creation date: 2025-11-28 09:19
tags: Pathologies
Hyperosmolar Hyperglycemic State
Background
Definitions
Hyperosmolar hyperglycemic state (HHS) is one of two conditions representing hyperglycemic crises, the other being diabetic ketoacidosis. HHS is also known as hyperosmotic hyperglycemic nonketotic state (HHNK). HHS is a life-threatening emergency.
Etiology
The predisposing factor of HHS is diabetes mellitus, however, it is much more common in patients with type 2 diabetes.
While well controlled diabetes rarely precipitates HHS, certain conditions may cause HHS. These include:
- Infection (50-60%)
- Medications (eg. thiazide diuretics, beta-blockers, glucocorticoids, atypical antipsychotics)
- Cardiovascular insults
- Stress response
Pathogenesis
Hyperosmolar hyperglycemic state occurs as a result of a deficiency in insulin.
Precipitation of hyperglycemia and hyperosmolality
A deficiency in insulin results in decreased glucose utilization by the peripheral tissue. A state of tissue “starvation” results in activation of counterregulatory hormones (eg. glucagon) which stimulates gluconeogenesis and glycogenolysis.
These factors result in a markedly high serum glucose is reflected in high plasma osmolality. This pulls water out of cells and expands extracellular fluid, resulting in hyponatremia.
Osmotic diuresis causes volume depletion and associated loss of electrolytes. In the most extreme cases, acute kidney injury and hypovolemic shock can occur.
Mild generation of ketones
As insulin is still present, albeit at a lower level, the generation of ketone bodies is minimal (insulin inhibits ketogenesis). Ketonemia and acidemia, if any at all, are often mild.
Clinical Presentation
Signs & Symptoms
Findings are consistent with hyperglycemia:
- Polyuria
- Polydipsia
- Recent weight loss
- Nausea and vomiting
- Signs of dehydration
- Neurological abnormalities (AMS, lethargy, coma, blurred vision, weakness)
Mental status is often altered due to hyperosmolality affecting neurologic function. Onset is often insidious (over the course of days to week).
History & Physical Exam
History and physical should be rapidly completed including an ABCDE approach with volume status assessment.
A few components to note include:
- Mental status
- Possible precipitating events (eg. source of infection, MI)
- Volume status
Presentation of a precipitating factor may be present:
- Signs of infection
- Chest pain/cardiac symptoms
A neurologic assessment should be made as severe dehydration can reduce cerebral blood flow.
Risk factors
Diagnosis
Criteria
- Hyperosmolality (effective serum osmolality >300 mOsm/kg or total serum osmolality >320 mOsm/kg)
Work-up
Initial evaluation consist of laboratory studies:
- Serum glucose
- Serum electrolytes (calculate anion gap), blood urea nitrogen, plasma creatinine
- CBC with differential
- Urinalysis and urine ketones by dipstick
- Plasma osmolality
- Serum beta-hydroxybutyrate
ABG or VBG should be obtained if serum bicarbonate is substantially reduced, with an ABG preferred if hypoxia is suspected. Additionally, an ECG should be obtained.
Differential
Red Flags / Complications
Complications of HHS include:
- Coma
- Seizures
- Stroke
The primary complications of insulin therapy are:
- Hypoglycemia
- Hypokalemia
In some cases, the following can develop:
- Cerebral edema
- Hyperchloremic acidosis (due to isotonic saline)
- Noncardiogenic pulmonary edema
Management
Fluid replacement
IV normal saline or lactated Ringer should be used. Fluid replacement is used to correct hypovolemia and hyperosmolality.
Reduction of osmolality should be approached with caution as rapid reduction can precipitate cerebral edema. Fluid and insulin therapy should be titrated to achieve the following:
- Reduce serum glucose ≤5-6.7 mmol/L per hour
- Reduce serum sodium ≤10 mmol/L over 24 hours
- Reduce plasma osmolality ≤3-8 mOsm/kg per hour
In patients with hypovolemic shock, isotonic fluid should be infused as quickly as possible.
In patients without shock, heart failure, or kidney failure, isotonic fluid is infused at a rate of 500-1000 mL/hr for first few hours.
After 2-3 hours of infusion, hypotonic fluid may be used in place of isotonic saline if sodium concentration is ≥135 mEq/L. It should be noted that sodium concentration must be corrected for degree of hyperglycemia (add 2 mEq/L for each 5.5 mmol/L elevation of glucose over 5.5 mmol/L).
For patients with kidney or cardiac function impairment, care must be given to avoid iatrogenic fluid overload. Small-volume boluses may be preferred over continuous infusion.
Insulin therapy
The exact timing of insulin therapy can vary by clinician preference, with some beginning insulin after glucose levels stabilize following fluid replacement. However, if serum potassium is ≥3.5, insulin is typically indicated immediately.
In general, IV regular insulin is the recommended choice (absence of acidosis and ketonemia is mild or absent).
- 0.05 units/kg per hour
Once glucose falls below 13.9 mmol/L:
- Add 5-10% dextrose to IV fluids
- Decrease insulin rate to 0.02-0.04 units/kg per hour
Note that subcutaneous insulin is not recommended due to the increased risk of excessive and rapid fall in serum glucose.
Electrolyte correction
Electrolytes are repleted as necessary.