Updated: 1/2/2021

Hyperosmolar Hyperglycemic State

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Snapshot
  • A 65-year-old woman with a past medical history significant for type 2 diabetes, glaucoma, and psoriasis presents to the emergency room for altered mental status. For the past few days, she has had increasing cough followed by polyuria, weakness, and fatigue. She has had a few tactile fevers at home. On physical exam, she is febrile and tachycardic. Her skin turgor is poor and she has dry mucous membranes. She is alert and oriented only to self, a change from her baseline. Laboratory results are significant for an elevated serum glucose of 730 mg/dL. Arterial blood gas shows a normal pH. No ketones are detected in the serum. Chest radiograph shows a new right lower lobe infiltrate. She is given a bolus of fluids and admitted to the intensive care unit for further management.
Introduction
  • Clinical definition
    • hyperosmolar hyperglycemic state (HHS) is also known as nonketotic hyperglycemic coma
    • a complication of diabetes mellitus characterized by
      • hyperglycemia
      • ↑ osmolality
      • dehydration
      • minimal or no ketoacidosis
  • Epidemiology
    • demographics
      • patients with type 2 diabetes
        • insulin resistance + increased serum insulin levels 
        • beta cell burnout in the long run
    • etiology
      • medication noncompliance
      • acute medical illness
        • myocardial infarction
        • stroke
        • pancreatitis
        • infection
  • Pathogenesis
    • hyperglycemia results in
      • osmotic diuresis
      • dehydration and electrolyte loss
      • increased intravascular osmolarity
      • impaired renal function
      • increased proinflammatory cytokines
  • Associated conditions
    • type 2 diabetes
Presentation
  • Symptoms
    • symptoms develop over days with gradual onset
    • polyuria
    • polydipsia
    • weight loss
    • weakness and fatigue
    • mental status changes
    • dehydration
      • may present with shock
    • blurry vision
      • from lens swelling secondary to osmotic pressure
Studies
  • Diagnostic testing
    • studies
      • ↑ blood glucose
      • small or absent ketones (β-hydroxybutyrate)
      • serum osmolality > 320 mOsm/kg
      • pH > 7.3
      • serum bicarbonate > 15-18 mmol/L
      • may have ↑ lactate
  • Diagnostic criteria
    • ↑ glucose-induced stupor/coma without ketonemia or acidosis
Differential
  • Diabetic ketoacidosis
    • distinguishing factors
      • often occurs in patients with type 1 diabetes
      • patients are acidotic and with ketones
      • more often presents with nausea, vomiting, and abdominal pain
Treatment
  • Management approach
    • mainstay of treatment is to normalize osmolality, normalize serum glucose, and replete fluids/electrolytes
  • First-line
    • intravenous fluid resuscitation
    • replete electrolytes 
      • especially potassium
        • with goal of 4-5 mEq/L
    • intravenous insulin
      • after fluid resuscitation
Complications
  • Thrombosis

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Questions (4)
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(M2.EC.17.4831) A 55-year-old man with no significant medical history returns for follow-up of a fasting blood glucose (FBG) of 110 mg/dL. His mother had a myocardial infarction at age 52. He weighs 90 kg and his body mass index is 35 kg/m2. His repeat FBG is 160 mg/dL and hemoglobin A1c (HbA1c) is 7.0%. He is started on metformin but is lost to follow-up. Two years later, his HbA1c is 7.6% despite maximal metformin usage, so the patient is started on glyburide. Three months later, his HbA1c is 7.3% while on both medications, and subsequently prescribed glargine and aspart. Three months later, he is brought by his wife to the emergency department for evaluation of altered mental status. His electronic medical record notes that he was started on nitrofurantoin recently for an urinary tract infection. He is disoriented to place and time. His temperature is 99°F (37.2°C), blood pressure is 83/59 mmHg, pulse is 130/min, respirations are 26/min. His basic metabolic panel is shown below:

Serum:
Na+: 119 mEq/L
Cl-: 90 mEq/L
K+: 4.2 mEq/L
HCO3-: 24 mEq/L
BUN: 25 mg/dL
Glucose: 1,400 mg/dL
Creatinine: 1.9 mg/dL

His urine dipstick is negative for ketones. A peripheral intravenous line is established. Which of the following is the best initial step in management?

QID: 109467
1

3% hypertonic saline

16%

(9/56)

2

Regular insulin

16%

(9/56)

3

Lactated ringer's solution

43%

(24/56)

4

Glargine insulin

0%

(0/56)

5

Regular insulin and potassium

25%

(14/56)

M 7 D

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(M2.EC.14.16) A 61-year-old female with congestive heart failure and type 2 diabetes is brought to the emergency room by her husband because of an altered mental status. He states he normally helps her be compliant with her medications, but he had been away for several days. On physical exam, her temperature is 37.2 C, BP 85/55, and HR 130. Serum glucose is 500 mg/dL. Which of the following is the first step in the management of this patient?

QID: 104341
1

IV ½ NS

5%

(4/81)

2

IV NS

65%

(53/81)

3

IV D5W

2%

(2/81)

4

Subcutaneous insulin injection

4%

(3/81)

5

IV insulin

21%

(17/81)

M 7 E

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Evidence (8)
EXPERT COMMENTS (2)
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