Hyponatremia

Background

• Defined as sodium concentration <135meq/L
• Patients often not symptomatic until <120meq/L, although this level varies by patients and may be higher if the change occurred abruptly
• Too fast of sodium correction (>10 mmol/L/day), especially if chronic, can cause osmotic demyelination syndrome (central pontine myelinolysis)

Clinical Features

Hyponatremia Symptoms by Severity

Severity	NOT severe	Moderately severe	Severe
Symptoms	Gait disturbances Falls Concentration Cognitive deficits	Nausea without vomiting Confusion Headache	Vomiting Cardiorespiratory distress Abnormal and deep somnolence Seizures Coma (GCS <8)

Symptoms from Rapid Correction of Sodium

• CHF
• Osmotic demyelination syndrome (central pontine myelinolysis)
  • Altered mental status
  • Dysphagia
  • Dysarthria
  • Paresis

Differential Diagnosis of Hypotonic Hyponatremia (by Volume Status)

Hypovolemic

Renal Causes

• Thiazide diuretic use
• Na-wasting nephropathy (RTA, CKD)
• Osmotic diuresis (glucose, urea)
• Aldosterone deficiency

Extra-renal Causes

• GI loss
• 3rd space loss
• Burns
• Pancreatitis
• Peritonitis

Hypervolemic

• Urinary Na >20
  • Renal failure
• Urinary Na <20
  • Nephrotic syndrome
  • Cirrhosis
  • CHF

Euvolemic

• SIADH
  • urine sodium is greater than 20-40 mEq/L
• Pain, stress, nausea
• Psychogenic polydipsia
• Hypothyroidism
• Drugs
  • NSAIDs, sulfonylurea, bupropion
• H₂0 intoxication
• Glucocorticoid deficiency

Pseudohyponatremia

• Hyperglycemia
  • Na+ decreases by 2.4mEq/L for each 100mg/dL increase in glucose over 100mg/dL
• Displaced sodium in lab specimen
  • Hyperlipidemia
  • Hyperproteinemia

Evaluation

Work-Up

Prior to giving treatment

• Urine
  • Urinalysis
  • Urine electrolytes (Urine sodium)
  • Urine urea
  • urine uric acid
  • urine osmolality
  • urine creatinine
• Serum
  • Chemistry including Ca/Mg/Phos
  • Serum osmolality
  • Uric acid
  • TSH
  • Cortisol

Diagnosis

True serum sodium (corrected) based on serum glucose

Algorithm for hyponatremia diagnosis

1. Correct for glucose (see table)
2. Determine volume status
3. Calculated osm (in true hyponatremia the osm is reduced)

Hypertonic Hyponatremia

Defined as osmolarity > 295mmol/L with the following causes:

1. Hyperglycemia
   • Sodium decreases by 2.4mEq/L for each 100mg/dL increase in glucose over 100mg/dL
2. Mannitol excess

Isotonic (pseudo) hyponatremia

Defined as osmolarity > 275-295mmol/L. Often referred to as pseudo hyponatremia because the elevated lipids or proteins interfere with the laboratory sodium reading. The following are common causes:

1. Hyperlipidemia
2. Hyperproteinemia

Hypotonic Hyponatremia

Defined as an osmolarity < 275 mmol/L and categorized as hypovolemic, hypervolemic or euvolemic

General Management

Must have sufficient confidence that the symptoms are caused by hyponatraemia; see Clinical Features for definition of categories.

NOT Severe/Moderately-Severe (Including Asymptomatic)

Adults:

1. Start prompt diagnostic assessment and provide cause-specific treatment
2. Check serum sodium concentration after 4 hours
   • Aim for a 5 mmol/l per 24-h increase in serum sodium concentration
   • Limit increase to 10 mmol/l in the first 24 h (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached
3. Manage the patient as in moderately-severe symptomatic hyponatraemia if the serum sodium concentration decreases 10 mmol/l

Moderately Severe Symptoms

Adults:

1. 3% hypertonic saline 150 mL bolus over 20 min
2. Start prompt diagnostic assessment and provide cause-specific treatment
3. Check serum sodium concentration after 1, 6 and 12 hours
   • Aim for a 5 mmol/l per 24-h increase in serum sodium concentration
   • Limit increase to 10 mmol/l in the first 24 h (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached
4. Consider DDAVP (2mcgs IV q8h) to prevent overcorrection
5. Manage the patient as in severely symptomatic hyponatraemia if the serum sodium concentration further decreases despite treating the underlying diagnosis (2D).

