Tolvaptan for hyponatremia with preserved sodium pool in critically ill patients

Ann Intensive Care. 2016 Dec;6(1):1. doi: 10.1186/s13613-015-0096-2. Epub 2016 Jan 4.


Background: Hyponatremia is the most common electrolyte disturbance in hospitalized patients, and it represents a well-established risk factor for ICU/hospital mortality. The majority of hyponatremic states are associated with elevated arginine vasopressin levels and a preserved sodium pool. Conventional treatment is either not pathophysiologically oriented or of limited effectiveness. The aim of the present study is to investigate the use of enteral Tolvaptan in critically ill hyponatremic patients.

Methods: This is a retrospective observational study in a general ICU. Patients with preserved sodium pool hyponatremia refractory to conventional therapy were enrolled. The hemodynamic, renal, and hepatic functions, together with sodium and water balance as close as possible to the drug administration and up to 72 h thereafter, were analyzed. The main outcome was a serum sodium increase of ≥ 4 mmol/L in 24 h; secondary endpoints were the ability to maintain serum sodium at 24 and 72 h, a decrease in urine sodium concentration and an increase in sodium-free diuresis.

Results: 38 patients were enrolled. The average dose of enteral Tolvaptan was 7.5 mg. 31 patients (81.6 %) increased their serum sodium >4 mmol/l/24 h; the average increase was 6.7 ± 3.4 mmol/l during the first 24 h (p < 0.001 vs baseline), and this was sustained at 72 h. No adverse effects were reported. Plasma sodium (R = -0.622, p < 0.001), urine sodium (R = -0.345, p < 0.001), central venous oxygen saturation (R = 0.401, p = 0.013), and BUN (R = -0.416, p = 0.031) before Tolvaptan were all significantly correlated with the absolute increase in serum sodium after the administration.

Conclusions: Enteral administration of Tolvaptan seems effective in the treatment of hyponatremia with preserved sodium pool in critically ill patients. Even if the study was underpowered to detect significant side effects or complications of unwarranted fast corrections of hyponatremia, we report no complications.

Keywords: Critical illness; Hyponatremia; Tolvaptan.