What is the management of Hyperosmolar Hyperglycemic State (HHS) and Diabetic Ketoacidosis (DKA)?

Management of Hyperosmolar Hyperglycemic State (HHS) and Diabetic Ketoacidosis (DKA)

For HHS and DKA management, prioritize aggressive fluid resuscitation with isotonic saline (15-20 mL/kg/hour initially), followed by continuous IV insulin at 0.1 units/kg/hour (with a 0.15 units/kg bolus for DKA but NOT for HHS), meticulous potassium replacement to maintain levels of 4-5 mEq/L, and careful monitoring to prevent cerebral edema—particularly avoiding osmolality reduction exceeding 3 mOsm/kg/H₂O per hour. 1, 2

Diagnostic Criteria

DKA Diagnosis

• Blood glucose >250 mg/dL, venous pH <7.3, serum bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia with anion gap >10-12 mEq/L 1, 2
• Severity classification: mild (pH 7.25-7.30, HCO₃ 15-18 mEq/L), moderate (pH 7.00-7.24, HCO₃ 10-15 mEq/L), severe (pH <7.00, HCO₃ <10 mEq/L) 1
• Measure β-hydroxybutyrate directly in blood, NOT urine ketones—the nitroprusside method only detects acetoacetate and acetone, missing the predominant ketoacid β-hydroxybutyrate, and paradoxically worsens during treatment as β-hydroxybutyrate converts to acetoacetate 3, 1

HHS Diagnosis

• Blood glucose ≥600 mg/dL, arterial pH ≥7.30, serum bicarbonate ≥15 mEq/L, minimal ketonuria, and effective serum osmolality ≥320 mOsm/kg H₂O 4, 2
• Calculate effective osmolality: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 3, 4
• Correct serum sodium for hyperglycemia: add 1.6 mEq/L for every 100 mg/dL glucose above 100 mg/dL 3, 4
• Mental status changes are common but NOT mandatory for diagnosis—patients meeting metabolic criteria warrant HHS management regardless of alertness 4

Initial Laboratory Workup

• Obtain immediately: plasma glucose, venous blood gases (arterial unnecessary after initial diagnosis), complete metabolic panel with calculated anion gap, serum osmolality, β-hydroxybutyrate, complete blood count, urinalysis, electrocardiogram, and HbA1c 1, 4
• Consider bacterial cultures (blood, urine, throat) and chest X-ray if infection suspected as precipitating factor 1, 4

Fluid Resuscitation

Initial Fluid Management

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour (approximately 1-1.5 L in average adult) to restore circulatory volume and tissue perfusion 1, 2
• Total estimated fluid deficit: approximately 6 liters for DKA, 9 liters for HHS 2
• Critical pitfall: The induced change in serum osmolality must NOT exceed 3 mOsm/kg/H₂O per hour to prevent cerebral edema 3

Subsequent Fluid Therapy

• After initial resuscitation, fluid choice depends on corrected serum sodium: use 0.45% NaCl if corrected sodium is normal or elevated, continue 0.9% NaCl if corrected sodium is low 3
• Switch to 5% dextrose with 0.45-0.75% NaCl when glucose reaches 250 mg/dL in DKA or 250-300 mg/dL in HHS while continuing insulin to clear ketones 3, 2
• In HHS specifically, maintain glucose at 250-300 mg/dL until hyperosmolarity and mental status improve and patient becomes clinically stable 3

Special Populations

• Pediatric patients (<20 years): Initial fluid is 0.9% NaCl at 10-20 mL/kg/hour for first hour, not exceeding 50 mL/kg over first 4 hours 3
• Continue at 1.5 times 24-hour maintenance requirements (approximately 5 mL/kg/hour) to achieve smooth rehydration over 48 hours 3
• Patients with renal or cardiac compromise: Require frequent assessment of cardiac, renal, and mental status during fluid resuscitation to avoid iatrogenic fluid overload 3

Insulin Therapy

DKA Insulin Protocol

• Once hypokalemia (K⁺ <3.3 mEq/L) is excluded, give IV bolus of regular insulin at 0.15 units/kg, followed by continuous infusion at 0.1 unit/kg/hour (5-7 units/hour in adults) 3, 1
• Target glucose decline of 50-75 mg/dL per hour 3, 1
• If glucose does not fall by 50 mg/dL in first hour, double insulin infusion rate hourly until steady decline achieved 3, 1

HHS Insulin Protocol—Critical Difference

• Do NOT give initial insulin bolus in HHS—start continuous infusion at 0.1 unit/kg/hour only after fluid resuscitation has begun 5, 6
• In HHS, glucose decline should initially be managed by fluid resuscitation alone before insulin administration 6

Pediatric Insulin Protocol

• No initial insulin bolus recommended—start continuous infusion at 0.1 unit/kg/hour 3

