Hyponatremia resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2]

Definition

Hyponatremia is defined as a serum sodium concentration < 135 meq/L.

Hyponatremia with low osmolality (hypotonic hyponatremia) is defined as hyponatremia with a serum osmolality below 280 mOsm/kg.

Hyponatremia with high osmolality (hypertonic hyponatremia) is defined as hyponatremia with a serum osmolality greater than 295 mOsm/kg.

Hyponatremia with normal osmolality (Isotonic hyponatremia) is defined as hyponatremia with a serum osmolality ranging between 280-295 mOsm/kg.

Causes

Each of the causes listed below can be life threatening when Na⁺ levels are severely low. (Below 125 meq/L)

Common Causes

Hyponatremia causes can be classified into 3 types based on calculating serum osmolality, which is calculated as follows:
Sosm(mmol/kg) = (2 x serum Na⁺ conc.) + (serum glucose conc./18) + (blood urea nitrogen/2.8)
Where Ssom is Serum osmolality.

♦ Hyponatremia with low serum osmolality

• Appropriate ADH secretion (Primary polydipsia, advanced renal failure, low dietary intake)
• Arterial blood volume depletion

1. True blood volume depletion (Diarrhea, vomiting, bleeding, use of diuretics)
2. Thiazide diuretic induced
3. Heart failure, cirrhosis

• Ecstasy consumption.
• Endocrine disorders such as hypothyroidism and adrenal failure.
• Syndrome of inappropriate antidiuretic hormone secretion(SIADH)

♦ Hyponatremia with high serum osmolality

• Marked hyperglycemia
• Mannitol infusion

♦ Hyponatremia with normal serum osmolality

• Pseudohyponatremia (hyperlipidemia, hyperproteinemia)

Diagnosis

Characterize the symptoms: ❑ Nausea and vomiting ❑ Headache ❑ Confusion ❑ Lethargy, fatigue, loss of appetite ❑ Restlessness and irritability ❑ Muscle weakness/spasms/cramps ❑ Seizures ❑ Decreased consciousness or coma. Na+ < 115 meq/L: Hyponatremic encephalopathy ❑ Symptoms mentioned above plus ❑ Brain stem compression ❑ Respiratory arrest ❑ Non-cardiogenic pulmonary edema

Examine the patient: ❑ Orthostatic vital signs - orthostatic hypotension ❑ Mental status examination - low score ❑ Jugular venous pressure ↑/↓ ❑ Peripheral edema

Check labs: ❑ Plasma osmolality ❑ Urine osmolality ❑ Urinary sodium concentration ❑ Serum uric acid/Creatinine ❑ TSH (Thyroid stimulating hormone) ❑ Serum cortisol level ❑ Serum proteins/triglyceride ❑ Random blood sugar

Consider alternative diagnosis: ❑ Adrenal Crisis ❑ Alcoholism ❑ Hypothyroidism ❑ Pulmonary/cardiogenic edema

Plasma osmolality

280-295 mOsm/kg - Isotonic hyponatremia

< 280 mOsm/kg - Hypotonic hyponatremia

> 295 mOsm/kg - Hypertonic hypernatremia

Pseudohyponatremia

Assess volume status

Hyperglycemia Mannitol infusion

Hypovolemia

Euvolemia

Hypervolemia

Urine sodium levels

Urine sodium levels

Urine sodium levels

>20 mEq/L

≤ 20 mEq/L

>20 mEq/L

>20 mEq/L

≤ 20 mEq/L

Cerebral salt wasting syndrome Adrenal failure Thiazide like diuretics

Vomiting & diarrhea treated with free water replacement

SIADH Primary polydipsia Exercise associated hyponatremia Nephrogenic syndrome of inappropriate antidiuresis Glucocorticoid def. Hypothyroidism Low solute intake

Acute kidney injury

Cirrhosis Heart failure

Treatment

Symptomatic hyponatremia

Asymptomatic hyponatremia

Acute hyponatremia (< 48 hours) Goals of treatment: Target Na+ levels = 125-130 mEq/L Daily ↑ in Na+ levels by 4-6 mmol/L

Chronic hyponatremia Goals of treatment: Target Na+ levels = 125-130 mEq/L Daily ↑ in Na+ levels by 4-8 mmol/L if low risk of ODS Daily ↑ in Na+ levels by 4-6 mmol/L if high risk of ODS

