HYPONATREMIA

HYPONATREMIA 

 DEFINITION

• Hyponatremia = Serum Na⁺ < 135 mEq/L
• Most common electrolyte abnormality in ICU

Severity classification

 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

 CLINICAL FEATURES

–occur in acute hyponatremia or chronic severe hyponatremia

Acute (<48 hr)

• Headache
• Vomiting
• Seizures
• Coma
• Brain edema
• Malaise/lethargy.
• Muscle cramps, myalgia.

Chronic (>48 hr)

• Subtle:
• Gait disturbance
• Falls
• Cognitive impairment

 COMPLICATIONS

1. CEREBRAL EDEMA

• Seen in acute hyponatremia 

2. OSMOTIC DEMYELINATION SYNDROME (ODS)

Overcorrection complication in chronic hyponatremia as brain is already adapted

ODS includes:

CPM + EPM together are called ODS.

• Central pontine myelinolysis(Serum osmolality rises rapidly—Water leaves brain cells—Oligodendrocytes shrink and die)
• Delayed onset (2–6 days)
• “Trident Sign” or “Bat-wing Sign” in the pons
• Clinical features-

Risk factors:

• Alcoholism
• Malnutrition
• Liver disease
• Hypokalemia

CLASSIFICATION

1. BASED ON SERUM OSMOLALITY

 2. HYPOTONIC HYPONATREMIA 

 A. HYPOVOLEMIC HYPONATREMIA

 Mechanism: Na⁺ loss > water loss → ↓ ECF → ADH ↑

 B. EUVOLEMIC HYPONATREMIA

 Mechanism: Normal Na⁺, ↑ total body water (ADH-mediated)

 C. HYPERVOLEMIC HYPONATREMIA

 Mechanism: Total Na⁺ ↑ but water ↑↑↑ (effective arterial volume↓)

 DIAGNOSTIC APPROACH TO HYPONATREMIA:

Serum Osmolality → Urine Osmolality → Urine Sodium → Volume Status → Etiology

STEP 1: SERUM OSMOLALITY

Proceed only if hypotonic

Correct Na in hyperglycemia

• Na ↑ by ~1.6 mEq/L per 100 mg/dL glucose

 STEP 2: URINE OSMOLALITY 

 If Urine Osm <100

• Primary polydipsia
• Low solute intake (beer potomania)

 If Urine Osm >100  ADH is active → proceed further

 STEP 3: URINE SODIUM

 STEP 4: VOLUME STATUS ASSESSMENT Clinical assessment

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 

INDICATIONS OF 3% N.S

• Symptomatic(irrespective of duration and severity)
• Acute Severe Asymptomatic
• Chronic severe asymptomatic—NO

1. ACUTE HYPONATREMIA (<48 hr)

• Brain not adapted → high risk cerebral edema
• More aggressive correction allowed(Hypertonic saline Bolus strategy)

 2. CHRONIC HYPONATREMIA (>48 hr)

• Brain adapted → risk of ODS
• Slow correction mandatory

3.Always rule out:

• Hypothyroidism
• Adrenal insufficiency

 HYPERTONIC SALINE (3%):Bolus strategy-

• can be safely infused via a well-functioning peripheral IV line 
• Hyponatremia should be Acute and symptomatic,acute severe  even asymptomatic.

Acute Moderate Asymptomatic Hyponatremia (Na 125–129 mEq/L): Does It Need 3% Saline?NO

Can repeat 2–3 times until:

• Symptoms improve
• Sodium rises by 4–6 mEq/L
• If the sodium has increased by ~6 mM and the symptoms have not resolved, then consider an alternative cause of the symptoms.

Initial Target

CONTROLLED CORRECTION LIMITS 

 Overcorrection management:

If Na rises too fast:

• Stop therapy
• Give free water (D5W)
• ± Desmopressin (DDAVP clamp strategy-DDAVP 2 mcg IV q8hrs scheduled)

4. CALCULATION OF SODIUM DEFICIT 

Na+ deficit=(Target Na+−Current Na+)×Total Body Water

• TBW = 0.6 (men), 0.5 (women), 0.45 (elderly)

– For a 70-kg symptomatic man with plasma Na 105 mEq/L, the amount of sodium needed to raise plasma Na by 6 mEq/L in the first 6 h is – Sodium required = 0.6 × 70 × 6 = 252 mEq/L

That is, approximately 500 mL 3%NS needed. Since 1000 mL of 3% NS has around 500 meq Na, so– 500 mL of 3% saline solution would be needed in the first 6 h, that is, 83 mL/h.

5.ADROGUÉ–MADIAS FORMULA

Predicted change in serum Na after 1 L infusion:

Dosing of 3% saline for hyponatremia

• For symptomatic/severe hyponatremia the traditional starting dose has been ~2 ml/kg body weight (e.g., ~150 ml).
•  Better approach -Adrogue-Madias equation to estimate the volume of hypertonic saline required to raise the sodium level by 3 mM (a reasonable initial sodium increase). 

6.Potassium is as osmotically active as sodium. So, giving potassium (usually for concurrent hypokalemia) can raise the serum sodium concentration and osmolality in hyponatremic patients. Intracellular sodium moves into the extracellular fluid in exchange for potassium and also extracellular chloride moves into the cells with potassium, so the increase in cell osmolality promotes free water entry into the cells and raises sodium.50 mEq of oral KCl will have about the same effect as 100 ml of 3% NaCl.50 mEq of oral KCl will have about the same effect as 100 ml of 3% NaCl.

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 but it is difficult to maintain compliance .In traumatic brain injury hypovolemia can precipitate vasospasm therefore fluid restriction or diuretics is not recommended here 3% N.S is recommended.
• Second line:oral urea(preferred European guidelines)-15-30 grams daily. 
• Oral salt tablets(1 gmNaCl =17 meq–Typical: 1–3 g NaCl per dose, 2–3 times/day with meals) .
• Use 3% saline,Isotonic saline is infrequently effective and often leads to further lowering of the serum sodium.
• loop diuretics(Furosemide:20–40 mg PO/IV TDS/QID) if urine output is very low and urine osmolality is more than twice the plasma osmolality (typically more than 550).
• Third line (refractory):Tolvaptan-blocks V2 receptor → aquaresis (water loss without Na loss)
• Vaptans are not a preferred therapy for critically ill patients(European guidelines) because Water loss is uncontrolled and unpredictable.Patients may develop overshoot hypernatremia.
• Vaptans be useful for outpatient therapy in patients who are unable to receive oral urea.These should be avoided in acute SIADH.
• Tolvaptan should not be used for longer than 1 month and should not be given to patients with liver disease (including cirrhosis).

 STOP fluid restriction when starting Tolvaptan

• Otherwise → massive aquaresis → rapid overcorrection → Osmotic demyelination syndrome

• Demeclocycline  600–1200 mg/day. (Nephrotoxic)

 C. HYPERVOLEMIC HYPONATREMIA

• Treatment is Double Edge Sword so The best approach to chronic, asymptomatic hyponatremia is to provide no specific therapy for the hyponatremia and focus on treating the cause

1. Fluid restriction:800–1000 mL/day

2. Loop diuretics:Furosemide if volume overload

3. Vasopressin antagonists:Tolvaptan

SIADH vs Cerebral Salt Wasting

REFERENCES

1. ICU Protocol by ISCCM(3rd edition)
2. Washington manual