Abstract

Objective: Evaluating the effectiveness and side effects of Tolvaptan in the patients with severe acute euvolemic and hypervolemic hyponatremia. Methodology: Randomized controlled trial in 42 patients with severe acute euvolemic or hypervolemic hyponatremia, randomly. These patients are divided into 2 groups: 20 patients following classic treatment and 22 patients managed by Tolvaptan with or without NaCl 0.9 %. Results: The classic treatment group required many managements, including maximum water restriction, average amount of NaCl 0.9% perfusion (500ml bottle) was 6.60 ± 1.5; medians of 3% NaCl perfusion (100ml bottle) and Furosemide (20mg ampoule) were 6.00 (5.00 – 7.00) and 1.00 (0.00 – 2.00) respectively, while the Tolvaptan group needed neither water restriction nor 3% NaCl nor Furosemide. The average amount of NaCl 0.9% (500ml bottle) used in the Tolvaptan group was 2.45 ± 1.34 less than in the classic group (6.60 ± 1.5), p < 0.001. The length (hour) of treatment to achieve the serum sodium target in both groups was greater than the expected duration: the median in the classical treatment group was 36.00 (24.00 - 46.00) compared with 22.00 (18.50 – 33.50), p = 0.001; The median treatment duration in the Tolvaptan group was 24.00 (23.50 - 35.00) vs 22.00 (20.00 - 35.00), p = 0.016. The real treatment duration of the Tolvaptan group was lower than that of the classic treatment group (p = 0.027). The median time needed to improve the symptoms of vomiting and fatigue was 03 h and 12h in the Tolvaptan group, lower than in the classic treatment group (06 h and 22 h), p = 0.002 and 0.001, respectively. As regards the side effects of treatment: Edema and hypokalemia were only seen in the classical treatment group with the rate of 20% and 55%, in contrast, Tolvaptan group did not develop the edema or hypokalemia, whereas 81.8% of patients of this group had polyuria, (p = 0.003 and p < 0.001). During the study, there were no patients with hypernatremia that exceeded the threshold evoking the risk of demyelination. The main dose of Tolvaptan was 7.5mg and 11.25mg (accounting for 45.5% and 36.4%), 13.6% used the 15mg dose and only 4.5% used the 18.75mg dose. Average urine flow (ml/h) of Tolvaptan group at the time of 03h; 06h; 12h and 24h was: 205.00 ± 61.00; 225.45 ± 52.44; 195.91 ± 48.17 and 167.27 ± 41.19, respectively. The average increase in serum sodium (mmol/L) of Tolvaptan group at the time of 03h; 06h; 12h and 24h was respectively 2.32 ± 0.78; 4.50 ± 0.67; 8.18 ± 1.44 and 13.68 ± 1.62. Conclusion: Using of Tolvaptan in management of severe acute euvolemic or hypervolemic hyponatremia is simpler and easier to be tolerated than that of classic method (without water restriction, hypertonic NaCl or furosemide). The initial dose of 7.5 mg Tolvaptan, which is titrated by a small dose of 3.75mg each 03 hours to a maximum of 18.75 mg, has shown to be safe and effective.