Transition to Subcutaneous Insulin

• Continue IV insulin until DKA resolves: glucose <200 mg/dL, bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 1, 2
• Administer basal subcutaneous insulin 2-4 hours BEFORE stopping IV insulin to prevent rebound hyperglycemia 1, 2
• Ketonemia takes longer to clear than hyperglycemia—continue insulin even after glucose normalizes until ketones clear 3, 1

Electrolyte Management

Potassium Replacement—Most Critical

• If initial potassium <3.3 mEq/L, DELAY insulin therapy and aggressively replace potassium first to prevent fatal cardiac arrhythmias 1, 7
• Once potassium <5.5 mEq/L and adequate urine output confirmed, add 20-40 mEq/L potassium to IV fluids (2/3 KCl or potassium-acetate, 1/3 KPO₄) 3, 1
• Target serum potassium 4-5 mEq/L throughout treatment 1, 2
• Typical potassium deficit: 3-5 mEq/kg in DKA, 5-15 mEq/kg in HHS 2
• Critical mechanism: Insulin stimulates potassium movement into cells, potentially causing life-threatening hypokalemia, respiratory paralysis, and ventricular arrhythmias 7

Phosphate and Magnesium

• Consider phosphate replacement for severe hypophosphatemia, using 1/3 of potassium replacement as KPO₄ 3, 2
• Monitor and replace magnesium as needed—hypomagnesemia is common 5

Bicarbonate Therapy—Generally NOT Recommended

• Avoid sodium bicarbonate due to risks of worsening ketosis, hypokalemia, and cerebral edema 2, 5
• Consider bicarbonate ONLY if pH <6.9, or when pH <7.2 with serum bicarbonate <10 mEq/L pre- and post-intubation to prevent hemodynamic collapse 5

Monitoring Strategy

Frequency of Monitoring

• Check glucose, electrolytes, BUN, creatinine, osmolality, and venous pH every 2-4 hours during treatment 1, 2
• After initial diagnosis, venous pH and anion gap adequately monitor acidosis resolution—repeated arterial blood gases are unnecessary 1
• Monitor β-hydroxybutyrate every 2-4 hours alongside other parameters to track ketosis resolution 1

Resolution Criteria

• DKA resolved when: glucose <200 mg/dL, bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 1, 2
• HHS resolved when: osmolality normalized, mental status improved, and patient clinically stable 3

Complications and Prevention

Cerebral Edema—Most Feared Complication

• Occurs in 0.7-1.0% of children with DKA, rare but frequently fatal 3
• Risk factors: Rapid overcorrection of hyperglycemia and hyperosmolarity, excessive fluid administration, failure to add dextrose when glucose reaches target 3, 5
• Prevention: Limit osmolality reduction to <3 mOsm/kg/H₂O per hour, avoid hypotonic fluids initially, monitor mental status closely 3, 1
• Characterized by deterioration in consciousness, lethargy, decreased arousal 3

Common Treatment Complications

• Hypoglycemia: From overzealous insulin treatment—add dextrose to fluids when glucose reaches 250 mg/dL (DKA) or 250-300 mg/dL (HHS) 3, 2
• Hypokalemia: From insulin administration and bicarbonate therapy—monitor and replace aggressively 3, 1
• Hyperchloremia and non-anion gap metabolic acidosis: From excessive saline use—transient and resolves spontaneously 3
• Hypoxemia and pulmonary edema: Rare, attributed to reduced colloid osmotic pressure; patients with widened alveolo-arteriolar oxygen gradient or pulmonary rales at higher risk 3

Airway Management in Critically Ill Patients

• Avoid BiPAP due to aspiration risk—use intubation and mechanical ventilation with careful acid-base and fluid status monitoring 5
• Consider bicarbonate if pH <7.2 pre-intubation to prevent metabolic acidosis and hemodynamic collapse from apnea during intubation 5

Special Considerations

Early Nutritional Support

• Initiate oral nutrition early once patient tolerates—reduces ICU and hospital length of stay 5

Balanced Crystalloid Solutions

• Balanced solutions (e.g., lactated Ringer's) show faster DKA resolution compared to normal saline in recent studies, though isotonic saline remains standard 5

British Guidelines Alternative Approach

• British guidelines recommend subcutaneous insulin glargine along with continuous IV regular insulin, showing faster DKA resolution and shorter hospital stays compared to IV insulin alone 5

Prevention of Recurrence

• Never discontinue insulin—common precipitant in urban populations due to economic reasons 3
• Educate on sick-day management: when to contact provider, supplemental short-acting insulin during illness, fever suppression, infection treatment, easily digestible liquid diet with carbohydrates and salt 3
• Monitor blood glucose and ketones when glucose >300 mg/dL 3