Treatment of Hyperglycemic Hyperosmolar Nonketotic Syndrome (HHNS)

Initial Assessment and Diagnosis

• HHNS is characterized by severe hyperglycemia, effective serum osmolality ≥320 mOsm/kg H₂O, arterial pH >7.3, bicarbonate >15 mEq/l, minimal ketonuria/ketonemia, and altered mental status or severe dehydration, according to the American Diabetes Association 1, 2
• Laboratory evaluation should include plasma glucose, blood urea nitrogen, creatinine, serum ketones, electrolytes with calculated anion gap, osmolality, urinalysis, arterial blood gases, complete blood count with differential, and electrocardiogram, as recommended by the American Diabetes Association 3, 2
• Serum sodium should be corrected for hyperglycemia, with an addition of 1.6 mEq to sodium value for each 100 mg/dl glucose >100 mg/dl, for a corrected serum value, based on guidelines from the American Diabetes Association 3

Fluid Therapy

• Initial fluid therapy should be isotonic saline at a rate of 15-20 ml/kg/h during the first hour to restore circulatory volume and tissue perfusion, as recommended by the American Diabetes Association 1, 2
• Total body water deficit in HHNS is typically 9 liters, approximately 100-200 ml/kg, according to the American Diabetes Association 1
• Fluid replacement should correct estimated deficits within the first 24 hours, with an induced change in serum osmolality not exceeding 3 mOsm/kg/h, based on guidelines from the American Diabetes Association 3

Insulin Therapy

• Once hypokalemia is excluded, administer an intravenous bolus of regular insulin at 0.15 U/kg body weight, followed by a continuous infusion at 0.1 U/kg/h, as recommended by the American Diabetes Association 3, 2
• If plasma glucose does not fall by 50 mg/dl from the initial value in the first hour, the insulin infusion may be doubled every hour until a steady glucose decline between 50-75 mg/h is achieved, based on guidelines from the American Diabetes Association 3
• Continue insulin infusion until mental status improves and hyperosmolarity resolves, as recommended by the American Diabetes Association 4

Electrolyte Management

• Total body deficits in HHNS typically include sodium, potassium, chloride, and phosphate, with amounts of 5-15 mEq/kg, 4-6 mEq/kg, 5-13 mEq/kg, and 3-7 mmol/kg, respectively, according to the American Diabetes Association 1
• Once renal function is assured and serum potassium is known, add 20-40 mEq/l potassium to the infusion, as recommended by the American Diabetes Association 3, 2

Monitoring and Ongoing Management

• During therapy, blood should be drawn every 2-4 hours for determination of serum electrolytes, glucose, blood urea nitrogen, creatinine, and osmolality, as recommended by the American Diabetes Association 5
• Monitor fluid input/output, hemodynamic parameters, and clinical examination to assess progress with fluid replacement, based on guidelines from the American Diabetes Association 3

Resolution Criteria and Transition of Care

• A structured discharge plan should be tailored to the individual patient to reduce length of hospital stay and readmission rates, as recommended by the American Diabetes Association 6, 4

Identification and Treatment of Precipitating Causes

• Obtain bacterial cultures of urine, blood, and other sites as needed and administer appropriate antibiotics if infection is suspected, as recommended by the American Diabetes Association 1

Hyperosmolar Non-Ketotic Coma Management

Insulin Administration and Monitoring

• The American Diabetes Association recommends adding dextrose to the hydrating solution while continuing insulin infusion at a reduced rate when blood glucose reaches 250-300 mg/dL, with a target blood glucose level of 250-300 mg/dL until hyperosmolarity and mental status improve 7
• Monitoring for signs of cerebral edema, such as lethargy, behavioral changes, seizures, incontinence, pupillary changes, bradycardia, and respiratory arrest, is crucial during treatment 8

Electrolyte Replacement and Complications

• Phosphate replacement (20-30 mEq/L potassium phosphate) may be considered in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL, according to the American Diabetes Association 8
• Hypoglycemia, hypokalemia, and hyperchloremic metabolic acidosis are potential complications that can occur due to overzealous insulin treatment, insulin administration, and fluid shifts, or excessive saline administration, respectively 8

Transition and Follow-up Care

• Successful transition from intravenous to subcutaneous insulin requires administration of basal insulin 2-4 hours before the intravenous insulin is stopped to prevent rebound hyperglycemia, as recommended by the American Diabetes Association 7

Hyperglycemic Hyperosmolar Nonketotic Coma (HHNK) Management

Special Considerations

• The American Diabetes Association, as reported in Diabetes Care, recommends against bicarbonate administration as it does not improve outcomes in patients with HHNK 9, 10
• For successful transition from intravenous to subcutaneous insulin, the American Association of Clinical Endocrinologists, as reported in Diabetes Care, suggests administering basal insulin 2-4 hours before stopping the intravenous insulin to prevent rebound hyperglycemia 10
• Identifying and treating any precipitating causes such as infection, myocardial infarction, or stroke is crucial, as recommended by the American Diabetes Association, as reported in Diabetes Care 9, 10

Treatment of Hyperglycemic Encephalopathy

Monitoring Requirements

• The American Diabetes Association recommends drawing blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, and osmolality to guide therapy and detect complications early 11
• Venous pH monitoring is adequate, and repeat arterial blood gases are generally unnecessary, as recommended by the American Diabetes Association 11

Insulin Therapy

• The American Diabetes Association suggests that continuous IV insulin infusion is the standard of care for critically ill patients, and sliding scale insulin alone should not be used 12

Critical Pitfalls to Avoid

• The American Diabetes Association advises against overly rapid correction of hyperglycemia and osmolality, as it increases the risk of cerebral edema, particularly in pediatric patients, and recommends not administering bicarbonate as it does not improve outcomes in HHS 11
• The American Diabetes Association recommends never starting insulin before excluding hypokalemia, as insulin drives potassium intracellularly and can precipitate life-threatening hypokalemia 11

Transition to Subcutaneous Insulin

• The American Diabetes Association recommends administering basal subcutaneous insulin 2-4 hours before discontinuing IV insulin infusion to prevent rebound hyperglycemia, with an overlap to prevent recurrence of hyperglycemia and metabolic decompensation 13

Management of Hyperosmolar Hyperglycemic State

Identification and Treatment of Precipitating Causes

• The American Diabetes Association recommends obtaining cultures and administering antibiotics if an infection is suspected, and treating common precipitating causes such as sepsis, myocardial infarction, and stroke simultaneously 14

Transition to Subcutaneous Insulin

• The American Diabetes Association suggests administering subcutaneous basal insulin 2-4 hours before discontinuing intravenous insulin infusion to prevent rebound hyperglycemia 14