Mild to moderate symptoms

Severe symptoms

Mild to moderate symptoms

Severe symptoms

Treat with 0.9% NaCl to achieve target Na+ levels

Treat with 3% NaCl to begin with Transition to 0.9% NaCl at Na+ levels > 125 mEq/L

Treat with 0.9% NaCl to achieve target Na+ levels

Treat with 3% NaCl to begin with Achieve 1st day target in 1st 6 hours and withhold any more fluids for the day Transition to 0.9% NaCl at Na+ levels > 125 mEq/L

Administer vaptans (vasopressin receptor antagonists): Contraindicated for hypovolemic hyponatremia Conivaptan: IV 20 mg loading dose over 30 minutes, followed by a continuous infusion of 20 mg/day Max infusion rate 40 mg/day Duration of treatment 4 days or target Na+ level Monitor with Na+ levels every 6-8 hours Tolvapatan: (Use only is Na+ < 125 mEq/L or pt. symptomatic) Begin with PO 15 mg on the first day Titrate to 30 mg/60 mg at 24-hour intervals if Na+ level < 135 mmol/L Increase in Na+ <5 mmol/L in last 24 hours Monitor with Na+ levels every 6-8 hours

Etiology based management

Hypovolemia

Euvolemia

Hypervolemia

Urine sodium level > 20 mEq/L Cerebral salt wasting syndrome: Differentiated from SIADH by renal sodium and fluid loss before development of hyponatremia Fluid restriction is not advised Adrenal failure: Frequent Na level monitoring Perform co-syntropin testing, treat empirically with high dose hyrdocortisone Fludrocortisone once diagnosis is confirmed Thiazide like diuretics: Stop thiazide diuretics Monitor rate of rise of Na+ Monitor urine osmolality & volume to detect hypercorrection Follow K+ levels, as they may drop with therapy

Urine sodium level ≤ 20 mEq/L Gastrointestinal losses: Correct K+ levels as appropriate Administer bicarbonate if acidosis develops Start antimemetics and specific therapy as indicated

Urine sodium level > 20 mEq/L SIADH: 1st line therapy is water restriction If on vaptans water restriction shouldn't be done Use enteral water or D5W to prevent over correction Decide chronic pharmacotherapy based on aetiology of SIADH Nephrogenic syndrome of inappropriate antidiuresis: Similar to SIADH Hypothyroidism: Causes hyponatremia only when severe Treat primary aetiology Glucocorticoid def.: Primary treatment is glucocorticoid replacement Monitor sodium levels and urine volume to prevent over correction Exercise associated hyponatremia: Treat with water restriction and observation Low solute intake: Provide proper nutrition of electrolytes and proteins Primary polydipsia: Water restriction

Urine sodium level > 20 mEq/L Acute kidney injury: Fluid restriction is the mainstay Vaptans are less effective

Urine sodium level ≤ 20 mEq/L Heart failure: Initiate treatment with fluid restriction Administer loop diruteics Vaptans are strongly recommended Liver cirrhosis: Use of tolvaptan is restrictive

Do's

1) Cerebral salt wasting syndrome causes hypo-osmolar hyponatremia with lab parameters similar to that seen in SIADH. It is associated with conditions like hypovolemia, hypotension, neurosurgical procedure, and subarachnoid hemorrhage (within previous 10 days). It is treated as hypoosmolar hyponatremia.

2) While deciding the rate of normal saline for hypovolemia hyponatremia, consideration of the following factors are helpful: patient's BMI (faster rates for higher BMI), cardiac (slower rate for low ejection fraction) and renal function (slower rates for low GFRs).

3) Common causes of SIADH are, small cell lung cancer, intracranial pathology, increased intrathoracic pathology, medications (thiazides, SSRI, tricyclic antidepressant, narcotics, phenothiazine, carbamazepine)

4) Vaptans such as conivaptan (intravenous), and tolvaptans (oral preparations) can be used for resistant euvolemic, and hypervolemic hyponatremia. These are very expensive and should be initiated in hospital.

Don'ts

1) Serum sodium shouldn't be corrected faster than 0.5 meq/h, as faster correction increases the risk for central pontine myelinolysis.

References

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