What is the best treatment approach for a patient with chronic hyponatremia?

Treatment for Chronic Hyponatremia

For chronic hyponatremia, the treatment approach must be determined by volume status (hypovolemic, euvolemic, or hypervolemic), with fluid restriction as the cornerstone for euvolemic and hypervolemic states, and the critical safety principle that correction must never exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1

Initial Assessment and Classification

• Determine chronicity: Chronic hyponatremia is defined as lasting >48 hours, which is critical because rapid correction risks osmotic demyelination syndrome 1, 2
• Assess volume status through physical examination looking for orthostatic hypotension, dry mucous membranes, decreased skin turgor (hypovolemic); peripheral edema, ascites, jugular venous distention (hypervolemic); or absence of these findings (euvolemic) 1
• Obtain essential laboratory tests: serum and urine osmolality, urine sodium concentration, serum uric acid, thyroid function, and cortisol to determine the underlying cause 1
• Urine sodium <30 mmol/L suggests hypovolemic hyponatremia with 71-100% positive predictive value for saline responsiveness 1
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1

Treatment Based on Volume Status

Hypovolemic Hyponatremia

• Discontinue diuretics immediately and administer isotonic saline (0.9% NaCl) for volume repletion 1
• Initial infusion rate: 15-20 mL/kg/h, then 4-14 mL/kg/h based on clinical response 1
• Maximum correction rate: 4-8 mmol/L per day, never exceeding 8 mmol/L in 24 hours 1
• For cirrhotic patients, use even more cautious correction (4-6 mmol/L per day) and consider albumin infusion alongside isotonic saline 1

Euvolemic Hyponatremia (SIADH)

• Fluid restriction to 1 L/day is the cornerstone of treatment 1, 2
• If no response to fluid restriction after 24-48 hours, add oral sodium chloride 100 mEq three times daily 1
• Pharmacological options for resistant cases:
  • Urea (effective but limited by poor palatability and gastric intolerance) 2
  • Vasopressin receptor antagonists (tolvaptan 15 mg once daily, titrate to 30-60 mg) for clinically significant hyponatremia resistant to fluid restriction 1, 3
  • Demeclocycline or lithium (less commonly used due to side effects) 1
• Tolvaptan considerations: Start at 15 mg once daily, avoid fluid restriction during first 24 hours to prevent overly rapid correction, monitor sodium every 8 hours initially 3

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

• Implement fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L 1
• Discontinue diuretics temporarily if sodium <125 mmol/L 1
• For cirrhotic patients, consider albumin infusion (8 g per liter of ascites drained) alongside fluid restriction 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it worsens ascites and edema 1
• Vasopressin receptor antagonists may be considered for persistent severe hyponatremia despite fluid restriction and maximization of guideline-directed medical therapy 1
• Important principle: In cirrhosis, it is sodium restriction (not fluid restriction) that results in weight loss, as fluid passively follows sodium 1

Critical Correction Rate Guidelines

• Standard correction rate: 4-8 mmol/L per day, maximum 8 mmol/L in 24 hours 1, 2
• High-risk patients (advanced liver disease, alcoholism, malnutrition, severe hyponatremia <115 mmol/L): limit to 4-6 mmol/L per day 1, 4
• For patients with serum sodium <115 mmol/L, consider limiting correction to <8 mmol/L in 24 hours due to higher risk of osmotic demyelination syndrome even with guideline-adherent correction 4
• Monitor serum sodium every 4 hours during initial correction phase 1

Management of Overcorrection

• If sodium correction exceeds 8 mmol/L in 24 hours, immediately discontinue current fluids and switch to D5W (5% dextrose in water) 1
• Consider administering desmopressin to slow or reverse the rapid rise in serum sodium 1
• Target relowering to bring total 24-hour correction to no more than 8 mmol/L from starting point 1

Special Populations

Cirrhotic Patients

• Hyponatremia in cirrhosis increases risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1
• Tolvaptan carries higher risk of gastrointestinal bleeding in cirrhosis (10% vs 2% placebo) 1, 3
• Fluid restriction may prevent further sodium decline but rarely improves it significantly 1

Neurosurgical Patients

• Distinguish between SIADH and cerebral salt wasting (CSW), as they require opposite treatments 1
• CSW requires volume and sodium replacement with isotonic or hypertonic saline, NOT fluid restriction 1
• For severe CSW symptoms, use 3% hypertonic saline plus fludrocortisone (0.1-0.2 mg daily) in ICU setting 1
• Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm 1

Common Pitfalls to Avoid

• Overly rapid correction exceeding 8 mmol/L in 24 hours leads to osmotic demyelination syndrome 1, 2
• Using fluid restriction in cerebral salt wasting worsens outcomes 1
• Inadequate monitoring during active correction 1
• Failing to recognize and treat the underlying cause 1
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant, as it increases fall risk (21% vs 5%) and mortality 1, 2

Monitoring Requirements

• Check serum sodium every 4 hours initially after starting treatment 1
• Once stable, monitor daily until target sodium reached 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1
• Track daily weight and fluid balance meticulously 1