2004, 113: e133-e140 Mark T. Harriet Lane, 20 th Edition, Table 10-1 Wolfsdorf J et al. Diabetes Care, 2006, 29: Wolfsdorf JI. Pediatric Diabetes, 2014, 15: Wolfsdorf JI et al. Pediatric Diabetes 2014, 15 (Suppl. 20):

104 Pathophysiology Absolute insulin deficiency or Stress, infection, or insufficient insulin intake Wolfsdorf J et al. Diabetes Care, 2006, 29:

105 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose

106 Pathophysiology Absolute insulin deficiency or Stress, infection, or insufficient insulin intake Wolfsdorf J et al. Diabetes Care, 2006, 29:

107 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: 0.05 (low dose) (standard) U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose

108 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: 0.05 (low dose) (standard) U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose If known diagnosis of diabetes and on insulin pump, make sure to disconnect pump while on insulin drip.

109 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: 0.05 (low dose) (standard) U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose

110 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: 0.05 (low dose) (standard) U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose

111 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: 0.05 (low dose) (standard) U/kg/hr after 1 st fluid bolus Goal glucose: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose

112 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose

113 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose

114 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin - NPO until then - If recent large consumption of glucose-containing fluids Consider gastric emptying early in therapy course intestinal absorption of glucose and electrolyte-free water Discontinue insulin drip after subcutaneous dose

115 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO 3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose - Harriet Lane: 1 hour after subcutaneous dose - Wolfsdorf et al.: minutes after rapid-acting insulin 1-2 hours after regular insulin Longer after intermediate/long-acting insulin - e.g., PM: basal SQ insulin, AM: discontinue insulin drip

116 Diabetic ketoacidosis (DKA): Management Fluids Electrolytes Insulin Monitoring Adapted from: Dunger DB et al. Pediatrics, 2004, 113: e133-e140 Mark T. Harriet Lane, 20 th Edition, Table 10-1 Wolfsdorf J et al. Diabetes Care, 2006, 29: Wolfsdorf JI. Pediatric Diabetes, 2014, 15: Wolfsdorf JI et al. Pediatric Diabetes 2014, 15 (Suppl. 20):

117 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

118 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

119 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

120 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

121 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

122 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

123 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

124 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

125 Diabetic ketoacidosis (DKA): Management we Monitoring q1h - Vital signs: HR, RR, BP, EKG (T wave changes), input/output - Capillary blood glucose (point of care): Cross check with venous sample - Insulin dose q2-4h - VBG - Electrolytes (including calcium, phosphate) - NS fluids: Risk of hyperchloremic metabolic acidosis - K + : Severity of hypokalemia may be marker of disease duration - Ca 2+ : Risk of hypocalcemia with phosphate supplementation - Phos: Phos depletion can persist for days after DKA resolution q6-8h: Cr, BUN, Hct qvoid: Urine ketones

126 Diabetic ketoacidosis (DKA): Management Summary Fluids: To restore intravascular volume and improve GFR ml/kg isotonic bolus IV fluids (1/2 NS NS) at x maintenance Electrolytes Whole body K+ depleted Need replacement Phosphorus therapy Ca 2+ Insulin: To normalize glucose levels, lipolysis & ketogenesis Insulin drip: units/kg/hr Monitoring: To identify deterioration

