Hyperosmolar Hyperglycemic State (HHS)

Hyperosmolar Hyperglycemic State (HHS)

David Ray Velez, MD

Table of Contents

Definition
Pathophysiology
Presentation
Diagnosis
Treatment

Definition

Hyperosmolar Hyperglycemic State (HHS) – Hyperglycemia and Hyperosmolar Plasma but No Acidosis or Ketonemia

  • Also Known As: Hyperosmotic Hyperglycemia Nonketotic State (HHNK)

Diabetic Ketoacidosis (DKA) – Hyperglycemia with Acidosis and Ketonemia

DKA/HHS Comparison

  • Diabetic Ketoacidosis (DKA)
    • Acidosis and Ketonemia
    • Hyperventilation and Abdominal Symptoms are More Common
    • More Common in the Young (< Age 65)
    • Glucose Generally 300-500 mg/dL
  • Hyperosmolar Hyperglycemic State (HHS)
    • No Acidosis or Ketonemia
    • Neurologic Symptoms are More Common (Due to Higher Osmolarity)
    • More Common in the Elderly (> Age 65)
    • Glucose Often > 1,000 mg/dL

Mixed-DKA/HHS Presentations are Relatively Common

Pathophysiology

Hyperglycemia

  • Frequently Exceeds 1,000 mg/dL
  • Primary Factors:
    • Insulin Deficiency and Resistance
    • Glucagon Excess (From Loss of Normal Inhibitory Effects of Insulin)
  • Caused By:
    • Impaired Peripheral Glucose Utilization
    • Increased Gluconeogenesis in the Liver and Kidney
    • Increased Glycogenolysis

Increased Plasma Osmolarity

  • Hyperglycemia Pulls Water Out of Cells to Expand the Extracellular Space and Decrease Sodium
  • Hyperglycemia Causes a Large Osmotic Diuresis – Further Reduces Sodium and Increases Osmolality
  • The Effect is Less Apparent in DKA

With a “Relative” Insulin Deficiency (Compared to an “Absolute” Insulin Deficiency) There is Less Lipolysis with Absent-Minimal Ketogenesis/Acidosis

Potassium Derangement

  • Large Total Potassium Deficit – Largely from Urinary Loss
    • Glucose Osmotic Diuresis
    • Excretion of Potassium Ketoacid Anion Salts
  • False Elevation in Labs Due to Extracellular Shift from Hyperosmolarity and Insulin Deficiency

Characteristically Occurs in Type 2 Diabetes, But Can Rarely Occur in Type 1 Diabetes

Common Triggering Events

  • Insufficient Insulin Therapy
  • Infection/Sepsis
    • Pneumonia
    • Urinary Tract Infection (UTI)
  • Surgery
  • Trauma
  • Severe Burns
  • Myocardial Infarction
  • Stroke
  • Pancreatitis
  • Mesenteric Ischemia
  • Medications
  • Undiagnosed Diabetes

Mortality of HHS (1-13%) is Generally Higher than DKA (0.2-5%)

Presentation

Presentation

  • Polyuria (Frequent Urination)
  • Polydipsia (Increased Thirst)
  • Weight Loss
  • Dehydration
  • Dry Skin and Mucous Membranes

Neurologic Symptoms – More Common than in DKA

  • Headache
  • Lethargy
  • Weakness
  • Obtunded/Confused
  • Coma
  • Focal Neurologic Signs (Hemiparesis/Hemianopsia)
  • Seizures

Respiratory Symptoms

  • Hyperventilation
  • Kussmaul Respirations – Rapid Deep Breaths Indicative of Metabolic Acidosis
  • “Fruity Odor” to Breath (From Acetone Exhalation)

Abdominal Symptoms – Much Less Common than in DKA

  • Abdominal Pain
  • Nausea and Vomiting

Diagnosis

Diagnosis is Based Primarily on Labs

Labs

  • High Glucose (May Exceed 1,000 mg/dL)
  • High Plasma Osmolarity
  • Normal or Minimally Reduced Bicarbonate – Minimal-No Metabolic Acidosis
  • No Urinary Ketones (Acetoacetic Acid, β-Hydroxybutyrate, and Acetone)
  • Low Sodium
  • Normal-High Potassium (Falsely Elevated Despite Large Total Body Losses)
    • May See Large Potassium Shifts with Early Resuscitation

American Diabetes Association Classification

  • Often Significant Overlap Between Syndromes
  Mild DKA Moderate DKA Severe DKA HHS
Glucose (mg/dL) > 250 > 250 > 250 > 600
Glucose (mmol/L) > 13.9 > 13.9 > 13.9 > 33.3
Arterial pH 7.25-7.30 7.00-7.24 < 7.00 > 7.30
Bicarbonate 15-18 10-15 < 10 > 18
Urine Ketones Positive Positive Positive Small
Serum Ketones (Nitroprusside Reaction) Positive Positive Positive Small
Serum Ketones (β-Hydroxy-butyrate) 3-4 mmol/L 4-8 mmol/L > 8 mmol/L < 0.6 mmol/L
Serum Osmolarity Variable Variable Variable > 320
Anion Gap > 10 > 12 > 12 Variable
Mental Status Alert Drowsy Stupor/ Coma Stupor/ Coma

Treatment

Primary Treatment: IV Fluids, Electrolyte Correction, and Insulin

Fluid Resuscitation

  • Start with Isotonic 0.9% Normal Saline (NS) or Lactated Ringer (LR)
  • Switch to D5 0.45% (1/2) NS Once Serum Glucose Declines to Prevent Hypoglycemia
    • HHS: Switch Once Glucose < 250-300 mg/dL
    • DKA: Switch Once Glucose < 200 mg/dL

Correct Electrolyte Derangements – Particularly Potassium

Insulin Administration

  • Generally Start with IV Regular Insulin Infusion (gtt)
  • Delay Insulin Administration if Potassium (K) < 3.3 mEq/L – May See Large Potassium Shifts with Early Resuscitation
  • Decline in Serum Glucose Should Not Exceed 90-120 mg/dL

Consider Sodium Bicarbonate for Severe Acidosis (pH < 6.9-7.0)

Hyperglycemic Crisis is Consider Resolved When:

  • Osmolarity < 300 mOsmol/kg
  • Glucose < 250 mg/dL
  • Urine Output > 0.5 cc/kg/hr
  • Patient is Mentally at Baseline

General Glucose Target

  • Goal Blood Glucose ≤ 140-180 mg/dL
  • Levels > 180 mg/dL Increase the Risk for Postoperative Complications (SSI, LOS, and Mortality)
    • Effect is More Pronounced in Non-Diabetic Patients than in Diabetic Patients
  • Overly Strict Glucose Control Increases the Risk of Hypoglycemia without Improved Outcomes