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Evidence summaries

Interventions for Chronic Nonhypovolaemic Hypotonic Hyponatraemia

In people with chronic hyponatraemia, vasopressin receptor antagonists appear to modestly raise serum sodium concentration at the cost of an absolute 3% increased risk the increase being too rapid. Level of evidence: "B"

The quality of evidence is downgraded by study limitations (unclear allocation concealment and missing outcome data/attrition bias).

Summary

A Cochrane review [Abstract] 1 included 35 studies with a total of 3 429 subjects, mostly older adults (median 65 years) with moderate hyponatraemia (median 129 mmol/L). Primary cause of hyponatraemia was a syndrome of inappropriate antidiuresis in 9 studies, heart failure in 7 studies, and liver cirrhosis in 6 studies. Twenty-eight studies (n=3 189) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. Studied vasopressin receptor antagonists included conivaptan, lixivaptan, satavaptan, tolvaptan and M0002 (also called SPD556 or RWJ 351647).

In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists had no effects on death at 6 months (RR 1.11, 95% CI 0.92 to 1.33; 15 studies, n=2 330). They reduced hospital stay (MD -1.63 days, 95% CI -2.96 to -0.30; 3 studies, n=610), had little or no difference to cognitive function, uncertain effects on health-related quality of life, and they increased the intermediate outcome of serum sodium concentration (MD 4.17 mmol/L, 95% CI 3.18 to 5.16; 21 studies, n=2 641), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (RR 2.49, 95% CI 1.95 to 3.18; 18 studies, n=2 014). They also increased the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (RR 1.67, 95% CI 1.16 to 2.40; 14 studies, n=2 058), and commonly caused side-effects such as thirst (OR 2.77, 95% CI 1.80 to 4.27; 13 studies, n=1 666) and polyuria (RR 4.69, 95% CI 1.59 to 13.85; 6 studies, n=1 272).

Data for other interventions such as fluid restriction, change in medical regimens, captopril or albumin were sparse and inconclusive.

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