127 Diabetic ketoacidosis (DKA): Management Fluids Electrolytes Insulin Laboratory values Assume 5-10% dehydration Total fluid deficit = 10 ml/kg q1% dehydration ml/kg bolus NS or LR over 1 hour Replace remaining fluid deficit equally over 48h + maintenance a Na Fluids should contain at least ½ NS b glc, Na K c ½ KCl or K acetate + ½ KPO 4 (Avoid PO 4 if Ca low or dropping d ) K > 6: No K initially K 4-6: 40 meq/l K < 4: 60 meq/l Bicarbonate Rarely used.. Consider only in cases of extreme acidosis (ph < 7.00), use with caution; may cause paradoxical CNS acidosis Insulin drip: U/kg/hr after 1 st fluid bolus e Goal glc: mg/dl/hr Glc or glc > 100 mg/dl/hr, add D 5 to fluids ph > 7.30, HCO3 > 15, anion gap resolved, and patient tolerating PO, start SC insulin Discontinue insulin drip 1 hr after SC dose Blood glc q1h VBG, electrolytes (including calcium, phosphate) q2h until stable, then q4h qvoid urine ketones a Additional fluids may be needed if there is a large negative fluid balance in the 1 st hours of treatment due to the osmotic diuresis when serum glc is high b Some DKA protocols recommend using NS rather than ½ NS during part of the replacement period in an effort to further risk of cerebral edema c Patients with DKA are total body K+ depleted and are at risk for severe hypokalemia during DKA therapy. However, serum K+ levels may be normal or as a result of shift of K+ to the extracellular compartment in the setting of acidosis. d Phosphate is depleted in DKA and will drop further with insulin therapy. Consider replacing ½ of K as KPO 4 for 1 st 8hr, then all as KCl. Excessive phosphate may induce hypocalcemic tetany. e Lower dose insulin infusions can be considered in very young patients. f Some protocols recommend waiting for urine ketones to decrease or clear before starting SC insulin. Adapted from Mark T. Harriet Lane, 20 th Ed, Table 10-1

128 Diabetic ketoacidosis Definition Pathophysiology Management Epidemiology Cerebral edema

129 Diabetic ketoacidosis (DKA): Epidemiology

130 Diabetic ketoacidosis (DKA): Epidemiology Frequency: 15-67%

131 Diabetic ketoacidosis (DKA): Epidemiology Risk factors At diabetes diagnosis Younger age (<4 yo) No 1 st degree relative with T1DM Delayed diagnosis Lower socioeconomic status

132 Diabetic ketoacidosis (DKA): Epidemiology Risk factors At diabetes diagnosis Established diagnosis Risk 1-10%/patient/year; 75% related to insulin omission/rx error Poor metabolic control Previous history of DKA Peripubertal, adolescent girls Co-morbid psychiatric disorder Psychosocial stressors Inappropriate disruption in insulin therapy GI illness with vomiting and inability to maintain hydration

133 Diabetic ketoacidosis (DKA): Epidemiology Frequency: 15-67% Risk factors At diabetes diagnosis Younger age (<4 yo) No 1 st degree relative with T1DM Lower socioeconomic status Established diagnosis Risk 1-10%/patient/year; 75% related in insulin omission/rx error Poor metabolic control Previous history of DKA Peripubertal, adolescent girls Co-morbid psychiatric disorder Psychosocial stressors Inappropriate disruption in insulin therapy

134 Diabetic ketoacidosis Definition Pathophysiology Management Epidemiology Cerebral edema

135 Cerebral edema Risk factors Presentation Diagnostic criteria Cause Management

136 Cerebral edema Risk factors Presentation Diagnostic criteria Cause Management

137 Cerebral edema Risk factors Age < 5 years Low PCO 2 BUN Related to dehydration Not associated with Na content in IV fluids Slow in Na with therapy Longer symptom duration Severity of acidosis Bicarbonate administration

138 Cerebral edema Risk factors Presentation Diagnostic criteria Cause Management

139 Presentation Timing Cerebral edema 4-12 hours after DKA therapy initiated May be as late as hours later Can present before DKA therapy

140 Presentation Timing Symptoms Cerebral edema Headache Recurrence of vomiting HR, BP O 2 saturation Change in neurological status Non-specific: Restlessness, irritability, drowsiness, incontinence Specific neuro signs» Cranial nerve palsies, abnormal pupillary response, posturing

141 Cerebral edema Risk factors Presentation Diagnostic criteria Cause Management

142 Cerebral edema: Diagnostic criteria Diagnostic criteria (any 1) Abnormal motor or verbal response to pain Decorticate or decerebrate posture Cranial nerve palsy (esp. CN III, IV, and VI) Abnormal neurogenic respiratory pattern E.g., grunting, tachypnea, Cheyne-Stokes respiration, apneusis Major criteria Minor criteria

