What are the management strategies for hyponatremia?

Management of Hyponatremia

Initial Assessment and Classification

Hyponatremia (serum sodium <135 mmol/L) requires immediate evaluation based on volume status, symptom severity, and onset timing to guide appropriate treatment and prevent life-threatening complications. 1

• Begin workup when serum sodium drops below 131 mmol/L, though even mild hyponatremia (130-135 mmol/L) warrants attention due to increased fall risk (21% vs 5%) and 60-fold increased mortality when <130 mmol/L 1, 2
• Obtain serum and urine osmolality, urine sodium concentration, urine electrolytes, serum uric acid, and assess extracellular fluid volume status 1
• Classify severity: mild (130-135 mmol/L), moderate (120-129 mmol/L), severe (<120 mmol/L) 1, 3
• Determine acuity: acute (<48 hours) vs chronic (>48 hours), as this fundamentally changes correction rates 1

Physical examination for volume status has poor accuracy (sensitivity 41%, specificity 80%), so supplement with laboratory findings 1:

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, urine sodium <30 mmol/L 1
• Euvolemic signs: normal volume status, urine sodium >20-40 mmol/L, urine osmolality >300 mOsm/kg (suggests SIADH) 1
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, urine sodium >20 mmol/L 1

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Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

For patients with seizures, coma, altered mental status, or cardiorespiratory distress, immediately administer 3% hypertonic saline—this is a medical emergency requiring urgent intervention, not fluid restriction. 1, 2

• Give 3% hypertonic saline as 100 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals 1
• Target correction of 6 mmol/L over first 6 hours or until severe symptoms resolve 1
• Maximum correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2
• Monitor serum sodium every 2 hours during initial correction phase 1
• Consider ICU admission for close monitoring 1

Mild to Moderate Symptomatic Hyponatremia

For patients with nausea, vomiting, headache, confusion, or gait instability without severe neurological symptoms 1:

• Hospital admission recommended for sodium 120-125 mmol/L with symptoms 1
• Treatment approach depends on volume status (see below)
• Monitor sodium every 4-6 hours initially 1
• Correction rate: 4-8 mmol/L per day, maximum 10-12 mmol/L in 24 hours 1

Asymptomatic Hyponatremia

Even asymptomatic patients with sodium <125 mmol/L require treatment due to increased risk of falls, fractures, cognitive impairment, and mortality 1, 2:

• Monitor sodium every 24-48 hours initially 1
• Treat based on volume status and underlying cause 1
• Slower correction acceptable: 4-6 mmol/L per day 1

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Treatment Based on Volume Status

Hypovolemic Hyponatremia

Discontinue diuretics immediately and administer isotonic saline (0.9% NaCl) for volume repletion—this is the definitive treatment for true volume depletion. 1

• Initial infusion rate: 15-20 mL/kg/h, then 4-14 mL/kg/h based on clinical response 1
• Urine sodium <30 mmol/L predicts good response to saline (positive predictive value 71-100%) 1
• Continue until clinical euvolemia achieved: normal blood pressure, moist mucous membranes, stable vital signs 1
• Maximum correction: 8 mmol/L in 24 hours 1

Common causes: gastrointestinal losses (vomiting, diarrhea), excessive diuretic use, burns, third-space losses 1

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day is the cornerstone of SIADH treatment, not saline administration which will worsen hyponatremia. 1

Diagnostic criteria for SIADH 1:

• Hypotonic hyponatremia with serum osmolality <275 mOsm/kg
• Inappropriately concentrated urine (osmolality >100 mOsm/kg, typically >300 mOsm/kg)
• Urine sodium >20-40 mmol/L
• Euvolemic state (no edema, no orthostatic hypotension)
• Normal thyroid, adrenal, and renal function

Treatment algorithm 1:

1. First-line: Fluid restriction to 1 L/day
2. If no response: Add oral sodium chloride 100 mEq (2.3 g) three times daily
3. Pharmacological options for resistant cases:
   • Urea 15-30 g/day (effective but poor palatability) 1, 2
   • Demeclocycline 600-1200 mg/day 1
   • Loop diuretics with salt supplementation 1
   • Tolvaptan 15 mg once daily, titrate to 30-60 mg (see vaptan section below) 1, 4

Common causes: malignancy (especially small cell lung cancer), CNS disorders, pulmonary disease, medications (SSRIs, carbamazepine, cyclophosphamide), postoperative states, pain, nausea 1, 5

