Dataset Information

Tolvaptan Versus Fluid Restriction in the Treatment of Hyponatremia Resulting from SIADH Following Pituitary Surgery.

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.

SUBMITTER: Kleindienst A

PROVIDER: S-EPMC7326480 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Tolvaptan Versus Fluid Restriction in the Treatment of Hyponatremia Resulting from SIADH Following Pituitary Surgery.

Kleindienst Andrea A Georgiev Simeon S Schlaffer Sven Martin SM Buchfelder Michael M

Journal of the Endocrine Society 20200609 7

<h4>Context</h4>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.<h4>Objective</h4>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 ...[more]

PMID: 32666012

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Project description:BACKGROUND:Tolvaptan effectively corrects hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but undesired overcorrection can occur. We hypothesized that pretherapy parameters can predict the rapidity of response to tolvaptan in SIADH. STUDY DESIGN:Multicenter historical cohort study. SETTING & PARTICIPANTS:Adults with SIADH or congestive heart failure (CHF) treated with tolvaptan for a serum sodium concentration ? 130 mEq/L at 5 US hospitals. PREDICTORS:Demographic and laboratory parameters. OUTCOMES:Rate of change in serum sodium concentration. MEASUREMENTS:Spearman correlations, analysis of variance, and multivariable linear mixed-effects models. RESULTS:28 patients with SIADH and 39 patients with CHF treated with tolvaptan (mean baseline serum sodium, 120.6 and 122.4 mEq/L, respectively) were studied. Correction of serum sodium concentration > 12 mEq/L/d occurred in 25% of patients with SIADH compared to 3% of those with CHF (P<0.001). Among patients with SIADH, the increase in serum sodium over 24 hours was correlated with baseline serum sodium concentration (r=-0.78; P<0.001), serum urea nitrogen concentration (SUN; r=-0.76; P<0.001), and estimated glomerular filtration rate (r=0.58; P=0.01). Baseline serum sodium and SUN concentrations were identified as independent predictors of change in serum sodium concentration in multivariable analyses. When patients were grouped into 4 categories according to baseline serum sodium and SUN median values, those with both low baseline serum sodium (?121 mEq/L) and low baseline SUN concentrations (?10mg/dL) exhibited a significantly greater rate of increase in serum sodium concentration (mean 24-hour increase of 15.4 mEq/L) than the other 3 categories (P<0.05). Among patients with CHF, only baseline SUN concentration was identified as an independent predictor of change in serum sodium concentration over time. LIMITATIONS:Lack of uniformity in serial serum sodium concentration determinations and documentation of water intake. CONCLUSIONS:Baseline serum sodium and SUN values are predictive of the rapidity of hyponatremia correction following tolvaptan use in SIADH. We advise caution when dosing tolvaptan in patients with both low serum sodium and SUN concentrations.

Project description:BackgroundCurrent hyponatraemia guidelines are divided on the use of tolvaptan in hospitalised patients with moderate to severe hyponatraemia, due to an uncertain risk-benefit ratio. We will conduct a randomised trial to test the hypothesis that early use of tolvaptan improves the rate of serum sodium correction and clinical outcomes compared with current standard first-line therapy, restriction of fluid intake, without increasing the risk of serum sodium overcorrection.MethodsWe will enrol hospitalised patients with euvolaemic or hypervolaemic hyponatraemia and serum sodium of 115-130 mmol/L at Austin Health, a tertiary care centre in Melbourne, Australia. Participants will be randomised 1:1 to receive either tolvaptan (initial dose 7.5 mg) or fluid restriction (initial limit 1000 ml per 24 h), with titration of therapy based on serum sodium response according to a pre-determined protocol over a 72-h intervention period. The primary endpoint will be the between-group change in serum sodium over time, from study day 1 to day 4. Secondary endpoints include serum sodium increment in the first 24 and 48 h, proportion of participants with normalised serum sodium, length of hospital stay, requirement for serum sodium re-lowering with intravenous dextrose or desmopressin, cognitive and functional measures (Confusion Assessment Method Short form, Timed Up and Go test, hyponatraemia symptom questionnaire), 30-day readmission rate, treatment satisfaction score and serum sodium 30 days after discharge. The trial will be overseen by an independent Data Safety Monitoring Board. Serum sodium will be monitored every 6-12 h throughout the study period, with pre-specified thresholds for commencing intravenous 5% dextrose if serum sodium rise targets are exceeded.DiscussionWe seek to inform future international guidelines with high-quality data regarding the utility and safety of tolvaptan compared to standard therapy fluid restriction in patients with moderate-severe hyponatraemia in hospital. If tolvaptan use in this patient group is endorsed by our findings, we will have established an evidence-based framework for tolvaptan initiation and monitoring to guide its use.Trial registrationAustralia and New Zealand Clinical Trials Registry ACTRN12619001683123 . Registered on December 2 2019.

Project description:IntroductionHyponatremia is a common condition of varying etiology among hospitalized patients and is associated with adverse outcomes. Treatment to normalize serum sodium is advisable. Tolvaptan received European Union marketing authorization for hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Post-marketing pharmacovigilance activities were required to characterize the safety profile of tolvaptan more fully in this population, which is often elderly with a high burden of comorbid illness.MethodsThis was a prospective, observational, multinational, post-authorization pharmacovigilance study (NCT01228682) in seven European countries. Hospitalized patients were enrolled who received tolvaptan for hyponatremia associated with SIADH and consented to data collection. Tolvaptan was initiated and assessments performed at physician discretion per local standards of care. To reflect actual clinical practice, no assessments or procedures were required outside the standard of care. Patients who continued to receive long-term tolvaptan following hospital discharge and provided consent received follow-up from their community physicians.ResultsA total of 252 patients (mean age 70.6 years) enrolled. Mean tolvaptan treatment duration was 139.4 days, median 18.5 (range 1-1130) days; most frequent dose was 15 mg/day (used in 75% of patients). Serum sodium increased from baseline (mean 123.2 mmol/l) during treatment week 1 and remained stable during follow-up, with little difference across doses of 7.5, 15, and 30 mg/day. Hyponatremia symptoms (e.g., confusion, unsteady gait, lethargy) were present in 122/252 (48.4%) patients at pre-treatment baseline, decreasing to 46/252 (18.3%) during treatment. Sixty-two patients (24.6%; mean baseline serum sodium 120 mmol/l) experienced rapid correction of hyponatremia within 72 h. No osmotic demyelination syndrome occurred.ConclusionIn clinical practice, tolvaptan improved serum sodium and decreased hyponatremia symptoms in hyponatremia secondary to SIADH. Serum sodium should be monitored during treatment to minimize risk of rapid correction.Trial registrationClinicaltrials.gov identifier NCT01228682.

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Tolvaptan Versus Fluid Restriction in the Treatment of Hyponatremia Resulting from SIADH Following Pituitary Surgery.

Publications

Tolvaptan Versus Fluid Restriction in the Treatment of Hyponatremia Resulting from SIADH Following Pituitary Surgery.

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