What are the management strategies for Diabetic Ketoacidosis (DKA) versus Hyperosmolar Hyperglycemic State (HHS)?

Management of DKA versus HHS

While both DKA and HHS require aggressive fluid resuscitation and insulin therapy, the key difference is that HHS demands more cautious fluid replacement over a longer period (aiming for osmolality reduction of 3-8 mOsm/kg/h) and insulin should be withheld until glucose stops falling with fluids alone, whereas DKA requires immediate insulin therapy alongside fluids. 1, 2

Diagnostic Criteria

DKA

• Blood glucose >250 mg/dL 3, 4
• Arterial pH <7.3 3, 4
• Serum bicarbonate <15 mEq/L 3, 4
• Moderate ketonuria or ketonemia 3, 4

HHS

• Blood glucose >600 mg/dL 3
• Venous pH >7.3 3
• Serum bicarbonate >15 mEq/L 3
• Altered mental status or severe dehydration 3
• Minimal or absent ketosis 2, 5

Note: Up to one-third of patients present with mixed features of both conditions and should be managed according to the dominant clinical presentation. 6, 5

Initial Fluid Resuscitation

DKA Protocol

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour 1, 4
• After the first hour, switch to 0.45% NaCl at 4-14 mL/kg/hour if corrected serum sodium is normal or elevated 1
• Continue 0.9% NaCl if corrected sodium is low 1
• Total fluid replacement should correct estimated deficits (typically 6L or 100 mL/kg) within 24 hours 4

HHS Protocol

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour 1
• Critical difference: HHS develops over days (not hours like DKA), resulting in more extreme dehydration and metabolic disturbances that require slower correction 2
• Monitor serum osmolality regularly and aim to reduce it by 3-8 mOsm/kg/h 2
• Rapid changes in osmolality may precipitate central pontine myelinolysis 2
• An initial rise in sodium level is expected and is NOT itself an indication for hypotonic fluids 2

Insulin Therapy: The Critical Difference

DKA Insulin Protocol

• Start continuous IV regular insulin at 0.1 units/kg/hour WITHOUT an initial bolus 1
• Never interrupt insulin infusion when glucose falls—instead add dextrose-containing fluids (5% dextrose with 0.45-0.75% NaCl) to maintain glucose 150-200 mg/dL while continuing insulin to clear ketosis 1, 7
• Continue insulin until complete resolution: pH >7.3, bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L 1

HHS Insulin Protocol

• Withhold insulin until the blood glucose level is no longer falling with IV fluids alone (unless ketonaemic) 2
• Fluid replacement alone will cause a fall in blood glucose level 2
• Early use of insulin (before fluids) may be detrimental 2
• Once insulin is started, use the same continuous IV infusion protocol as DKA (0.1 units/kg/hour) 1
• Maintain glucose at 250-300 mg/dL until hyperosmolarity and mental status improves 3

Common pitfall: Starting insulin too early in HHS can worsen outcomes by causing rapid osmolality shifts. 2

Potassium Management (Identical for Both)

• If K+ <3.3 mEq/L, DELAY insulin therapy until potassium is repleted to >3.3 mEq/L to prevent life-threatening arrhythmias and cardiac arrest 1, 8
• Once K+ is <5.5 mEq/L and renal function is assured, add 20-40 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO4) 1, 4
• Target serum potassium 4-5 mEq/L throughout treatment 1
• Total body potassium is depleted despite potentially normal or elevated initial serum levels due to acidosis 4, 8

Bicarbonate Therapy (Primarily for DKA)

• Generally not recommended for pH >6.9, as studies show no benefit on clinical outcomes and potential harm (worsening ketosis, hypokalemia, cerebral edema risk) 1
• Consider bicarbonate ONLY if pH <6.9: give 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/h 1
• Bicarbonate is rarely needed in HHS since significant acidosis is typically absent 2, 5

Monitoring Protocol

For Both Conditions

• Check blood glucose every 1-2 hours 1
• Draw blood every 2-4 hours for electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 1, 7
• Venous pH (typically 0.03 units lower than arterial pH) and anion gap can be followed instead of repeated arterial blood gases 3, 1

HHS-Specific Monitoring

• Measure or calculate serum osmolality regularly to monitor response to treatment 2
• Monitor for complications including myocardial infarction, stroke, seizures, cerebral edema, and central pontine myelinolysis 2
• HHS has a higher mortality rate than DKA 2

DKA-Specific Monitoring

• Direct measurement of β-hydroxybutyrate in blood is preferred over nitroprusside method 3, 7
• Nitroprusside only measures acetoacetic acid and acetone, not β-hydroxybutyrate (the predominant ketone body) 3, 7
• During therapy, β-hydroxybutyrate is converted to acetoacetic acid, which may falsely suggest worsening ketosis 3

Resolution Criteria and Transition

DKA Resolution

• Glucose <200 mg/dL 3, 1
• Serum bicarbonate ≥18 mEq/L 3, 1
• Venous pH >7.3 3, 1
• Anion gap ≤12 mEq/L 1

HHS Resolution

• Normalization of serum osmolality 2
• Improvement in mental status 3, 2
• Clinical stability 3

Transition to Subcutaneous Insulin (Both Conditions)

• Administer subcutaneous basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin to prevent rebound ketoacidosis and hyperglycemia 1, 7
• If patient is NPO, continue intravenous insulin and fluid replacement 3

Critical pitfall: Premature termination of IV insulin therapy before complete resolution or insufficient timing of subcutaneous insulin before discontinuation of IV insulin are the most common management errors. 9

Precipitating Factors to Address

Common to Both

• Infection (obtain cultures and start antibiotics if suspected) 3, 4
• Insulin omission or inadequate dosing 3, 8
• New-onset diabetes 4
• Medications: corticosteroids, thiazides, sympathomimetic agents, SGLT2 inhibitors 1, 4

HHS-Specific

• Inadequate fluid intake in elderly patients unable to recognize or treat evolving dehydration 3
• Nursing home residents require adequate supervision to prevent HHS 3

Complications to Monitor

DKA-Specific

• Cerebral edema (more common in children and adolescents) 3, 10
• Hypoglycemia from overzealous insulin treatment 3, 8
• Hyperchloremic non-anion gap metabolic acidosis (transient, not clinically significant) 3

HHS-Specific

• Vascular occlusion (myocardial infarction, stroke) 6, 2
• Seizures 2
• Central pontine myelinolysis from rapid osmolality changes 2
• Higher mortality rate compared to DKA 2

Common to Both

• Hypokalemia from insulin administration and acidosis correction 3, 8
• Hyperglycemia from premature discontinuation of IV insulin 3
• Hypophosphatemia (replacement indicated if <1.0 mg/dL or with cardiac dysfunction, anemia, or respiratory depression) 3