Hyperosmolar Hyperglycemic State (HHS) Symptoms and Treatment
Hyperosmolar hyperglycemic state(HHS) is a serious acute metabolic complication of diabetes mellitus that is characterized by hyperglycemia (>600 mg/dl), hyperosmolarity (>330 mOsm/L) and, dehydration without ketosis or acidosis.
Hyperosmolar hyperglycemic state is the most serious complication in patients with type 2 diabetes mellitus and whenever it occurs, it is a medical emergency
It usually occurs in middle aged or elderly individuals with type 2 diabetes mellitus and it may be the presenting feature in around 25% of individuals.
HHS is the type 2 diabetes equivalent of diabetic ketoacidosis (DKA) in type 1 diabetes individuals. Its metabolic differences occur because in individuals with type 2 diabetes mellitus there is a small quantity of insulin remaining enough to suppress lipolysis and the associated acidosis.
This complication is more common is Afro-Caribbean.
HHS occurs less frequently when compared to diabetic ketoacidosis but once it occurs it has a higher mortality rate of about 15%.
What are the Precipitating causes of hyperosmolar hyperglycaemic state?
Hyperosmolar hyperglycemic state is not a disease per-se, but a consequence to another condition or an underlying pathology associated with an increase in the levels of the counter-regulatory hormones.
The most common precipitating causes for hyperosmolar hyperglycemic state are;
- Infection (The most common factor with the most commonly encountered infection being pneumonia and urinary tract infections),
- Myocardial infarction (Heart attack), stroke or trauma. These patients usually have an acute dramatic increase of stress hormone ‘cortisol’ and glucagon and an associated adrenaline levels.
- Drugs such as the use of diuretics
- Steroid medications
- Inadequate or reduced fluid intake
- Omission of oral hypoglycaemic drugs
- Insulin deficiency.
- Renal failure.
- States of increased glucagon, cortisol, and catecholamine levels (counteregulatory hormones) may cause uncontrolled hyperglycemia.
Hyperosmolar hyperglycaemic state may be complicated by thromboembolism or rhabdomyolysis (muscle breakdown).
Characteristics of hyperglycemic hyperosmolar state
Hyperosmolar hyperglycemic state is characterized by;
- Severe hyperosmolality,
- Hyperglycemia, and
- No ketoacidosis.
These features are in comparison with diabetic ketoacidosis that is characterized by hyperglycemia, dehydration, and acidosis because of an accumulation of ketone bodies in the blood.
The exact incidence of hyperosmolar hyperglycemic state is unknown but it is estimated that HHS accounts up to 1% of all hospital admissions in diabetic patients.
Hyperglycemic hyperosmolar state is more common in the elderly patients and the one with type 2 diabetes mellitus as compared to diabetic ketoacidosis that is more common in the young patients and ones with type 1 diabetes mellitus.
Its mortality rate is about 15-20% as compared to 2% mortality in patients with diabetic ketoacidosis.
Its outcome is usually dependent on the cause, degree of dehydration, underlying comorbidities and, the patient’s age.
Pathophysiology of Hyperosmolar Hyperglycemic State
The main triggers for hyperglycemic hyperosmolar state is a relative insulin deficiency and inadequate fluid intake. The state of insulin deficiency impairs glucose utilization in skeletal muscle and increases the production of glucose in the liver through glycogenolysis and gluconeogenesis process.
Failure of glucose entry to cells for utilization causes an increase in the levels of the counter-regulatory hormones(catecholamines) as a result of increased gluconeogenesis, hastened conversion of glycogen to glucose, and inadequate utilization of glucose by peripheral tissues due to insulin resistance.
High blood glucose level (hyperglycemia) causes osmotic diuresis that leads to intravascular volume depletion. Together with dehydration, the hydration status of the individual is exacerbated.
Since the insulin deficiency I hyperglycemic hyperosmolar state is relative and not absolute deficiency, there is no development of ketosis because the available insulin is sufficient to prevent production of ketone bodies. There is also a possibility that the liver is less capable of ketone body synthesis or the available insulin/glucagon ratio does not favor ketogenesis.
HHS is associated with lower levels of counterregulatory hormones and free fatty acids have than in DKA in some studies.
Patients who present with severe hyperglycemia have higher chances of developing osmotic diuresis, severe dehydration and polyuria. This leads to development of severe dehydration and the patient would eventually enter a hyperosmolar state. Due to this reason, patients in hyperosmolar hyperglycemic state usually have a much higher serum glucose level when compared to those with diabetic ketoacidosis.
Most of this glucose the sera of these patient is as a result of increased hepatic production of glucose.
Normally, a severe hyperglycemia draws water from the cells as a result of a created osmolar gradient leading to diuresis; therefore, these patients in hyperosmolar hyperglycemic state have severe dehydration, a contraction in the extracellular and the intracellular volume.
Diagnosis of Hyperosmolar Hyperglycemic State
The criteria for the diagnosis of hyperosmolar hyperglycemic state (HHS)syndrome can be summarized as:
- A marked plasma glucose concentration more than 600 mg/Dl,
- Hyperosmolarity (effective serum osmolality above 320 mOsm/L),
- An arterial pH above 7.3 (No acidosis),
- A serum bicarbonate concentration above 18 mEq/L,
- Absent urine or serum ketone bodies.
- Serum beta-hydroxybutyrate that is below 3 mmol/L,
- Patients may have a variable mental status but, most patients are in stupor coma.
- Prerenal azotemia.
