Hyperosmolar Hyperglycemic State

Aka: Hyperosmolar Hyperglycemic State, Hyperosmolar Hyperglycemic Nonketotic Coma, Hyperglycemic Dehydration Syndrome, Hyperosmolar Nonketotic Diabetic Syndrome

1. Pathophysiology
   1. Diuresis secondary to glucosuria
   2. Water loss exceeds sodium loss
      1. Results in hyperosomality and Hypernatremia
2. Predisposing Factors
   1. Uncontrolled of undiagnosed Type II Diabetes Mellitus
   2. Advanced age
   3. Infection (Pneumonia, UTI, Sepsis, Cellulitis)
      1. Causes more than 50% of hyperosmolar hyperglycemia
   4. Medications
      1. See Medication Causes of Hyperglycemia
   5. Vascular event
      1. Cerebrovascular Accident
      2. Pulmonary Embolism
      3. Myocardial Infarction
      4. Mesenteric thrombosis
   6. Endocrine Disease
      1. Acromegaly
      2. Cushing's Disease or ACTH producing tumors
      3. Thyrotoxicosis
   7. Comorbid illness
      1. Subdural Hematoma
      2. Acute Pancreatitis
      3. Severe Burn Injury
      4. Substance Abuse (Alcohol Abuse or Cocaine use)
      5. Renal Insufficiency
3. Symptoms
   1. Insidious onset of symptoms over days to weeks
   2. Symptoms related to hyperglycemia
      1. Polyuria
      2. Polydipsia
      3. Weight loss
   3. Symptoms common at presentation
      1. Weakness
      2. Visual changes
      3. Leg cramps
   4. Neurologic changes occur later
      1. Progressive Decreased Level of Consciousness (50%)
      2. Seizures (5%)
4. Signs
   1. Fever (low grade)
   2. Severe dehydration
   3. Neurologic deficit (related to hyperosmolality)
      1. Decreased Level of Consciousness (Coma in 30%)
      2. Transient Hemiparesis
      3. Hyperreflexia or areflexia
      4. Seizures occur in 25%
5. Differential Diagnosis
   1. Diabetic Ketoacidosis (arterial pH <7.30 with ketosis)
6. Diagnosis
   1. Severe dehydration with Serum Osmolality >320
   2. Altered Level of Consciousness
   3. Hyperglycemia with Serum Glucose >600
   4. Minimal to no ketosis
      1. Minimal to acidosis (arterial pH >7.30)
7. Labs
   1. Blood Glucose 600-2000 mg/dl
   2. Serum Osmolarity >320 mOsm
      1. Often > 350 mOsm/liter
      2. Coma seen if Osms exceed 340 mOsm/liter
      3. Water deficit 100-200 ml/kg
   3. BUN markedly elevated (70-90 mg/dl)
   4. Serum Ketones not detected
   5. No Metabolic Acidosis
      1. Arterial Blood Gas with arterial pH > 7.30
      2. Serum bicarbonate >15 meq/L
   6. Electrolytes
      1. Sodium deficit: 7-13 meq/kg
         1. Usually elevated
            1. Lowered 1.6 meq/L each 100 mg/dl Glucose rise
            2. See corrected Serum Sodium
      2. Potassium deficit: 5-15 meq/kg
      3. Calcium deficit 50-100 meq/kg
      4. Magnesium deficit 50-100 meq/kg
8. Monitoring
   1. Bedside fingerstick glucose every 30-60 minutes
   2. Recheck labs every 2-4 hours until stable
      1. Electrolytes
      2. Blood Urea Nitrogen and Serum Creatinine
      3. Serum Glucose
9. Management: Fluid Replacement
   1. Initial
      1. Normal saline 1 Liter/hour
      2. Run normal saline until stable vitals and urine
   2. Later
      1. Fluid
         1. Hypernatremia: 1/2NS
         2. Hyponatremia (uncommon): NS
      2. Rate
         1. Estimate: 150 to 500 cc/hour
         2. Calculation: 4-14 cc/kg/hour
   3. Overall
      1. 50% of loss replaced in first 12 hours
      2. 50% of loss replaced over next 24 hours
10. Management: Serum Potassium
    1. Serum Potassium <3.3
       1. Hold Insulin until Serum Potassium >3.3
       2. Replace potassium with 40 meq
          1. Potassium Chloride 27 meq
          2. Potassium Phosphate 13 meq
    2. Serum Potassium >5.0
       1. Hold Potassium Replacement in IV Fluids
       2. Recheck Serum Potassium every 2 hours
    3. Serum Potassium >3.3 and <5.0
       1. Keep Serum Potassium >4.0 and <5.0
       2. Add 30 meq of potassium to each liter of IV fluid
          1. Potassium chloride 20 meq/Liter
          2. Potassium phosphate 10 meq/Liter
11. Management: Phase 3 - Blood Glucose Control
    1. Precautions
       1. Hypokalemia must be corrected prior to Insulin
       2. Hold Insulin until Serum Potassium >3.3
    2. Adult IV Insulin administration
       1. Initial
          1. Give IV bolus of 0.15 units/kg
          2. Start 0.1 units/kg/hour Insulin Drip
       2. Maintenance
          1. Anticipate Serum Glucose drop of 50-70 mg/dl/hour
             1. If inadequate drop, then increase drip
                1. Increase Insulin Infusion rate by 50-100%
                2. Continue at increased rate until adequate
          2. When Serum Glucose <300 mg/dl
             1. Keep Serum Glucose at 250 to 300 mg/dl until
                1. Serum Osmolality <315 mOsm/kg
                2. Alert mental status
             2. Decrease rate by 50% (to 0.05 units/kg) or
             3. Discontinue Insulin Drip and start SC dosing
    3. Glucose monitoring
       1. Glucose monitoring every 30 minutes to 1 hour
       2. Target glucose decrease 50-70 mg/dl/hour
    4. Dextrose Administration
       1. Add 5% Dextrose to fluids when glucose < 300 mg/dl
12. Complications
    1. Mortality (10-40%): Significantly higher than DKA
    2. Seizures
    3. Deep Vein Thrombosis
    4. Pulmonary Embolus
    5. Pancreatitis
    6. Renal Failure
13. Prevention
    1. Maximize glucose control and compliance
    2. Ensure adequate hydration
    3. Monitor for dehydration, infection, and hyperglycemia
14. References
    1. Chiasson (2003) CMAJ 168:859-66
    2. Stoner (2005) Am Fam Physician 71:1723-30
    3. Trence (2001) Endocrinol Metab Clin North Am 30:817-31