Hyperglycemic EmergenciesDKA/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 85 160

3.1 18 21

7.29|33|18|95|98%

What are the acid-base disturbances?

42 BS

Case

136 85 160

3.1 18 21

7.29|33|18|95|98%

What other tests need to be done?

42 BS

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: Pathophysiology

Glucose

Pyruvate

Acetyl-CoA

Ketoacids

Kreb’s

+ PFKInsulin

fat cellTG

FFA

HSL

Liver Cell

FattyAcyl-CoA

Insulin -

VLDL (TG)

GlucagonInsulin

+

+

DKA: Pathophysiology

Glucose

Pyruvate

Acetyl-CoA

Ketoacids

Kreb’s

+ PFKInsulin

fat cellTG

FFA

HSL

Liver Cell

FattyAcyl-CoA

Insulin -

VLDL (TG)

GlucagonInsulin

+

+

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,pancreatitis)

New-onset DM

Insulin omission

Infections

10-20%

5-39%

33%

20-38%

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+

K+ K+

H+ H+

Ketoacidosis

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:

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• ICU: pH < 6.9, severe K (< 3, > 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.

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

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…

Hyperglycemia

Osmotic Diuresis

Volume Contraction

Pre-renal azootemia

HONC

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

Acute illness(MI, GIB, trauma,pancreatitis)

New-onset DM

Infection

Noncompliance

10-15%

33%

40-60%

5-15%

HONC: Management

1. Coma Management• ABCs, O2, narcan, D50W, thiamine, etc.

2. Monitoring3. 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:• 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

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. Monitoring3. 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)