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Hyperosmolar Hyperglycemic State (HHS) - "Hyperosmolar Coma"

Terminology

1. Ketosis (and mild acidosis) may be present to varying degrees
2. Frank coma is uncommon - altered sensorium without full coma is more typical

• Goldman-Cecil Medicine, p. 2483

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Epidemiology & Risk Factors

• Primarily affects elderly patients with type 2 diabetes (most cases in those ≥65 years)
• Often the first manifestation of previously undiagnosed type 2 diabetes
• Risk factors:
  • Older age and impaired cognition (reduced thirst perception / inability to access water)
  • Medications that alter carbohydrate metabolism (glucocorticoids, phenytoin, thiazides)
  • Intercurrent illness (infections, stroke, MI, pancreatitis, GI illness)
  • Total parenteral nutrition (high glucose content)
• Goldman-Cecil Medicine, p. 2484

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Pathophysiology

1. Profound hyperglycemia develops (often >600 mg/dL, sometimes >1000 mg/dL) due to inadequate insulin action
2. Glucose-induced osmotic diuresis causes massive fluid loss
3. The elderly and cognitively impaired cannot drink enough to compensate (glucose is also a weaker dipsogen than other osmoles)
4. Progressive hemoconcentration and prerenal azotemia further reduce renal glucose excretion - a vicious cycle
5. Ketosis is absent or minimal because enough residual insulin remains in type 2 diabetes to suppress lipolysis, even though it is insufficient to normalize blood glucose. Portal insulin concentrations are higher than in DKA, limiting hepatic ketogenesis
6. Hyperosmolarity directly causes cerebral dysfunction - osmotic shifts dehydrate neurons

• Goldman-Cecil Medicine, p. 2484; Bradley and Daroff's Neurology, p. 1789

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Clinical Features

• Depressed consciousness / coma
• Focal neurological deficits (hemiplegia, aphasia, hemisensory deficits)
• Seizures - including epilepsia partialis continua (Kojewnikov's syndrome)
• Hemichorea (rare, characteristic)
• Level of consciousness correlates with degree and duration of hyperosmolarity
• Bradley and Daroff's Neurology, p. 1790; Goldman-Cecil Medicine, p. 2484

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Diagnostic Criteria

2 × Na (mEq/L) + Glucose (mg/dL) / 18

• Elevated BUN and creatinine (prerenal AKI)
• Elevated hematocrit (hemoconcentration)
• Serum sodium may be falsely low (dilutional due to osmotic water shift)
• Normal or near-normal anion gap (no significant ketoacidosis)
• Goldman-Cecil Medicine, p. 2485; Plum and Posner's Stupor and Coma, p. 397

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Precipitating Factors

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Management

1. Fluid Resuscitation (PRIORITY)

• 1 L normal saline (0.9% NaCl) per hour for the first 3 hours to restore blood pressure/volume and begin reducing osmolality
• If serum Na >150 mmol/L: switch to 0.45% (half-normal) saline for 1-2 L, then 5% dextrose once glucose <11.2 mmol/L (200 mg/dL)
• Blood glucose must NOT fall more than 100 mg/dL/hour (optimal rate: 50 mg/dL/h)
• Maintain blood glucose 10-15 mmol/L (180-270 mg/dL) for the first 24 hours

2. Insulin

• Start with fluids ALONE initially
• Add low-dose IV insulin (0.05 units/kg/h) ONLY if:
  • Significant ketonemia (3-hydroxybutyrate >1 mmol/L or ketonuria >2+), OR
  • Plasma glucose falling at <5 mmol/h (90 mg/dL/h) despite adequate fluids
• Insulin infusion rate may be decreased when plasma glucose <300 mg/dL

3. Potassium Replacement

• If K+ = 3.5-5.5 mmol/L: add 20 mmol KCl per liter of IV fluid
• If K+ <3.5 mmol/L: add 40 mmol KCl per liter

4. Monitoring

• Arterial and central venous catheters for hemodynamic monitoring
• Avoid volume overload in elderly patients with cardiac comorbidities
• Treat the precipitating cause
• Bradley and Daroff's Neurology, p. 1790; Goldman-Cecil Medicine, p. 2485

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Complications of Treatment

• Cerebral edema - from overly rapid correction of osmolality (more common in DKA but occurs in HHS too)
• Thrombotic complications - HHS is a procoagulant/inflammatory state, increasing risk of DVT, PE, and stroke
• Stroke may both precipitate HHS and occur as a complication of HHS

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Mortality

• Older patient age
• More severe underlying comorbidities
• Greater degree of dehydration and hemodynamic compromise at presentation
• Bradley and Daroff's Neurology, p. 1790

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DKA vs HHS: Quick Comparison

Key point: A mixed picture (HHS + DKA) can occur in ketosis-prone type 2 diabetes (more common in people of African or Hispanic origin). In that scenario, the pH is <7.3 but osmolality is also markedly elevated.