143 Cerebral edema: Diagnostic criteria Diagnostic criteria (any 1) Major criteria (2 or minor criteria) Altered mentation/fluctuating level of consciousness Sustained heart rate deceleration ( > 20 beats/min) not attributable to improved intravascular volume or sleep Age-inappropriate incontinence Minor criteria

144 Cerebral edema: Diagnostic criteria Diagnostic criteria (any 1) Major criteria (2 or minor criteria) Minor criteria (2 + 1 major criteria) Vomiting Headache Lethargy or not easily arousable Diastolic blood pressure > 90 mmhg Age < 5 years

145 Cerebral edema: Diagnostic criteria Diagnostic criteria (any 1) Abnormal motor or verbal response to pain Decorticate or decerebrate posture Cranial nerve palsy (esp. CN III, IV, and VI) Abnormal neurogenic respiratory pattern E.g., grunting, tachypnea, Cheyne-Stokes respiration, apneusis Major criteria (2 or minor criteria) Altered mentation/fluctuating level of consciousness Sustained heart rate deceleration ( > 20 beats/min) not attributable to improved intravascular volume or sleep Age-inappropriate incontinence Minor criteria (2 + 1 major criteria) Vomiting Headache Lethargy or not easily arousable Diastolic blood pressure > 90 mmhg Age < 5 years

146 Cerebral edema Risk factors Presentation Diagnostic criteria Cause Management

147 Cerebral edema Risk factors Presentation Diagnostic criteria Cause: Poorly understood Management

148 Cerebral edema Risk factors Presentation Diagnostic criteria Cause Management

149 Management: Cerebral edema As soon as suspected (Do not wait for imaging can initially be normal) IV fluid rate Mannitol: g/kg over 30 minutes 3% saline: 5-10 ml/kg over 30 minutes Intubation to protect airway Hyperventilation: Associated with poorer outcome Do not use unless medically needed (e.g., ICP)

150 Management: Cerebral edema As soon as suspected (Do not wait for imaging can initially be normal) IV fluid rate Mannitol: g/kg over 30 minutes 3% saline: 5-10 ml/kg over 30 minutes Intubation to protect airway Hyperventilation: Associated with poorer outcome Do not use unless medically needed (e.g., ICP)

151 Cerebral edema: Summary Risk factors Young child with long symptom duration Severe acidosis, dehydration at presentation Presentation Can present before until 48h after therapy initiation. Diagnostic criteria exist Neurological changes Management If consider it, give it. If high risk, have ready at bedside Mannitol: g/kg over 30 minutes 3% saline: 5-10 ml/kg over 30 minutes

152 Outline Yes Diabetes? No Diabetic ketoacidosis? Yes No Treat 1 condition New Onset? Yes No Type 1 or Type 2? T1DM T2DM

153 Outline Yes Diabetes? No Diabetic ketoacidosis? Yes No Treat 1 condition New Onset? Yes No Type 1 or Type 2? T1DM T2DM

154 Subcutaneous insulin therapy: New onset If not initially in DKA If previously in DKA Insulin types Insulin dose calculation

155 Subcutaneous insulin therapy: New onset If not initially in DKA If previously in DKA Insulin types Insulin dose calculation

156 Subcutaneous insulin therapy: New onset If not initially in DKA Give IV fluids if needed. Allow PO. Give insulin - no matter what time of day.

157 DKA pathophysiology Absolute insulin deficiency or Stress, infection, or insufficient insulin intake Wolfsdorf J et al. Diabetes Care, 2006, 29:

158 Subcutaneous insulin therapy: New onset If not initially in DKA If previously in DKA Insulin types Insulin dose calculation

159 Subcutaneous insulin therapy: New onset If previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip.

160 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose - Harriet Lane: 1 hour after subcutaneous dose - Wolfsdorf et al.: minutes after rapid-acting insulin 1-2 hours after regular insulin Longer after intermediate/long-acting insulin - e.g., PM: basal SQ insulin, AM: discontinue insulin drip

161 Subcutaneous insulin therapy: New onset If not initially in DKA If previously in DKA Insulin types Insulin dose calculation

