hyperglycemic-hyperosmolar syndrome; hyperglycemic-hyperosmolar nonketotic coma (HHNC)

Etiology

• precipitating illness
  • sepsis
  • myocardial infarction
  • stroke
  • GI bleed
• lapse of therapy
• dehydration
  • diuretics
  • elder abuse, neglect
• trauma, stress
• pharmaceuticals that increase risk
  • glucocorticoids
  • atypical antipsychotics
  • SGLT2 inhibitors
  • case report implicating quetiapine

Epidemiology

• 17.5 cases per 100,000 people.
• more common than diabetic ketoacidosis (DKA) in the elderly
• prevalence is slightly higher in females than in males
• 16.5 per 10,000 person years type 1 diabetes
• 3.9 per 10,000 person years type 2 diabetes

Pathology

• hyperglycemia increases serum osmolality, causing water to move out of cells
• greater free water loss than DKA
  • often profound dehydration
  • high plasma viscosity
  • diminished cardiac output
• more often fatal than DKA
  • risk of
    • myocardial infarction
    • stroke
    • mesenteric thrombosis

Clinical manifestations

• onset is insidious; may take days-weeks to develop
• despite the name, coma is present in fewer than 10% of cases
• dehydration
  • tachycardia may be an early sign dehydration
  • hypotension may be a later sign of dehydration
• drowsiness & lethargy
• delirium (may be more extreme than DKA)
• focal or generalized seizures
• visual changes or disturbances
• hemiparesis
• sensory deficits
• tachypnea may result from respiratory compensation for metabolic acidosis
• hypoxemia can be a concurrent problem affecting mentation

Diagnostic criteria

• plasma osmolality > 320 mOsm/kg
• plasma glucose > 600 mg/dL (more extreme than DKA)
• serum ketones: negative or low
• serum bicarbonate normal
• arterial blood gas: pH normal

Laboratory

• comprehensive metabolic panel
  • hyponatremia or hypernatremia may be present
  • total body K+ is likely low regardless of its serum value
  • a mild anion gap metabolic acidosis may be present
  • BUN & serum creatinine levels are likely to be elevated due to dehydration
  • serum glucose usually is elevated dramatically, often to greater than 800 mg/dL
• serum osmolarity usually is greater than 320 mOsm/dL
  • if the calculated value is significantly lower than the measured value, consider toxic alcohol ingestion as a source of unmeasured osmoles that can trigger HHNC
• serum ketones can be normal in pure HHNC, but mild-to-moderate ketosis can be present when the disease has features both of HHNC and of DKA ('overlap cases')
• creatine phosphokinase (CPK) with isoenzymes should be measured routinely because both MI & rhabdomyolysis can trigger HHNC, & both can be secondary complications of HHNC
• coagulation studies PT & aPTT] are useful as part of a screen for disseminated intravascular coagulation
• blood cultures should be obtained to search for bacteremi
• arterial blood gases
  • in most cases of HHNC, the pH is > 7.25
  • metabolic acidosis (pH < 7.35 in 39%)
• CSF cell count, glucose, protein, & culture are indicated in patients with an acute alteration of consciousness & clinical features suggestive of possible CNS infection
• hemoglobin A1C may be useful as an indicator of the patient's glucose control over the previous several weeks.

Radiology

• chest radiograph is useful to screen for pneumonia
• abdominal radiographs indicated for abdominal pain or vomiting
• indications for head CT scans controversial

Complications

• acute kidney injury (65%)
• mortality rate is high (10-20%)

Differential diagnosis

• overlap syndrome with features of both (38%)
  • hyperglycemic-hyperosmolar syndrome
  • diabetic ketoacidosis (DKA)

Management

• airway management is the top priority
• IV access, large bore if possible + central line
  • fluid deficits in HHNC are large; the fluid deficit of an adult may be 10 L or more
  • isotonic fluid replacement
    • restore intravascular volume
    • improve cardiac output
    • bolus of 500 mL isotonic saline
    • 250 mL bolus if history of CHF &/or renal insufficiency
    • 1-2 L of isotonic saline in the first 2 hours
• insulin therapy
  • do not start insulin therapy until serum K+ > 3.3 meq/L
    • use KCl at 20-30 meq/hour through central line
    • do not start KCl until adequate urine output
  • start insulin if serum K+ > 5.2 meq/L
  • insulin utilized without concomitant vigorous fluid replacement increases risk of shock
  • serum K+ expected to decrease
    • after initiation of insulin therapy, add KCl 20-30 meq to each liter of IV fluids to maintain serum postassium at 4.0-5.0 meq/L
  • serum sodium expected to increase
    • use 1/2 normal saline if serum sodium normal or high
• once serum glucose drops to 300 mg/dL, change IV fluid to contain dextrose (D5W-1/2NS, D5W-NS) 150-250 mL/hr
• maintain plasma glucose 250-300 mg/dL until patient is alert & hyperosmolar state resolves
• insulin, electrolyte & fluid management similar to DKA
  • after plasma glucose < 200 mg/dL AND patient is eating, switch to subcutaneous insulin
• identify precipitating cause

Notes

• with insulin therapy, a decrease in serum osmolality is expected to move water intracellularly increasing serum sodium
• serum sodium increase also expected to co-occur with serum K+ decrease as mechanism involves Na+/K+ ATPase
• there is also a Na+/glucose cotransporter

More general terms

• coma
• encephalopathy
• hyperglycemia
• diabetes mellitus complication

Additional terms

• diabetes mellitus type 2 (insulin-resistant)
• diabetic ketoacidosis (DKA)