Vasopressin-2 Antagonists for Treatment of Hyponatremia in Cirrhosis - A Systematic Review and Meta-Analysis

Abstract

Purpose: Hyponatremia is a common electrolyte abnormality in patients with cirrhosis and affects their outcome. Vasopressin-2 (V2) receptor antagonists increase free water clearance and are useful for treatment of hyponatremia. Randomized controlled trials (RCTs) have shown conflicting data on efficacy and safety of V2 receptor antagonists in the treatment of hyponatremia in cirrhotic patients. A systematic review and meta-analysis of all RCTs was performed to assess safety and efficacy of V2 receptor antagonists in the treatment of hyponatremia in patients with cirrhosis. Methods: Pub Med, Ovid, Cochrane reviews, EMBASE and ISI web of science databases were searched for all RCTs on treatment of hyponatremia using V2 receptor antagonists. Studies including patients with hyponatremia of different causes but not reporting data on cirrhotics were excluded. Data was extracted into a predefined Excel spreadsheet for patient demographics, sample size (in treated and control patients), type and dose of V2 receptor antagonist, change [post treatment - baseline (mean±SD)] on various outcomes (Table), and adverse effects. Data were entered into comprehensive meta-analysis 9.2 software and analyzed using random effects model. Heterogeneity and publication bias across the studies (reported if > 2 studies) were assessed using Chi-2 and Egger's tests respectively. Meta-regression was performed to assess heterogeneity for year of publication, type and dose of drug, baseline serum sodium, time at which change is reported (12-168 hrs), and percent males.Table: [324] Pooled data on vasopressin-2 receptor antagonists for treatment of hyponatremia in cirrhosisResults: Total 6 studies (n=342, 169 treated) were analyzed. Pooled data showed a significant increase in serum sodium with a decrease in urine osmolality (Table). However, there was no change in other parameters. The drugs were safe with similar proportion of patients among treated and control groups experiencing adverse effects with pooled OR of 1.29 (95% CI 0.73-2.25); P=0.93. Most common side effect was increased thirst. There was marked heterogeneity but no publication bias across the studies. Meta regression showed that the year of study publication along with type and dose of the drug contributed to data heterogeneity. Conclusion: Vasopressin-2 receptor antagonists are effective and safe for treatment of hyponatremia in patients with cirrhosis. Further studies are needed to determine efficacy and safety of long-term use of vasopressin receptor antagonists for treatment of hyponatremia in patients with cirrhosis.