Hyperglycemic Emergencies DKA/HONC

1. Hyperglycemic EmergenciesDKA/HONC William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University

2. Case • 40 y.o. male, T1DM x 20y • Normally on Novolin 30/70 38/20 • Presents with decr LOC, confusion • 80/60, P120 reg, JVP < SA, dry mucus mem • RR 32, fruity odor to breath • CBG 39 mM

3. Case • 85 160 3.1 18 21 7.29|33|18|95|98% What are the acid-base disturbances? 42 BS

4. Case • 85 160 3.1 18 21 7.29|33|18|95|98% What other tests need to be done? 42 BS

5. DKA A collection of severe and potentially life-threatening metabolic disturbances: • Hyperglycemia  Osmotic diuresis • Urinary loss of fluids & electrolytes • ECFv contraction • Depletion of total body K+ stores (even though may be hyperkalemic 2° to cell shift) • Ketone production  Metabolic acidosis • Compensatory Respiratory alkalosis (hopefully!) • Uncontrolled lipolysis  severe  TG

6. fat cell TG DKA: Pathophysiology Insulin - Ketoacids Glucose HSL FFA Insulin + PFK Liver Cell Pyruvate Fatty Acyl-CoA Acetyl-CoA + Kreb’s Glucagon Insulin + VLDL (TG)

7. fat cell TG DKA: Pathophysiology Insulin - Ketoacids Glucose HSL FFA Insulin + PFK Liver Cell Pyruvate Fatty Acyl-CoA Acetyl-CoA + Kreb’s Glucagon Insulin + VLDL (TG)

8. DKA risk factors • T1DM • 1st presentation • Acute-illness • Insulin omission (inappropriate sick-day management, noncompliance, Eating Disorders) • T2DM • During stress • Ethnicity: African-American, Hispanic • Extremes of age • Poor glycemic control • MDI with CSII

9. DKA: Precipitating Factors Acute illness (MI, GIB, trauma, 10-20% pancreatitis) 20-38% New-onset DM 5-39% Insulin omission 33% Infections

10. DKA: Diagnosis • Symptoms & Signs: • Polyuria, polydipsia, weight-loss • Fatigue • N/V, abdominal pain •  ECFv, Kussmaul’s, Acetone breath, mild impairment in cognition • Laboratory: • pH < 7.3, serum HCO3 < 15 mEq/L, AG > 14 mM • Raised serum ketones (and urine ketones) • BS > 14 mM (occasionally normal or only mild  BS)

11. DKA: Management • Monitoring • IV Fluid Resuscitation (3-9L deficit) • Potassium (“no pee no K”) • K+ deficit 3-5 mEq/Kg • IV insulin • Identify & Rx underlying cause • Noncompliance, infection, MI, etc.

12. DKA: Monitoring • Consider ICU: • pH < 6.9, inadequate respiratory compensation • decreased LOC • Severe K+ disturbance (K+ < 3.0 or > 6.0 mEq/L) • Stepdown/Telemetry: all others • Ward: • Only very mild DKA! • pH > 7.2, serum HCO3 > 20, AG < 14 • ECFv near normal • Not elderly, no hi-risk DKA precipitant (ex. MI)

13. DKA: Monitoring • CBG q1-2h on IV insulin gtt • q2h: Serum lytes, creatinine, glucose • q4-6h: • pH > 7.2, HCO3 > 20, AG < 15 • ECFv stable and IV fluids @ maintenance rates • normal K+ • Calcium profile: • Initially, then q12-24h unless abnormal • Phospate levels can be high at 1st but drop with Rx of DKA • Flowcharts to record biochemical parameters shown to be useful

14. DKA: Monitoring • EKG, cardiac enzymes: r/o ACS (silent MI) • Septic w/up: cultures, CXR, urinalysis, etc. • Consider pulmonary embolism?

