Tolvaptan in the Management of Acute Euvolemic Hyponatremia After Transsphenoidal Surgery: A Retrospective Single-Center Analysis

Abstract

IntroductionSyndrome of inappropriate antidiuresis (SIAD) can be a complication of hypothalamus-pituitary surgery. The use of tolvaptan in this setting is not well established, hence the primary aim of this study was to assess the sodium correction rates attained with tolvaptan compared with standard treatments (fluid restriction and/or hypertonic saline). Furthermore, we compared the length of hospital stay in the two treatment groups and investigated the occurrence of overcorrection and side effects including osmotic demyelination syndrome.MethodsWe retrospectively reviewed 308 transsphenoidal surgical procedures performed between 2011 and 2019 at our hospital. We selected adult patients who developed post-operative SIAD and recorded sodium monitoring, treatment modalities and outcomes. Correction rates were adjusted based on pre-treatment sodium levels.ResultsTwenty-nine patients (9.4%) developed post-operative SIAD. Tolvaptan was administered to 14 patients (median dose 15 mg). Standard treatments were employed in 14 subjects (fluid restriction n=11, hypertonic saline n=1, fluid restriction and hypertonic saline n=2). Tolvaptan yielded higher adjusted sodium correction rates (12.0 mmolL-1/24h and 13.4 mmolL-1/48h) than standard treatments (1.8 mmolL-1/24h, p<0.001, and 4.5 mmolL-1/48h, p=0.004, vs. tolvaptan). The correction rate exceeded 10 mmolL-1/24h or 18 mmolL-1/48h in 9/14 and 2/14 patients treated with tolvaptan, respectively, and in no patient who received standard treatments. No side effects including osmotic demyelination occurred. Tolvaptan was associated with a shorter hospital stay (11vs.15 days, p=0.01).ConclusionsTolvaptan is more effective than fluid restriction (with or without hypertonic saline) and allows for a shortened hospital stay in patients with SIAD after transsphenoidal surgery. However, its dose and duration should be carefully tailored, and close monitoring is recommended to allow prompt detection of overcorrection.

A Conspectus of Euvolemic Hyponatremia, Its Various Etiologies, and Treatment Modalities: A Comprehensive Review of the Literature

“…With a 100% sensitivity and 66.7% specificity, NT-proBNP can accurately predict hypovolemia and a cut-off value of 125 pg/ml differentiates CSW from SIADH (with 87.50% sensitivity and 93.33% specificity) [81]. The incidence of SIADH following transsphenoidal surgeries ranges from 1.8% to 37%, and tolvaptan has been reported to yield significant sodium correction rates, notwithstanding adverse effects, therefore reducing the length of hospital stay [83][84][85][86][87][88]. Hyponatremia due to SIADH is also associated with schwannoma, owing to adrenal insufficiency and panhypopituitarism caused by an intra-or suprasellar mass [89].…”

Disorders of Salt and Water Balance After Pituitary Surgery

“…Baseline plasma sodium ≤121 mmol/L and blood urea nitrogen ≤10 mg/dL (plasma urea of ≤3.7 mmol/L) are associated with a significantly greater rise in plasma sodium following tolvaptan ( 89 ). The use of tolvaptan for SIAD in the postoperative pituitary surgery setting is mostly limited to retrospective studies and case reports or series ( 90–93 ). In postoperative pituitary patients, a single-dose of tolvaptan is effective in normalizing plasma sodium and reducing the duration of hospital admission ( 90 ); however, it is associated with a risk of overcorrection.…”

“…The use of tolvaptan for SIAD in the postoperative pituitary surgery setting is mostly limited to retrospective studies and case reports or series ( 90–93 ). In postoperative pituitary patients, a single-dose of tolvaptan is effective in normalizing plasma sodium and reducing the duration of hospital admission ( 90 ); however, it is associated with a risk of overcorrection. In a retrospective study, Indirli et al found higher correction rates of plasma sodium with tolvaptan (median dose 15 mg) than standard treatment which included fluid restriction and/or hypertonic saline (12 mmol/L/24 hour vs 1.8 mmol/L/24 hours).…”

“…In a retrospective study, Indirli et al found higher correction rates of plasma sodium with tolvaptan (median dose 15 mg) than standard treatment which included fluid restriction and/or hypertonic saline (12 mmol/L/24 hour vs 1.8 mmol/L/24 hours). However overcorrection of plasma sodium of >10 mmol/L/24 hour occurred in 64% of patients treated with tolvaptan ( 90 ). A similar effect on plasma sodium was observed between doses of 7.5 mg and 15 mg tolvaptan ( 90 ).…”

“…However overcorrection of plasma sodium of >10 mmol/L/24 hour occurred in 64% of patients treated with tolvaptan ( 90 ). A similar effect on plasma sodium was observed between doses of 7.5 mg and 15 mg tolvaptan ( 90 ). Similarly, in a prospective observational study, Kleindienst et al reported a dose of tolvaptan 7.5 mg was more effective than fluid restriction in correction of SIAD following pituitary surgery (sodium increase 7.8 mmol/L/24 hour vs 3.5 mmol/L/24 hour).…”