Definition

• Significant hyperglycemia in the absence of ketosis, with hyperosmolality and mental status changes.
• Most often in type 2 diabetics, but approximately 30% of patients ages 65 and above presenting with HONKC/HHS do not have prior history of diabetes.
• Mortality 15%, given the incidence in the elderly who often have comorbidities, with insidious onset and delayed presentation.

Etiologies

• Pathogenesis is similar to DKA (ineffective/decreased insulin, elevation of glucagon, catecholamines, cortisol, growth hormone, and inability of glucose to enter cells) with some exceptions.
  • Enough insulin to prevent lipolysis (therefore no ketones).
  • Greater dehydration.
  • Smaller increase in counter-regulatory hormones.
• Precipitating events are infection, MI, CVA, intoxication/ingestion (often cocaine), pancreatitis, med non-adherence, and medications (e.g. corticosteroids, thiazides, sympathomimetic agents and second-generation antipsychotics).

• Symptoms/signs: polyuria and polydipsia with resulting dehydration, weakness, nausea/vomiting, abdominal pain, tachycardia, hypotension, confusion (often when serum osm >310 mOsm/L), stupor or coma (often when serum osm >330 mOsm/L).
• Labs: severe hyperglycemia (often as high as >600 mg/dL), hyperosmolality, pseudohyponatremia (often hypernatremia when adjusted for hyperglycemia), prerenal azotemia, no ketoacidosis.
• Relevant formulas:
  • Corrected sodium = measured sodium + 2.4 x (plasma glucose – 100)/100.
  • Anion gap = Na – (Cl + HCO3) (use measured Na level).
  • Calculated osmolality = 2 (Na + K) + glucose/18 + BUN/2.8. Coma may occur when the calculated osmolality >330 mg/dL

Management

• Treat similarly to DKA, with mainstays of therapy being fluids, an insulin drip, and careful monitoring and repletion of electrolytes.
• Send initial labs, if not already done in the emergency department: CBC, BMP, Mg, Phos, serum ketones (β-hydroxybutyrate), serum osm, UA, ABG, HbA1C. Evaluate for precipitating event.
• Keep patient NPO initially.
• Monitor I/O’s q 2 hours, and check electrolytes q 2 hours x 3, then q 4 hours.
• Volume resuscitation: fluid deficit often 6-10 liters. Replete with 1L/hr x 2-4 hours to start.
• Give NS initially, once the patient is euvolemic or near euvolemic switch to ½ NS if the corrected sodium is greater than 150 meq/L.
• Change to D5NS or D5½NS when BG <250 mg/dL. This decreases the risk of hypoglycemia and of cerebral edema from too rapid a decline in serum glucose.
• Watch for volume overload and pulmonary edema. (not associated with cerebral edema).
• Potassium replacement: K is less depleted than in DKA because of the absence of acidosis, but insulin therapy still makes some repletion necessary.
• Insulin: loading dose of 0.1 unit/kg IV push, followed by a maintenance drip of 0.1U/kg/hr (or conservatively 5 units/hour for many patients). Goal is to decrease glucose by 50-70 mg/hr. For insulin infusions, see your hospital-specific standardized protocol.
• Once glycemic control has been attained, convert the insulin infusion to subcutaneous insulin. See Endocrinology: Inpatient Diabetes Guidelines.

Key Points

• Look for precipitating factors when evaluating a patient with HONKC/HSS.
• Pathogenesis and treatment are similar to DKA. However, patients are generally less acidotic and more volume depleted.

Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32(7):1335.

Kitabchi AE. Hyperglycemic crises in diabetes mellitus: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am 2006;35(4):725-51