162

163

164

165

166

167 Thus, fast-acting insulin given BEFORE eating (ideally). - For children < 5yo, usually give AFTER eating.

168

169

170

171

172

173

174

175 NPH: 70% Novolog: 30% NPH: 70% Regular insulin: 30%

176 Subcutaneous insulin therapy: New onset If not initially in DKA If previously in DKA Insulin types Insulin dose calculation

177 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio Correction factor

178 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio Correction factor

179 Insulin dose calculation Total daily dose of insulin (basal + bolus) unit/kg/day

180 Insulin dose calculation Total daily dose of insulin (basal + bolus) unit/kg/day Younger kids: Closer to 0.5 Older/pubertal kids: Closer to 1

181 Insulin dose calculation Total daily dose of insulin (basal + bolus) unit/kg/day Younger kids: Closer to 0.5 Older/pubertal kids: Closer to 1 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair

182 Insulin dose calculation Total daily dose of insulin (basal + bolus) unit/kg/day Younger kids: Closer to 0.5 Older/pubertal kids: Closer to 1 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day

183 Insulin dose calculation Total daily dose of insulin (basal + bolus) unit/kg/day Younger kids: Closer to 0.5 Older/pubertal kids: Closer to 1 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg

184 Insulin dose calculation Total daily dose of insulin (basal + bolus) unit/kg/day Younger kids: Closer to 0.5 Older/pubertal kids: Closer to 1 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day

185 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio Correction factor

186 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Total daily dose / 2

187 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Total daily dose / 2 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair

188 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Total daily dose / 2 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day

189 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Total daily dose / 2 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Basal insulin = / 2

190 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Total daily dose / 2 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Basal insulin = / 2 =

191 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Total daily dose / 2 Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Basal insulin = / 2 = units (detemir or glargine)

192 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio Correction factor

193 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio: 450/TDD or 500/weight (kg)

194 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio: 450/TDD or 500/weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day

195 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio: 450/TDD or 500/weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Insulin:carb ratio: (aspart/glulisine/lispro) - 450/TDD = 450/26-500/weight = 500/35

196 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio: 450/TDD or 500/weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Insulin:carb ratio: (aspart/glulisine/lispro) - 450/TDD = 450/26 = /weight = 500/35 = 14.29

197 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio: 450/TDD or 500/weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Insulin:carb ratio: (aspart/glulisine/lispro) - 450/TDD = 450/26 = (1 unit q17 grams CHO) - 500/wgt = 500/35 = (1 unit q14 grams CHO)

198 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Insulin:carb ratio Correction factor

199 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Correction factor = 1800/TDD or weight (kg)

200 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Correction factor = 1800/TDD or weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day

201 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Correction factor = 1800/TDD or weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Correction factor (aspart/glulisine/lispro) /TDD = 1800/ /weight = 1800/35

202 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Correction factor = 1800/TDD or weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Correction factor (aspart/glulisine/lispro) /TDD = 1800/26 = /weight = 1800/35 = 51

203 Insulin dose calculation Total daily dose of insulin (basal + bolus) Basal insulin Bolus insulin Correction factor = 1800/TDD or weight (kg) Case example: 11 yo boy (Case 4) Weight: 35 kg, body odor, no axillary/pubic hair TDD = 0.75 unit/kg/day * 35 kg = units/day Correction factor (aspart/glulisine/lispro) /TDD = 1800/26 = (1 unit q70 mg/dl > 150) /wgt = 1800/35 = (1 unit q50 mg/dl > 150)

204 Insulin dose calculation: Summary Total daily dose (TDD) = unit/kg/day Basal insulin = TDD/2 Bolus insulin Insulin:carb ratio = 450/TDD or 500/weight (kg) Correction factor = 1800/TDD or weight (kg)

205 Insulin dose calculation: Summary Total daily dose (TDD) = unit/kg/day Basal insulin = TDD/2 Bolus insulin (<5yo: AFTER PO) Insulin:carb ratio = 450/TDD or 500/weight (kg) Correction factor = 1800/TDD or weight (kg) Case example: 11 yo prepubertal boy (35 kg) Basal insulin: 13 units Bolus insulin: Insulin:carb: 1 unit q14-17 grams CHO Correction factor: 1 unit q50-70 > 150

