What is hyponatremia, its causes, diagnosis, classification, signs, symptoms, and management?

Hyponatremia: Definition, Causes, Diagnosis, Classification, Signs and Symptoms, and Management

Definition

Hyponatremia is defined as a serum sodium concentration below 135 mmol/L and represents the most common electrolyte disorder encountered in clinical practice. 1, 2 It affects approximately 5% of adults in the general population and up to 35% of hospitalized patients 3.

Classification

Hyponatremia is classified based on three critical parameters that guide diagnosis and treatment 1:

By Severity

• Mild: 130-135 mmol/L 1
• Moderate: 120-125 mmol/L 1
• Severe: <120 mmol/L 1

By Volume Status

• Hypovolemic hyponatremia: ECF contraction with sodium depletion from gastrointestinal losses, burns, dehydration, or excessive diuretic use 1
• Euvolemic hyponatremia: Normal volume status, most commonly caused by SIADH 1, 2
• Hypervolemic hyponatremia: Fluid overload states including heart failure, cirrhosis, and renal disease 1, 4

By Onset Timing

• Acute: <48 hours duration 1
• Chronic: >48 hours duration 1

This distinction is critical because chronic hyponatremia requires slower correction rates (4-6 mmol/L per day maximum) to prevent osmotic demyelination syndrome, while acute hyponatremia can be corrected more rapidly without this risk 1.

Causes

Euvolemic Hyponatremia (Most Common: SIADH)

• Malignancies: Particularly small cell lung cancer 1
• CNS disorders: Subarachnoid hemorrhage, meningitis, head trauma 1
• Pulmonary diseases: Pneumonia, tuberculosis 1
• Medications: SSRIs, carbamazepine, NSAIDs, opioids, chemotherapy agents 1
• Postoperative states, pain, nausea, and stress (nonosmotic ADH stimulation) 1

Hypovolemic Hyponatremia

• Gastrointestinal losses: Vomiting, diarrhea 1
• Renal losses: Diuretics (especially thiazides), salt-wasting nephropathy 1
• Third-space losses: Burns, pancreatitis 1

Hypervolemic Hyponatremia

• Heart failure: Non-osmotic vasopressin release due to decreased effective arterial volume 1
• Cirrhosis with ascites: Portal hypertension causing systemic vasodilation and activation of renin-angiotensin-aldosterone system 1
• Nephrotic syndrome and advanced renal disease 4

Special Populations

• Neurosurgical patients: Cerebral salt wasting (CSW) is more common than SIADH and requires fundamentally different treatment 1
• Cirrhotic patients: Hyponatremia occurs in approximately 60% of patients and is mostly dilutional 1

Signs and Symptoms

Symptom Severity Correlates with Three Factors

1. Rapidity of onset (acute vs. chronic) 1
2. Severity of sodium decrease 1
3. Duration of hyponatremia 1

Mild to Moderate Symptoms

• Nausea and vomiting 1
• Headache 1
• Weakness and fatigue 3
• Confusion and cognitive impairment 3
• Gait disturbances 3

Severe Symptoms (Medical Emergency)

• Seizures 1
• Coma or altered mental status 1
• Cardiorespiratory distress 3
• Somnolence or obtundation 3

Chronic Mild Hyponatremia Complications

Even mild chronic hyponatremia (130-135 mmol/L) is not benign and is associated with 1, 3:

• Increased fall risk: 21% in hyponatremic patients vs. 5% in normonatremic patients 1
• Increased fracture rates: 23.3% vs. 17.3% over 7.4 years follow-up 3
• Cognitive impairment and attention deficits 1
• 60-fold increase in hospital mortality when sodium <130 mmol/L (11.2% vs. 0.19%) 1

Diagnosis

Initial Diagnostic Workup

The diagnostic approach must be systematic and algorithmic 1:

Step 1: Confirm True Hyponatremia

• Serum osmolality to exclude pseudohyponatremia (normal: 275-290 mOsm/kg) 1
• Serum glucose: Adjust sodium by 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL 1

Step 2: Assess Volume Status

Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) and should be supplemented with laboratory findings 1:

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

Step 3: Essential Laboratory Tests

• Urine osmolality: <100 mOsm/kg indicates appropriate ADH suppression; >100 mOsm/kg suggests impaired water excretion 1
• Urine sodium concentration:
  • <30 mmol/L suggests hypovolemic hyponatremia (71-100% positive predictive value for saline responsiveness) 1

