Hyperglycemic Emergencies DKA/HONC

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Hyperglycemic EmergenciesDKA/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 lt SA, dry mucus mem
• RR 32, fruity odor to breath
• CBG 39 mM

3
Case

• 85 160
• 3.1 18 21
• 7.2933189598
• What are the acid-base disturbances?

42 BS
4
Case

• 85 160
• 3.1 18 21
• 7.2933189598
• What other tests need to be done?

42 BS
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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

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DKA Pathophysiology
fat cell TG
Insulin -
Ketoacids
Glucose
HSL
FFA
PFK
Insulin
Liver Cell
Pyruvate
Fatty Acyl-CoA
Acetyl-CoA

Krebs
Glucagon Insulin

VLDL (TG)
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DKA Pathophysiology
fat cell TG
Insulin -
Ketoacids
Glucose
HSL
FFA
PFK
Insulin
Liver Cell
Pyruvate
Fatty Acyl-CoA
Acetyl-CoA

Krebs
Glucagon Insulin

VLDL (TG)
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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

9
DKA Precipitating Factors
Acute illness
(MI, GIB, trauma,
10-20
pancreatitis)
20-38
New-onset DM
5-39
Insulin omission
33
Infections
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DKA Diagnosis

• Symptoms Signs
• Polyuria, polydipsia, weight-loss
• Fatigue
• N/V, abdominal pain
• ? ECFv, Kussmauls, Acetone breath, mild
  impairment in cognition
• Laboratory
• pH lt 7.3, serum HCO3 lt 15 mEq/L, AG gt 14 mM
• Raised serum ketones (and urine ketones)
• BS gt 14 mM (occasionally normal or only mild ?
  BS)

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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.

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DKA Monitoring

• Consider ICU
• pH lt 6.9, inadequate respiratory compensation
• decreased LOC
• Severe K disturbance (K lt 3.0 or gt 6.0 mEq/L)
• Stepdown/Telemetry all others
• Ward
• Only very mild DKA!
• pH gt 7.2, serum HCO3 gt 20, AG lt 14
• ECFv near normal
• Not elderly, no hi-risk DKA precipitant (ex. MI)

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DKA Monitoring

• CBG q1-2h on IV insulin gtt
• q2h Serum lytes, creatinine, glucose
• q4-6h
• pH gt 7.2, HCO3 gt 20, AG lt 15
• ECFv stable and IV fluids _at_ 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

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DKA Monitoring

• EKG, cardiac enzymes r/o ACS (silent MI)
• Septic w/up cultures, CXR, urinalysis, etc.
• Consider pulmonary embolism?

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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.

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DKA Mortality

• Adults 2-4
• Hypokalemia
• MI, CVA, penumonia, pulm embolism, etc.
• Kids 0.2-0.4
• Cerebral edema

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DKA Potassium

• K defecit 3-5 mEq/Kg (350 mEq for 70Kg)
• Normal to high serum K

Ketoacidosis
H
H
K
K
Insulin
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DKA Potassium

• K deficit 3-5 mEq/kg (350 mEq 70kg)
• Need K with initial IV fluid insulin Rx unless
• Anuric
• K gt 5.5 mEq/L or hyperkalemic ECG changes

Initial K Replacement
gt 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
lt 3 mEq/L 40 mEq/h
gt 20 mEq/h Cardiac monitor gt 60 mEq/L Central
line
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DKA IV Insulin

• Might delay starting IV insulin for a few hours
  if K severely low (lt 3.0 mEq/L) and metabolic
  acidosis not severe (pH gt 7.0)
• Humulin R or Novolin Toronto
• Bolus 0.1-0.2 U/kg IV
• Then IV gtt _at_ 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)

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DKA IV Insulin

• Using insulin to treat 2 different and separate
  metabolic disturbances in DKA
• Ketoacidosis
• Hyperglycemia

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DKA IV Insulin

• If AG not correcting and/or BS not decreasing
  then increase IV gtt rate 1.5-2X
• If BS lt 13 but AG still not corrected do NOT
  decrease insulin IV gtt.
• Instead start IV glucose gtt
• D5W-D10W _at_ 100-200 cc/h
• Once AG corrected than titrate IV insulin to BS
• When BS lt 13 and AG normal reduce IV insulin gtt
  to 1-2 U/h and add IV glucose if not already done.

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DKA Switch to S.C. insulin

• Can consider switch to SC insulin when
• AG normalized
• BS lt 15 mM
• Insulin IV gtt requirements lt 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
• Dont necessarily have to be d/c on insulin SC (I
  often do!)
• Once acute stress resolved, many do well on OHA

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DKA Other Rx

• Bicarbonate
• May exacerbate hypokalemia
• Only give if pH lt 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 gt 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

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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

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DKA Management

• Monitoring
• ICU pH lt 6.9, severe K (lt 3, gt 6), decr LOC
• IV Fluid Resuscitation (3-9L deficit)
• Potassium (no pee no K)
• IV insulin
• Identify Rx underlying cause
• Noncompliance, infection, MI, etc.

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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 2622108-13
• 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
  84633-8
• RCT Heber et al, 1977, Arch Intern Med
  1371377-80
• No clinical benefit to giving IV HCO3
• RCT Gamba et al, 1991, Rev Invest Clin
  43234-48
• No benefit to giving IV phosphate
• RCT Fischer et al, 1983, JCEM57177-80

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HONCHyperosmolar Non-Ketotic Coma

• T2DM, elderly (mean age 60-73), F gt M
• Pathogenesis poorly understood
• Mild ECFv? instigating factor
• Insulin/Glucagon ratio sufficient to limit DKA
• Diminished thirst or access to water
• Vicious cycle develops

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HONC
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HONC Diagnosis

• Signs Symptoms
• Polyuria, Polydipsia, fatigue x weeks/months
• N/V (lt than in DKA)
• Dehydration ? Overt Shock
• Fever 50
• Decreased LOC Confusion/Lethargy (40-50),
  Stupor or coma (27-54)
• Laboratory
• BS gt 33 mM, Serum OSM gt 320 mM
• pH gt 7.3, HCO3 gt 20 mEq/L, Ketones negative
• (33 cases mild DKA, hi-AG acidosis for other
  reasons)

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HONC Precipitating Factors
Acute illness
(MI, GIB, trauma,
10-15
pancreatitis)
5-15
New-onset DM
33
Infection
40-60
Noncompliance
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HONC Management

• Coma Management
• ABCs, O2, narcan, D50W, thiamine, etc.
• Monitoring
• IV Fluid Resusciation (10L free water defecit)
• Insulin?
• Potassium (Deficit 300-500 mEq)
• Identify Rx underlying precipitant!

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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

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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

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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)

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HONC Management

• Coma Management
• ABCs, O2, narcan, D50W, thiamine, etc.
• Monitoring
• IV Fluid Resusciation (10L free water defecit)
• 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 _at_ 1-2 U/h
• Potassium (Deficit 300-500 mEq)
• Replace as in DKA
• Identify Rx underlying precipitant!

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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)