CORE EM: Hyperglycemic Hyperosmolar Syndrome (HHS)

Definition: An acute decompensated state in which patients manifest a change in mental status in the setting of hyperglycemia, hyperosmolarity and severe volume depletion. Altered mental status can present as focal neurologic defects or global encephalopathy.

Pathophysiology

• Decreased activity of insulin leads to increased serum glucose via gluconeogenesis, glycogenolysis and decreased cellular glucose uptake
• Resultant hyperglycemia leads to fluid shift from intracellular to extracellular space
• Increased circulating glucose spills into urine resulting in osmotic diuresis
• Decreased circulating volume leads to reduction in glomerular filtration rate (GFR) and hypotonic urine
• Hypotonic diuresis produces dehydration and creates cycle of hyperglycemia, hypernatremia and increased osmolarity

Causes:

• Non-compliance with medications and/or diet
• Inadequate access to fluids to counteract losses
• Common acute conditions exacerbating chronic diabetes: infection (i.e. sepsis), myocardial ischemia/infarction, pulmonary embolism, trauma, burns, GI hemorrhage etc.

Clinical Manifestations

• The development of HHS is typically prolonged in comparison to DKA
• History
  • Polydipsia, polyuria, polyphagia
  • Weakness
  • Weight loss
  • Nausea/Vomiting
  • Confusion
  • 20% without a known history of DM II
  • Chronic renal insufficiency a common comorbid condition
• Physical Examination
  • Hypotension
  • Tachycardia
  • Dehydration (dry mucous membranes, delayed capillary refill)
  • Neurologic Manifestations
    • Decreased level of consciousness
    • Seizures
    • Focal neurologic findings
    • Stroke-like syndromes

Diagnostic Testing

• Blood glucose generally > 600 mg/dL
• Serum osmolarity > 350 mOsm/L
• Renal Function
  • Elevated BUN:Cr ratio common indicating pre-renal causes
  • Acute Kidney Injury (AKI) from hypoperfusion will often co-exist
• Ketoacidosis generally absent (though starvation ketosis may be present)
• Electrolyte disturbances
  • Profound hypokalemia secondary to osmotic diuresis
  • Hyponatremia often results from hyperglycemia and will correct without directed management on sodium
  • Phosphate and magnesium levels commonly low

Basics: ABCs, IV, Cardiac Monitor and 12-lead EKG

• Establish at least 2 large-bore (16-18 gauge) peripheral IVs as patients may require multiple medications
• Carefully consider underlying cause of decompensation and HHS

Initial Management

• Intravenous fluids
  • Role
    • Replenish intravascular depletion resulting from osmotic diuresis
    • Correct increased serum osmolarity
    • Correct decreased GFR
  • Initial Fluid Dose
    • Patients with HHS frequently have concomitant comorbid conditions like CHF and chronic renal insufficiency
    • May not tolerate large volumes of fluid well
    • Consider smaller boluses (10 cc/kg) with repeat cardiac and lung assessment
  • 0.9% NaCl (Normal Saline)
    • Most commonly employed fluid
    • Problems
      • NS is far from “normal”
      • Large volume infusions (> 2-3 liters) can cause hyperchloremic metabolic acidosis (unclear impact on patient)
  • Lactated Ringers
    • Closer to physiologic solution
    • Does not cause hyperchloremic metabolic acidosis
  • Other options: balanced solutions (i.e. Plasma-Lyte)
• Insulin therapy
  • Patients with HHS will typically have adequate basal insulin levels and additional insulin may not be necessary
• Electrolyte Disorder Correction
  • Potassium
    • Aggressive repletion frequently necessary
      • Patients hundreds of mEq depleted
    • Supplementation (see hypokalemia post)
      • Oral: KCl 40 mEq every hour (if patient safe for oral route)
      • Intravenous: KCl 10-40 mEq in each liter of fluid (caution: infusion of > 10 mEq potassium/hour will cause burning in peripheral vein)
  • Sodium
    • Typically dilutional hyponatremia
    • Will correct without specific treatment
  • Magnesium
    • HypoK = HypoMg (Boyd 1984)
      • Both electrolytes lost during osmotic diuresis
      • Cannot replete intracellular potassium without magnesium
      • Serum magnesium level may not correlate with total body stores
    • Dose: 1-2 gm MgSO₄
  • Phosphorous
    • If PO₄ < 1.0 mEq, consider repletion with KPO₄

Take Home Points

• HHS is defined by hyperglycemia and hyperosmolarity due to volume depletion with resultant altered mental status
• Profound hypokalemia is common as a result of osmotic diuresis. Replete aggressively
• Hypokalemia = hypomagnesemia. Replete both of these electrolytes simultaneously
• Fluid repletion is the key point in management but careful repletion is vital as patients may not tolerate aggressive administration
• All patients should have an exhaustive investigation of the cause of their decompensation. Look for signs of infection, ischemia, trauma etc.

Read More

Cydulka RK, Maloney GE: Diabetes Mellitus and Disorders of Glucose Homeostasis; in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 126: p 1652-1668.

References

Boyd JC et al. Relationship of potassium and magnesium concentrations in serum to cardiac arrhythmias. Clin Chem 1984; 30(5): 754-7. PMID: 6713638