What are the etiology, pathophysiology, clinical features, and treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and Cerebral Salt Wasting (CSW) Syndrome?

SIADH and Cerebral Salt Wasting Syndrome: Etiology, Pathophysiology, Clinical Features, and Treatment

Both Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and Cerebral Salt Wasting (CSW) Syndrome are important causes of hyponatremia in neurosurgical patients, with distinct pathophysiologies requiring different treatment approaches. 1

Etiology

SIADH

• Results from excessive, inappropriate secretion of antidiuretic hormone (ADH) despite normal or low plasma osmolality 2
• Common causes include:
  • Neoplasia (particularly small cell lung cancer)
  • Neurological diseases (subarachnoid hemorrhage, traumatic brain injury, meningitis)
  • Pulmonary diseases (pneumonia, tuberculosis)
  • Medications (antidepressants, antipsychotics, anticonvulsants) 3

CSW

• Occurs primarily in patients with intracranial pathology, especially subarachnoid hemorrhage 4
• Caused by excessive natriuresis due to increased secretion of natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide) 5
• Common causes include:
  • Subarachnoid hemorrhage
  • Traumatic brain injury
  • Brain tumors
  • Neurosurgical procedures 4

Pathophysiology

SIADH

• Inappropriate ADH secretion leads to increased water reabsorption in the renal collecting ducts 3
• Persistent ADH activity despite hypo-osmolality causes:
  • Water retention
  • Dilutional hyponatremia
  • Increased extracellular fluid volume (though often clinically inapparent)
  • Decreased plasma osmolality
  • Increased urine osmolality 6

CSW

• Increased secretion of natriuretic peptides causes:
  • Direct renal sodium wasting
  • Inhibition of the renin-angiotensin-aldosterone system
  • Reduced sympathetic outflow
  • Volume depletion due to natriuresis and diuresis
  • Hyponatremia due to sodium loss and secondary ADH release from volume depletion 7, 5

Clinical Features

SIADH

• Euvolemic hyponatremia (no clinical signs of volume depletion)
• Serum sodium <135 mEq/L
• Plasma osmolality <275 mOsm/kg
• Inappropriately high urine osmolality (>100 mOsm/kg)
• Urine sodium >40 mEq/L
• Normal renal, adrenal, and thyroid function 2, 6
• Symptoms based on severity and rate of sodium decline:
  • Mild: Headache, irritability, difficulty concentrating
  • Moderate: Nausea, vomiting, confusion
  • Severe: Seizures, coma, respiratory arrest 6

CSW

• Hypovolemic hyponatremia (clinical signs of volume depletion)
• Serum sodium <135 mEq/L
• Evidence of dehydration (dry mucous membranes, decreased skin turgor)
• Orthostatic hypotension
• Tachycardia
• Negative fluid balance
• Weight loss
• High urine output despite hypovolemia
• Urine sodium >40 mEq/L
• Symptoms similar to SIADH but may include more pronounced signs of volume depletion 4, 7

Treatment

SIADH

Fluid restriction to 1 L/day is the first-line treatment for asymptomatic or mild SIADH-induced hyponatremia, while hypertonic 3% saline is reserved for severe symptomatic cases. 2

• For asymptomatic or mild symptomatic hyponatremia:

  • Fluid restriction to 1 L/day 2
  • High protein diet to augment solute intake 8
  • Oral sodium chloride supplementation (100 mEq three times daily) if needed 8
  • Pharmacologic options for refractory cases:
    • Urea
    • Diuretics (loop diuretics with salt tablets)
    • Demeclocycline
    • Lithium (rarely used due to toxicity) 1
    • Vasopressin receptor antagonists (tolvaptan) for euvolemic or hypervolemic hyponatremia 9

• For severe symptomatic hyponatremia (seizures, coma):

  • 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 2
  • Total correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 2, 10
  • Monitor serum sodium every 2 hours initially 2
  • ICU admission for close monitoring 2

CSW

Cerebral salt wasting should be treated with replacement of serum sodium and intravenous fluids, with fludrocortisone as an important adjunctive therapy. 1, 4

• Volume repletion with isotonic (0.9%) or hypertonic (3%) saline depending on severity 10
• Fludrocortisone (0.1-0.4 mg daily) to enhance sodium reabsorption in the distal tubule 1
• Hydrocortisone may be used to prevent natriuresis, especially in subarachnoid hemorrhage patients 1
• For severe symptomatic hyponatremia:
  • 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 10
  • Total correction should not exceed 8 mmol/L in 24 hours 10
  • ICU admission for close monitoring 10

Important Distinctions and Pitfalls

• Volume status assessment is crucial for differentiating between SIADH (euvolemic) and CSW (hypovolemic) 7
• Fluid restriction is contraindicated in CSW as it can worsen volume depletion and outcomes, especially in subarachnoid hemorrhage patients 1, 10
• Correction rate should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome, with even more cautious correction (4-6 mmol/L per day) for patients with advanced liver disease, alcoholism, or malnutrition 10
• Monitor serum sodium frequently during treatment (every 2-4 hours initially) 2, 10
• Failing to recognize and treat the underlying cause is a common pitfall 2, 10
• Distinguishing between SIADH and CSW is critical in neurosurgical patients, as treatment approaches differ significantly 10