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 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 physiology: Insulin & Lipids

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

DKA: Pathophysiology Insulin - Ketoacids Glucose HSL FFA Insulin + PFK fat cell TG 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 T2DM Extremes of age Poor glycemic control 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 10-20% (MI, GIB, trauma, pancreatitis) 20-38% New-onset DM 5-39% Insulin omission 33% Infections

DKA: Diagnosis Symptoms & Signs: Laboratory: 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: Stepdown/Telemetry: all others Ward: 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% Kids 0.2-0.4% Hypokalemia MI, CVA, pneumonia, pulm. embolism, etc. Kids 0.2-0.4% Cerebral edema

K+ DKA: Potassium Insulin 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] Replacement > 5.5 mEq/L nil (initially) 5.2-5.5 mEq/L 10 mEq/h 4-5.2 mEq/L 20 mEq/h 3-4 mEq/L 30 mEq/h < 3 mEq/L 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: 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 Phosphate 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 IV Fluid Resuscitation (3-9L deficit) 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