Hyperglycemic Hyperosmolar State in Children

Background

• Hyperosmolar hyperglycemic state (HHS) is a metabolic emergency occurring in patients with diabetes mellitus.
• HHS is usually characterized by extremely elevated serum glucose, increased osmolality, significant dehydration, and minimal ketoacidosis.
• HHS is less common than diabetic ketoacidosis (DKA), and occurs more often in type 2 diabetes, but can occur in children with type 1 diabetes.
  • Both HHS and DKA are due to an insulin deficiency that impairs glucose utilization and results in hyperglycemia, but insulin levels in HHS usually are sufficient to prevent ketogenesis.
  • Both HHS and DKA are often precipitated by unrecognized new-onset diabetes mellitus, medication noncompliance in patients with known diabetes, concurrent infection, or other physiologic stressors.
• The goal of prompt recognition and treatment of HHS is to prevent serious complications such as thrombosis, cerebral edema, rhabdomyolysis, renal failure, and death. HHS has a high mortality rate.

Evaluation

• Clinical presentation of hyperosmolar hyperglycemic state (HHS) overlaps with diabetic ketoacidosis (DKA), and includes gradual development (over days to weeks) of polyuria, polydipsia, weight loss, weakness, and mental status changes.
• Check bedside glucose, and if very elevated, obtain subsequent testing:
  • first check
    • serum glucose, electrolytes, blood urea nitrogen (BUN), creatinine, beta-hydroxybutyrate (serum ketones), and complete blood count
    • arterial (or venous) blood gas
    • urinalysis, urine ketones
  • if serum glucose > 600 mg/dL and no acidosis, check osmolality
  • urine, blood, or throat culture if infection suspected
• Diagnostic criteria - serum glucose > 600 mg/dL (33 mmol/L), effective serum osmolality > 320-330 mOsm/kg, arterial pH > 7.3 or venous pH > 7.25, serum bicarbonate > 15 mEq/L (15 mmol/L), and little or no ketonemia and ketonuria
• Follow-up testing may include:
  • creatinine kinase to assess for rhabdomyolysis
  • urine, throat, and blood cultures if an infection is suspected

Management

• Admit children with hyperosmolar hyperglycemic state (HHS) to intensive care for close monitoring, including continuous cardiac monitoring, hourly clinical assessments, and frequent blood testing.
• Provide fluid resuscitation (Strong recommendation).
  • Give 0.9% saline 20 mL/kg IV bolus and repeat until peripheral perfusion is restored.
  • Once perfusion is restored, change to 0.45%-0.75% saline IV at a rate sufficient to provide maintenance fluids plus replacement of fluid deficit over 24-48 hours. (Assume a fluid deficit of 12%-15% of body weight.)
  • Adjust the fluid composition and rate based on hemodynamic status and frequent blood testing, targeting a 75-100 mg/dL/hour (4.1-5.5 mmol/L/hour) decrease in serum glucose and a 0.5 mEq/L/hour decrease in serum sodium.
• Provide potassium replacement if potassium is < 5 mEq/L (establish adequate renal function first), and consider magnesium replacement in children with low magnesium and hypocalcemia.
• Give insulin by continuous IV infusion.
  • In children without significant ketosis or acidosis (most children with HHS), consider starting insulin only when the rate of decrease in serum glucose is < 50 mg/dL/hour (2.7 mmol/L/hour) with IV fluids alone (Weak recommendation). Start insulin at 0.025-0.05 units/kg/hour and titrate to achieve a 50-75 mg/dL/hour (2.7-4.1 mmol/L/hour) decrease in serum glucose.
  • In children with concomitant diabetic ketoacidosis (DKA), start insulin at 0.05-0.1 units/kg/hour immediately after initial fluid boluses and manage as for DKA (Strong recommendation).
• In children with a fever and increasing creatinine kinase levels, consider dantrolene to treat a malignant hyperthermia-like syndrome associated with HHS (Weak recommendation).
• Follow-up after resolution should include review of current home insulin plans and reinforcement of diabetes management while sick to prevent recurrences.