What are the key differences in managing Hyperosmolar Hyperglycemic State (HHS) versus Diabetic Ketoacidosis (DKA)?

Key Differences in Managing HHS versus DKA

The most critical management difference is that HHS requires aggressive fluid resuscitation as the primary intervention with delayed insulin administration, while DKA demands immediate insulin therapy alongside fluids to clear ketoacidosis. 1, 2

Diagnostic Thresholds

DKA:

• Blood glucose >250 mg/dL 3, 1
• Arterial pH <7.3 3, 1
• Bicarbonate <15 mEq/L 3, 1
• Moderate to severe ketonuria/ketonemia 3, 1

HHS:

• Blood glucose >600 mg/dL 3, 1
• Venous pH >7.3 3, 1
• Bicarbonate >15 mEq/L 3, 1
• Altered mental status or severe dehydration 3, 1
• Minimal ketone production 4

Pathophysiological Distinctions

The fundamental difference lies in insulin availability: DKA results from absolute insulin deficiency causing unrestrained lipolysis and ketone body production with high anion gap metabolic acidosis, while HHS has sufficient residual insulin to suppress lipolysis but not enough to prevent severe hyperglycemia. 4

Fluid deficits are more extreme in HHS:

• DKA: approximately 6 liters total body water deficit 4
• HHS: approximately 9 liters total body water deficit 4

Time course differs significantly: HHS develops over days to weeks allowing more severe dehydration and hyperosmolarity to accumulate, while DKA evolves rapidly over hours to days. 4

Initial Fluid Management Algorithm

Both conditions start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour. 1

After initial resuscitation:

• If corrected serum sodium is normal or elevated: switch to 0.45% NaCl at 4-14 mL/kg/hour 1
• If corrected serum sodium is low: continue 0.9% NaCl 1
• Correct sodium for hyperglycemia by adding 1.6 mEq to measured sodium for each 100 mg/dL glucose elevation 3

Critical difference: In HHS, fluid replacement alone will cause blood glucose to fall significantly, and this is the cornerstone of therapy. 5, 2

Insulin Therapy: The Major Management Divergence

DKA Protocol:

• Start continuous IV regular insulin at 0.1 units/kg/hour immediately after excluding hypokalemia (K+ >3.3 mEq/L) 3, 1
• Adult patients receive an initial IV bolus of 0.15 units/kg 3
• Pediatric patients should NOT receive an initial bolus 3
• Target glucose decline of 50-75 mg/dL per hour 3
• Continue insulin until ketoacidosis resolves, not just until glucose normalizes 3

HHS Protocol:

• Withhold insulin until blood glucose is no longer falling with IV fluids alone, unless ketonemia is present 1, 2
• This is the single most important management distinction from DKA 2
• Early insulin use before adequate fluid resuscitation may be detrimental in HHS 2
• When glucose reaches 300 mg/dL in HHS, start insulin at 0.1 units/kg/hour 3

Potassium Management (Identical for Both)

Never start insulin if potassium <3.3 mEq/L - this prevents life-threatening arrhythmias and cardiac arrest. 1

Once K+ <5.5 mEq/L and renal function is confirmed:

• Add 20-40 mEq/L potassium to IV fluids 1
• Use 2/3 KCl and 1/3 KPO4 3, 1

Monitoring Intensity

Check blood glucose every 1-2 hours during active management. 1

Draw blood every 2-4 hours for:

• Electrolytes, glucose, BUN, creatinine 3, 1
• Osmolality 3, 1
• Venous pH (for DKA) 3, 1

For HHS specifically: Monitor serum osmolality regularly and aim to reduce it by 3-8 mOsm/kg/hour. 2 Rapid changes in osmolality can precipitate central pontine myelinolysis, a devastating complication more common in HHS. 2

For DKA specifically: Monitor β-hydroxybutyrate (β-OHB) in blood as the preferred method, not nitroprusside urine ketones which can be misleading during treatment. 3 As β-OHB converts to acetoacetate during therapy, nitroprusside testing may falsely suggest worsening ketosis. 3

Resolution Criteria

DKA resolution requires ALL of the following:

• Glucose <200 mg/dL 3
• Serum bicarbonate ≥18 mEq/L 3
• Venous pH ≥7.3 3

HHS resolution:

• Osmolality normalized 2
• Mental status returned to baseline 2
• Adequate hydration restored 2

Transition to Subcutaneous Insulin

Critical timing to prevent rebound: Administer subcutaneous basal insulin (intermediate or long-acting) 2-4 hours before stopping IV insulin. 1 This overlap period is essential in both conditions but particularly critical in DKA to prevent rebound ketoacidosis. 1

Bicarbonate Therapy

Only consider bicarbonate if pH <6.9 in DKA: Give 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour. 1 Bicarbonate is rarely if ever needed in HHS given the minimal acidosis. 4

Complications to Anticipate

DKA-specific:

• Cerebral edema (especially in children) 3, 1
• Hyperchloremic non-anion gap metabolic acidosis from aggressive saline resuscitation 1

HHS-specific:

• Vascular occlusion (MI, stroke) 1, 6
• Seizures 1
• Central pontine myelinolysis from overly rapid osmolality correction 1, 2
• Mortality rate approximately 10-fold higher than DKA 6

Common Pitfalls

In HHS: Starting insulin too early before adequate fluid resuscitation can worsen outcomes. 2 The initial rise in sodium during fluid resuscitation is expected and normal - do not switch to hypotonic fluids prematurely based on rising sodium alone. 2

In DKA: Stopping IV insulin too soon (when glucose normalizes but ketoacidosis persists) causes rebound ketoacidosis. 3 Ketonemia takes longer to clear than hyperglycemia. 3

In both: Inadequate overlap between IV and subcutaneous insulin leads to metabolic decompensation. 1

Mixed presentations occur in up to one-third of patients and require tailoring the approach based on prominent features, though the three-pronged therapy (fluids, insulin, electrolytes) applies to all cases. 5