From the Guidelines
Hyperglycemic hyperosmolar state (HHS) is a serious diabetic emergency that requires immediate treatment with aggressive fluid resuscitation and insulin therapy to prevent morbidity and mortality. The most recent and highest quality study, 1, recommends continuous intravenous insulin infusion as the standard of care for critically ill and mentally obtunded patients with HHS.
Key Components of Treatment:
- Aggressive fluid resuscitation with normal saline at 15-20 mL/kg in the first hour, followed by continued IV fluids based on hemodynamic status
- Insulin therapy initiated with an IV bolus of regular insulin at 0.1 units/kg, followed by a continuous infusion at 0.1 units/kg/hour
- Electrolyte replacement, particularly potassium, as levels will drop with insulin therapy
- Blood glucose monitoring hourly, aiming for a gradual decrease of 50-75 mg/dL per hour, with adjustment to insulin rates as needed
- Identification and addressing of underlying causes such as infection, medication effects, or other precipitating factors
Important Considerations:
- HHS carries a mortality rate of 10-20%, significantly higher than diabetic ketoacidosis, primarily due to the advanced age and comorbidities of affected patients, as well as the profound dehydration that can lead to thrombosis, rhabdomyolysis, and multiorgan failure if not promptly treated, as noted in 1
- Recent studies have reported that the administration of a low dose of basal insulin analog in addition to intravenous insulin infusion may prevent rebound hyperglycemia without increased risk of hypoglycemia, as seen in 1
- The use of bicarbonate in people with DKA or HHS is generally not recommended, as it made no difference in the resolution of acidosis or time to discharge, as stated in 1
From the FDA Drug Label
Hyperglycemia, diabetic ketoacidosis, or hyperosmolar coma may develop if the patient takes less Humulin R U-100 than needed to control blood glucose levels Severe sustained hyperglycemia may result in hyperosmolar coma or death
The patient is at risk for hyperosmolar coma if they take less insulin than needed to control blood glucose levels, and severe sustained hyperglycemia may result in hyperosmolar coma or death 2.
From the Research
Definition and Diagnosis of Hyperglycemic Hyperosmolar State
- Hyperglycemic hyperosmolar state is a life-threatening emergency characterized by marked elevation of blood glucose and hyperosmolarity with little or no ketosis 3, 4, 5, 6.
- Diagnosis is based on elevated glucose, elevated serum osmolality, minimal or absent ketones, and a neurologic abnormality, most commonly altered mental status 4, 5, 6.
- Serum osmolality is calculated using the formula [(2×Na+ ) + glucose+urea] and is typically ≥320 mOsm/kg in HHS 5.
Clinical Features and Precipitating Causes
- Clinical features of HHS include profound dehydration, neurologic symptoms ranging from lethargy to coma, and marked hypovolaemia 3, 5.
- Precipitating causes of HHS include underlying infections, certain medications, nonadherence to therapy, undiagnosed diabetes mellitus, substance abuse, and coexisting disease 3, 6.
- In children and adolescents, HHS is often present when type 2 diabetes is diagnosed 3.
Treatment and Management
- Treatment involves fluid resuscitation, correction of electrolyte abnormalities, and insulin therapy 3, 4, 5, 6.
- Fluid replacement should be aggressive, with an average of 9 L of 0.9% saline over 48 hours in adults, and caution should be exercised in the elderly 3, 5.
- Insulin therapy should be started once osmolality stops falling with fluid replacement, unless there is ketonaemia, and should be administered as a fixed rate intravenous insulin infusion (FRIII) 5.
- Potassium replacement should be according to potassium levels, and glucose infusion should be started once glucose <14 mmol/L 5.
- Underlying precipitants must be identified and treated, and prevention of harm (VTE, osmotic demyelination, fluid overload, foot ulceration) is crucial 5.