What are the differences in treatment approaches for Diabetic Ketoacidosis (DKA) versus Hyperosmolar Hyperglycemic State (HHS)?

Treatment Approaches for DKA vs HHS

The primary difference in treatment between DKA and HHS is that fluid replacement is the cornerstone of HHS management, while insulin therapy is the cornerstone for DKA, though both conditions require aggressive fluid resuscitation, insulin therapy, and electrolyte management. 1, 2

Diagnostic Criteria Differences

• DKA diagnostic criteria: blood glucose >250 mg/dl, arterial pH <7.3, bicarbonate <15 mEq/l, and moderate ketonuria or ketonemia 1
• HHS diagnostic criteria: blood glucose >600 mg/dl, arterial pH >7.3, bicarbonate >15 mEq/l, effective serum osmolality >320 mOsm/kg, and altered mental status or severe dehydration 1, 2

Fluid Therapy Differences

• HHS requires more aggressive fluid replacement due to greater dehydration (total body water deficit ~9 liters or 100-200 mL/kg) compared to DKA (total body water deficit ~6 liters) 1, 2
• Both conditions initially require isotonic saline (0.9% NaCl) at 15-20 mL/kg/h during the first hour 1, 2
• Subsequent fluid choice depends on hydration status, serum electrolytes, and urine output in both conditions 1
• In HHS, fluid replacement alone will cause a significant fall in blood glucose level, and insulin may be withheld until glucose is no longer falling with IV fluids alone 3

Insulin Therapy Differences

• In DKA, insulin therapy should be initiated immediately with an IV bolus of regular insulin at 0.1 units/kg body weight, followed by continuous infusion at 0.1 unit/kg/h 1
• In HHS, insulin therapy may be initiated with a slightly higher IV bolus of regular insulin at 0.15 units/kg body weight, followed by the same continuous infusion rate 2
• In DKA, insulin should be continued until resolution of ketoacidosis (pH >7.3, serum bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L) even if blood glucose normalizes 1, 4
• In HHS, when plasma glucose reaches 300 mg/dL, insulin infusion can be decreased to 0.05-0.1 units/kg/h 2
• Mild DKA may be treated with subcutaneous rapid-acting insulin analogs combined with aggressive fluid management, which is not typically recommended for HHS 1, 4

Electrolyte Management Differences

• Potassium deficits are typically greater in HHS (5-15 mEq/kg) compared to DKA (3-5 mEq/kg) 1, 2
• Both conditions require close monitoring of potassium levels and replacement to maintain serum K+ between 4-5 mmol/L 4, 2
• Phosphate replacement is generally not beneficial in DKA but may be considered in specific situations (cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL) 1

Monitoring Differences

• In DKA, direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring ketone resolution 1, 4
• In HHS, calculated serum osmolality should be monitored regularly with a goal to reduce osmolality by 3-8 mOsm/kg/h 2, 3
• Both conditions require monitoring of serum electrolytes, glucose, blood urea nitrogen, creatinine every 2-4 hours 1, 2
• DKA additionally requires monitoring of venous pH and anion gap to assess resolution of acidosis 1

Resolution Criteria Differences

• DKA resolution requires: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3 1, 4
• HHS resolution is primarily based on normalization of osmolality and improvement in mental status 2, 3

Transition to Subcutaneous Insulin

• For both conditions, basal insulin should be administered 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1
• Recent studies show that low-dose basal insulin analog given with IV insulin may prevent rebound hyperglycemia in both conditions 1

Common Pitfalls to Avoid

• In DKA: Premature termination of insulin therapy before complete resolution of ketosis can lead to recurrence 4, 5
• In HHS: Early use of insulin before adequate fluid resuscitation may be detrimental 3
• In both conditions: Inadequate fluid resuscitation and electrolyte replacement can worsen outcomes 4, 2
• In HHS: Rapid correction of osmolality may precipitate cerebral edema or central pontine myelinolysis 3
• In DKA: Bicarbonate administration is generally not recommended unless pH is <6.9 1

Special Considerations for Mixed States

• As many as one-third of patients may present with mixed features of both DKA and HHS 6
• In mixed cases, treatment should be tailored according to the prominent clinical features present 6
• In adults with mixed features, fluids may be administered more rapidly than in younger patients or in patients with DKA alone 6
• In younger patients with mixed features, rapid correction of metabolic abnormalities should be avoided to decrease the risk of cerebral edema 6