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

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Presentation on theme: "Hyperglycemic Emergencies DKA/HONC William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University."— Presentation transcript:

1 Hyperglycemic Emergencies DKA/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 |33|18|95|98% What are the acid-base disturbances? 42 BS

4 Case |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 DKA: Pathophysiology Glucose Pyruvate Acetyl-CoA Ketoacids Kreb’s + PFKInsulin fat cell TG FFA HSL Liver Cell Fatty Acyl-CoA Insulin - VLDL (TG) Glucagon Insulin + +

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

8 DKA risk factors T1DM 1 st 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, pancreatitis) New-onset DM Insulin omission Infections 10-20% 5-39% 33% 20-38%

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 14 mM Raised serum ketones (and urine ketones) BS > 14 mM (occasionally normal or only mild  BS)

11 DKA: Management 1.Monitoring 2.IV Fluid Resuscitation (3-9L deficit) 3.Potassium (“no pee no K”) K + deficit 3-5 mEq/Kg 4.IV insulin 5.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 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 maintenance rates normal K + Calcium profile: Initially, then q12-24h unless abnormal Phospate levels can be high at 1 st 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: cc/h over 12h in order to replace ½ estimated deficit Then lower to 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 % Cerebral edema

17 DKA: Potassium K + defecit: 3-5 mEq/Kg (350 mEq for 70Kg) Normal to high serum K + K+K+ K+K+ H+H+ H+H+ Ketoacidosis 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 Initial [K]Replacement > 5.5 mEq/Lnil (initially) mEq/L10 mEq/h mEq/L20 mEq/h 3-4 mEq/L30 mEq/h < 3 mEq/L40 mEq/h > 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 ( 7.0) Humulin R or Novolin Toronto Bolus U/kg IV Then IV 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: 1.Ketoacidosis 2.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: 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 1 st 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 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 1.Monitoring ICU: pH 6), decr LOC 2.IV Fluid Resuscitation (3-9L deficit) 3.Potassium (“no pee no K”) 4.IV insulin 5.Identify & Rx underlying cause Noncompliance, infection, MI, etc.

26

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: Low-dose insulin ( U/Kg bolus, then rate of U/Kg/h) has similar rate of recovery and less hypokalemia than high-dose insulin ( U/h) RCT: Kitabchi et al, 1976, Ann Intern Med: 84:633-8 RCT: Heber et al, 1977, Arch Intern Med: 137: No clinical benefit to giving IV HCO3 RCT: Gamba et al, 1991, Rev Invest Clin: 43: No benefit to giving IV phosphate RCT: Fischer et al, 1983, JCEM:57:177-80

28 HONC Hyperosmolar 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 Volume Contraction Pre-renal azootemia 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, pancreatitis) New-onset DM Infection Noncompliance 10-15% 33% 40-60% 5-15%

32 HONC: Management 1.Coma Management ABCs, O 2, narcan, D50W, thiamine, etc. 2.Monitoring 3.IV Fluid Resusciation (10L free water defecit) 4.Insulin? 5.Potassium (Deficit mEq) 6.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 cc/h initially Correct ½ deficit over 1 st 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 1.Coma Management ABCs, O 2, narcan, D50W, thiamine, etc. 2.Monitoring 3.IV Fluid Resusciation (10L free water defecit) 4.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, 1-2 U/h 5.Potassium (Deficit mEq) Replace as in DKA 6.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)


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