Treatment: Hyponatremia

Three considerations are critical in the therapy of hyponatremia. First, the presence, absence, and/or severity of symptoms determine the urgency of therapy (see above for acute symptomatic hyponatremia). Second, pts with hyponatremia that has been present for >48 h (“chronic hyponatremia”) are at risk for osmotic demyelination syndrome, typically central pontine myelinolysis, if serum Na⁺ is corrected by >10-12 mM within the first 24 h and/or by >18 mM within the first 48 h. Third, the response to interventions, such as hypertonic saline or vasopressin antagonists, can be highly unpredictable, such that frequent monitoring of serum Na⁺ (initially every 2-4 h) is imperative.

Treatment of acute symptomatic hyponatremia should include hypertonic saline to acutely increase serum Na⁺ by 1-2 mM/h to a total increase of 4-6 mM; this increase is typically sufficient to alleviate acute symptoms, after which corrective guidelines for “chronic” hyponatremia are appropriate (see below). A number of equations and algorithms have been developed to estimate the required rate of hypertonic solution; one popular approach is to calculate a “Na⁺ deficit,” where the Na⁺ deficit = 0.6 × body weight × (target [Na⁺] - starting [Na⁺]). Regardless of the method used to determine the rate of administered hypertonic saline, the increase in serum [Na⁺] can be highly unpredictable, due to rapid changes in the underlying physiology; serum [Na⁺] should be monitored every 2-4 h during and after treatment with hypertonic saline. The administration of supplemental O₂ and ventilatory support can also be critical in acute hyponatremia, if pts develop acute pulmonary edema or hypercapnic respiratory failure. IV loop diuretics will help treat associated acute pulmonary edema and will also increase free H₂O excretion by interfering with the renal countercurrent multiplier system. It is noteworthy that vasopressin antagonists do not have a role in the management of acute hyponatremia.

The rate of correction should be comparatively slow in chronic hyponatremia (<10-12 mM in the first 24 h and <18 mM in the first 48 h), so as to avoid osmotic demyelination syndrome. Vasopressin antagonists are highly effective in SIADH and in hypervolemic hyponatremia due to heart failure or cirrhosis. Abnormalities in liver function tests have been reported during the use of tolvaptan; hence, therapy with this agent should be restricted to 1-2 months with close monitoring of liver function. Should pts overcorrect serum [Na⁺] in response to vasopressin antagonists, hypertonic saline, or isotonic saline (in chronic hypovolemic hyponatremia), hyponatremia can be safely reinduced or stabilized by the administration of the vasopressin agonist DDAVP and the administration of free H₂O, typically IV D₅W; again, close monitoring of the response of serum [Na⁺] is essential to adjust therapy. Alternatively, the treatment of pts with marked hyponatremia can be initiated with the twice-daily administration of DDAVP to maintain constant AVP bioactivity, combined with the administration of hypertonic saline to slowly correct the serum [Na⁺] in a more controlled fashion, thus reducing upfront the risk of overcorrection.