Hypervolemic Hyponatremia

Implement fluid restriction to 1-1.5 L/day for sodium <125 mmol/L—hypertonic saline is contraindicated unless life-threatening symptoms are present, as it worsens fluid overload. 1

For heart failure patients 1:

• Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L
• Continue diuretics to eliminate fluid retention (loop diuretics are cornerstone)
• Target weight loss: 0.5-1.0 kg/day
• Correct hypokalemia and hypomagnesemia aggressively while maintaining diuresis
• Consider vaptans for persistent severe hyponatremia despite fluid restriction and guideline-directed medical therapy 1, 4
• Critical principle: Do not stop diuretics due to mild hyponatremia in volume-overloaded patients—persistent volume overload increases mortality 1

For cirrhosis patients 1:

• Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L
• Temporarily discontinue diuretics if sodium <125 mmol/L
• Albumin infusion alongside fluid restriction (6-8 g per liter of ascites drained if paracentesis performed) 1
• Sodium restriction (2-2.5 g/day, 88-110 mmol/day) more important than fluid restriction—fluid passively follows sodium 1
• Avoid hypertonic saline unless life-threatening symptoms, as it worsens ascites and edema 1
• Maximum correction: 4-6 mmol/L per day due to extremely high risk of osmotic demyelination syndrome 1

Critical point: Only 1.2% of cirrhotic patients with ascites have sodium ≤120 mmol/L—chronic hyponatremia in cirrhosis is seldom acutely morbid unless rapidly corrected 1

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Special Populations and High-Risk Considerations

Patients at High Risk for Osmotic Demyelination Syndrome

For patients with advanced liver disease, alcoholism, malnutrition, severe hyponatremia, or prior encephalopathy, limit correction to 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours—these patients have dramatically increased risk of osmotic demyelination. 1

High-risk factors 1:

• Advanced liver disease or cirrhosis
• Chronic alcoholism
• Malnutrition
• Severe hyponatremia (<120 mmol/L)
• Hypokalemia, hypophosphatemia
• Prior hepatic encephalopathy

If overcorrection occurs 1:

• Immediately discontinue current fluids and switch to D5W (5% dextrose in water)
• Consider administering desmopressin to slow or reverse rapid sodium rise
• Goal: bring total 24-hour correction to ≤8 mmol/L from starting point
• Monitor for osmotic demyelination syndrome signs: dysarthria, dysphagia, oculomotor dysfunction, quadriparesis (typically 2-7 days after rapid correction)

Neurosurgical Patients: SIADH vs Cerebral Salt Wasting (CSW)

In neurosurgical patients, distinguishing SIADH from cerebral salt wasting is critical—they require opposite treatments, and using fluid restriction in CSW worsens outcomes and can be fatal. 1

SIADH characteristics 1:

• Euvolemic state (normal to slightly elevated CVP)
• Urine sodium >20-40 mmol/L
• Urine osmolality >300 mOsm/kg
• Treatment: Fluid restriction to 1 L/day

Cerebral salt wasting characteristics 1:

• True hypovolemia (CVP <6 cm H₂O)
• Urine sodium >20 mmol/L despite volume depletion
• Clinical signs: hypotension, tachycardia, dry mucous membranes
• More common in poor clinical grade, ruptured anterior communicating artery aneurysms, hydrocephalus
• Treatment: Volume and sodium replacement with isotonic or hypertonic saline, NOT fluid restriction

CSW treatment protocol 1:

• Aggressive volume resuscitation with normal saline 50-100 mL/kg/day or hypertonic saline for severe cases
• Fludrocortisone 0.1-0.2 mg daily for severe symptoms or subarachnoid hemorrhage patients
• Hydrocortisone may prevent natriuresis in subarachnoid hemorrhage patients
• Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm—this is contraindicated 1

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Pharmacological Interventions

Vasopressin Receptor Antagonists (Vaptans)

Tolvaptan is FDA-approved for euvolemic and hypervolemic hyponatremia, but should be reserved for patients who fail fluid restriction and conventional therapy due to risk of overly rapid correction and significant adverse effects. 4

Indications 1, 4:

• Euvolemic hyponatremia (SIADH) refractory to fluid restriction
• Hypervolemic hyponatremia (heart failure, cirrhosis) with persistent severe hyponatremia despite fluid restriction and guideline-directed therapy
• Starting dose: 15 mg once daily, titrate to 30-60 mg based on response

