Medication Summary
The primary treatments used in the management of hyponatremic patients rely on the use of intravenous sodium-containing fluids (normal saline or hypertonic saline) and fluid restriction. This is followed by use of loop diuretics (eg, furosemide), arginine vasopressin (AVP) receptor antagonists (eg, tolvaptan), [53, 54] or urea [56] ; less commonly, salt tablets, or demeclocycline are used.
Diuretics
Furosemide (Lasix)
Loop diuretics can increase renal free water excretion. It inhibits sodium/potassium/chloride cotransport system, thereby increasing solute delivery to distal renal tubules, which acts to increase free water excretion. Elderly patients may have greater sensitivity to effects of loop diuretics.
Antibiotics
Class Summary
Certain antibiotics may affect renal ADH action.
Demeclocycline (Declomycin)
Demeclocycline (Declomycin) can cause insensitivity of distal renal tubules to the action of ADH and produce a nephrogenic diabetes insipidus. Effects are seen within 5 days and are reversed within 2-6 days following cessation of therapy. Demeclocycline can be nephrotoxic, cause nausea, vomiting, and photosensitivity.
Arginine Vasopressin Antagonists
Class Summary
V2 receptor antagonism of AVP in the renal collecting duct results in aquaresis (excretion of free water). [53, 54, 55, 57, 58]
Conivaptan (Vaprisol)
Arginine vasopressin antagonist (V1A, V2), indicated for euvolemic (dilutional) and hypervolemic hyponatremia, increases urine output of mostly free water, with little electrolyte loss. Over 80% of conivaptan is excreted in feces and the rest in urine. Conivaptan is an intravenous injection that can be administered for up to 4 days.
Tolvaptan (Samsca)
Selective vasopressin V2-receptor antagonist is indicated for euvolemic or hypervolemic hyponatremia, associated with SIADH or congestive heart failure. Initiate or reinitiate in hospital environment only. Tolvaptan can cause serious and potentially fatal liver injury; hence, duration of use is limited to 30 days to minimize risk of liver injury.water).
Salt
Sodium chloride
Oral salt tablets in conjunction with loop diuretics can be used to help excrete urinary free water.
Sodium chloride tablets (1 gram) are osmotically active and ingesting 9 grams of sodium chloride in one day equals the addition of an extra 154 mEq each of sodium and chloride. Salt tablets should be avoided in the treatment of hypervolemic hyponatremia (e.g. heart failure).
Urea Supplements
Class Summary
Oral urea is an osmotic agent that increases urinary free water excretion. It is effective, safe, well tolerated and cost effective for treatment of SIADH associated hyponatremia. A modest but expected elevation of BUN is the result of normal urea metabolism and should not be interpreted as a reduction in kidney function. Urea has been shown to have a direct antinatriuretic effect and free water excretion leading to increased serum sodium levels. [50, 59] The use of urea is contraindicated in patients with hypovolemic hyponatremia. Furthermore, urea is relatively contraindicated in patients with cirrhosis due to potential metabolization into ammonium by urease producing bacteria in the colon, which can lead to hyperammonemia.
Vasopressin Analog
Desmopressin
Desmopressin (DDAVP), synthetic analogue of the antidiuretic hormone arginine vasopressin, increases cyclic adenosine monophosphate (cAMP), in a dose dependent manner, in renal tubular cells which increases water permeability resulting in decreased urine volume and increased urine osmolality.
Tables
United States Guidelines |
European Guidelines |
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Symptomatic Acute Hyponatremia < 24-48 hours |
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Urgent correction goal to aim to prevent brain herniation |
Increase serum Na+ by 4-6 mmol/L |
Increase serum Na+ by 5 mmol/L |
Treatment based on symptoms |
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Severe symptoms |
Bolus 100 mL of 3% NaCl over 10 minutes x 3 as needed |
Bolus 150 mL of 3% NaCl over 20 minutes, 2- 3 times as needed, checking Na every 20 minutes (First-hour management, regardless of acute or chronic condition) |
Moderate symptoms with low risk of herniation |
Continuous infusion of 3% NaCl at 0.5-2 mL/kg/h |
Bolus 150 mL 3% NaCl over 20 minutes, x 1 to prevent further decrease in Na |
Limit not to exceed |
None in true acute hyponatremia |
None in true acute hyponatremia |
Chronic Hyponatremia > 48 hours |
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Correction rate |
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Goal in symptomatic patients using hypertonic saline |
4-8 mmol/L/d if low risk for ODS 4-6 mmol/L/d if high risk of ODS For patients with severe symptoms, the first day’s increase can be accomplished during first 6 h |
Avoid > 10 mmol/L in the first 24 h And > 8 mmol/l during every 24 h thereafter |
Limit to avoid potential harm in asymptomatic patients |
10-12 mmol/L/d, but max 18 mmol in 48 h if at low risk for ODS 8 mmol/L/d if at high risk of ODS |
10 mmol/L in the first 24 h and 8 mmol/l during every 24 h thereafter |
Managing Overcorrection of Chronic Hyponatremia |
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Baseline serum Na+ ≥ 120 mmol/L: Intervention probably unnecessary |
Start once above mentioned limits are exceeded |
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Baseline serum Na+ < 120 mmol/L: Replace water orally or as D5W at 3 mL/kg/h with or without desmopressin (2-4 µg every 8 h parenterally) Withhold any vasopressin receptor antagonists (vaptans) used Consider dexamethasone, 4 mg every 6 hr for 24 hr following excessive correction |
Consult an expert to discuss infusion containing electrolyte-free water (10 mL/kg) over 1 h with or without 2 µg desmopressin IV every 8 h |
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Other Treatment Options |
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Hypovolemic hyponatremia |
Isotonic saline |
Isotonic saline or balanced solution at 0.5-1.0 mL/kg/h |
Euvolemic hyponatremia (SIADH) |
Fluid restriction of 500 mL/d below the 24-h urine volume (first-line treatment) Urea, vaptan, or demeclocycline (second-line treatment) |
Fluid restriction (first-line) Urea or loop diuretics + oral NaCl (second-line) Do not recommend vaptans Recommend against lithium or demeclocycline |
Hypervolemic hyponatremia |
Fluid restriction, loop diuretic Vaptans |
Fluid restriction Recommend against vaptans and demeclocycine |
