What is the treatment approach for hyponatremia?

Treatment of Hyponatremia

The treatment of hyponatremia depends critically on symptom severity and volume status, with severe symptomatic cases requiring immediate 3% hypertonic saline to correct sodium by 6 mmol/L over 6 hours, while asymptomatic cases are managed based on whether the patient is hypovolemic (isotonic saline), euvolemic (fluid restriction), or hypervolemic (fluid restriction with underlying disease management), always limiting total correction to 8 mmol/L per 24 hours to prevent osmotic demyelination syndrome. 1

Initial Assessment

Symptom Severity Classification

• Severe symptoms include seizures, coma, altered mental status, confusion, obtundation, somnolence, or cardiorespiratory distress—these constitute a medical emergency requiring immediate intervention 1, 2
• Mild symptoms include nausea, vomiting, weakness, headache, and mild neurocognitive deficits 3
• Asymptomatic hyponatremia still requires treatment as even mild chronic hyponatremia increases fall risk (21% vs 5% in normonatremic patients), fractures, and mortality (60-fold increase with sodium <130 mmol/L) 1, 2

Volume Status Determination

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, tachycardia 1
• Euvolemic signs: absence of edema, normal blood pressure, normal skin turgor, moist mucous membranes 1
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, pulmonary congestion 1

Essential Laboratory Workup

• Serum and urine osmolality, urine sodium concentration, urine electrolytes, serum uric acid 1
• Urinary sodium <30 mmol/L suggests hypovolemic hyponatremia (71-100% positive predictive value for saline response) 1
• Serum uric acid <4 mg/dL suggests SIADH (73-100% positive predictive value) 1

Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

Immediate hypertonic saline administration is mandatory—do not delay for diagnostic workup. 1, 2

• Administer 3% hypertonic saline as 100 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals until symptoms improve 1
• Target correction: 6 mmol/L over the first 6 hours or until severe symptoms resolve 1
• Maximum correction limit: 8 mmol/L in 24 hours (never exceed this to prevent osmotic demyelination syndrome) 1, 2, 4
• Monitoring frequency: Check serum sodium every 2 hours during initial correction 1
• ICU admission is recommended for close monitoring 1

Asymptomatic or Mildly Symptomatic Hyponatremia

Treatment is determined by volume status:

Hypovolemic Hyponatremia

• Discontinue diuretics immediately 1
• Administer isotonic saline (0.9% NaCl) for volume repletion 1, 3
• For severe dehydration with neurological symptoms, consider hypertonic saline with careful monitoring 1
• Correction rate should not exceed 8 mmol/L in 24 hours 1

Euvolemic Hyponatremia (SIADH)

• Fluid restriction to 1 L/day is the cornerstone of treatment 1, 4
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1
• For resistant cases, consider urea or vaptans (tolvaptan 15 mg once daily) 1, 2, 4
• Avoid fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

• Fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L 1, 3
• Discontinue diuretics temporarily if sodium <125 mmol/L 1
• Albumin infusion should be considered in cirrhotic patients 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it may worsen edema and ascites 1
• Treat underlying condition (optimize heart failure management, manage cirrhosis) 3
• Vaptans may be considered for persistent severe hyponatremia despite fluid restriction and maximization of guideline-directed medical therapy 1, 5

Special Populations and High-Risk Considerations

Patients at High Risk for Osmotic Demyelination Syndrome

• Advanced liver disease, alcoholism, malnutrition, or prior encephalopathy require even more cautious correction: 4-6 mmol/L per day maximum 1, 4
• Chronic hyponatremia (>48 hours duration) requires slower correction than acute hyponatremia 1

Neurosurgical Patients

• Distinguish between SIADH and cerebral salt wasting (CSW) as treatment approaches differ fundamentally 1
• CSW treatment: volume and sodium replacement with isotonic or hypertonic saline, plus fludrocortisone for severe symptoms 1
• Never use fluid restriction in CSW—this worsens outcomes 1
• In subarachnoid hemorrhage patients at risk of vasospasm, avoid fluid restriction and consider fludrocortisone or hydrocortisone 1

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, 5
• Reserve hypertonic saline for life-threatening symptoms only 1

Pharmacological Options

Vasopressin Receptor Antagonists (Vaptans)

• Tolvaptan is FDA-approved for euvolemic or hypervolemic hyponatremia 5
• Starting dose: 15 mg once daily, can titrate to 30 mg then 60 mg daily 5
• Efficacy: Significantly increases serum sodium compared to placebo (mean increase 4.0 mEq/L at Day 4 vs 0.4 mEq/L with placebo) 5
• Contraindicated with strong CYP3A inhibitors (ketoconazole increases tolvaptan AUC 5.4-fold) 5
• Avoid in cirrhosis due to increased bleeding risk unless benefits clearly outweigh risks 1, 5
• Close monitoring required to prevent overly rapid correction 1, 5

Urea

• Effective second-line therapy for SIADH when fluid restriction fails 1, 2, 4
• Approximately half of SIADH patients do not respond to fluid restriction alone 4
• Adverse effects include poor palatability and gastric intolerance 2

Critical Safety Considerations and Common Pitfalls

Preventing Osmotic Demyelination Syndrome

• Never exceed 8 mmol/L correction in 24 hours for chronic hyponatremia 1, 2, 4
• High-risk patients: limit to 4-6 mmol/L per day 1
• If overcorrection occurs, immediately discontinue current fluids, switch to D5W (5% dextrose in water), and consider desmopressin to relower sodium 1
• Watch for signs of osmotic demyelination syndrome 2-7 days after rapid correction: dysarthria, dysphagia, oculomotor dysfunction, quadriparesis 1

Common Pitfalls to Avoid

• Do not ignore mild hyponatremia (130-135 mmol/L)—it increases mortality and fall risk 1
• Do not use fluid restriction in cerebral salt wasting—this worsens outcomes 1
• Do not use hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Do not fail to monitor adequately during active correction 1
• Do not use normal saline for SIADH—it may worsen hyponatremia 1
• Do not use lactated Ringer's for hyponatremia treatment—it is hypotonic (130 mEq/L sodium) and can worsen hyponatremia 1

Monitoring During Treatment

Severe Symptoms

• Check serum sodium every 2 hours during initial correction 1
• After resolution of severe symptoms, check every 4 hours 1

Mild Symptoms or Asymptomatic

• Check serum sodium every 4-6 hours initially, then daily once stable 1
• Monitor for signs of overcorrection or osmotic demyelination syndrome 1