206 Outline Yes Diabetes? No Diabetic ketoacidosis? Yes No Treat 1 condition New Onset? Yes No Type 1 or Type 2? T1DM T2DM

207 Insulin administration: Methods

208 Insulin administration: Methods

209 Insulin administration: Methods

210 Subcutaneous insulin therapy: Known Previously in DKA Hyperglycemia, ketonuria without DKA Admission for surgery

211 Subcutaneous insulin therapy: Known Previously in DKA Hyperglycemia, ketonuria without DKA Admission for surgery

212 Subcutaneous insulin therapy: Known Previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip

213 Diabetic ketoacidosis (DKA): Management we Insulin Insulin drip: U/kg/hr after 1 st fluid bolus Goal glc: mg/dl/hr < 100 mg/dl/hr Glc or glc > 100 mg/dl/hr: Add dextrose to fluids (D 5 -D 12.5 ) ph > 7.30, HCO3 > 15, anion gap resolved, glucose < 200. Patient able to tolerate PO: Start subcutaneous insulin Discontinue insulin drip after subcutaneous dose - Harriet Lane: 1 hour after subcutaneous dose - Wolfsdorf et al.: minutes after rapid-acting insulin 1-2 hours after regular insulin Longer after intermediate/long-acting insulin - e.g., PM: basal SQ insulin, AM: discontinue insulin drip

214 Subcutaneous insulin therapy: Known Previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip Modified home insulin regimen (i.e., sick day guidelines)

215 Sick day management

216 Use inpatient - For known diabetes - More insulin resistant Sick day management

217 Sick day management Use inpatient - For known diabetes - More insulin resistant - Not for new onset - Better off with any insulin than when they came in - Initial doses are an estimate with frequent adjustments

218 Sick day management

219 Sick day management Thus, need to check blood glucose and ketones q2hours

220 Sick day management Thus, need to check blood glucose and ketones q2hours

221 Sick day management Thus, need to check blood glucose and ketones q2hours Insulin dose = bolus (aspart/glulisine/lispro)

222 Sick day management Thus, need to check blood glucose and ketones q2hours Insulin dose = bolus (aspart/glulisine/lispro)

223 Sick day management Thus, need to check blood glucose and ketones q2hours

224 Sick day management Thus, need to check blood glucose and ketones q2hours

225 Sick day management

226 Sick day management

227 Sick day management

228 Sick day management

229 Sick day management

230 Sick day management Ketone clearance is not necessary for discharge if you know the patient is not acidotic. Ketones may persist despite clinical improvement. β-hydroxybutyrate : Acetoacetate ratio Normal = 3:1, DKA = 8:1. With clinical improvement, β-ohbutyrate Acetoacetate Acetoacetate is measured on urine ketone sticks.

231 Subcutaneous insulin therapy: Known Previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip Modified home insulin regimen (i.e., sick day guidelines) If on insulin pump and allowed to run the pump

232 Subcutaneous insulin therapy: Known Previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip Modified home insulin regimen (i.e., sick day guidelines) If on insulin pump and allowed to run the pump If on insulin pump and need to transition to injections

233 Subcutaneous insulin therapy: Known Previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip Modified home insulin regimen (i.e., sick day guidelines) If on insulin pump and allowed to run the pump Remove old site, place new one. Basal rate via pump Bolus (carbs, glc) insulin» Via syringe until ketone small-trace, then administer via pump

234 Subcutaneous insulin therapy: Known Previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip Modified home insulin regimen (i.e., sick day guidelines) If on insulin pump and allowed to run the pump If on insulin pump and need to transition to injections Remove old site. Calculate basal insulin equivalent and give as detemir/glargine.» Instructions not to run basal rate via pump x 24h from basal injection dose

