HYPONATREMIA
DEFINITION
- Hyponatremia = Serum Na⁺ < 135 mEq/L
- Most common electrolyte abnormality in ICU
Severity classification
|
Severity |
Serum Na⁺ |
|
Mild |
130–134 |
|
Moderate |
125–129 |
|
Severe |
<125 |
PATHOPHYSIOLOGY
Hyponatremia is fundamentally a disorder of water balance, NOT sodium deficit
- Excess ADH (vasopressin) → water retention → dilution of Na⁺
ADH PHYSIOLOGY
- Released from posterior pituitary
- Stimuli:
- ↑ Osmolality (primary)
- ↓ Effective circulating volume (strong non-osmotic stimulus)
HYPONATREMIA + HYPERGLYCEMIA Correction:
- Na⁺ ↑ by ~1.6 mEq/L per 100 mg/dL glucose rise
ICU-SPECIFIC CAUSES OF HYPONATREMIA
Most common ICU cause → SIADH + non-osmotic ADH
NON-OSMOTIC ADH RELEASE
almost every critically ill patient has inappropriate ADH activation
|
CAUSE |
|
Pain, stress |
|
Nausea/vomiting |
|
Hypotension |
|
Mechanical ventilation (positive pressure) |
|
Post-operative state |
CLINICAL FEATURES
Acute (<48 hr)
- Headache
- Vomiting
- Seizures
- Coma
- Brain edema
Chronic (>48 hr)
- Subtle:
- Gait disturbance
- Falls
- Cognitive impairment
COMPLICATIONS
1. CEREBRAL EDEMA
- Seen in acute hyponatremia
2. OSMOTIC DEMYELINATION SYNDROME (ODS)
Overcorrection complication
- Central pontine myelinolysis
- Delayed onset (2–6 days)
Risk factors:
- Alcoholism
- Malnutrition
- Liver disease
- Hypokalemia
CLASSIFICATION
1. BASED ON SERUM OSMOLALITY
|
CATEGORY |
MECHANISM |
ETIOLOGY |
|
Hypotonic (True)<275 mOsm/kg |
Excess free water |
See detailed classification below |
|
Isotonic (Pseudo)275–295 |
Lab artifact (↓ plasma water fraction) |
Hyperlipidemia, hyperproteinemia (e.g. multiple myeloma) |
|
Hypertonic>295 |
Osmotic shift (water moves out of cells) |
Diabetes mellitus (hyperglycemia), mannitol, glycine (TURP), radiocontrast |
2. HYPOTONIC HYPONATREMIA
A. HYPOVOLEMIC HYPONATREMIA
Mechanism: Na⁺ loss > water loss → ↓ ECF → ADH ↑
|
SUBTYPE |
URINE Na⁺ |
ETIOLOGY |
|
Extrarenal Na⁺ loss |
<30 mEq/L RAAS activation → Na retention → low urine Na |
– Vomiting – Diarrhea – Nasogastric suction – Burns – Pancreatitis (3rd spacing) – Trauma |
|
Renal Na⁺ loss |
>30 mEq/L |
Drugs: • Thiazide diuretics (most common) • Loop diuretics Endocrine: • Primary adrenal insufficiency (↓ aldosterone) Renal: • Salt-wasting nephropathy • Tubulopathies Neuro: • Cerebral salt wasting |
B. EUVOLEMIC HYPONATREMIA
Mechanism: Normal Na⁺, ↑ total body water (ADH-mediated)
|
ETIOLOGY GROUP |
CAUSES |
|
SIADH |
Core causes: • CNS: stroke, hemorrhage, tumor, infection • Pulmonary: pneumonia, TB, ARDS • Malignancy: small cell lung cancer • Post-op pain/nausea Drugs: • Selective serotonin reuptake inhibitors • Carbamazepine • Cyclophosphamide |
|
Endocrine |
– Hypothyroidism – Secondary adrenal insufficiency (↓ cortisol) |
|
Primary polydipsia |
Psychiatric disorders, psychogenic polydipsia |
|
Low solute intake |
Beer potomania, tea-toast diet |
|
Reset osmostat |
Chronic illness, pregnancy, elderly |
C. HYPERVOLEMIC HYPONATREMIA
Mechanism: Total Na⁺ ↑ but water ↑↑↑ (effective arterial volume↓)
|
ETIOLOGY |
PATHOPHYSIOLOGY |
|
Heart failure |
↓ cardiac output → ADH + RAAS activation |
|
Cirrhosis |
Splanchnic vasodilation → ↓ effective volume |
|
Nephrotic syndrome |
↓ oncotic pressure → edema → RAAS activation |
|
Advanced renal failure |
↓ water excretion |
DIAGNOSTIC APPROACH TO HYPONATREMIA:
Serum Osmolality → Urine Osmolality → Urine Sodium → Volume Status → Etiology
STEP 1: SERUM OSMOLALITY
|
Type |
Serum Osm |
Meaning |
|
Hypotonic |
<275 |
True hyponatremia |
|
Isotonic |
275–295 |
Pseudo(Hyperlipidemia,Hyperproteinemia) |
|
Hypertonic |
>295 |
Osmotic shift(Diabetes mellitus ,Mannitol,Glycine (TURP) ) |
Proceed only if hypotonic
Correct Na in hyperglycemia
- Na ↑ by ~1.6 mEq/L per 100 mg/dL glucose
STEP 2: URINE OSMOLALITY
|
Urine Osm |
Diagnosis |
|
<100 mOsm/kg |
Dilute urine → ADH suppressed |
|
>100 mOsm/kg |
Concentrated urine → ADH active |
If Urine Osm <100
- Primary polydipsia
- Low solute intake (beer potomania)
If Urine Osm >100 ADH is active → proceed further
STEP 3: URINE SODIUM
|
Urine Na⁺ |
Meaning |
|
<30 mEq/L |
