Hyperglycemic Hyperosmolar State (HHS)

How to Cite This Chapter: Steen O, Rodríguez-Gutiérrez R, Vélez-Viveros CA, Portillo-Sánchez P, Quintanilla-Siller A, Lavalle-Gonzalez FJ, Sieradzki J, Płaczkiewicz-Jankowska E. Hyperglycemic Hyperosmolar State (HHS). McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.13.3.2. Accessed October 20, 2021.
Last Updated: March 20, 2021
Last Reviewed: March 20, 2021
Chapter Information

Definition, Etiology, PathogenesisTop

Hyperglycemic hyperosmolar state (HHS) is a hyperglycemic emergency that shares a number of characteristics with diabetic ketoacidosis (DKA). However, unlike DKA, where the ketoacidosis is prominent, the major features of HHS are volume depletion and hyperosmolarity. HHS was previously referred to as hyperosmolar nonketotic coma (HONKC), but this term was abandoned since the majority of patients do not in fact present with a coma.

HHS is characterized by severe hyperglycemia, increased plasma osmolality, dehydration, and often prerenal azotemia. Despite the marked hyperglycemia, little or no ketosis or acidosis is typically observed. This is explained by higher endogenous insulin levels and lower counterregulatory hormone levels (particularly glucagon, cortisol, and growth hormone) in HHS compared with patients with DKA.

HHS develops mainly in patients with type 2 diabetes mellitus and may occur as a first manifestation of the disease. Precipitating factors include omission or errors of insulin therapy, acute infection (eg, urinary tract infection or pneumonia), cardiovascular or respiratory event (eg, myocardial infarction, stroke, or pulmonary embolism [PE]), cardiac or other surgery, abdominal crisis (eg, pancreatitis), thyrotoxicosis, trauma, drugs (eg, atypical antipsychotic agents, cocaine, diuretic agents, glucocorticoids, lithium, possibly interferon, sodium-glucose cotransporter 2 [SGLT-2] inhibitors), and excessive alcohol consumption.

The prognosis in HHS is markedly worse compared with DKA.

Clinical FeaturesTop

Signs and symptoms of HHS are very similar to those of DKA, although in HHS there is more marked volume depletion and decreased level of consciousness (proportional to the serum osmolality). HHS may also present with more neurologic symptoms, such as seizures and stroke-like symptoms. These are reversible once the hyperosmolality resolves. In HHS the symptoms present more insidiously (over several days) compared with DKA (<1-2 days), resulting in more severe hyperglycemia (often ≥34 mmol/L [612 mg/dL]), higher serum osmolality (>320 mOsm/kg), and more profound dehydration. All these contribute to the decreased level of consciousness. As mentioned, minimal ketosis is observed with HHS (in contrast to DKA). In addition, compared with DKA, patients with HHS do not generally develop hyperventilation (Kussmaul breathing) or abdominal pain. Inadequate fluid intake is commonly seen in HHS, particularly in older individuals with impaired thirst mechanisms.

Symptoms include manifestations of the precipitant disease as well as impaired mental status to coma.

Signs include tachycardia, tachypnea, low jugular venous pressure, features of extreme dehydration, and hypotension. Neurologic signs, such as abnormal movements, seizures, hemiparesis, and hemianopia, may occur.

DiagnosisTop

The initial evaluation is the same as in DKA. Diagnosis is based on laboratory test results and clinical features (Table 6.2-7).

Differential Diagnosis

The differential diagnosis of HHS includes DKA with concomitant hyperosmolality, coma due to a primary neurologic condition, hepatic or uremic coma (or other metabolic coma), poisoning or drug intoxication, and dehydration secondary to other causes (eg, diabetes insipidus, excessive use of diuretics).

TreatmentTop

1. Fluid resuscitation: Similarly to DKA, fluid resuscitation therapy is considered the most critical part of treatment in HHS, due to the severe dehydration. The estimated water deficit is ~100 to 200 mL/kg of body weight. The rate of correction of blood glucose should not exceed 2.8 to 3.9 mmol/L/h due to the risk of cerebral edema with rapid reductions in osmolality.