- An anion gap is variable but a small anion-gap metabolic acidosis may be present secondary to increased production of lactic acid.
- Moderate ketonuria, if present, is secondary to starvation
The measured serum sodium may be normal or slightly low despite the marked hyperglycemia. The corrected serum sodium is usually increased.
Clinical Features a Patient with of Hyperosmolar Hyperglycemic State
Patients who develop hyperosmolar hyperglycemic state syndrome have an altered mental status such as stupor and coma.
Features of dehydration such as tachycardia, hypotension, sunken eyes, decreased skin turgor are present secondary to the severe dehydration.
If the underlying cause of HHS is a myocardial infarction, the patient may present with arrhythmia or other cardiac rhythms different from sinus tachycardia.
These patients may also present with:
- Rales on chest auscultation
- Dullness to chest percussion
- Bronchial breathing sounds
- Change in the urine color
These patients will present with features of predisposing factors or the underlying disease condition such as features of pneumonia and urinary tract infections.
Diabetic patients who present with polyuria, may have an associated severe dehydration.
A stroke patient who has hyperosmolar hyperglycemic state may develop some lateralizing signs in response to pain.
Nausea, vomiting, and abdominal pain and the Kussmaul type of respirations are notably absent but present in diabetic ketoacidosis.
Like mentioned above, HHS is often precipitated by a serious, concurrent illness such as myocardial infarction or stroke. Sepsis, pneumonia, or any other serious infections are frequent precipitants and should be ruled out.
Diagnostics and Diagnostic Workup
Suspected patients who present with a coma should have their plasma glucose levels checked to exclude hypoglycemia and hyperglycemia.
Arterial blood gases analysis is indicated to rule out acidosis. Usually patients with hyperosmolar hyperglycemic state have a PH of above 7.3 and serum bicarbonate levels are above 18 mEq/L.
Determine effective serum osmolality, by calculating using the formula: 2 (Na) + 18/glucose.
Serum electrolyte levels. Evaluation of serum electrolytes should be done to determine the concentration of sodium because these are the two main constituents in the serum that affect the osmolar gradient.
Kidney function tests should be done to find out the nature and severity of present electrolyte derangements.
Complete blood count to identify the likelihood of inflammation shown by an elevated white blood cells.
A blood cultures and acute phase reactants assays are performed to check for the source of infection.
Treatment of Hyperosmolar Hyperglycemic State
The management hyperosmolar hyperglycemic states is similar to the treatment of diabetic ketoacidosis with rehydration therapy and electrolyte replacement together with intravenous insulin.
The management is divided into three sections
- Treatment of underlying precipitating factor
- Insulin therapy and
These patients will need to be admitted and managed as inpatients.
Rehydration to correct the volume depletion is key. This is because in HHS, fluid losses and dehydration are usually more pronounced than in DKA because of a longer duration of the illness.
Fluid replacement should initially stabilize the hemodynamic status of the patient by administering 500–3000 L of 0.9% normal saline over the first 2–4 hours of admission.
Because the fluid deficit in HHS is accumulated over a longer duration, the rate of reversing the hyperosmolar state must balance the need for free water repletion. This is usually associated with a risk that too rapid a reversal may worsen the patient’s neurologic function.
If the serum sodium levels of the patient is more than 150 mmol/L, then 0.45% saline should be used for rehydration.
A careful monitoring of the patient’s fluid status, laboratory values, and insulin infusion rate is crucial.
After hemodynamic stability is achieved, the IV fluid administration is directed at reversing the free water deficit using hypotonic fluids (0.45% saline initially, then 5% dextrose in water [D5W]).
The calculated free water deficit (which averages 9–10 L) should be reversed over the next 1–2 days (infusion rates of 200–300 mL/h of hypotonic solution).
Potassium repletion is usually necessary and should be dictated by repeated measurements of the serum potassium. In patients taking diuretics, the potassium deficit can be quite large and may be accompanied by magnesium deficiency.
Hypophosphatemia may occur during therapy and can be improved by using KPO4 and beginning nutrition.
Treatment of precipitating factor
Identify and treat the underlying or precipitating factor aggressively.
Rehydration and volume expansion lowers the plasma glucose initially, but also insulin is required.
This insulin regimen begins with administration of intravenous insulin bolus of 0.1 unit/kg followed by intravenous insulin at a constant infusion rate of 0.1 unit/kg per hour until glucose level is below 250mg/dL.
Insulin infusion rate is increased twofold if the serum glucose levels do not fall as expected.
As in DKA, glucose should be added to IV fluid when the plasma glucose falls to 11.1–13.9 mmol/L (200–250 mg/dL), and the insulin infusion rate should be decreased to 0.02–0.1 unit/kg per hour.
The insulin infusion should be continued until euglycemia and the patient has resumed eating then can be transferred to a subcutaneous insulin regimen.
Heparin is usually administered because of the high risk of thromboembolic events
Management of HHS in children
In children fluid therapy is started first and insulin should not be administered as a bolus initially/ Insulin infusion is started only if the blood glucose levels don not normalize with fluids alone. Then the insulin dose of 0.025 to 0.05 units per kg per hour are administered. If these children develop hyperosmolar diabetic ketoacidosis, then the insulin dose should be increased to 0.05 to 0.1 units per kg per hour
Children should receive fluid therapy at 20ml/kg in bolus and repeated until adequate tissue perfusion is achieved.
Dantrolene may also be required in the induction of muscle relaxation.