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Hyperglycemic Emergencies DKA/HONC. William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University. DKA. A collection of severe and potentially life-threatening metabolic disturbances: Hyperglycemia Osmotic diuresis
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Hyperglycemic EmergenciesDKA/HONC William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University
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
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)
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)
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 Acute illness (MI, GIB, trauma, 10-20% pancreatitis) 20-38% 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 • 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.
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, pneumonia, 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 > 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: • Ketoacidosis • 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 cardiovascular 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 • 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.
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