Vasopressin Receptor Antagonists for the Treatment of Hyponatremia: Systematic Review and Meta-analysis

Background

In patients with euvolemic and hypervolemic hyponatremia, the effect of vasopressin antagonists is yet undefined.

Study Design

Systematic review and meta-analysis of randomized controlled trials (RCTs).

Setting & Population

In- and outpatients with euvolemic or hypervolemic hyponatremia.

Selection Criteria for Studies

We included all RCTs regardless of publication status or language.

Intervention

Vasopressin antagonists with or without fluid restriction versus placebo or no treatment with or without fluid restriction.

Outcomes

Response rate defined as normalization of serum sodium level or significant increase in serum sodium level at 3-7 days (primary) and later, change from baseline serum sodium level at 3-7 days and later, adverse events, rate of rapid sodium level correction, and rate of hypernatremia.

Results

15 RCTs were identified. Vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% CI, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% CI, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former. Change from baseline serum sodium level was significantly increased both early (weighted mean difference, 5.27 mEq/L; 95% CI, 4.27-6.26, 13 trials) and late (weighted mean difference, 3.49 mEq/L; 95% CI, 2.56-4.41, 8 trials). Although there was an increased rate of rapid sodium correction (RR, 2.52; 95% CI, 1.26-5.08, 8 trials) with vasopressin antagonists, hypernatremia rates were not significantly higher (RR, 2.21; 95% CI, 0.61-7.96; 5 trials), adverse events were not increased, and there were no reports of osmotic demyelination syndrome.

Limitations

Significant heterogeneity in the primary outcome.

Conclusions

Vasopressin antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia.

Index Words: Vasopressin receptor antagonists, hyponatremia, systematic review