Tolvaptan Versus Fluid Restriction in the Treatment of Hyponatremia Resulting from SIADH Following Pituitary Surgery
Andrea Kleindienst, Simeon Georgiev, Sven Schlaffer, Michael Buchfelder
Abstract
CONTEXT: The relevance of hyponatremia has been acknowledged by guidelines from the United States (2013) and Europe (2014). However, treatment recommendations differ due to limited evidence. OBJECTIVE: In hyponatremia following pituitary surgery-caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion-we compared fluid restriction with the pharmacological increase of water excretion by blocking the vasopressin 2 receptors with tolvaptan at a low and a moderate dose. DESIGN: Prospective observational study. SETTING: Neurosurgical Department of a University hospital with more than 200 surgical pituitary procedures per year. PATIENTS: Patients undergoing pituitary surgery and developing serum sodium below 136 mmol/L. The diagnosis of SIADH was established by euvolemia (daily measurement of body weight and fluid balance), inappropriately concentrated urine (specific gravity), and exclusion of adrenocorticotropic and thyroid-stimulating hormone deficiency. INTERVENTION: Patients were treated with fluid restriction (n = 40) or tolvaptan at 3.75 (n = 38) or 7.5 mg (n = 48). MAIN OUTCOME MEASURES: Treatment efficacy was assessed by the duration of hyponatremia, sodium nadir, and length of hospitalization. Safety was established by a sodium increment below 10 mmol/L per day and exclusion of side effects. RESULTS: Treatment with 7.5 mg of tolvaptan resulted in a significant attenuation of hyponatremia and in a significant overcorrection of serum sodium in 30% of patients. The duration of hospitalization did not differ between treatment groups. CONCLUSIONS: Tolvaptan at a moderate dose is more effective than fluid restriction in the treatment of SIADH. Overcorrection of serum sodium may be a side effect of tolvaptan even at low doses.