Hyperosmolar hyperglycemic state

Hyperosmolar hyperglycemic state (HHS) is a complication of diabetes mellitus (predominantly type 2) in which high blood sugars cause severe dehydration, increases in osmolarity (relative concentration of solute) and a high risk of complications, coma and death. It is diagnosed with blood tests. It is related to diabetic ketoacidosis (DKA), another complication of diabetes more often (but not exclusively) encountered in people with type 1 diabetes; they are differentiated with measurement of ketone bodies, organic molecules that are the underlying driver for DKA but are usually not detectable in HHS.

The treatment of HHS consists of correction of the dehydration with intravenous fluids, reduction of the blood sugar levels with insulin, and management of any underlying conditions that might have precipitated the illness, such as an acute infection.

Older names for HHS are hyperosmolar non-ketotic coma (HONK), nonketotic hyperosmolar coma, hyperosmolar hyperglycemic nonketotic syndrome (favoured by the American Diabetes Association).^[1]

Signs and symptoms

According to the consensus statement published by the American Diabetes Association, diagnostic features of HHS may include the following:

• Plasma glucose level >600 mg/dL (>30 mmol/L)
• Serum osmolality >320 mOsm/kg
• Profound dehydration, up to an average of 9L (and therefore substantial thirst (polydipsia))
• Serum pH >7.30
• Bicarbonate >15 mEq/L
• Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3 mmol/L)
• Some alteration in consciousness

Additionally it may also lead to:

• Neurologic signs including focal signs such as sensory or motor impairments or focal seizures or motor abnormalities, including flaccidity, depressed reflexes, tremors or fasciculations.
• Hyperviscosity and increased risk of blood clot formation

Diagnosis

The major differential diagnosis is diabetic ketoacidosis (DKA). In contrast to DKA, serum glucose levels in HHS are extremely high, usually greater than 40-50 mmol/L, but an anion-gap metabolic acidosis is absent or mild. Altered mental status is also more common in HHS than DKA. Although traditionally DKA has been associated with Type I Diabetes, whereas HHS has been associated with Type II, HHS can be seen in patients of both types. HHS also tends to have an elderly preponderance.

Cranial imaging is not used for diagnosis of this condition. However, if MRI is performed, it may show cortical restricted diffusion with unusual characteristics of reversible T2 hypointensity in the subcortical white matter.^[2]

Pathophysiology

Nonketotic coma is usually precipitated by an infection,^[3] myocardial infarction, stroke or another acute illness. A relative insulin deficiency leads to a serum glucose that is usually higher than 33 mmol/l (600 mg/dl), and a resulting serum osmolarity that is greater than 320 mOsm. This leads to excessive urination (more specifically an osmotic diuresis), which, in turn, leads to volume depletion and hemoconcentration that causes a further increase in blood glucose level. Ketosis is absent because the presence of some insulin inhibits hormone-sensitive lipase mediated (fat tissue breakdown).

Management

Intravenous fluids

Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12  liters. Attempts to correct this usually take place over 24 hours with initial rates of normal saline often in the range of 1 L/h for the first few hours.^[4]

Electrolyte replacement

Severe potassium deficits often occur in HHS. They usually range around 350 mEq in a 70 kg person. This is generally replaced at a rate 10 mEq per hour as long as there is urinary output.^[5]

Insulin

Insulin is given to reduce blood glucose concentration; however, as it also causes the movement of potassium into cells, serum potassium levels must be sufficiently high or dangerously low blood potassium levels may result. Once potassium levels have been verified to be greater than 3.3 mEq/l, then an insulin infusion of 0.1 units/kg is begun.^[6]

References