Efficacy and safety of two different tolvaptan doses in the treatment of hyponatremia in the Emergency Department

Abstract

Hyponatremia (plasma sodium concentration or [Na] <136 mEq/L) is the most common electrolyte unbalance in clinical practice. Although it constitutes a negative prognostic factor, it frequently remains underdiagnosed and undertreated. Tolvaptan is an oral V-receptor antagonist which produces aquaresis. Given its emerging role in the treatment of dilutional hyponatremia, we aimed to compare the efficacy and safety of two different doses of this drug in an Emergency Department (ED) setting. Consecutive patients with moderate-severe euvolemic or hypervolemic hyponatremia were sequentially assigned to the 15 mg Group and to the 7.5 mg Group, and were revaluated at 6, 12 and 24 h. Further evaluations and administrations were scheduled daily until [Na] correction was achieved or the maximum period of 72 h was exceeded. A 1-month follow-up was performed. Twenty-three patients were enrolled: 12 were included in the 15 mg Group, 11 in the 7.5 mg Group. Both doses significantly elevated the [Na] over 24 h, although the 15 mg Group showed faster corrections than the 7.5 mg Group (12 vs 6 mEq/L/24 h; P = 0.025). An optimal correction rate (within 4-8 mEq/L/24 h) was observed in 45.4 % of the 7.5 mg Group against 25.0 % (P n.s.). The standard dose led to dangerous overcorrections (>12 mEq/L/24 h) in 41.7 % of the patients, while the low dose did not cause any (P = 0.037). No osmotic demyelination syndrome was observed. A 7.5 mg tolvaptan dose can be considered both effective and safe in treating hyponatremia in the ED, while a 15 mg dose implicates too high risk of overcorrection.

Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone

“…In contrast, the group receiving TLV 7.5 mg dose had a median increase in serum sodium of 6 mmol/L (range, 1–11 mmol/L). Castello et al 23 also found that in patients with lower starting levels of serum sodium there was a tendency to see larger increases in serum sodium levels. The authors concluded that a daily dose of 7.5 mg TLV was both effective and safe, whereas 15 mg TLV had a high risk of overcorrection.…”

“…Two small studies have focused on the overcorrection of serum sodium within the first 24 hours of treatment with 15 mg TLV in patients with hypervolemic or euvolemic hyponatremia. 23 24 Castello et al 23 investigated the efficacy and safety of two different doses of TLV (7.5 and 15 mg) in patients with hypervolemic and euvolemic hyponatremia and reported that the group receiving TLV 15 mg showed a median increase in serum sodium of 12 mmol/L (range, 6–25 mmol/L) and this correction rate exceeded the values recommended by recent guidelines in 75% of patients, although no ODS was reported. In contrast, the group receiving TLV 7.5 mg dose had a median increase in serum sodium of 6 mmol/L (range, 1–11 mmol/L).…”

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan

“…Although conventional diuretics, particularly furosemide, decrease the serum level of Na, tolvaptan increases free water excretion without introducing major systemic electrolyte loss. Instead, the serum Na concentration increases dose-dependently ( 6 ).…”

Copeptin in hyponatremia: is there a role for this biomarker in the diagnostic workup?

“…Our research group essentially agrees with this final statement, particularly if copeptin levels are obtained in an emergency medicine context. In fact, in the last few years we carried out many studies focused on the diagnosis and treatment of hyponatremia in the ED [ 17 , 18 ]. For example, data we obtained from 22 patients with hypovolemic hyponatremia confirmed the wide variability of copeptin levels even in the same subgroup of patients (IQR 9.71–100.95 pmol/L) [ 18 ].…”

“…Unpublished data obtained from a secondary analysis of 18 euvolemic and hypervolemic patients with hyponatremia enrolled in another ED trial [ 17 ], once again demonstrates a wide variability in copeptin levels without significant differences between euvolemic and hypervolemic patients.…”