Hyperglycemic Hyperosmolar State in Adults

Background

• Hyperglycemic hyperosmolar state (HHS) is a metabolic emergency occurring in patients with diabetes mellitus, though about 7%-17% of patients present with HHS as their initial diagnosis of diabetes.
• It is characterized by extremely elevated serum glucose, increased osmolality, significant dehydration, and minimal ketoacidosis.
• Both HHS and diabetic ketoacidosis (DKA) are often precipitated by medication nonadherence in patients with known diabetes, underlying infection, other concurrent medical illness (such as pancreatitis, acute myocardial infarction, or stroke), gastrointestinal bleed, or drugs that affect carbohydrate metabolism.
• Compared with DKA, HHS
  • occurs more often in patients with type 2 diabetes
  • is characterized by relative insulin deficiency (insulin secretion is sufficient to prevent significant ketone production)
  • is associated with higher morbidity and mortality

Evaluation

• Suspect HHS in patients with gradual development (over days to weeks) of polyuria, polydipsia, weight loss, weakness, extreme dehydration, and mental status changes.
• In addition to history, vital signs, and physical exam, initial evaluation should include:
  • serum glucose, electrolytes, blood urea nitrogen (BUN), creatinine, beta-hydroxybutyrate (ketones), and complete blood count with differential
  • arterial (or venous) blood gas
  • urine dipstick and urinalysis for ketones if beta-hydroxybutyrate is not measured
  • urine, blood, and/or sputum Gram stain and culture if infection is suspected
  • electrocardiogram
  • chest x-ray if a pulmonary or cardiac condition or abnormality is suspected
• Diagnostic criteria for HHS include glucose > 600 mg/dL (33.3 mmol/L) per United States criteria (> 540 mg/dL [30 mmol/L] per British criteria), effective serum osmolality > 320 mOsm/kg, arterial pH > 7.3, serum bicarbonate > 15-18 mEq/L (15-18 mmol/L), little or no ketonemia and ketonuria, and stupor or coma. However, some patients with HHS can have mild to moderate ketonemia from concomitant DKA and/or starvation.
• Diagnostic calculators include:
  • Anion Gap Calculator
  • Osmolar Gap Calculator
  • Osmolality Estimator (serum)
  • Sodium Correction in Hyperglycemia

Management

• Admit the patient to the intensive care unit. Initial monitoring includes hourly serum glucose, and frequent (every 2-4 hours) electrolytes (especially potassium, sodium, and anion gap), calculated osmolality, and venous pH. Assess dehydration with hemodynamic monitoring (blood pressure) and by measuring urine output.
• Provide fluid resuscitation. Patients with HHS are estimated to require about 7-12 L of fluid replacement.
  • Ideally, water deficit may be replaced by patient taking fluids orally in addition to IV fluids.
  • Begin with 0.9% saline IV at 1-1.5 L/hour (15-20 mL/kg/hour) for the first hour. Alternatively, can be given at an initial rate of 500–1,000 mL/hour during the first 2–4 hours.
  • Reduce the infusion rate to 250-500 mL/hour only after intravascular volume depletion has been corrected.
  • Calculate the corrected serum sodium. Avoid rapid correction of sodium, and do not exceed serum sodium reduction > 10 mmol/L (10 mEq/L) per 24 hours.
  • If sodium remains persistently high in patients who are no longer hypovolemic, consider changing to 0.45% saline.
• Professional organizations vary on recommendations for potassium management.
  • American Diabetes Association (ADA) recommends potassium 20-30 mEq/hour IV (and withhold insulin) until potassium level ≥ 3.3 mEq/L, then 20-30 mEq per L of IV fluid to maintain serum potassium level 4-5 mEq/L. Do not give potassium if serum potassium level ≥ 5.2 mEq/L.
  • Joint British Diabetes Societies Inpatient Care Group recommends potassium 40 mEq/L in infusion solution in patients with potassium levels < 3.3 mEq/L or 3.3-5.5 mEq/L. Do not give potassium if serum potassium level > 5.5 mEq/L.
• Limit magnesium replacement to symptomatic hypomagnesemia or symptomatic hypocalcemia.
• Professional organizations vary on recommended indications for insulin administration.
  • ADA recommends starting insulin in all patients with adequate serum potassium levels, regardless of degree of ketonemia.
  • Joint British Diabetes Societies Inpatient Care Group recommends insulin only in patients with significant ketonemia (beta-hydroxybutyrate > 1 mmol/L) or 2+ ketonuria (for mixed DKA-HHS).
  • If insulin is given, consider dose of 0.05-0.14 units/kg/hour in patients with adequate serum potassium, and adjust to maintain glucose 200-300 mg/dL (11.1-16.7 mmol/L) until the patient is mentally alert.
• Hyperglycemic hyperosmolar state is a prothrombotic state. All patients will require mechanical or pharmacologic venous thromboembolism prophylaxis throughout hospitalization.
• Once the hyperglycemic hyperosmolar state is resolved, transition to subcutaneous insulin therapy and provide patient education regarding prevention measures with attention to diabetes self-management and sick day instructions.