Hyponatremia

Aka: Hyponatremia, Low Serum Sodium

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II. Definitions

  1. Hyponatremia
    1. Serum Sodium < 135 meq/L
  2. Acute Hyponatremia
    1. Hyponatremia present <48 hours
  3. Chronic Hyponatremia
    1. Hyponatremia present >48 hours (or unknown)

III. Epidemiology

  1. Most common Electrolyte abnormality in U.S. hospitalized patients (affects 15-30% of patients)
  2. Identified in up to 7% of outpatients in U.S.

IV. Pathophysiology

  1. See Sodium and Water Homeostasis
  2. Sodium is the principal osmole of extracellular fluid (which in turn comprises 20% of total body weight)
  3. Hyponatremia is a water excess state
    1. Hypoosmolar Hyponatremia is most common

V. Symptoms: Acute Hyponatremia (develops over <24-48 hours)

  1. Symptom onset when Serum Sodium <125 meq/L
    1. Nausea
    2. Vomiting
    3. Headache
    4. Lethargy
    5. Dizziness
  2. Later or Severe Hyponatremia (Serum Sodium <120 meq/L)
    1. Seizure
    2. Coma
    3. Confusion
    4. Ataxia
    5. Respiratory depression

VI. Symptoms: Chronic Hyponatremia (develops over >48 hours)

  1. Lethargy
  2. Confusion
  3. Muscle cramps
  4. Neurologic Impairment

VII. Causes: Most common

  1. Excessive free water replacement (with or without Sodium losses)
    1. Nausea, Vomiting or Diarrhea
    2. Excessive, prolonged sweating with Exercise
    3. Psychogenic Polydipsia
    4. Hypotonic Saline infusion (e.g. D5 1/2NS)
  2. Excessive Sodium renal excretion (salt wasting)
    1. Diuretics (esp. Thiazide Diuretics, trimethoprim)
    2. Cerebral salt wasting (underlying neurologic disorder)
    3. Low Aldosterone (Mineralcorticoid deficiency)
  3. Syndrome Inappropriate ADH Secretion (SIADH)
    1. Malignancy (e.g. Small Cell Lung Cancer, Pancreatic Cancer)
    2. Lung Infections (e.g. Pneumonia, Empyema, Tuberculosis, Legionella, ARDS)
    3. Neurologic disorders (e.g. Brain Mass, Meningitis, Intracranial Hemorrhage, CVA)
    4. Medications
      1. Amiodarone
      2. Neuropsychiatric agents (e.g. Amitriptyline, Carbamazepine, SSRI, Haloperidol)
      3. Opioids and NSAIDs
  4. Edematous States
    1. Renal Failure or Nephrotic Syndrome
    2. Congestive Heart Failure
    3. Cirrhosis or other severe liver disease

VIII. Labs

  1. Core labs
    1. Comprehensive Metabolic Panel
    2. Serum Osmolality
    3. Urine Sodium
    4. Urine Creatinine
    5. Urine Osmolality
  2. Other labs to consider
    1. Brain Natriuretic Peptide (BNP)
    2. Thyroid Stiumulating Hormone (TSH)

IX. Evaluation: Approach

  1. Is the patient hypervolemic?
    1. See Hypervolemic Hypoosmolar Hyponatremia
    2. Hyponatremia due to Edematous State (Cirrhosis, CHF, Nephrotic Syndrome) or Renal Failure
  2. Measure Serum Osmolarity
    1. Many smaller labs are unable to provide a measured Serum Osmolality
    2. Most cases of Hyponatremia are Hypoosmolar Hyponatremia
      1. Exception: Severe Hyperglycemia (Hyperosmolar Hyponatremia)
        1. Obtain bedside Glucose
      2. Pseudohyponatremia (Normoosmolar Hyponatremia) is rare
  3. Choose an approach (typically Hypoosmolar Hyponatremia, except in severe Hyperglycemia)
    1. Hypoosmolar Hyponatremia (Serum Osms <280)
      1. Most common type of Hyponatremia
      2. Hypovolemic Hypoosmolar Hyponatremia
        1. Fluid losses (e.g. Gastroenteritis)
        2. Third spacing (e.g. Pancreatitis)
        3. Renal Sodium losses
      3. Isovolemic Hypoosmolar Hyponatremia
        1. SIADH
        2. Water Intoxication
        3. Hypothyroidism
        4. Medications
      4. Hypervolemic Hypoosmolar Hyponatremia
        1. Edematous State (Cirrhosis, CHF, Nephrotic Syndrome)
        2. Renal Failure
    2. Hyperosmolar Hyponatremia (Serum Osms >300)
      1. Hyperglycemia (typical cause) with water shifting from cells to the extracellular compartment
      2. Serum Sodium falls 1.6 mEq/L per Serum Glucose increase of every 100 mg/dl (over 100 mg/dl)
      3. May also occur with hypertonic infusions (Glucose, Mannitol, Glycine)
    3. Normoosmolar Hyponatremia (Serum Osms 280-300)
      1. Known as Pseudohyponatremia, and occurs in severe Hyperlipidemia or hyperproteinemia
      2. Rare now with newer methadology for Serum Sodium measurement (Sodium electrode)
      3. Consider if known comorbidity
        1. Severe Hypertriglyceridemia (>1500 mg/dl)
        2. Serum Protein >10 g/dl (e.g. Multiple Myeloma)

X. Management

  1. See specific Hyponatremia protocols based on serum osmolarity (esp. Hypoosmolar Hyponatremia)
  2. Do NOT correct Serum Sodium any faster than 6-12 meq/L (mmol/L) per day (most critical single tenet)
  3. See Hyponatremia Management

XI. Prognosis: Mortality

  1. Acute Hyponatremia (Serum Sodium <120 meq/L): 50%
    1. Mortality associated with cerebral edema
  2. Chronic Hyponatremia: 10%
    1. Mortality associated with underlying condition
    2. Also associated with gait instability, falls and Fractures

XII. Prevention

  1. Avoid states of excessive free water intake concurrent with impaired renal water excretion
  2. Avoid Thiazide Diuretics

XIII. References

  1. Le and Drogell (2015) Crit Dec Emerg Med 29(11): 13-19
  2. Kone in Tisher (1993) Nephrology, p. 87-100
  3. Levinsky in Wilson (1991) Harrison's IM, p. 281-84
  4. Rose (1989) Acid-Base and Electrolytes, p. 601-38
  5. Braun (2015) Am Fam Physician 91(5): 299-307 [PubMed]
  6. Miller (2023) Am Fam Physician 108(5): 476-86 [PubMed]

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