What is the treatment for Hyperosmolar Hyperglycemic State (HHS)?

From the Guidelines

The treatment for Hyperosmolar Hyperglycemic State (HHS) should focus on aggressive fluid replacement, insulin therapy, and addressing underlying causes, with continuous intravenous insulin infusion being the standard of care in critically ill patients, as recommended by the most recent guidelines 1. The initial management requires immediate intravenous fluid resuscitation with normal saline (0.9% NaCl) at 15-20 mL/kg/hr for the first hour, then adjusted based on hemodynamic status.

• After the first 1-2 liters, switch to 0.45% saline if serum sodium is normal or elevated.
• Insulin therapy should begin with an IV bolus of regular insulin at 0.1 units/kg followed by continuous infusion at 0.1 units/kg/hr, titrated to reduce glucose by 50-70 mg/dL per hour.
• Once glucose reaches 250-300 mg/dL, add dextrose to IV fluids while continuing insulin to prevent hypoglycemia.
• Potassium replacement is crucial when levels fall below 5.2 mEq/L, typically giving 20-30 mEq/L in IV fluids.
• Phosphate replacement may be needed if levels are below 1 mg/dL. Throughout treatment, monitor electrolytes, glucose, renal function, and mental status hourly. Identifying and treating the precipitating cause (often infection, medication non-adherence, or acute illness) is essential for complete resolution, as emphasized in recent guidelines 1. HHS requires this aggressive approach because of its high mortality rate (10-20%) and the severe dehydration (often 8-12 liters) and hyperglycemia (typically >600 mg/dL) that characterize this condition. The use of bicarbonate is generally not recommended, as it has been shown to make no difference in the resolution of acidosis or time to discharge 1. Successful transition from intravenous to subcutaneous insulin requires administration of basal insulin 2–4 h before the intravenous insulin is stopped to prevent recurrence of ketoacidosis and rebound hyperglycemia, as highlighted in the latest standards of care 1.

From the Research

Treatment Overview

The treatment for Hyperosmolar Hyperglycemic State (HHS) involves a multi-step approach to address the severe dehydration, hyperglycemia, and electrolyte imbalances that characterize this condition. The primary goals are to restore circulating volume, gradually reduce blood glucose levels, and prevent complications such as cerebral edema and hypokalemia.

Key Components of Treatment

• Fluid Replacement: The use of intravenous (IV) 0.9% sodium chloride solution is recommended to restore circulating volume and reverse dehydration 2, 3, 4, 5. The amount of fluid replacement can vary, with adults typically requiring an average of 9 L of 0.9% saline over 48 hours 4.
• Insulin Administration: Insulin therapy should be initiated once the patient's osmolality stops falling with fluid replacement alone, unless there is significant ketonaemia 2, 3. The initial dose and infusion rate may vary, but a common approach is to start with a bolus of 0.1 units of regular human insulin per kg of body weight, followed by a continuous infusion of 0.1 units per kg per hour 4, 5.
• Electrolyte Replacement: Potassium replacement is crucial to prevent hypokalemia, and the rate of replacement should be guided by the patient's potassium levels 3, 4, 5.
• Glucose Monitoring and Management: Blood glucose levels should be closely monitored, and the goal is to achieve a gradual decline in glucose levels to prevent hypoglycemia and other complications 2, 3, 4.
• Identification and Treatment of Underlying Causes: It is essential to identify and treat the underlying precipitating causes of HHS, such as infections, certain medications, or non-adherence to therapy 2, 3, 4, 5.

Monitoring and Prevention of Complications

• Osmolality Monitoring: Regular measurement of serum osmolality is necessary to monitor the response to treatment and adjust the rate of fluid replacement and insulin administration as needed 2, 3.
• Prevention of Cerebral Edema: In children and adolescents, dehydration should be corrected at a rate of no more than 3 mOsm per hour to avoid cerebral edema 4.
• Prevention of Hypoglycemia and Hypokalemia: Close monitoring of blood glucose and potassium levels is necessary to prevent these complications, and adjustments to insulin and potassium replacement should be made as needed 3, 4, 5.