Tolvaptan Use in SIAD (Syndrome of Inappropriate Antidiuresis)

Background: SIAD (Syndrome of Inappropriate Antidiuresis) is the commonest cause of hyponatraemia in hospital inpatients. Hyponatraemia is associated with increased length of stay and worse primary clinical outcomes. Our study aimed to evaluate the effectiveness of Tolvaptan, a selective, non-peptide, Vasopressin receptor antagonist, treatment in hospitalised patients with SIAD. Method and Baseline Characteristics: A Retrospective analysis of 9 patients treated with Tolvaptan for a confirmed diagnosis of SIAD was carried out. Information was collected from the inpatient records and biochemical test results. Serum Sodium levels on admission ranged between 104- 124mmol/ L (Normal range 136 -145 mmol/L). Average inpatient days solely due to hyponatraemia was 24 days. The number of in-patient days on fluid restriction ranged from 8-22 days depending on timing of referral to endocrine department. Tolvaptan was only started at a stable serum sodium at 118 mmol/L or greater. Four patients also had a prior trial of demeclocycline. Tolvaptan was started at its smallest dose of 7.5mg OD under strict monitoring of serum sodium with locally agreed protocol. Aetiology of SIAD included lung malignancy, acute demyelinating polyneuropathy, listeria meningitis, autoimmune encephalitis, SSRI (Selective Serotonin Reuptake inhibitor) use, Aspergillosis and Idiopathic (n=3). Results: Serum sodium level improved to >128 mmol/L in 2 days of starting Tolvaptan in all cases. After discharge, there was remote virtual clinic monitoring from the endocrinology team at 2 weeks, 4- 6 weeks and 3 months with a view to stop the medication. No adverse events were observed during use of Tolvaptan in the patient population. Tolvaptan 7.5mg OD was either stopped completely after 4-6 weeks or switched to 7.5mg alternate days depending on the clinical course of underlying pathology. Average duration of Tolvaptan treatment was 4.5 months excluding one patient with chronic lung pathology. 3 patients had further hospital admission on stopping Tolvaptan treatment and treatment with Tolvaptan had to be re-initiated. Conclusion: This study confirms the efficacy of Tolvaptan use in SIAD related hyponatremia. Tolvaptan serves as a cost effective treatment option for hospitalised patients who have either failed to respond to demeclocycline or fluid restriction. In our case cohorts, cost comparison of Low dose Tolvaptan with retrospective calculation of total inpatient days of fluid restriction and use of demeclocycline showed a better outcome and clinical effectiveness with low dose Tolvaptan. We recommend earlier use of Tolvaptan in SIAD under guidance from specialist team as a safe, cost effective and in some cases, as a hospital admission-avoidance strategy.