Abstract

Decreases in the concentration of sodium in plasma constitute hyponatremia, the commonest electrolyte disorder in clinical medicine. It is now well established that its presence conveys an increased mortality risk even when the decrement is mild. In addition, recent evidence suggests that chronic and apparently asymptomatic hyponatremia is associated with increased morbidity including neurocognitive deficits and bone fractures. Furthermore, hyponatremia is associated with higher health care-related expenses. Consequently, exploring new therapeutic strategies that increase plasma sodium in a safe and effective manner is of paramount importance. In this regard, there are scant data to support the use of traditional management strategies for hyponatremia (fluid restriction, salt tablets, loop diuretics, and normal saline). Furthermore, data from a large hyponatremia registry reveal the limited efficacy of these therapies. More recently vasopressin receptor antagonists provide a promising treatment for hyponatremia by targeting its most common mechanism, namely, increased vasopressin activity. However, uncertainty still lingers as to the optimal indications for the use of vasopressin receptor antagonists in hyponatremia and a few reports have described complications resulting from their misuse. This review summarizes the appropriate and inappropriate uses of vasopressin receptor antagonists in the treatment of hyponatremia.

Highlights

  • The posterior pituitary hormone vasopressin has a primordial role in the pathogenesis of hyponatremia, the commonest electrolyte disorder in inpatients [1,2,3]

  • The analysis suggests that patients randomized to a VRA are significantly more likely to normalize plasma sodium concentration (PNa) and/or increase it by more than 5 mmol/L with tolvaptan having the largest effect (RR = 3.3, 95% CI: 1.97–5.54)

  • Long-term use of VRAs remains necessary in certain patients (e.g., SIADH from malignancy) as hyponatremia will recur upon discontinuation of the drug as observed in the SALT trials

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Summary

Frontiers in Medicine

Vasopressin Receptor Antagonists in Hyponatremia: Uses and Misuses. Exploring new therapeutic strategies that increase plasma sodium in a safe and effective manner is of paramount importance. In this regard, there are scant data to support the use of traditional management strategies for hyponatremia (fluid restriction, salt tablets, loop diuretics, and normal saline). More recently vasopressin receptor antagonists provide a promising treatment for hyponatremia by targeting its most common mechanism, namely, increased vasopressin activity. Uncertainty still lingers as to the optimal indications for the use of vasopressin receptor antagonists in hyponatremia and a few reports have described complications resulting from their misuse. This review summarizes the appropriate and inappropriate uses of vasopressin receptor antagonists in the treatment of hyponatremia

INTRODUCTION
APPROPRIATE USES OF VRAs
INAPPROPRIATE USES OF VRAs
Strongly advise against its use
REMAINING UNCERTAINTIES ABOUT THE USE OF VRAs IN HYPONATREMIA
Effects of VRAs on Morbidity
Effects of VRAs on Mortality
Guideline Recommendations Regarding Use of VRAs in Hyponatremia
Findings
CONCLUSION
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