What medications are used to treat hyponatremia?

Medications for Hyponatremia

The primary medications for treating hyponatremia include 3% hypertonic saline for severe symptomatic cases, vasopressin receptor antagonists (tolvaptan, conivaptan) for euvolemic and hypervolemic hyponatremia, and adjunctive agents like fludrocortisone for cerebral salt wasting, with treatment selection based on symptom severity, volume status, and underlying etiology. 1

Hypertonic Saline (3% NaCl)

For severe symptomatic hyponatremia (seizures, coma, altered mental status), 3% hypertonic saline is the first-line medication, administered as 100-150 mL IV boluses over 10 minutes, repeatable up to three times at 10-minute intervals until symptoms resolve. 1, 2, 3 The target is to increase sodium by 4-6 mmol/L over the first 6 hours or until severe symptoms abate, with a strict maximum correction of 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1, 2, 4

• Continuous infusion can be calculated using: body weight (kg) × desired rate of sodium increase (mmol/L per hour) = infusion rate (mL/kg per hour). 5
• Monitor serum sodium every 2 hours during initial correction for severe symptoms. 1, 2
• Critical contraindication: Avoid in hypervolemic hyponatremia (cirrhosis, heart failure) without life-threatening symptoms, as it worsens fluid overload. 1

Vasopressin Receptor Antagonists (Vaptans)

Tolvaptan (Oral)

Tolvaptan is FDA-approved for clinically significant euvolemic and hypervolemic hyponatremia (serum sodium <125 mEq/L or symptomatic hyponatremia resistant to fluid restriction) in heart failure and SIADH. 4

• Dosing: Start 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily based on response. 4
• Must initiate in hospital with close sodium monitoring due to risk of overly rapid correction (>12 mEq/L/24 hours can cause osmotic demyelination). 4
• Duration limit: Do not use for more than 30 days due to hepatotoxicity risk. 4
• Contraindications: Hypovolemic hyponatremia, inability to sense thirst, anuria, concurrent strong CYP3A inhibitors, and ADPKD outside FDA-approved REMS. 4
• Cirrhosis caution: Higher risk of gastrointestinal bleeding (10% vs 2% placebo) and increased all-cause mortality with long-term use. 1

Conivaptan (IV)

Conivaptan is administered intravenously for short-term treatment of euvolemic or hypervolemic hyponatremia. 1 It provides rapid water diuresis but requires hospital monitoring for overcorrection risk. 6

Fludrocortisone

For cerebral salt wasting (CSW), particularly in neurosurgical patients with subarachnoid hemorrhage, fludrocortisone is recommended alongside volume and sodium replacement. 1, 2 This mineralocorticoid reduces natriuresis and helps prevent vasospasm in at-risk patients. 1

• Typically combined with 3% hypertonic saline and aggressive volume resuscitation in severe CSW cases requiring ICU admission. 1
• Critical distinction: CSW requires volume replacement, NOT fluid restriction (which worsens outcomes). 1, 2

Hydrocortisone

In subarachnoid hemorrhage patients, hydrocortisone may prevent natriuresis and reduce hyponatremia rates. 1 This is particularly useful in neurosurgical patients at risk for vasospasm where fluid restriction is contraindicated. 1

Oral Sodium Chloride Tablets

For mild symptomatic or asymptomatic SIADH not responding to fluid restriction, add sodium chloride 100 mEq orally three times daily. 1, 2 This is used as adjunctive therapy after initial fluid restriction to 1 L/day fails. 1, 2

• Calculate sodium deficit: Desired increase in Na (mEq/L) × (0.5 × ideal body weight in kg). 1
• Home preparation with table salt is not recommended due to formulation errors. 1

Urea

Urea is an effective second-line treatment for SIADH, particularly when fluid restriction fails. 1, 7 Dosing of 40 g in 100-150 mL normal saline every 8 hours has been effective in neurosurgical patients. 1

• Provides controlled water diuresis without the rapid correction risk of vaptans. 3, 7
• Drawback: Poor palatability and gastric intolerance limit adherence. 3

Demeclocycline

Demeclocycline is a second-line option for chronic SIADH resistant to fluid restriction. 1, 2, 8 It induces nephrogenic diabetes insipidus, reducing water reabsorption. 8

• Reserved for persistent cases due to side effect profile. 8
• Less commonly used than vaptans or urea in current practice. 2

Lithium

Lithium may be considered for refractory euvolemic hyponatremia (SIADH), though it is less commonly used due to significant side effects including nephrotoxicity and narrow therapeutic index. 1

Loop Diuretics

Loop diuretics are useful in managing edematous hyponatremic states (hypervolemic hyponatremia) and chronic SIADH. 1, 8 They promote free water excretion while removing excess volume. 8

• Contraindication: Avoid in hypovolemic hyponatremia until euvolemia is achieved, as they worsen volume depletion. 1
• Discontinue temporarily if sodium drops below 125 mmol/L in cirrhotic patients. 1

Albumin Infusion

For cirrhotic patients with hypervolemic hyponatremia, albumin infusion (6-8 g per liter of ascites drained) alongside fluid restriction improves serum sodium levels. 1 This should be attempted before considering tolvaptan in cirrhosis. 1

Critical Safety Considerations

High-risk populations (advanced liver disease, alcoholism, malnutrition, severe hyponatremia) require slower correction rates of 4-6 mmol/L per day, not exceeding 8 mmol/L in 24 hours. 1, 2, 4

If overcorrection occurs, immediately discontinue current fluids, switch to D5W (5% dextrose in water), and consider desmopressin to slow or reverse the rapid sodium rise. 1 Watch for osmotic demyelination syndrome signs (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically appearing 2-7 days after rapid correction. 1, 4

Avoid fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm, as this worsens outcomes. 1, 2