What are the management strategies for hyponatremia in patients with varying volumes and underlying conditions, such as Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), heart failure, or liver disease?

Management of Hyponatremia

Initial Assessment and Classification

Hyponatremia (serum sodium <135 mmol/L) requires immediate evaluation based on symptom severity, volume status, and serum osmolality to guide treatment. 1

• Obtain serum and urine osmolality, urine sodium, uric acid, and assess extracellular fluid volume status when sodium drops below 131 mmol/L 1
• Classify by volume status: hypovolemic (ECF contraction, orthostatic hypotension, dry mucous membranes), euvolemic (no edema, normal skin turgor), or hypervolemic (peripheral edema, ascites, jugular venous distention) 1, 2
• Determine chronicity: acute (<48 hours) versus chronic (>48 hours), as this fundamentally changes correction rates 1
• Exclude pseudohyponatremia by checking serum osmolality and glucose (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 1

Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

For patients with seizures, coma, confusion, or altered mental status, immediately administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until symptoms resolve. 1, 2

• Give 100 mL boluses of 3% saline over 10 minutes, repeatable up to three times at 10-minute intervals until symptoms improve 1
• Never exceed 8 mmol/L total correction in 24 hours to prevent osmotic demyelination syndrome 1, 2
• Monitor serum sodium every 2 hours during initial correction 1
• After severe symptoms resolve, switch to monitoring every 4 hours 1

Asymptomatic or Mildly Symptomatic Hyponatremia

Treatment depends entirely on volume status:

Treatment Based on Volume Status

Hypovolemic Hyponatremia

Discontinue diuretics immediately and administer isotonic saline (0.9% NaCl) for volume repletion. 1, 3

• Urine sodium <30 mmol/L predicts 71-100% response to saline infusion 1
• Initial infusion rate: 15-20 mL/kg/h, then 4-14 mL/kg/h based on response 1
• Once euvolemic, reassess if sodium improves; if not, consider SIADH 1
• In cirrhotic patients, consider albumin infusion alongside isotonic saline 1

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day is the cornerstone of treatment for SIADH. 1, 2

• If no response to fluid restriction after 24-48 hours, add oral sodium chloride 100 mEq three times daily 1
• For persistent cases despite fluid restriction, consider tolvaptan 15 mg once daily, titrating to 30-60 mg as needed 1, 4
• Alternative pharmacological options include urea, demeclocycline, or lithium (less commonly used due to side effects) 1, 2
• Diagnostic criteria: urine osmolality >300 mOsm/kg, urine sodium >20-40 mmol/L, serum uric acid <4 mg/dL (73-100% positive predictive value) 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Implement fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L. 1, 3

• Temporarily discontinue diuretics if sodium <125 mmol/L 1
• In cirrhotic patients, consider albumin infusion alongside fluid restriction 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it worsens ascites and edema 1
• For persistent hyponatremia despite fluid restriction and maximized guideline-directed therapy, consider tolvaptan with extreme caution 4
• Note: It is sodium restriction, not fluid restriction, that results in weight loss as fluid passively follows sodium 1

Critical Correction Rate Guidelines

The maximum correction rate must not exceed 8 mmol/L in 24 hours for all patients to prevent osmotic demyelination syndrome. 1, 2

• Standard correction rate: 4-8 mmol/L per day, not exceeding 10-12 mmol/L in 24 hours 1
• High-risk patients (advanced liver disease, alcoholism, malnutrition, prior encephalopathy) require even slower correction: 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours 1
• For severe symptomatic patients: correct 6 mmol/L in first 6 hours, then only 2 mmol/L additional in next 18 hours 1
• Acute hyponatremia (<48 hours) can be corrected more rapidly without risk of osmotic demyelination 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 1
• Target relowering to bring total 24-hour correction to no more than 8 mmol/L from starting point 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1

Special Populations

Neurosurgical Patients (Cerebral Salt Wasting vs. SIADH)

In neurosurgical patients, distinguish cerebral salt wasting (CSW) from SIADH, as they require opposite treatments. 1

• CSW requires volume and sodium replacement with isotonic or hypertonic saline, NOT fluid restriction 1
• CSW characteristics: true hypovolemia (CVP <6 cm H₂O), urine sodium >20 mmol/L despite volume depletion, orthostatic hypotension 1
• For severe CSW symptoms: 3% hypertonic saline plus fludrocortisone 0.1-0.2 mg daily in ICU 1
• Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm 1
• Consider hydrocortisone to prevent natriuresis in subarachnoid hemorrhage patients 1

Cirrhotic Patients

Patients with cirrhosis require more cautious correction (4-6 mmol/L per day) due to higher risk of osmotic demyelination. 1

• Hyponatremia in cirrhosis increases risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1
• Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 1
• Albumin infusion may be beneficial 1
• Tolvaptan carries higher risk of gastrointestinal bleeding in cirrhosis (10% vs 2% placebo) 1, 4

Pharmacological Interventions

Tolvaptan (Vasopressin Receptor Antagonist)

Tolvaptan 15 mg once daily may be considered for clinically significant hyponatremia resistant to fluid restriction in euvolemic or hypervolemic states. 1, 4

• Starting dose: 15 mg once daily, titrate to 30-60 mg based on response 1, 4
• In clinical trials, tolvaptan increased serum sodium by 3.7 mEq/L at Day 4 and 4.6 mEq/L at Day 30 compared to placebo 4
• Use with extreme caution in cirrhosis due to increased bleeding risk and mortality concerns 1
• Monitor closely to avoid overly rapid correction (>8 mmol/L/day) 1, 4
• Avoid fluid restriction during first 24 hours of tolvaptan therapy 4

Common Pitfalls to Avoid

• Overly rapid correction exceeding 8 mmol/L in 24 hours causes 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—it increases fall risk (21% vs 5%) and mortality (60-fold increase with sodium <130 mmol/L) 1, 2
• Misdiagnosing volume status in heart failure patients with hyponatremia 1