What is Hyperosmolar Hyperglycemic State (HHS)?

From the Guidelines

HHS stands for Hyperosmolar Hyperglycemic State, a serious complication of diabetes characterized by extremely high blood sugar levels (typically above 600 mg/dL), severe dehydration, and altered mental status without significant ketoacidosis, as defined in the most recent guidelines 1.

Definition and Characteristics

HHS occurs predominantly in older adults with type 2 diabetes. The diagnostic criteria for HHS include blood glucose >600 mg/dl, arterial pH >7.3, bicarbonate >15 mEq/l, mild ketonuria or ketonemia, and effective serum osmolality >320 mOsm/kg H2O, as outlined in previous studies 1.

Treatment Approach

Treatment requires immediate hospitalization for aggressive fluid replacement with normal saline, insulin therapy, and electrolyte management, particularly potassium, phosphate, and magnesium, as recommended in recent guidelines 1. The underlying cause must be identified and treated, which often includes infection, medication non-compliance, or other acute illness.

Management Goals

Management goals include restoration of circulatory volume and tissue perfusion, resolution of hyperglycemia, and correction of electrolyte imbalance and ketosis, as stated in previous studies 1.

Insulin Therapy

In critically ill and mentally obtunded patients with DKA or HHS, continuous intravenous insulin is the standard of care, as noted in the most recent guidelines 1. However, there is no significant difference in outcomes for intravenous regular insulin versus subcutaneous rapid-acting analogs when combined with aggressive fluid management for treating mild or moderate DKA, as reported in previous studies 1.

Key Considerations

HHS develops gradually as hyperglycemia leads to osmotic diuresis, causing profound dehydration and electrolyte imbalances. Without the ketone production seen in diabetic ketoacidosis, patients may not seek treatment until severely ill, contributing to its high mortality rate of 10-20%, as highlighted in the example answer. Some key points to consider in the treatment of HHS include:

• Aggressive fluid replacement to restore circulatory volume and tissue perfusion
• Insulin therapy to resolve hyperglycemia
• Electrolyte management to correct imbalances and prevent complications
• Identification and treatment of the underlying cause of HHS
• Close monitoring of the patient's condition and adjustment of treatment as needed, as recommended in the most recent guidelines 1.

From the Research

Definition and Characteristics of Hyperosmolar Hyperglycemic State (HHS)

• Hyperosmolar Hyperglycemic State (HHS) is a serious acute complication of diabetes decompensation, especially in type 2 diabetes (T2DM), with critical prognosis 2.
• Primary characteristics of HHS include extreme hyperglycemia, severe dehydration, plasma hyperosmolarity, frequent disorders of consciousness, and absent or minimum ketoacidosis 2.
• HHS is a life-threatening emergency manifested by marked elevation of blood glucose and hyperosmolarity with little or no ketosis 3.

Causes and Precipitating Factors of HHS

• The most frequent cause of HHS is serious cardiovascular disease, acute stroke, particularly genitourinary and/or respiratory infections, conditions preventing the patient from adequate water intake during osmotic diuresis, the consequences of inappropriate medication therapy, social conditions, and often the first manifestation especially in type 2 diabetes 2.
• Underlying infections are the most common precipitating causes of HHS, while other causes include certain medications, nonadherence to therapy, undiagnosed diabetes mellitus, substance abuse, and coexisting disease 3.

Clinical Features and Diagnosis of HHS

• Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg, marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L 4.
• HHS is diagnosed by an elevated glucose, elevated serum osmolality, minimal or absent ketones, and a neurologic abnormality, most commonly altered mental status 5.

Treatment and Management of HHS

• Treatment of HHS involves fluid resuscitation, correction of electrolyte abnormalities, and insulin therapy 6, 3, 4.
• The aims of therapy are to improve clinical status, replace fluid losses, gradual decline in osmolality, and prevent hypoglycaemia and hypokalaemia 4.
• HHS resolution criteria include osmolality <300 mOsm/kg, hypovolaemia corrected, cognitive status returned to pre-morbid state, and blood glucose <15 mmol/L 4.