1. Hyperglycemic Emergencies DKA/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 < SA, dry mucus mem
RR 32, fruity odor to breath
CBG 39 mM

3. Case
7.29|33|18|95|98%
What are the acid-base disturbances?
42 BS

4. Case
7.29|33|18|95|98%
What other tests need to be done?
42 BS

5. 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

6. 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)

7. 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)

8. 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

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

10. 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)

11. 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.

12. 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)

13. 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 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

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

15. 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:
cc/h over 12h in order to replace ½ estimated deficit
Then lower to 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.

16. DKA: Mortality Adults 2-4% Kids 0.2-0.4% Hypokalemia
MI, CVA, penumonia, pulm embolism, etc.
Kids %
Cerebral edema

17. 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

18. 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)
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

19. 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 U/kg IV
Then IV 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)

20. DKA: IV Insulin
Using insulin to treat 2 different and separate metabolic disturbances in DKA:
Ketoacidosis
Hyperglycemia

21. 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:
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.

22. 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

23. DKA: Other Rx Bicarbonate Phosphate 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 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

24. 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

25. 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.

27. 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:
Low-dose insulin ( U/Kg bolus, then rate of U/Kg/h) has similar rate of recovery and less hypokalemia than high-dose insulin ( U/h)
RCT: Kitabchi et al, 1976, Ann Intern Med: 84:633-8
RCT: Heber et al, 1977, Arch Intern Med: 137:
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

28. HONC Hyperosmolar 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…

29. HONC Hyperglycemia Osmotic Diuresis Pre-renal azootemia
Volume Contraction
Pre-renal azootemia

30. HONC: Diagnosis Signs & Symptoms: Laboratory:
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)

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

32. HONC: Management Coma Management Monitoring
ABCs, O2, narcan, D50W, thiamine, etc.
Monitoring
IV Fluid Resusciation (10L free water defecit)
Insulin?
Potassium (Deficit mEq)
Identify & Rx underlying precipitant!

33. 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

34. 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 cc/h initially
Correct ½ deficit over 1st 12h
Correct total deficit by 36h
Lower fluid rates if elderly or known CHF

35. 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)

36. HONC: Management Coma Management Monitoring
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, 1-2 U/h
Potassium (Deficit mEq)
Replace as in DKA
Identify & Rx underlying precipitant!

37. HONC: Prognosis Hi-mortality: 30% complicating illness:
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)