Updated: 7/3/2019

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
    • 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)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.EC.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 90/60 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. What is the best initial step in management? Review Topic

QID: 109467
1

3% hypertonic saline

15%

(7/47)

2

Regular insulin

17%

(8/47)

3

Lactated ringer's solution

45%

(21/47)

4

Glargine insulin

0%

(0/47)

5

Regular insulin and potassium

23%

(11/47)

M2

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PREFERRED RESPONSE 3

(M2.EC.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? Review Topic

QID: 104341
1

IV ½ NS

5%

(4/77)

2

IV NS

65%

(50/77)

3

IV D5W

3%

(2/77)

4

Subcutaneous insulin injection

4%

(3/77)

5

IV insulin

22%

(17/77)

M2

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PREFERRED RESPONSE 2
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