Consider the following starting points for a reasonable regimen of fluid resuscitation (to be used with caution in patients with cardiovascular disease [CVD] or renal disease and in the elderly):

1) Administer 1000 mL of 0.9% NaCl IV over the first hour in severe hypovolemia.

2) Administer 500 mL/h of 0.45% NaCl (if corrected serum [Na+] is normal or elevated) or 0.9% NaCl (if corrected serum [Na+] is low) IV for the subsequent 4 to 6 hours.

3) Administer 250 mL/h of 0.45% or 0.9% NaCl until correction of water deficit is achieved.

4) When serum glucose reaches ≤11.1 mmol/L (200 mg/dL), change to 5% glucose (dextrose) with 0.45% NaCl at a rate of 150 to 250 mL/h.

5) In patients with heart failure it may be necessary to reduce the infusion rates.

6) In case of hypotension use 0.9% NaCl or a balanced isotonic (crystalloid) solution.

2. Reduce hyperglycemia: Start IV insulin (use regular insulin)Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due the risk of bias, imprecision, indirectness, and lack of further recent studies. Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by various routes. N Engl J Med. 1977 Aug 4;297(5):238-41. PubMed PMID: 406561.:

1) Start with an IV bolus of 0.1 IU/kg followed by a continuous insulin infusion at a rate of 0.1 IU/kg/h.

2) When glucose level decreases to ≤15 mmol/L [270 mg/dL], reduce the insulin infusion rate to 0.05 IU/kg/h.

3) Titrate the insulin infusion rate to maintain glucose at ~11.1 mmol/L (200 mg/dL).

3. Correct potassium deficit as in DKA.

4. Search for the precipitating cause and treat accordingly.

Once HHS resolves (ie, effective serum osmolality <310 mOsm/kg, plasma glucose ≤15 mmol/L [270 mg/dL] on <2 IU/h of IV insulin, and recovery to premorbid level of consciousness) and the patient is alert and able to eat, the IV insulin infusion can be transitioned to subcutaneous insulin. The insulin infusion should be maintained for 1 to 2 hours after transitioning to subcutaneous rapid-acting insulin in order to prevent rebound hyperglycemia. In patients treated before with insulin, their previous insulin regimen can be restarted.

Complications and prognosisTop

Complications of HHS include electrolyte abnormalities (eg, hypokalemia) and resultant arrhythmias; hypoglycemia (from insulin treatment); rhabdomyolysis (the mechanism is not completely understood, but it may be due to severe hyperosmolality, severe hypophosphatemia, or both); venous or arterial thromboembolism (due to hypotension and hyperviscosity of blood from volume contraction—which is why thromboprophylaxis with subcutaneous heparin or low-molecular-weight heparin is recommended; see Primary Prevention of Venous Thromboembolism); cerebral edema from rapid lowering of plasma osmolality (rarely fatal in HHS, presumably due to underlying cerebral atrophy in many of older patients); acute respiratory distress syndrome (ARDS) (the mechanism is not entirely understood); and heart failure from fluid overload.

The estimated mortality rate in HHS is ~20% and is 10 times higher than that reported for DKA. Prognosis depends on the presence of comorbidities, age, and severity of dehydration.

TablesTop

Table 6.2-7. Diagnostic criteria for hyperglycemic hyperosmolar state (HHS)

Parameters

Values typical for HHS

Blood glucose level

≥33.3 mmol/L (600 mg/dL)

pH

>7.30

Serum bicarbonate level

>15 mmol/L

Urine/serum ketones

 Absent or trace

Effective serum osmolalitya

>320 mOsm/kg H2Ob

Level of consciousness

Stupor/coma

Anion gap

Variable

a Effective serum osmolality = [2 × Na (mmol/L)] + [glucose (mmol/L)] or [2 × Na (mEq/L)] + [glucose (mg/dL)/18]

b Reference range: 280 to 300 mOsm/kg H2O.

We would love to hear from you

  • Do you have any comments?
  • Have you found a mistake?
  • Would you like to suggest a feature?

We use cookies to ensure you get the best browsing experience on our website. Refer to our Cookies Information and Privacy Policy for more details.