Download DKA/HONK - Dr. William Harper

Hyperglycemic Emergencies
DKA/HONC
William Harper, MD, FRCPC
Endocrinology & Metabolism
Assistant Professor of Medicine,
McMaster University
Case
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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:
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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)
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Ketone production  Metabolic acidosis
» Compensatory Respiratory alkalosis (hopefully!)
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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:
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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”)
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K+ deficit 3-5 mEq/Kg
4. IV insulin
5. Identify & Rx underlying cause
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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:
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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
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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:
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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
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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
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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
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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
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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:
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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
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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
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25% body water lost (deficit 4-12 L)
If hypotensive:
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Once ECFv normal change to 1/2NS:
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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?
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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:
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Bolus 0.1 U/kg, Rate 1-2 U/h (or 0.1 U/kg/h)
HONC: Management
1. Coma Management
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ABCs, O2, narcan, D50W, thiamine, etc.
2. Monitoring
3. IV Fluid Resusciation (10L free water defecit)
4. Insulin?
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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)
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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)