Contraindications and cautions 4:

• Contraindicated with strong CYP3A inhibitors (ketoconazole increases tolvaptan AUC 5.4-fold)
• Avoid with moderate CYP3A inhibitors and grapefruit juice
• Use with extreme caution in cirrhosis: 10% gastrointestinal bleeding risk vs 2% placebo 4
• Higher mortality in heart failure subgroup (42% vs 38% placebo) 4
• Risk of overly rapid correction and osmotic demyelination syndrome 4

Monitoring 4:

• Check sodium every 6-8 hours initially to prevent overcorrection
• Monitor for hypernatremia (1.7% incidence vs 0.8% placebo)
• Watch for thirst (12% vs 2%), dry mouth (7% vs 2%), polyuria (25% vs 7%)
• Avoid in patients requiring strong CYP3A inhibitors

Clinical pearl: In cirrhotic patients, albumin infusion should be tried before tolvaptan due to bleeding risk 1

Alternative Pharmacological Options

Urea 1, 2:

• Dose: 15-30 g/day orally (or 40 g in 100-150 mL normal saline every 8 hours IV for neurosurgical patients)
• Effective for SIADH and can be beneficial in CSW when combined with volume replacement
• Poor palatability and gastric intolerance limit use
• Promotes electrolyte-sparing free water excretion

Demeclocycline 1:

• Dose: 600-1200 mg/day
• Induces nephrogenic diabetes insipidus
• Less commonly used due to side effects

Loop diuretics with salt supplementation 1:

• For euvolemic SIADH refractory to fluid restriction
• Promotes free water excretion while replacing sodium losses

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Critical Safety Principles and Common Pitfalls

The 8 mmol/L Rule

Never exceed 8 mmol/L sodium correction in 24 hours for chronic hyponatremia—this single principle prevents osmotic demyelination syndrome, a devastating and potentially fatal complication. 1, 2

• For average-risk patients: 4-8 mmol/L per day, maximum 10-12 mmol/L in 24 hours 1
• For high-risk patients (cirrhosis, alcoholism, malnutrition): 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours 1
• Exception: Acute hyponatremia (<48 hours) can be corrected more rapidly (1-2 mmol/L per hour) without osmotic demyelination risk 2, 5

Common Pitfalls to Avoid

Using fluid restriction in cerebral salt wasting 1:

• This worsens outcomes and can be fatal
• CSW requires volume and sodium replacement, not restriction

Ignoring mild hyponatremia (130-135 mmol/L) 1:

• Associated with falls (21% vs 5%), fractures, cognitive impairment, and increased mortality
• Requires investigation and treatment of underlying cause

Administering normal saline for SIADH or hypervolemic hyponatremia 1:

• Normal saline worsens hyponatremia in SIADH (patient excretes sodium but retains water)
• Worsens fluid overload in heart failure and cirrhosis without improving sodium

Stopping diuretics in heart failure due to mild hyponatremia 1:

• Persistent volume overload increases mortality more than mild hyponatremia
• Continue diuretics and manage hyponatremia with fluid restriction

Using hypertonic saline in cirrhotic patients without life-threatening symptoms 1:

• Worsens ascites and edema
• Reserve for severe neurological symptoms only

Inadequate monitoring during active correction 1:

• Check sodium every 2 hours for severe symptoms
• Check every 4-6 hours for moderate symptoms
• Failure to monitor leads to overcorrection and osmotic demyelination

Failing to recognize and treat underlying cause 1:

• Medications (diuretics, SSRIs, carbamazepine)
• Endocrine disorders (hypothyroidism, adrenal insufficiency)
• Malignancy
• Heart failure, cirrhosis, renal disease

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Monitoring and Follow-Up

Frequency of sodium monitoring 1:

• Severe symptoms: every 2 hours during initial correction
• Moderate symptoms: every 4-6 hours
• Mild symptoms or asymptomatic: every 24-48 hours initially

Clinical monitoring 1:

• Daily weights (target 0.5-1.0 kg/day loss in hypervolemic states)
• Volume status assessment
• Neurological examination for osmotic demyelination signs
• Fluid balance tracking

Laboratory monitoring 1:

• Serum sodium, potassium, magnesium
• Serum and urine osmolality
• Urine sodium concentration
• Renal function (creatinine, BUN)