15. DKA: IV Fluids • IV NS 0.5-1L/h x 1-2h or longer so no more tachycardia, hypotension, orthostatic changes, low JVP. • Then change to 1/2 NS: • 200-500 cc/h over 12h in order to replace ½ estimated deficit • Then lower to 100-150 cc/h until deficit restored and eating/drinking well • If hypotension recalcitrant to fluids consider AI (Schmidt PGAS II) and send stat plasma cortisol and ACTH, then give solucortef 100 mg IV q8h.

16. DKA: Mortality • Adults 2-4% • Hypokalemia • MI, CVA, penumonia, pulm embolism, etc. • Kids 0.2-0.4% • Cerebral edema

17. DKA: Potassium • K+ defecit: 3-5 mEq/Kg (350 mEq for 70Kg) • Normal to high serum K+ Ketoacidosis H+ H+ K+ K+ Insulin

18. DKA: Potassium • K+ deficit 3-5 mEq/kg (350 mEq 70kg) • Need K with initial IV fluid & insulin Rx unless: • Anuric • K > 5.5 mEq/L or hyperkalemic ECG changes > 20 mEq/h: Cardiac monitor > 60 mEq/L: Central line

19. DKA: IV Insulin • Might delay starting IV insulin for a few hours if K+ severely low (< 3.0 mEq/L) and metabolic acidosis not severe (pH > 7.0) • Humulin R or Novolin Toronto • Bolus 0.1-0.2 U/kg IV • Then IV gtt @ 0.1-0.2 U/kg/h (50 U of regular insulin in 500cc D5W; 1U/10cc) • Aim is to demonstrate correction of Anion Gap (AG) and decrease in BS 4.4 mM/L/h • Monitoring serial serum ketones NOT useful as most assays measure Acetoacetate only: ßHß (not detected) DKA Rx Acetoacetate (detected)

20. DKA: IV Insulin • Using insulin to treat 2 different and separate metabolic disturbances in DKA: • Ketoacidosis • Hyperglycemia

21. DKA: IV Insulin • If AG not correcting and/or BS not decreasing then increase IV gtt rate 1.5-2X • If BS < 13 but AG still not corrected do NOT decrease insulin IV gtt. • Instead start IV glucose gtt: • D5W-D10W @ 100-200 cc/h • Once AG corrected than titrate IV insulin to BS • When BS < 13 and AG normal: reduce IV insulin gtt to 1-2 U/h and add IV glucose if not already done.

22. DKA: Switch to S.C. insulin • Can consider switch to SC insulin when: • AG normalized • BS < 15 mM • Insulin IV gtt requirements < 2U/h • Patient able to eat • Overlap insulin IV gtt with 1st SC insulin by 2-4h to avoid recurrent ketosis • T2DM patients with DKA: • Don’t necessarily have to be d/c on insulin SC (I often do!) • Once acute stress resolved, many do well on OHA

23. DKA: Other Rx • Bicarbonate • May exacerbate hypokalemia • Only give if pH < 6.9 AND evidence of cardiovascualr instability (arrythmia, CHF, hypotension) • 1-2 amps bicarb in 1L D5W IV with 10-20 mEq of added KCl given over 2h or until pH > 7.1 • Phosphate • Routine IV not recommended • Rx symptomatic hypophosphatemia (rhabdo, unexplained CHF or respiratory failure, severe confusion) • 10cc K Phos soln (3.0mEq Pi and 4.4 mEq K/cc) in 1L NS IV over 8-12h

24. DKA: Other Rx • Cerebral Edema • Usually only kids • Persistent decreased LOC despite standard Rx of DKA • CT scan to confirm diagnosis • Decadron 10 mg IV • Mannitol 25 mg IV

25. DKA: Management • Monitoring • ICU: pH < 6.9, severe K (< 3, > 6), decr LOC • IV Fluid Resuscitation (3-9L deficit) • Potassium (“no pee no K”) • IV insulin • Identify & Rx underlying cause • Noncompliance, infection, MI, etc.