235 Subcutaneous insulin therapy: Known Previously in DKA Start subcutaneous insulin BEFORE discontinuing insulin drip Modified home insulin regimen (i.e., sick day guidelines) If on insulin pump and allowed to run the pump If on insulin pump and need to transition to injections Remove old site. Calculate basal insulin equivalent and give as detemir/glargine.» Instructions not to run basal rate via pump x 24h from basal injection dose

236 Pump injection: Basal dose calculation

237 Pump injection: Basal dose calculation Option 1: Take the basal rates and calculate 24 h total

238 Pump injection: Basal dose calculation Option 1: Take the basal rates and calculate 24 h total

239 Pump injection: Basal dose calculation Option 1: Take the basal rates and calculate 24 h total Option 2: Take the lowest rate and multiply by 24

240 Pump injection: Basal dose calculation Option 1: Take the basal rates and calculate 24 h total Option 2: Take the lowest rate and multiply by 24 (Consider if wide variation in basal rates to avoid overestimation)

241 Sick day management: Summary Check blood sugars and urine ketones frequently (i.e., q2h) If moderate/large ketones: Give more bolus insulin. Need insulin and glucose to clear ketones. If on a pump: Change out the site and give insulin via syringe until ketones small. Then can give bolus insulin via pump. If unable to use the pump, give basal insulin (detemir/glargine) via syringe. Wait 24h before restarting pump basal rate.

242 Subcutaneous insulin therapy: Known Previously in DKA Hyperglycemia, ketonuria without DKA Admission for surgery

243 Subcutaneous insulin therapy: Known Previously in DKA Hyperglycemia, ketonuria without DKA Follow sick day guidelines as mentioned above If on pump, change site but keep basal rate running. Otherwise DKA. Admission for surgery

244 Subcutaneous insulin therapy: Known Previously in DKA Hyperglycemia, ketonuria without DKA Admission for surgery

245 Subcutaneous insulin: Known diabetes Surgery If getting general anesthesia Admit prior to surgery Aim for 1 st case of the day Procedure type Minor Major Duration < 2 hours 2 hours Discharge Likely same day Unlikely same day Dextrose IV fluids? No Yes Insulin Continue home basal insulin (or pump if anesthesiologist comfortable). Rapid-acting insulin only if glc. Insulin drip - 2 h before surgery - q1h glc checks Rhodes ET et al. Pediatric Diabetes, 2014, 15 (Suppl 20):

246 Subcutaneous insulin: Known diabetes Dextrose For major surgery ( 2h), any surgery when NPH has been given. 5% dextrose; 10% if concern for hypoglycemia. If glucose > % NaCl without dextrose - insulin supply Sodium Potassium Once glucose < 250, add 5% dextrose. Rhodes ET et al. Pediatric Diabetes, 2014, 15 (Suppl 20):

247 Subcutaneous insulin: Known diabetes Dextrose Sodium Hypotonic (< 0.9% NaCl) MIVF Risk of acute hyponatremia Thus, many use % NaCl. Compromise: D NS, monitor electrolytes Change to 0.9 NaCl if Na concentration falling. Potassium Rhodes ET et al. Pediatric Diabetes, 2014, 15 (Suppl 20):

248 Subcutaneous insulin: Known diabetes Dextrose Sodium Potassium Monitor electrolytes. After surgery, add 20 mmol/l KCl. Some add K+ if infusion > 12h. Rhodes ET et al. Pediatric Diabetes, 2014, 15 (Suppl 20):

249 Subcutaneous insulin: Known diabetes Dextrose For major surgery ( 2h), any surgery when NPH has been given. 5% dextrose; 10% if concern for hypoglycemia. If glucose > % NaCl without dextrose - insulin supply Once glucose < 250, add 5% dextrose. Sodium Hypotonic (< 0.9% NaCl) MIVF Risk of acute hyponatremia Thus, many use % NaCl. Compromise: D NS, monitor electrolytes Change to 0.9 NaCl if Na concentration falling Potassium Monitor electrolytes. After surgery, add 20 mmol/l KCl. Some add K+ if infusion > 12h. Rhodes ET et al. Pediatric Diabetes, 2014, 15 (Suppl 20):

