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]

Definitions

Term	Definitions
Hyponatremia	Hyponatremia is defined as a serum sodium concentration < 135 mEq/L.
Hypotonic hyponatremia	Hyponatremia with low osmolality (hypotonic hyponatremia) is defined as hyponatremia with a serum osmolality below 280 mOsm/kg.
Hypertonic hyponatremia	Hyponatremia with high osmolality (hypertonic hyponatremia) is defined as hyponatremia with a serum osmolality greater than 295 mOsm/kg.
Isotonic hyponatremia	Hyponatremia with normal osmolality (Isotonic hyponatremia) is defined as hyponatremia with a serum osmolality ranging between 280-295 mOsm/kg.
Hyponatremia based on ECF volume
Hypovolemic hyponatremia	Hyponatremia plus decreased ECF volume. Usually diagnosed by HPE showing water depletion plus spot urine sodium <20 to 30 mmol/L, unless kidney is the source of sodium loss.
Euvolemic hyponatremia	Hyponatremia plus normal ECF volume. Majority of cases are of this type. Usually diagnosed by spot urine sodium ≥ 20 to 30 mmol/L, unless secondarily sodium depleted.
Hypervolemia hyponatremia	Hyponatremia plus increased ECF volume. Usually diagnosed by HPE showing water retention plus spot urine sodium <20 to 30 mmol/L

Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Hyponatremia is by itself life threatening and should be treated as such irrespective of the causes, if severe in nature ( <115 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 sodium conc.) + (serum glucose conc./18) + (blood urea nitrogen/2.8)
Where Ssom is Serum osmolality.

Class	Causes
Hyponatremia with low serum osmolality	Appropriate ADH secretion (Primary polydipsia, advanced renal failure, low dietary intake) Arterial blood volume depletion True blood volume depletion (Diarrhea, vomiting, bleeding, use of diuretics) Thiazide diuretic induced 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)

Management

Diagnostic Approach

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 sodium < 115 meq/L: Hyponatremic encephalopathy ❑ Symptoms mentioned above plus ❑ Brain stem compression (altered thirst, hunger, dilated pupils) ❑ Decorticate/decerebrate posturing ❑ 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

Therapeutic Approach

Symptomatic hyponatremia

Asymptomatic hyponatremia

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

Chronic hyponatremia Goals of treatment: ❑ Target sodium levels = 125-130 mEq/L ❑ Daily ↑ in sodium levels by 4-8 mmol/L if low risk of ODS ❑ Daily ↑ in sodium 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 sodium levels or treat with vaptans

❑ Treat with 3% NaCl to begin with (100 ml infused over 10 minutes and repeated once if needed) ❑ Transition to 0.9% NaCl/vaptans at sodium levels > 125 mEq/L

❑ Treat with 0.9% NaCl to achieve target sodium levels or treat with vaptans

❑ 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/vaptans at sodium levels > 125 mEq/L

Administer [[Hyponatremia medical therapy#Vaptan Drugs|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 sodium level ❑ Monitor with sodium levels every 6-8 hours Tolvapatan: (Use only if sodium < 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 sodium level < 135 mmol/L Increase in sodium <5 mmol/L in last 24 hours ❑ Monitor with sodium 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 ❑ Administer fludrocortisone once diagnosis is confirmed Thiazide like diuretics: ❑ Stop thiazide diuretics ❑ Monitor rate of rise of sodium ❑ 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 antiemetics 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 - Replace glucocorticoids ❑ Monitor sodium levels and urine volume to prevent over correction Exercise associated hyponatremia: ❑ Treat with free water restriction and observation Low solute intake: ❑ Provide proper nutrition of electrolytes and proteins Primary polydipsia: ❑ Implement free water restriction

Urine sodium level > 20 mEq/L Acute kidney injury: ❑ Implement free water restriction (mainstay) ❑ vaptans are less effective

Urine sodium level ≤ 20 mEq/L Heart failure: ❑ Initiate treatment with fluid restriction ❑ Administer loop diuretics ❑ vaptans are strongly recommended Liver cirrhosis: ❑ Use tolvaptan restrictively based on LFT's

†ADH: Anti diuretic hormone; SIADH: Syndrome of inappropriate antidiuretic hormone secretion; NaCl: Sodium chloride; LFT: Liver function test;IV: Intravenous; PO: Per oral; ECF:Extra cellular fluid; HPE:History and physical examination; ODS: Osmotic demyelination syndrome

Do's

• Categorize hyponatremia based on volume status, use history, physical examination and labs.
• Do the following to prevent over correction of sodium levels:

Replace water losses or administer desmopressin after correction by 6-8 mmol/L during the first 24 hours of therapy.

Withhold the next dose of vaptans if the correction is >8 mmol/L.

Consider therapeutic re-lowering of serum sodium if correction exceeds therapeutic limits.

Consider administration of high-dose glucocorticoids (eg, dexamethasone, 4 mg every 6 hours) for 24-48 hours following the excessive correction.

• Follow these steps to re lower serum sodium:

Administer desmopressin to prevent further water losses: 2-4 mg every 8 hours parenterally.

Replace water orally or as 5% dextrose in water intravenously: 3 mL/kg/h.

Recheck serum sodium hourly and continue therapy infusion until serum sodium is reduced to goal.

• Initiate vaptans treatment only in hospital setting, so as to regularly monitor serum sodium levels.
• Fluid restriction:

Restrict all intake that is consumed by drinking, not just water.

Aim for a fluid restriction that is 500 mL/d below the 24-hour urine volume.

Do not restrict sodium or protein intake unless indicated.

• Gastrointestinal losses:

Measure urine chloride, if vomiting is present to confirm the presence of solute and volume depletion.

Treat typically as a chronic hyponatremia.

• Thiazide diuretic induce:

Treat typically as chronic hyponatremia.

Be vary of rapid correction.

Serially follow changes in urine osmolality together with urine volume.

Measure serum sodium every 6 hours to begin with.

Adjust potassium levels in fluids as needed.

Dont's

• Stop tolvaptan if signs of liver failure develop.
• vaptans:

Do not use to treat hypovolemic hyponatremia.

Do not use in conjunction with other treatments for hyponatremia.

Do not use immediately after cessation of other treatments for hyponatremia, particularly 3% NaCl.

Do not use for severe, symptomatic hyponatremia, as 3% NaCl provides a quicker and more certain correction of serum sodium than vaptans.

• Do not use Isotonic normal saline as primary therapy for SIADH.

References

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