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

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

Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Severe hyponatremia ( <115 mEq/L) is by itself life threatening and should be treated as such irrespective of the cause.

Common Causes

Causes of hyponatremia are classified based on patients volume status as follows:

Hypovolemic hyponatremia:

• Cerebral salt wasting syndrome
• Adrenal failure
• Thiazide diuretics
• Vomiting & diarrhea treated with free water replacement

Euvolemic hyponatremia:

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

Hypervolemic hyponatremia:

• Acute kidney injury
• Cirrhosis
• Heart failure

Management

Shown below is an algorithm depicting management of hyponatremia based on Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations (2013)

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 Hyponatremic encephalopathy: (sodium < 115 meq/L) ❑ Altered thirst, hunger, dilated pupils (Brain stem compression) ❑ Decorticate or decerebrate posturing ❑ Respiratory arrest ❑ Non-cardiogenic pulmonary edema

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

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

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

❑ Check serum osmolality Serum osmolality (mmol/kg) = (2 x serum sodium concentration) + (serum glucose concentration/18) + (blood urea nitrogen/2.8)

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 deficiency ❑ Hypothyroidism ❑ Low solute intake

❑ Acute kidney injury

❑ Cirrhosis ❑ Heart failure

Therapeutic Approach

Initial Management

Symptomatic 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 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

Additional Management Shown below is an algorithm depicting the management of symptomatic and asymptomatic hyponatremia based on underlying etiology.

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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