250 Subcutaneous insulin: Known diabetes Insulin infusion Goal glucose: mg/dl. Check glc q1h while on drip. Insulin solution: 1 unit insulin/ml (50 units regular insulin to 50 ml 0.9% NaCl) Glc (mg/dl): units/kg/hr units/kg/hr units/kg/hr > units/kg/hr < 90 Do not stop insulin drip. rate instead. < 55 Stop insulin drip temporarily. (not > min) Rhodes ET et al. Pediatric Diabetes, 2014, 15 (Suppl 20):

251 Subcutaneous insulin: Known diabetes Rhodes ET et al. Pediatric Diabetes, 2014, 15 (Suppl 20):

252 Outline Yes Diabetes? No Diabetic ketoacidosis? Yes No Treat 1 condition New Onset? Yes No Type 1 or Type 2? T1DM T2DM

253 Management Glucose management Acute complications Further lab evaluation

254 Management Glucose management Acute complications Further lab evaluation

255 Glucose management Check glucose levels Count carbohydrates Administer insulin

256 Glucose management Check glucose levels Count carbohydrates Administer insulin

257 Glucometer

258 Glucose management Check glucose levels: qac, qhs, q2am ± q5am Count carbohydrates Administer insulin

259 Glucose management Check glucose levels: qac, qhs, q2am ± q5am Count carbohydrates Administer insulin

260 Glucose management Check glucose levels: qac, qhs, q2am ± q5am Count carbohydrates Administer insulin

261 Glucose management Check glucose levels Count carbohydrates Administer insulin

262 Carbohydrate counting Serving Size 1 cup (4 oz) Serving Per Container 3 The serving size for the food is 1 cup. There are 3 servings or 3 cups in this container. Total carbohydrate 10g The total carbohydrate tells how many grams of carbohydrates are in 1 serving Sugar is already included in the total carbohydrate amount. This value shows the amount of natural or added sugar.

263 Carbohydrate counting: Portion size 1 cup of cereal flakes Grain Products Fist 1 c green salad Vegetable and Fruit baseball 1 pancake ½ c cooked rice, pasta, or potato 1 slice of bread 1 piece of cornbread 1.5 oz cheese ½ c ice cream 1 tsp margarine or spreads Dairy and Cheese Compact Disc ½ baseball Cassette Tape Bar of soap 4 stacked dice ½ baseball 1 die 1 baked potato 1 medium fruit ½ c fresh fruit ¼ c raisins 3 oz meat, fish, poultry 3 oz grilled/bake d fish 1 tbsp peanut butter Fist baseball ½ baseball large egg Meats and Alternatives deck of cards checkbook ping pong ball

264 Glucose management Check glucose levels Count carbohydrates Administer insulin

265 Glucose management Check glucose levels Count carbohydrates Administer insulin: Based on glucose + carbs

266 Thus, fast-acting insulin given BEFORE eating (ideally). - For children < 5yo, usually give AFTER eating (allow 30 min to eat).

267 Thus, wait at least 2 hours before another insulin administration.

268 Thus, give once a day.

269 Management Glucose management: Summary Check glucose levels: qac, qhs ± q2am, 5am Count carbohydrates: Use resources Administer insulin: Based on glucose + carbs

270 Management Glucose management Acute complications Further lab evaluation

271 Case The nurse calls you just after lunchtime glucose check to inform you that your patient s blood sugar is 59 mg/dl. He has not yet had lunch. What do you do? A: Take more history. B: Don t worry, nothing s wrong. C: Give the patient juice. D: Give 25 ml of D25. E: Let him eat lunch.

272 Hypoglycemia: Symptoms

273 Hypoglycemia: Treatment fast-acting

274 Hypoglycemia: Treatment fast-acting

275 Hypoglycemia: Treatment Repeat until glucose > 70 fast-acting

276 Case The nurse calls you just after lunchtime glucose check to inform you that your patient s blood sugar is 59 mg/dl. He has not yet had lunch. What do you do? A: Take more history B: Don t worry, nothing s wrong C: Give the patient juice (and repeat blood sugar in 15 min) D: Give 25 ml of D25 E: Let him eat lunch

277 Severe hypoglycemia: Glucagon