What is the approach to assessing hyponatremia, including definition, differential diagnosis, history, physical examination, investigations, empiric treatment, and indications for referral?

Approach to Assessment of Hyponatremia

Definition

Hyponatremia is defined as serum sodium <135 mmol/L, with levels <131 mmol/L requiring comprehensive workup and treatment. 1

• Mild: 126-135 mmol/L 1
• Moderate: 120-125 mmol/L 1
• Severe: <120 mmol/L 1
• Affects approximately 5% of adults and 35% of hospitalized patients 2

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Differential Diagnosis

Based on Volume Status

Hypovolemic Hyponatremia 1, 3

• Extrarenal losses: vomiting, diarrhea, third-spacing, burns (urine Na <30 mmol/L) 3
• Renal losses: diuretics, cerebral salt wasting, adrenal insufficiency, salt-losing nephropathy (urine Na >20 mmol/L) 3

Euvolemic Hyponatremia 1, 3

• SIADH (most common): malignancy (especially small cell lung cancer), CNS disorders, pulmonary disease, medications 3
• Hypothyroidism 1
• Adrenal insufficiency 1
• Polydipsia 3

Hypervolemic Hyponatremia 1, 3

• Heart failure 1
• Cirrhosis with ascites 1
• Advanced renal failure 3
• Nephrotic syndrome 1

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History

Key Characteristics to Elicit

Onset and Duration 1

• Acute (<48 hours) vs. chronic (>48 hours) - critical for determining correction rate 1
• Rapidity of development determines symptom severity 2

Symptom Severity 1, 2

• Severe symptoms: seizures, coma, somnolence, obtundation, cardiorespiratory distress 2
• Moderate symptoms: nausea, vomiting, confusion, headache 1
• Mild/chronic symptoms: weakness, cognitive impairment, gait disturbances, falls 2

Red Flags

• Seizures or altered mental status requiring immediate hypertonic saline 1, 2
• Rapid onset (<48 hours) with neurological symptoms 1
• History of falls (21% of hyponatremic patients vs. 5% normonatremic) 1
• Sodium <120 mmol/L (60-fold increase in mortality when <130 mmol/L) 1

Risk Factors

Medications 1, 4

• Diuretics (especially thiazides) 1
• SSRIs, carbamazepine, NSAIDs 1
• Chemotherapy agents 1

Medical Conditions 1, 2

• Advanced liver disease, alcoholism, malnutrition (higher risk of osmotic demyelination) 1
• Heart failure, cirrhosis 1
• Malignancy (especially lung cancer) 1
• Recent neurosurgery or subarachnoid hemorrhage 1, 5
• Postoperative state 6

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Physical Examination (Focused)

Volume Status Assessment

Note: Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) - laboratory confirmation essential 5, 3

Hypovolemia Signs 5, 3

• Orthostatic hypotension, tachycardia 5
• Dry mucous membranes, decreased skin turgor 5
• Sunken eyes, furrowed tongue 1
• Confusion, non-fluent speech, extremity weakness 1

Euvolemia Signs 1

• No edema, no orthostatic hypotension 1
• Normal skin turgor, moist mucous membranes 1

Hypervolemia Signs 1, 5

• Jugular venous distention 1
• Peripheral edema, ascites 5
• Orthopnea, dyspnea 1

Neurological Examination

• Mental status changes, confusion 1
• Gait assessment (falls risk) 2
• Seizure activity 1

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Investigations

Initial Laboratory Workup

Essential First-Line Tests 1, 5, 4

• Serum osmolality (normal 275-290 mOsm/kg) - rules out pseudohyponatremia 3, 4
• Urine osmolality 1, 5
  • <100 mOsm/kg: appropriate ADH suppression (polydipsia) 3

  • 300-500 mOsm/kg: inappropriate ADH activity (SIADH or CSW) 3

• Urine sodium 1, 5
  • <30 mmol/L: hypovolemic hyponatremia (71-100% PPV for saline response) 5, 3

  • 20-40 mmol/L: SIADH (if euvolemic) or CSW (if hypovolemic) 5, 3

Additional Tests 1, 4

• Serum creatinine, BUN (elevated in hypovolemia) 1
• Serum uric acid (<4 mg/dL has 73-100% PPV for SIADH) 5, 3
• TSH (rule out hypothyroidism) 1, 4
• Morning cortisol (rule out adrenal insufficiency) 4
• Liver function tests (assess for cirrhosis) 1

Advanced/Invasive Monitoring

When Available in Neurosurgical Patients 3

• Central venous pressure: <6 cm H₂O suggests CSW; 6-10 cm H₂O suggests SIADH 3
• Note: ADH and natriuretic peptide levels NOT recommended (Class III evidence) 3

