What is the recommended management of hyponatremia in adults, including initial treatment for acute symptomatic hyponatremia (serum sodium less than 125 mmol/L) and subsequent therapy based on volume status (hypovolemic, euvolemic such as syndrome of inappropriate antidiuretic hormone secretion, and hypervolemic)?

Management of Hyponatremia in Adults

For acute symptomatic hyponatremia with serum sodium <125 mmol/L, immediately administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until symptoms resolve, never exceeding 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1

Initial Assessment and Classification

Determine the acuity of onset (acute <48 hours versus chronic >48 hours) and assess symptom severity, as these factors dictate the urgency and rate of correction. 1 Acute hyponatremia causes more severe symptoms at the same sodium level compared to chronic hyponatremia. 2

Evaluate volume status through physical examination, looking for:

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 1
• Euvolemic signs: normal skin turgor, moist mucous membranes, no edema, no orthostatic changes 1
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, pulmonary congestion 1

Obtain essential laboratory tests: serum and urine osmolality, urine sodium concentration, serum creatinine, thyroid-stimulating hormone (TSH), and serum uric acid. 1 A serum uric acid <4 mg/dL has a 73-100% positive predictive value for SIADH. 1

Management of Acute Symptomatic Severe Hyponatremia

Severe Symptoms (Seizures, Coma, Altered Mental Status)

Administer 3% hypertonic saline immediately with an initial goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve. 1 This can be given as 100 mL boluses over 10 minutes, repeated up to three times at 10-minute intervals. 1

Monitor serum sodium every 2 hours during the initial correction phase for severe symptoms. 1 Total correction must not exceed 8 mmol/L in any 24-hour period to prevent osmotic demyelination syndrome. 1, 3

Consider ICU admission for close monitoring during treatment of severe symptomatic hyponatremia. 1

Management Based on Volume Status

Hypovolemic Hyponatremia

Discontinue diuretics immediately and administer isotonic saline (0.9% NaCl) for volume repletion. 1 Initial infusion rate should be 15-20 mL/kg/h, then 4-14 mL/kg/h based on response. 1

A urinary sodium <30 mmol/L has a positive predictive value of 71-100% for response to 0.9% saline infusion, confirming the diagnosis of hypovolemic hyponatremia. 1

Continue isotonic fluids until euvolemia is achieved, monitoring for improvement in orthostatic vital signs, skin turgor, and mucous membrane moisture. 1

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day is the cornerstone of treatment for mild to moderate asymptomatic SIADH. 1, 4 If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily. 1

For severe symptomatic SIADH, administer 3% hypertonic saline with careful monitoring, targeting correction of 6 mmol/L over 6 hours. 1

Pharmacological options for resistant cases include vasopressin receptor antagonists (tolvaptan starting at 15 mg once daily, titrate to 30-60 mg), demeclocycline, or lithium. 1, 5 However, these should be used with caution due to the risk of overly rapid correction. 1

Diagnostic criteria for SIADH require: hypotonic hyponatremia, inappropriately concentrated urine (urine osmolality >100 mOsm/kg), elevated urine sodium (>20-40 mmol/L), clinical euvolemia, and normal renal, thyroid, and adrenal function. 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Implement fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L. 1, 6 This is the first-line treatment for hypervolemic hyponatremia. 1

Discontinue diuretics temporarily if sodium <125 mmol/L until sodium improves. 1

For cirrhotic patients, consider albumin infusion (8 g per liter of ascites removed) alongside fluid restriction. 1 Albumin can help improve serum sodium levels in patients with cirrhosis and hyponatremia. 1

Avoid hypertonic saline unless life-threatening symptoms are present, as it may worsen edema and ascites. 1 Hypertonic saline in hypervolemic hyponatremia without severe neurological symptoms is a common pitfall to avoid. 1

Vasopressin receptor antagonists (tolvaptan) may be considered for clinically significant hyponatremia resistant to fluid restriction, starting at 15 mg once daily. 1 However, use with extreme caution in cirrhosis due to higher risk of gastrointestinal bleeding (10% vs 2% placebo). 1

Critical Correction Rate Guidelines

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 more cautious correction at 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours. 1, 3 These patients have a 0.5-1.5% risk of osmotic demyelination syndrome even with careful correction. 1

If overcorrection occurs, immediately discontinue current fluids and switch to D5W (5% dextrose in water), and consider administering desmopressin to slow or reverse the rapid rise in serum sodium. 1 The goal is to bring the total 24-hour correction back to ≤8 mmol/L from baseline. 1

Special Considerations for Neurosurgical Patients

Distinguish between SIADH and cerebral salt wasting (CSW), as they require opposite treatments. 1 CSW is more common in neurosurgical patients than SIADH. 1

SIADH characteristics: euvolemic state, urine sodium >20-40 mmol/L, urine osmolality >300 mOsm/kg, central venous pressure 6-10 cm H₂O. Treatment is fluid restriction. 1

CSW characteristics: hypovolemic with orthostatic changes, urine sodium >20 mmol/L despite volume depletion, central venous pressure <6 cm H₂O. Treatment is volume and sodium replacement with isotonic or hypertonic saline, NOT fluid restriction. 1

For severe CSW symptoms, administer 3% hypertonic saline plus fludrocortisone (0.1-0.2 mg daily) in ICU setting. 1

In subarachnoid hemorrhage patients at risk of vasospasm, hyponatremia should NOT be treated with fluid restriction, as this worsens outcomes. 1 Consider fludrocortisone or hydrocortisone to prevent natriuresis. 1

Monitoring During Treatment

For severe symptoms: monitor serum sodium every 2 hours during initial correction. 1

After resolution of severe symptoms: monitor every 4 hours. 1

For mild symptoms or asymptomatic patients: monitor every 24-48 hours initially. 1

Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction. 1, 3

Common Pitfalls to Avoid

Overly rapid correction exceeding 8 mmol/L in 24 hours is the most critical error, leading to osmotic demyelination syndrome. 1, 3

Using fluid restriction in cerebral salt wasting can worsen outcomes and precipitate cerebral ischemia. 1

Inadequate monitoring during active correction increases the risk of overcorrection. 1

Failing to recognize and treat the underlying cause leads to recurrent hyponatremia. 1

Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant is a mistake, as even mild chronic hyponatremia increases fall risk (21% vs 5% in normonatremic patients) and mortality (60-fold increase with sodium <130 mmol/L). 1, 2, 3