  • 20-40 mmol/L with high urine osmolality (>300 mOsm/kg) suggests SIADH 1

• Serum uric acid: <4 mg/dL has 73-100% positive predictive value for SIADH 1
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1
• Serum creatinine and BUN to assess renal function 1

Step 4: Special Considerations in Neurosurgical Patients

Distinguishing SIADH from cerebral salt wasting is critical because they require opposite treatments 1:

SIADH characteristics:

• Euvolemic state 1
• Urine sodium >20-40 mmol/L 1
• Urine osmolality >500 mOsm/kg 1
• Normal to slightly elevated central venous pressure 1

Cerebral salt wasting characteristics:

• True hypovolemia with low CVP (<6 cm H₂O) 1
• Urine sodium >20 mmol/L despite volume depletion 1
• Clinical signs of extracellular volume depletion 1
• More common in poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 1

Management

Critical Safety Principle: Correction Rate Limits

The single most important principle in hyponatremia management is to never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome. 1

• 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): 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours 1

Management 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. 1, 3

• Initial goal: Correct by 6 mmol/L over 6 hours or until severe symptoms resolve 1
• Administration: 100 mL boluses of 3% saline over 10 minutes, can repeat up to three times at 10-minute intervals 1
• Total 24-hour limit: Do not exceed 8 mmol/L correction 1
• Monitoring: Check serum sodium every 2 hours during initial correction 1
• ICU admission for close monitoring 1

Mild to Moderate Symptomatic or Asymptomatic Hyponatremia

Treatment is determined by volume status 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: 15-20 mL/kg/h for first hour, then 4-14 mL/kg/h based on response 1
• Monitoring: Urine sodium <30 mmol/L predicts good response to saline 1
• Correction rate: Do not exceed 8 mmol/L in 24 hours 1
• Special consideration for cirrhosis: Consider albumin infusion (6-8 g per liter of ascites drained) alongside isotonic saline, with more cautious correction (4-6 mmol/L per day) 1

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day is the cornerstone of treatment for SIADH. 1

• First-line: Fluid restriction to 1000 mL/day 1
• If no response: Add oral sodium chloride 100 mEq three times daily 1
• Pharmacological options for resistant cases:
  • Tolvaptan (vasopressin receptor antagonist): Start 15 mg once daily, titrate to 30-60 mg 1, 5
  • Tolvaptan increased serum sodium by 3.7 mEq/L at Day 4 and 4.6 mEq/L at Day 30 compared to placebo (p<0.0001) 5
  • Caution: Risk of overly rapid correction; avoid in cirrhosis due to 10% gastrointestinal bleeding risk vs. 2% with placebo 1
  • Urea: 40 g in 100-150 mL normal saline every 8 hours 1
  • Demeclocycline or lithium: Less commonly used due to side effects 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Implement fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L. 1

• Discontinue diuretics temporarily if sodium <125 mmol/L 1
• For cirrhosis: Consider albumin infusion alongside fluid restriction 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it worsens ascites and edema 1
• Sodium restriction (not fluid restriction) results in weight loss as fluid passively follows sodium 1
• Vaptans may be considered for persistent severe hyponatremia despite fluid restriction and maximization of guideline-directed medical therapy 1

Special Population: Cerebral Salt Wasting (Neurosurgical Patients)

Treatment focuses on volume and sodium replacement, NOT fluid restriction. 1

• Isotonic or hypertonic saline based on severity 1
• For severe symptoms: 3% hypertonic saline plus fludrocortisone 0.1-0.2 mg daily 1
• Aggressive volume resuscitation with crystalloid or colloid agents 1
• Never use fluid restriction in CSW as it worsens outcomes 1
• In subarachnoid hemorrhage patients at risk of vasospasm: Never use fluid restriction; consider fludrocortisone or hydrocortisone 1

Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours, immediately intervene to prevent osmotic demyelination syndrome. 1

• Discontinue current fluids and switch to D5W (5% dextrose in water) 1
• Consider administering desmopressin to slow or reverse the rapid rise 1
• Target: Bring total 24-hour correction to no more than 8 mmol/L from starting point 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1

Common Pitfalls to Avoid

• Overly rapid correction exceeding 8 mmol/L in 24 hours leading to osmotic demyelination syndrome 1
• Inadequate monitoring during active correction 1
• Using fluid restriction in cerebral salt wasting (worsens outcomes) 1
• Failing to recognize and treat the underlying cause 1
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant 1
• Stopping diuretics prematurely in volume-overloaded heart failure patients due to mild hyponatremia 1
• Misdiagnosing volume status in heart failure patients with hyponatremia 1