Expected Findings by Diagnosis

SIADH 3

• Serum osmolality <275 mOsm/kg, urine osmolality >500 mOsm/kg 3
• Urine sodium >20-40 mmol/L 3
• Euvolemia on exam 3
• Serum uric acid <4 mg/dL 5

Cerebral Salt Wasting 1, 5

• Urine sodium >20 mmol/L 5
• Signs of volume depletion 5
• CVP <6 cm H₂O (if available) 3

Hypovolemic Hyponatremia 5

• Urine sodium <30 mmol/L (extrarenal losses) 5
• Elevated BUN/creatinine ratio 1

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Empiric Treatment

Based on Symptom Severity

Severe Symptomatic (Seizures, Coma, Obtundation) 1, 2

• Administer 3% hypertonic saline immediately 1, 2
• Goal: Increase sodium by 6 mmol/L over 6 hours OR until symptoms resolve 1
• Bolus method: 100 mL of 3% saline over 10 minutes, repeat up to 3 times at 10-minute intervals 1
• Maximum correction: 8 mmol/L in 24 hours 1, 2
• ICU admission for monitoring 1
• Check sodium every 2 hours during initial correction 1

Moderate/Asymptomatic - Based on Volume Status 1

Hypovolemic:

• Discontinue diuretics 1
• Isotonic saline (0.9% NaCl) for volume repletion 1
• Maximum correction: 8 mmol/L in 24 hours 1

Euvolemic (SIADH):

• Fluid restriction to 1 L/day (cornerstone of treatment) 1, 3
• Add oral sodium chloride 100 mEq three times daily if no response 1
• Consider urea, demeclocycline, or vaptans for resistant cases 1

Hypervolemic (Heart Failure/Cirrhosis):

• Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 1
• Discontinue diuretics temporarily 1
• Consider albumin infusion in cirrhotic patients 1
• Avoid hypertonic saline unless life-threatening symptoms 1

Special Populations

High-Risk for Osmotic Demyelination 1

• Advanced liver disease, alcoholism, malnutrition, prior encephalopathy 1
• More cautious correction: 4-6 mmol/L per day 1

Neurosurgical Patients/Subarachnoid Hemorrhage 1, 5

• Distinguish SIADH from cerebral salt wasting 1, 5
• For CSW: Volume and sodium replacement with isotonic/hypertonic saline + fludrocortisone 1
• Do NOT use fluid restriction in CSW or patients at risk for vasospasm 1

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Indications to Refer

Immediate Referral/ICU Admission

• Severe symptomatic hyponatremia (seizures, coma) requiring hypertonic saline 1
• Sodium <120 mmol/L with any symptoms 1
• Rapid correction requiring intensive monitoring 1
• Cerebral salt wasting in neurosurgical patients 1

Specialist Consultation

Nephrology 1

• Refractory hyponatremia despite appropriate treatment 1
• Complex cases requiring vaptans 1
• Suspected osmotic demyelination syndrome 1

Endocrinology 1

• Suspected adrenal insufficiency or hypothyroidism 1
• SIADH from endocrine causes 1

Hepatology 1

• Cirrhotic patients with sodium <130 mmol/L 1
• Consideration for liver transplantation 1

Neurosurgery/Neurology 1, 5

• Post-neurosurgical hyponatremia 5
• Subarachnoid hemorrhage with hyponatremia 1
• Suspected or confirmed osmotic demyelination syndrome 1

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Critical Pitfalls

Diagnostic Pitfalls

• Relying solely on physical examination for volume status (sensitivity only 41.1%) 5, 3
• Misdiagnosing CSW as SIADH in neurosurgical patients - leads to harmful fluid restriction 1, 5
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant 1
• Obtaining ADH or natriuretic peptide levels (not evidence-based) 3
• Failing to check serum osmolality first to rule out pseudohyponatremia 3, 4

Treatment Pitfalls

• Overly rapid correction exceeding 8 mmol/L in 24 hours → osmotic demyelination syndrome 1, 2
• Using fluid restriction in CSW or subarachnoid hemorrhage patients at risk for vasospasm 1
• Inadequate monitoring during active correction 1
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Failing to recognize and treat the underlying cause 1
• Administering normal saline in SIADH (worsens hyponatremia) 1
• Not adjusting correction rates for high-risk patients (liver disease, alcoholism, malnutrition) 1

Monitoring Pitfalls

• Insufficient sodium monitoring frequency during correction 1
• Missing signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) appearing 2-7 days post-correction 1
• Not having a plan for overcorrection (use D5W or desmopressin to relower sodium) 1