What are the common causes, diagnostic approach, and treatment recommendations for hyponatremia (salt deficiency) in an adult patient?

Hyponatremia (Salt Deficiency): Causes, Diagnosis, and Treatment

Common Causes

Hyponatremia affects approximately 5% of adults and 35% of hospitalized patients, making it the most common electrolyte disorder encountered in clinical practice 1. The causes vary by volume status:

Hypovolemic Hyponatremia

• Gastrointestinal losses (vomiting, diarrhea) with urinary sodium <30 mmol/L 2
• Excessive diuretic use, particularly thiazide diuretics 2
• Renal salt wasting with urinary sodium >20 mmol/L 2
• Burns and third-spacing of fluids 2

Euvolemic Hyponatremia

• Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is the most common cause, characterized by inappropriate urinary concentration despite low plasma osmolality 2, 1
• Medications including SSRIs, carbamazepine, cyclophosphamide, NSAIDs, and opioids 2
• Malignancies, particularly small cell lung cancer (affects 1-5% of lung cancer patients) 2
• CNS disorders and pulmonary diseases 2
• Postoperative states, pain, nausea, and stress (nonosmotic AVP release) 2
• Hospital-acquired hyponatremia from hypotonic IV fluids affects 15-30% of hospitalized patients and is entirely preventable by using isotonic maintenance fluids 2

Hypervolemic Hyponatremia

• Advanced liver cirrhosis with portal hypertension (21.6% of cirrhotic patients have sodium ≤130 mmol/L) 2
• Congestive heart failure 2, 3
• Renal disease with impaired water excretion 3

Diagnostic Approach

Initial Assessment

Begin by confirming true hyponatremia (serum sodium <135 mmol/L) and pursue full workup when sodium drops below 131 mmol/L 2. The diagnostic algorithm should proceed systematically:

Step 1: Measure serum osmolality to exclude pseudohyponatremia 2, 4:

• High osmolality (>295 mOsm/kg): hyperglycemia-induced (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 2
• Normal osmolality (275-295 mOsm/kg): pseudohyponatremia from hyperlipidemia or hyperproteinemia 2
• Low osmolality (<275 mOsm/kg): true hypotonic hyponatremia requiring further evaluation 2

Step 2: Assess volume status clinically 2, 4:

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins, tachycardia 2
• Euvolemic: absence of edema, normal blood pressure, moist mucous membranes 2
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, pulmonary congestion 2

Note: Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) and should be supplemented with laboratory findings 2.

Step 3: Obtain urine studies 2, 4:

• Urine osmolality: <100 mOsm/kg indicates appropriate ADH suppression; >100 mOsm/kg suggests impaired water excretion 2
• Urine sodium concentration:
  • <30 mmol/L: suggests hypovolemic hyponatremia (71-100% positive predictive value for saline responsiveness) 2

  • 20-40 mmol/L with high urine osmolality (>300 mOsm/kg): suggests SIADH 2

Step 4: Additional diagnostic tests 2:

• Serum creatinine and BUN (elevated in hypovolemia) 2
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 2
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 2
• Liver function tests if cirrhosis suspected 2

Special Diagnostic Considerations in Neurosurgical Patients

In patients with CNS pathology, distinguishing SIADH from cerebral salt wasting (CSW) is critical because they require opposite treatments 2:

SIADH characteristics 2:

• Euvolemic state
• Urine sodium >20-40 mmol/L
• Urine osmolality >500 mOsm/kg
• Normal to slightly elevated central venous pressure
• Treatment: fluid restriction

Cerebral salt wasting characteristics 2:

• True hypovolemia with CVP <6 cm H₂O
• Urine sodium >20 mmol/L despite volume depletion
• Clinical signs of hypovolemia
• Treatment: volume and sodium replacement (fluid restriction worsens outcomes and can be fatal) 2

Treatment Recommendations

Classification by Severity and Symptom Status

Severity classification 2, 4:

• Mild: 130-135 mmol/L
• Moderate: 120-129 mmol/L (or 125-129 mmol/L by some definitions)
• Severe: <120 mmol/L (or <125 mmol/L)

Symptom classification guides urgency 1, 4:

• Mild symptoms: nausea, vomiting, weakness, headache, mild neurocognitive deficits 1
• Severe symptoms: delirium, confusion, seizures, coma, cardiorespiratory distress 1

Severe Symptomatic Hyponatremia (Medical Emergency)

For patients with severe symptoms (seizures, coma, altered mental status), immediately administer 3% hypertonic saline with an initial goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 2, 1. This can be given as 100 mL boluses over 10 minutes, repeated up to three times at 10-minute intervals 2.

