Endocrine Abstracts

Introduction: Tolvaptan is the only V2-receptor antagonist authorized for use in Europe in patients with SIADH. Its initiation requires hospitalization. Our goal was to analyze the safety and efficacy of tolvaptan started in a Hospital Day-Ward.

Material and methods: Retrospective descriptive study of 33 ambulatory patients with mild/moderate SIADH-induced chronic sustained hyponatremia initiating tolvaptan therapy in the Day-Ward of a tertiary center over a 4-year period (2014-2017). Following obtention of Blood/urine samples, 7.5mg of tolvaptan were administered at 08:15AM, with patients instructed to drink freely. Blood/urine tests repeated 6, 24 and 48 hours post-initial tolvaptan dose (ITD). Electrolytes in mmol/L, osmolality(Osm) in mOsm/kg. If serum 6-hour sodium(SNa) rose<5, patients returned the following morning. “Braking protocol”: If 6-hour SNa rose 5 mmol, 3 mcg DDAVP were administered sc; 6 mmol rise: DDVP +5% dextrose iv 2cc/kg/hour for 2 hours; ≥ 7: DDAVP + dextrose 3cc/kg/hour 3 hours, with patients returning the following morning. “Braked” patients received 7.5mg on day 2, non-braked 15mg, with overcorrection ruled out. A 24h-hour SNa increment>10 or 48-hour rise>18 was considered overcorrection. Results as Mean (Standard Deviation) or median [Interquartile range].

Results: Age: 71.7 (9.09). 25/33 women. Principal SIADH etiologies: 11/33 oncological, 6/33 pharmacological, 5/33 neurological. Baseline: SNa 129.6 (2.6), SOsm 270 (7.2), Urine(U) Na 76 [54-118], UOsm 378 [279-519]. 6-hours post-ITD: SNa rose 3.1(2.4). 8/33 presented SNa ascent≥5 and Braking protocol applied. 24-hours post-ITD: SNa rose 3.7 (2.3) from baseline. In 15/33 SNa rose ≤2 mmol/L, in 18/33 SNa rose 3-10 mmol/L, with no significant difference between “braked” and “non-braked” patients. No patient presented overcorrection. Men presented a significantly higher 24h-SNa rise than women: 4.9 (2.8) versus 3.2 (1.9) respectively (P=0.043). 48-hours post-ITD: SNa rose 5.55 (2.74) from baseline. 22/33 (66.7%) of patients attained SNa≥135. The maximum 48-hour rise: 12. SNa levels at 6, 24 and 48 hours post-tolvaptan initiation were all significantly higher than at baseline (P<0.0001 in all). Neither initial SNa nor UOsm predicted the 6, 24 or 48-hour SNa increment. No side effects were observed.

Conclusions: Two-thirds of the patients attained eunatremia after 48 hours, with no cases of overcorrection. The protocol is safe and effective for initiation of tolvaptan therapy in a day-ward, avoiding the need for conventional hospitalization in these ambulatory SIADH patients.