Severe Symptoms

Adults:

1. 3% hypertonic saline 150 mL bolus over 20 min
2. Check serum sodium concentration after 20 min
3. Repeat infusion of 150 ml 3% hypertonic saline for the next 20 min
4. Repeat twice or until a target of 5 mmol/l increase in serum sodium concentration is achieved
   • Each 100 mL will raise sodium by ~2 mmol/l
   • In general, 200-400 mL of 3% hypertonic saline is reasonable dose in most adult patients with severe symptomatic hyponatremia, which may be given IV over 1-2 hr until resolution of seizures.
5. If you do not have 3% hypertonic saline you can give two ampules (100ml) of crash cart hypertonic bicarbonate (1 mEq/ml sodium bicarbonate equivalent to giving ~200 ml of 3% saline, which will raise the serum sodium by ~3 mM).
   • Sodium bicarbonate should be given slowly (each ampule over 5-10 minutes). Bicarbonate is contraindicated in patients with metabolic alkalosis.

Pediatrics:

• 2 mL/kg of 3% over 10-60 minutes can be infused with a repeat of up to 3 times.

Cause-Specific Treatment

Hypertonic hyponatremia

• Correct underlying disorder which is often hyperglycemia
• Often volume depleted due to osmotic diuresis and normal saline provides adequate volume repletion

Isotonic (pseudo) hyponatremia

• No treatment needed

Hypotonic hyponatremia

1. Hypovolemic
   • Give normal saline, but be cautious of raising the serum sodium more than 10 mmol/L/day and causing osmotic demyelination syndrome (central pontine myelinolysis)
2. Euvolemic
   • Water restrict
   • Treat underlying cause
3. Hypervolemic
   • Water restriction
   • Diuresis
   • Treat underlying cause

Calculating Sodium Replacement Therapy

Max correction 10mEq/L in first 24hr (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached (lowers risk of osmotic demyelination syndrome)

Step 1

Calculate total body water

• TBW(kg) = Wt(kg) x 0.6 = [Wt(lb) x 0.45] x 0.6 = Wt(lb) x 0.27

Step 2

Calculate mEq deficit

• (Desired Na - Measured Na) ~ must be ≤ 10

Step 3

Calculate NS rate to be given over 24hr

• NS rate (cc/hr) = TBW x mEq deficit x 0.27
• If using 3% sodium chloride (to avoid volume overload) divide above rate by 3.33

Sodium Containing fluid Concentrations

Fluid type	Sodium Concentration
1/2 Normal Saline	77 mEq/L
Normal Saline	154 mEq/L
Lactated Ringers	130 mEq/L
3% Saline	513 mEq/L

DDAVP Combined with Hypertonic Saline

• Limited evidence suggests usage of DDAVP in combination with HTS can safely increase sodium, while lowering risk for over-correction
  • DDAVP prevents free water excretion renally
  • Give 3% hypertonic saline based on calculations above
  • Give desmopressin 1-2 µg IV q6 hours
  • Patients must be PO water restricted
• Goal sodium is 6 mEq/L over first 24 hours

Disposition

• Admit if symptomatic or if Na <125mEq/L
• Manage severely symptomatic patients in "an environment where close biochemical and clinical monitoring can be provided" (e.g. ICU)

See Also

• Electrolyte abnormalities
• Osmotic demyelination syndrome

External Links

• IBCC Hyponatremia Josh Farkas
• EMCrit Hyponatremia Management
• DDxOf: Differential Diagnosis of Electrolyte Abnormalities
• PulmCrit DDAVP Clamp