gms | German Medical Science

Objective: Hyponatremia is frequently encountered in patients with intracranial processes, and contributes substantially to the related morbidity and mortality. The pathophysiology of hyponatremia is not completely understood, and may in part be explained by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Currently, water restriction is the treatment of choice, but counteracting directly the effects of the excessive ADH (syn. vasopressin) release would be more rational. Recently, a selective vasopressin V2 receptor antagonist, Tolvaptan, has become available and offers a causal treatment for SIADH. However, the exact Tolvaptan titration is crucial since a complete ADH antagonism would eliminate renal water reabsorption and result in diabetes insipidus.

Method: In all patients undergoing pituitary surgery since 2009, we prospectively examine the effect of water restriction (< 1l per day), or Tolvaptan given at 3.75 mg or 7.5 mg in hyponatremic patients (Na⁺ < 133 mmol/l). The patient surveillance was standardized with a routine preoperative MRI scan and comprehensive neuroendocrine testing. All operations were performed by the same surgeon. Postoperatively, fluid balance and electrolytes were measured daily for 10 days. The study design was approved by the local Ethical Committee. Statistical analysis was performed with SPSS and p<0.05 was accepted as significant.

Results: 51 patients were treated with fluid restriction, 45 patients with 3.75 mg Tolvaptan (total 7.38±0.75 mg per patient) and 15 patients with 7.5 mg Tolvaptan (11.75±1.54 mg, p<0.05, recruitment ongoing). No adverse effects were noted. The control group comprised of 182 normonatremic patients (Na⁺ > 135 mmol/l). A substantial postoperative serum sodium nadir occurred despite Tolvaptan treatment at 3.75 mg (day 7 131.5±0. 9 mmol/l; day 8 132.3±0.8 mmol/l) or fluid restriction (day 7 132.7±0.7 mmol/l; day 8 132.1±0.8 mmol/l), while Tolvaptan at 7.5 mg resulted in a more rapid normalization (nadir day 5 133.4±1.4 mmol/l; day 7 134.5±1.3 mmol/l, p<0.03; day 8 135.5±1.2 mmol/l, p<0.03).

Conclusions: A treatment with the selective vasopressin V2 receptor antagonist Tolvaptan in a moderate dose offers a safe and effective treatment in neurosurgical patients suffering from Hyponatremia. However, since the cumulative dose of 11.75 mg Tolvaptan applied in our study was below the 15 mg preparation commercially available, a tight patient surveillance is recommended.