title: Tolvaptan for hyponatremia with preserved sodium pool in critically ill patients.
abstract: BACKGROUND
  Hyponatremia is the most common electrolyte disturbance in hospitalized patients, and it represents a well-established risk factor for ICU/hospital mortality. The majority of hyponatremic states are associated with elevated arginine vasopressin levels and a preserved sodium pool. Conventional treatment is either not pathophysiologically oriented or of limited effectiveness. The aim of the present study is to investigate the use of enteral Tolvaptan in critically ill hyponatremic patients.
  
  
  METHODS
  This is a retrospective observational study in a general ICU. Patients with preserved sodium pool hyponatremia refractory to conventional therapy were enrolled. The hemodynamic, renal, and hepatic functions, together with sodium and water balance as close as possible to the drug administration and up to 72 h thereafter, were analyzed. The main outcome was a serum sodium increase of ≥ 4 mmol/L in 24 h; secondary endpoints were the ability to maintain serum sodium at 24 and 72 h, a decrease in urine sodium concentration and an increase in sodium-free diuresis.
  
  
  RESULTS
  38 patients were enrolled. The average dose of enteral Tolvaptan was 7.5 mg. 31 patients (81.6 %) increased their serum sodium >4 mmol/l/24 h; the average increase was 6.7 ± 3.4 mmol/l during the first 24 h (p < 0.001 vs baseline), and this was sustained at 72 h. No adverse effects were reported. Plasma sodium (R = -0.622, p < 0.001), urine sodium (R = -0.345, p < 0.001), central venous oxygen saturation (R = 0.401, p = 0.013), and BUN (R = -0.416, p = 0.031) before Tolvaptan were all significantly correlated with the absolute increase in serum sodium after the administration.
  
  
  CONCLUSIONS
  Enteral administration of Tolvaptan seems effective in the treatment of hyponatremia with preserved sodium pool in critically ill patients. Even if the study was underpowered to detect significant side effects or complications of unwarranted fast corrections of hyponatremia, we report no complications.
authors.affiliation: Unità Operativa di Anestesia e Rianimazione, Azienda Ospedaliera San Paolo-Polo Universitario, Via A. Di Rudinì, 8, 20142, Milan, Italy. michele.umbrello@fastwebnet.it.|Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy. michele.umbrello@fastwebnet.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Umbrello
authors.affiliation: Unità Operativa di Anestesia e Rianimazione, Azienda Ospedaliera San Paolo-Polo Universitario, Via A. Di Rudinì, 8, 20142, Milan, Italy.
authors.forename: Elena S
authors.initials: ES
authors.lastname: Mantovani
authors.affiliation: Unità Operativa di Anestesia e Rianimazione, Azienda Ospedaliera San Paolo-Polo Universitario, Via A. Di Rudinì, 8, 20142, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Formenti
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Casiraghi
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Ottolina
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Taverna
authors.affiliation: Unità Operativa di Anestesia e Rianimazione, Azienda Ospedaliera San Paolo-Polo Universitario, Via A. Di Rudinì, 8, 20142, Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Pezzi
authors.affiliation: Unità Operativa di Anestesia e Rianimazione, Azienda Ospedaliera San Paolo-Polo Universitario, Via A. Di Rudinì, 8, 20142, Milan, Italy.|Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mistraletti
authors.affiliation: Unità Operativa di Anestesia e Rianimazione, Azienda Ospedaliera San Paolo-Polo Universitario, Via A. Di Rudinì, 8, 20142, Milan, Italy.|Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Iapichino
keywords: Critical illness; Hyponatremia; Tolvaptan