Body trying to conserve Na → hypovolemia / edematous states |
|
>30 mEq/L |
Kidney wasting Na → SIADH / renal cause |
STEP 4: VOLUME STATUS ASSESSMENT Clinical assessment
|
Status |
Clinical features |
|
Hypovolemic |
Dry mucosa, tachycardia, orthostasis |
|
Euvolemic |
No edema, normal exam |
|
Hypervolemic |
Edema, ascites |
STEP 6: EXCLUDE ENDOCRINE CAUSES (MANDATORY)
- TSH → rule out hypothyroidism
- Morning cortisol → rule out adrenal insufficiency
VERY IMPORTANT:Never diagnose SIADH without excluding these
SIADH diagnostic criteria
- Serum Osm <275
- Urine Osm >100
- Urine Na >30
- Euvolemic
- Normal thyroid + adrenal function
TREATMENT
1. ACUTE HYPONATREMIA (<48 hr)
- Brain not adapted → high risk cerebral edema
- More aggressive correction allowed
- Hypertonic saline early
2. CHRONIC HYPONATREMIA (>48 hr)
- Brain adapted → risk of ODS
- Slow correction mandatory
3.Always rule out:
- Hypothyroidism
- Adrenal insufficiency
2. EMERGENCY MANAGEMENT
Indications:
- Seizures
- Coma
- Severe confusion
- Signs of cerebral edema
HYPERTONIC SALINE (3%):Bolus strategy
- 100 mL 3% NaCl over 10 minutes
- Repeat up to 3 boluses if symptoms persist
- Increase Na⁺ by 4–6 mEq/L in first 6 hours
- Enough to reverse cerebral edema (NOT normalize Na)
Monitoring:
- Serum Na⁺ every 2–4 hours
- Neurological status continuously
CONTROLLED CORRECTION LIMITS
|
Patient category |
Max correction |
|
Normal risk |
≤8–10 mEq/L / 24 hr |
|
High-risk (alcoholic, malnourished, liver disease, hypokalemia) |
≤6 mEq/L / 24 hr |
Overcorrection management:
If Na rises too fast:
- Stop therapy
- Give free water (D5W)
- ± Desmopressin (DDAVP clamp strategy)
4. CALCULATION OF SODIUM DEFICIT
Na+ deficit=(Target Na+−Current Na+)×Total Body Water
- TBW = 0.6 (men), 0.5 (women), 0.45 (elderly)
5. ETIOLOGY BASED TREATMENT
A. HYPOVOLEMIC HYPONATREMIA
Treatment = Volume resuscitation
Fluid:0.9% Normal saline
B. EUVOLEMIC HYPONATREMIA
1. SIADH (MOST COMMON)
First line:Fluid restriction ≤800–1000 mL/day
Second line:Oral salt tablets + loop diuretics
Typical: 1–3 g NaCl per dose, 2–3 times/day
Daily elemental Na⁺ delivered ≈ 34–103 mEq/day (per ~2–6 g NaCl)
Furosemide:20–40 mg PO/IV once or twice daily
Third line (refractory):Tolvaptan-blocks V2 receptor → aquaresis (water loss without Na loss)
|
Step |
Dose |
|
Start |
15 mg once daily (oral) |
|
Titrate |
Increase to 30 mg, then 60 mg once daily |
|
Interval |
Titrate every 24 hours based on Na response |
STOP fluid restriction when starting Tolvaptan
- Otherwise → massive aquaresis → rapid overcorrection → Osmotic demyelination syndrome
- Demeclocycline
- Rarely used (nephrotoxicity)
C. HYPERVOLEMIC HYPONATREMIA
1. Fluid restriction:800–1000 mL/day
2. Loop diuretics:Furosemide
3. Vasopressin antagonists:Tolvaptan
SIADH vs Cerebral Salt Wasting
|
PARAMETER |
Syndrome of Inappropriate Antidiuretic Hormone Secretion |
Cerebral Salt Wasting (CSW) |
|
Core problem |
Water retention |
Sodium loss |
|
Primary mechanism |
Excess ADH → ↑ water reabsorption |
↑ Natriuretic peptides + ↓ sympathetic tone → renal Na loss |
|
Volume status (MOST IMPORTANT) |
Euvolemic (or mild hypervolemia) |
Hypovolemic |
|
Etiology |
CNS disorders, pulmonary disease, drugs (SSRIs, carbamazepine), malignancy |
CNS injury: SAH, TBI, neurosurgery |
|
Onset (neuro patients) |
Usually later |
Often early (first few days) |
|
Serum sodium |
↓ |
↓ |
|
Serum osmolality |
↓ (<275) |
↓ (<275) |
|
Urine osmolality |
↑ (>100) |
↑ (>100) |
|
Urine sodium |
↑ (>30–40 mEq/L) |
↑ (>30–40 mEq/L) |
|
Urine output |
Normal or mildly ↑ |
High (polyuria) |
|
Fluid balance |
Normal/slightly positive |
Negative balance |
|
Hematocrit |
Normal |
↑ (hemoconcentration) |
|
BUN / Creatinine |
Normal/low |
↑ (prerenal pattern) |
|
Serum uric acid |
↓ |
↓ initially |
|
FE uric acid (FEUA) |
>12% |
>12% initially |
|
After Na correction (KEY TEST) |
Uric acid remains low |
Uric acid normalizes |
|
Natriuretic peptides (BNP/ANP) |
Normal/slightly ↑ |
Significantly ↑ |
|
Treatment (CRUCIAL DIFFERENCE) |
Fluid restriction |
Fluid + salt replacement |
|
Drug therapy |
Tolvaptan, demeclocycline |
Fludrocortisone (optional) |