Critical correction rate limits 2, 1:

• Total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 2
• For high-risk patients (advanced liver disease, alcoholism, malnutrition, prior encephalopathy), limit to 4-6 mmol/L per day 2

Monitoring during acute correction 2:

• Check serum sodium every 2 hours during initial correction
• After symptom resolution, check every 4 hours
• ICU admission recommended for close monitoring 2

Treatment Based on Volume Status

Hypovolemic Hyponatremia

Administer isotonic saline (0.9% NaCl) for volume repletion 2, 4:

• Initial infusion rate: 15-20 mL/kg/h for first hour 2
• Subsequent rate: 4-14 mL/kg/h based on clinical response 2
• Discontinue diuretics immediately 2
• Consider albumin infusion in cirrhotic patients 2

Urinary sodium <30 mmol/L predicts good response to saline with 71-100% positive predictive value 2.

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day (or <800 mL/day for refractory cases) is the cornerstone of treatment 2, 4:

• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 2
• For resistant cases, consider pharmacological options:
  • Vasopressin receptor antagonists (vaptans): tolvaptan 15 mg once daily, titrate to 30-60 mg 2
  • Urea, demeclocycline, or lithium (less commonly used due to side effects) 2

For severe symptomatic SIADH, use 3% hypertonic saline as described above 2.

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Implement fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L 2, 4:

• Discontinue diuretics temporarily if sodium <125 mmol/L 2
• For cirrhotic patients, consider albumin infusion (8 g per liter of ascites removed) 2
• Avoid hypertonic saline unless life-threatening symptoms are present, as it may worsen ascites and edema 2

In cirrhosis, sodium restriction (2-2.5 g/day) rather than fluid restriction results in weight loss, as fluid passively follows sodium 2.

For heart failure patients with persistent severe hyponatremia despite water restriction and maximization of guideline-directed medical therapy, vasopressin antagonists may be considered short-term 2.

Special Considerations for Cerebral Salt Wasting

CSW requires fundamentally different treatment than SIADH 2:

• Volume and sodium replacement with isotonic or hypertonic saline (50-100 mL/kg/day) 2
• For severe symptoms: 3% hypertonic saline plus fludrocortisone 0.1-0.2 mg daily in ICU 2
• Never use fluid restriction in CSW—it worsens outcomes and can be fatal 2
• In subarachnoid hemorrhage patients at risk of vasospasm, avoid fluid restriction and consider hydrocortisone to prevent natriuresis 2

Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours 2:

• Immediately discontinue current fluids and switch to D5W (5% dextrose in water) 2
• Consider administering desmopressin to slow or reverse the rapid rise 2
• Goal: bring total 24-hour correction back to ≤8 mmol/L from baseline 2

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

Common Pitfalls to Avoid

Critical errors in hyponatremia management 2:

• Overly rapid correction exceeding 8 mmol/L in 24 hours leads to osmotic demyelination syndrome 2
• Using fluid restriction in cerebral salt wasting worsens outcomes 2
• Inadequate monitoring during active correction 2
• Failing to recognize and treat the underlying cause 2
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 2
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant—even mild hyponatremia increases fall risk (21% vs 5% in normonatremic patients) and mortality (60-fold increase with sodium <130 mmol/L) 2
• Misdiagnosing CSW as SIADH in neurosurgical patients leads to inappropriate fluid restriction 2

Key Clinical Pearls

Even mild chronic hyponatremia has significant clinical consequences 1:

• Associated with cognitive impairment and gait disturbances 1
• Increased rates of falls (23.8% vs 16.4%) and fractures (23.3% vs 17.3% over 7.4 years) 1
• Secondary cause of osteoporosis 1

In cirrhotic patients, hyponatremia reflects worsening hemodynamic status and increases risk of 2:

• Spontaneous bacterial peritonitis (OR 3.40) 2
• Hepatorenal syndrome (OR 3.45) 2
• Hepatic encephalopathy (OR 2.36) 2