What are the key differences in management and treatment for an adult patient with a history of diabetes presenting with severe hyperglycemia, differentiating between Hyperosmolar Hyperglycemic State (HHS) and Diabetic Ketoacidosis (DKA)?

HHS vs DKA: Key Differences in Management

Both conditions require aggressive fluid resuscitation and insulin therapy, but HHS demands more cautious fluid replacement over 48 hours with lower initial insulin rates, while DKA prioritizes earlier insulin initiation and faster metabolic correction. 1

Diagnostic Distinctions

DKA Criteria

• Blood glucose >250 mg/dL (though can be lower in euglycemic DKA) 2, 3
• Arterial pH <7.3 with serum bicarbonate <15 mEq/L 1, 2
• Moderate to severe ketonemia/ketonuria (β-hydroxybutyrate preferred measurement) 1, 3
• Anion gap >10-12 mEq/L 3

HHS Criteria

• Blood glucose ≥600 mg/dL (significantly higher than DKA) 1, 4
• Effective serum osmolality ≥320 mOsm/kg (calculated as 2[Na+] + glucose/18) 1, 4
• Arterial pH >7.3 and bicarbonate ≥15 mEq/L (minimal acidosis) 1, 4
• Absent or mild ketonemia (≤3.0 mmol/L) 4
• Severe dehydration with altered mental status common 4, 5

Mixed Presentations

• One-third of patients present with overlapping features of both DKA and HHS 6
• When mixed features exist, tailor therapy to the dominant clinical presentation 6

Fluid Resuscitation: Critical Differences

DKA Fluid Management

• Start with 0.9% NaCl at 15-20 mL/kg/hour (1-1.5 L) in the first hour 1, 2
• Total water deficit averages 6 liters (100 mL/kg) 1
• Switch to 0.45% NaCl at 4-14 mL/kg/hour if corrected sodium is normal/elevated 1
• Add 5-10% dextrose when glucose reaches 250 mg/dL while continuing insulin 1, 2

HHS Fluid Management

• Start with 0.9% NaCl at 15-20 mL/kg/hour in the first hour (same initial rate) 1, 4
• Total water deficit averages 9 liters (100-220 mL/kg) - significantly higher than DKA 1, 4
• Osmolality decline must not exceed 3 mOsm/kg/hour to prevent cerebral edema 1, 4
• Replace fluid deficits evenly over 48 hours (slower than DKA's 24-hour target) 4
• Add dextrose when glucose reaches 300 mg/dL (higher threshold than DKA) 1

Critical Pitfall: In HHS, overly rapid fluid correction increases risk of osmotic demyelination and cerebral edema, particularly in elderly patients 4, 5. Monitor osmolality every 2-4 hours 4.

Insulin Therapy: Timing and Approach Differences

DKA Insulin Protocol

• Start insulin immediately after excluding hypokalemia (K+ >3.3 mEq/L) 2, 3
• Continuous IV regular insulin at 0.1 units/kg/hour without bolus 1, 2
• Target glucose decline of 50-75 mg/dL per hour 1, 2
• Continue insulin until ketoacidosis resolves (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L), regardless of glucose levels 2, 7
• Never stop insulin when glucose normalizes - add dextrose instead to prevent recurrent ketosis 2, 7

HHS Insulin Protocol

• Delay insulin until osmolality stops falling with fluid replacement alone, unless significant ketonemia is present 4
• If ketonemia present, start insulin simultaneously with fluids 4
• Use same insulin rate (0.1 units/kg/hour) once initiated 1
• Target glucose of 10-15 mmol/L (180-270 mg/dL) in first 24 hours - higher than DKA target 4
• Fluid replacement is the cornerstone of HHS therapy, not insulin 6, 8

Key Distinction: In HHS, residual beta-cell function prevents ketosis but not hyperglycemia, so insulin is less urgent than aggressive rehydration 8, 5. In DKA, absolute insulin deficiency drives ketoacidosis, making insulin therapy immediately essential 6, 8.

Electrolyte Management

Potassium Replacement (Same for Both)

• Delay insulin if K+ <3.3 mEq/L - aggressively replace potassium first to prevent fatal arrhythmias 2, 3
• Add 20-30 mEq/L potassium (2/3 KCl, 1/3 KPO4) once K+ is 3.3-5.5 mEq/L and urine output confirmed 1, 2
• Target serum K+ of 4-5 mEq/L throughout treatment 2, 3
• Total body potassium deficit: 3-5 mEq/kg in DKA, 5-15 mEq/kg in HHS 1

Sodium Considerations

• Correct sodium for hyperglycemia: add 1.6 mEq/L for every 100 mg/dL glucose above 100 1, 3
• Total sodium deficit: 7-10 mEq/kg in DKA, 5-13 mEq/kg in HHS 1

Bicarbonate Administration

• NOT recommended for pH >6.9-7.0 in either condition 2, 7
• No benefit demonstrated; may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 2, 7

Monitoring Frequency

Both Conditions Require

• Blood glucose every 1-2 hours 7
• Electrolytes, BUN, creatinine, osmolality, venous pH every 2-4 hours 1, 3
• Direct β-hydroxybutyrate measurement preferred over nitroprusside method 1, 3
• Venous pH adequate for monitoring after initial arterial blood gas 3

HHS-Specific Monitoring

• Osmolality every 2-4 hours to ensure decline ≤3 mOsm/kg/hour 4
• Neurological status checks - altered mental status more common in HHS 4, 5
• Cardiac monitoring in elderly patients with fluid overload risk 4

Resolution Criteria

DKA Resolution

• Glucose <200 mg/dL 2, 3
• Serum bicarbonate ≥18 mEq/L 2, 3
• Venous pH >7.3 2, 3
• Anion gap ≤12 mEq/L 2, 3

HHS Resolution

• Osmolality <300 mOsm/kg 4
• Hypovolemia corrected (urine output ≥0.5 mL/kg/hour) 4
• Mental status returned to baseline 4
• Blood glucose <15 mmol/L (270 mg/dL) 4

Transition to Subcutaneous Insulin

For both conditions: Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin to prevent rebound hyperglycemia and recurrent ketoacidosis 2, 7. This overlap period is essential and a common source of treatment failure 2, 9.

Special Populations and Pitfalls

Age-Related Considerations

• HHS mortality remains ~15% (higher than DKA's 3.4-4.6%) 8
• Elderly patients with HHS: increased risk of fluid overload, thrombotic events, and cardiovascular complications 4, 5
• Cerebral edema risk higher in children with DKA - avoid rapid osmolality correction 1, 2

Mixed DKA/HHS Cases

• Treat based on dominant features 6
• In adults with mixed features, fluid administration may be more aggressive given low cerebral edema risk 6
• In younger patients with mixed features, avoid rapid correction to minimize cerebral edema risk 6

Common Management Errors

• Premature insulin discontinuation before ketoacidosis resolves in DKA 2, 9
• Overly rapid fluid replacement in HHS causing osmotic demyelination 4
• Inadequate potassium monitoring leading to life-threatening hypokalemia 2, 3
• Stopping insulin when glucose normalizes without adding dextrose 2, 7
• Failure to identify precipitating cause (infection most common for both) 1, 4