27. DKA Rx: EBM • In patients not in shock, recovery is more rapid with slower rates of IV fluids (500 mL/h x 4h, then 250 mL/h) • RCT: Adrogue et al, 1989, JAMA: 262:2108-13 • Low-dose insulin (0.1-0.2 U/Kg bolus, then rate of 0.1-0.2 U/Kg/h) has similar rate of recovery and less hypokalemia than high-dose insulin (50-150 U/h) • RCT: Kitabchi et al, 1976, Ann Intern Med: 84:633-8 • RCT: Heber et al, 1977, Arch Intern Med: 137:1377-80 • No clinical benefit to giving IV HCO3 • RCT: Gamba et al, 1991, Rev Invest Clin: 43:234-48 • No benefit to giving IV phosphate • RCT: Fischer et al, 1983, JCEM:57:177-80

28. HONCHyperosmolar Non-Ketotic Coma • T2DM, elderly (mean age 60-73), F > M • Pathogenesis poorly understood • Mild ECFv instigating factor • Insulin/Glucagon ratio sufficient to limit DKA • Diminished thirst or access to water • Vicious cycle develops…

29. Hyperglycemia Osmotic Diuresis Pre-renal azootemia Volume Contraction HONC

30. HONC: Diagnosis • Signs & Symptoms: • Polyuria, Polydipsia, fatigue x weeks/months • N/V (< than in DKA) • Dehydration  Overt Shock • Fever 50% • Decreased LOC: Confusion/Lethargy (40-50%), Stupor or coma (27-54%) • Laboratory: • BS > 33 mM, Serum OSM > 320 mM • pH > 7.3, HCO3 > 20 mEq/L, Ketones negative (33% cases mild DKA, hi-AG acidosis for other reasons)

31. HONC: Precipitating Factors Acute illness (MI, GIB, trauma, 10-15% pancreatitis) 5-15% New-onset DM 33% Infection 40-60% Noncompliance

32. HONC: Management • Coma Management • ABCs, O2, narcan, D50W, thiamine, etc. • Monitoring • IV Fluid Resusciation (10L free water defecit) • Insulin? • Potassium (Deficit 300-500 mEq) • Identify & Rx underlying precipitant!

33. HONC: Monitoring • ICU or Stepdown best • Vitals q1h • Lytes, creatinine, glucose q2-4h • Serum OSM, Urine OSM/USG • Cultures, EKG, cardiac enzymes • CT brain (R/O CVA, SDH, etc.) • Consider pulmonary embolism

34. HONC: IV Fluids • 25% body water lost (deficit 4-12 L) • If hypotensive: • Start with NS: 1L/h x 1-2h • Once ECFv normal change to 1/2NS: • IV 200-500 cc/h initially • Correct ½ deficit over 1st 12h • Correct total deficit by 36h • Lower fluid rates if elderly or known CHF

35. HONC: Insulin? • Patients can be treated successfully without insulin • If IV fluids inadequate BS and serum OSM will not drop despite insulin • Majority of studies used insulin • Hi-dose Insulin: severe hypokalemia, shock • Therefore if going to use insulin, use low doses: • Bolus 0.1 U/kg, Rate 1-2 U/h (or 0.1 U/kg/h)

36. HONC: Management • Coma Management • ABCs, O2, narcan, D50W, thiamine, etc. • Monitoring • IV Fluid Resusciation (10L free water defecit) • Insulin? • IV fluids will decrease BS by 4 mM/L/h by itself • For most patients insulin not absolutely neccesary • Insulin IV bolus 5-10 U, gtt @ 1-2 U/h • Potassium (Deficit 300-500 mEq) • Replace as in DKA • Identify & Rx underlying precipitant!

37. HONC: Prognosis • Hi-mortality: • Earlier series 58% • Recent studies 12-17% (but some with mixed DKA) • 30% complicating illness: • LRTI, GI bleed, ARF, CVA, MI, Pulm embolism • DVT prophylaxsis beneficial? • Independent mortality predictors: • Advanced age • High osmolality, elevated ureas • After recovery: • Discharged on Insulin or OHA (I prefer insulin!) • Monitor closely for water intake/dehydration (especially nursing home patients)