Hyponatremia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Medical Therapy

Hyponatremia must be corrected slowly in order to lessen the chance of the development of central pontine myelinolysis (CPM), a severe neurological disease. In fact, overly rapid correction of hyponatremia is the most common cause of that potentially devastating disorder. During treatment of hyponatremia, the serum sodium should not be allowed to rise by more than 8 mmol/l over 24 hours (i.e. 0.33 mmol/l/h rate of rise). In practice, too rapid correction of hyponatremia and thence CPM is most likely to occur during the treatment of hypovolemic hyponatremia. In particular, once the hypovolemic state has been corrected, the signal for ADH release disappears. At that point, there will be an abrupt water diuresis (since there is no longer any ADH acting to retain the water). A rapid and profound rise in serum sodium can then occur. Should the rate of rise of serum sodium exceed 0.33 mmol/l/h over several hours, vasopressin may be administered to prevent ongoing rapid water diuresis.

Vaptan Drugs

The “vaptan” class of drugs contains a number of compounds with varying selectivity, several of which are either already in clinical use or in clinical trials as of 2010.

Unselective (mixed V1A, V2)

• Conivaptan

V1A selective

• Relcovaptan

V1B selective

• Nelivaptan

V2 selective

• Lixivaptan

• Mozavaptan

• Satavaptan

• Tolvaptan

The V2-receptor antagonists tolvaptan and conivaptan allow excretion of electrolyte free water and are effective in increasing serum sodium in euvolemic and hypervolemic hyponatremia.

Rate of Na Correction

The rate of correction of hyponatremia should be 0.5-1.0meq/L/hr, with not more than a 12 meq/l correction in 24 hrs. If the patient has ongoing seizures (or [Na⁺]<115 meq/li), correction can be attempted at up to 2 meq/L/hr, but only while seizure activity lasts and the [Na⁺] exceeds 125-130 meq/Li.

Contraindicated medications

Hyponatremia is considered an absolute contraindication to the use of the following medications:

• Acetazolamide

Hypovolemic hyponatremia is considered an absolute contraindication to the use of the following medications:

• Tolvaptan
• Conivaptan