A systematic review of known interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia and a meta‐analysis of the vaptans

Abstract

International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review and metaanalysis to investigate the efficacy and safety of interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomized and quasi-randomized controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic nonhypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesized in a meta-analysis. A total of 45 716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans") significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified. Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia.

Blockade of Arginine Vasopressin receptors prevents blood-brain barrier breakdown in Experimental Autoimmune Encephalomyelitis

“…Our results are well in agreement with other experimental studies showing that AVP is involved in the pathophysiology of brain damage, Bhandari et al 31 effectively attenuated the brain edema secondary to intracerebral hemorrhage (ICH) in animals treated with Tolvaptan, an AVP-V2 receptor antagonist; they also showed a decrease in BBB permeability to Evans blue tracer in the Tolvaptan-treated ICH animals as compared to the ICH group 31 . Other animal experiments found that blockade of AVP-V1 receptors reduces brain edema and BBB disruption in stroke 32 .…”

Prognostic and predictive role of hyponatremia in cancer patients

“…Meanwhile, the author is truly convinced that it is worth to correct hyponatremia in patients, including cancer patients, because of the overall beneficial effect on the quality of life, which includes clinical improvement, such as amelioration of neurocognitive and motor performance, reduced length of stay in the hospital and re-admission probability [44][45][46] .…”

Hyponatremia in dogs and cats

“…These drugs increase renal excretion of solute‐free water and have been used for the treatment of nonhypovolemic hyponatremia when routine therapy is ineffective or when long‐term treatment is necessary. A recent meta‐analysis reported that vaptans significantly improve serum [Na + ] when compared to placebo, although they have been associated with an increased likelihood of overly rapid correction of serum [Na + ], and adverse effects including liver injury have been reported . The vaptans are not currently recommended for routine therapy of hyponatremia in human medicine and their exact role remains controversial …”