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Hyperglycemic Emergencies DKA/HONC William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University 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 Case 136 85 3.1 18 160 42 BS 21 7.29|33|18|95|98% What are the acid-base disturbances? Case 136 85 3.1 18 160 42 BS 21 7.29|33|18|95|98% What other tests need to be done? DKA A collection of severe and potentially lifethreatening 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 DKA: Pathophysiology Ketoacids Glucose fat cell TG Insulin - HSL FFA Insulin + PFK Liver Cell Pyruvate Acetyl-CoA Kreb’s Fatty Acyl-CoA + Glucagon Insulin + VLDL (TG) DKA: Pathophysiology Ketoacids Glucose fat cell TG Insulin - HSL FFA Insulin + PFK Liver Cell Pyruvate Acetyl-CoA Kreb’s Fatty Acyl-CoA + Glucagon Insulin + VLDL (TG) 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 DKA: Precipitating Factors 10-20% 20-38% Acute illness (MI, GIB, trauma, pancreatitis) New-onset DM 5-39% Insulin omission 33% Infections 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) 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. 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) 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 DKA: Monitoring • EKG, cardiac enzymes: r/o ACS (silent MI) • Septic w/up: cultures, CXR, urinalysis, etc. • Consider pulmonary embolism? 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. DKA: Mortality • Adults 2-4% • Hypokalemia • MI, CVA, penumonia, pulm embolism, etc. • Kids 0.2-0.4% • Cerebral edema DKA: Potassium • K+ defecit: 3-5 mEq/Kg (350 mEq for 70Kg) • Normal to high serum K+ Ketoacidosis H+ H+ + K K+ Insulin 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] > 5.5 mEq/L 5.2-5.5 mEq/L 4-5.2 mEq/L 3-4 mEq/L < 3 mEq/L Replacement nil (initially) 10 mEq/h 20 mEq/h 30 mEq/h 40 mEq/h > 20 mEq/h: Cardiac monitor > 60 mEq/L: Central line 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) DKA: IV Insulin • Using insulin to treat 2 different and separate metabolic disturbances in DKA: 1. Ketoacidosis 2. Hyperglycemia 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. 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 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 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 DKA: Management 1. Monitoring • 2. 3. 4. 5. 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. 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 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… HONC Hyperglycemia Pre-renal azootemia Volume Contraction Osmotic Diuresis 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) HONC: Precipitating Factors 10-15% 5-15% Acute illness (MI, GIB, trauma, pancreatitis) New-onset DM 33% Infection 40-60% Noncompliance HONC: Management 1. Coma Management • ABCs, O2, narcan, D50W, thiamine, etc. 2. Monitoring 3. IV Fluid Resusciation (10L free water defecit) 4. Insulin? 5. Potassium (Deficit 300-500 mEq) 6. Identify & Rx underlying precipitant! 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 HONC: IV Fluids • • 25% body water lost (deficit 4-12 L) If hypotensive: • • Once ECFv normal change to 1/2NS: • • • • Start with NS: 1L/h x 1-2h 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 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) HONC: Management 1. Coma Management • ABCs, O2, 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, gtt @ 1-2 U/h 5. Potassium (Deficit 300-500 mEq) • Replace as in DKA 6. Identify & Rx underlying precipitant! 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)