To the Editor:

We have read with great interest the study by Solà et al.1 Two years ago, our group showed that terlipressin has an affinity to V2 receptors.2 Resultant hyponatremia has been suggested,2-4 and it is now supported by this large, retrospective clinical study with a relevant control group. The observed hyponatremia is likely a result of both V1a and V2 receptor activation. Terlipressin induces natriuresis via V1a receptor stimulation.5 The combination with V2 receptor–induced antidiuresis due to an increased abundance of aquaporin 2 in the renal collecting duct is likely responsible for the observed hyponatremia.2 The rise in natriuresis induced by terlipressin is most likely due to a combination of two actions: (1) a rise in blood pressure and a contribution of pressure natriuresis, in which an increase in arterial blood pressure reduces sodium reabsorption in the whole kidney, and (2) a stimulation of V1a receptors in the collecting duct, which induces natriuresis and counteracts the antinatriuretic effects of V2.

In our study of 62 patients with bleeding esophageal varices, the serum sodium level decreased from 136 ± 6 to 130 ± 7, and the decrease in the serum sodium level correlated with the duration of treatment (Pearson correlation = −0.48, P < 0.001).4 A recent randomized study of bleeding esophageal varices also found the development of hyponatremia during terlipressin therapy to be related to the duration of the treatment.3 This reinforces the recommendation to use short-term terlipressin in patients with variceal bleeding to prevent side effects such as hyponatremia. Thus, the results of a recent study of patients with bleeding esophageal varices suggested that 2 days of terlipressin treatment combined with banding may be equally as effective as 5 days of terlipressin treatment.6


  1. Top of page
  • 1
    Solà E, Lens S, Guevara M, Martín-Llahí M, Fagundes C, Pereira G, et al. Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension. HEPATOLOGY 2010; 52: 1783-1790.
  • 2
    Krag A, Bendtsen F, Pedersen EB, Holstein-Rathlou NH, Møller S. Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects. Am J Physiol Renal Physiol 2008; 295: F1295-F1300.
  • 3
    Bruha R, Marecek Z, Prochazka V, Lata J, Spicak J, Ehrmann J, et al. Double-blind randomized multicenter study comparing the efficacy and safety of 10-day to 5-day terlipressin treatment of bleeding esophageal varices. Hepatogastroenterology 2009; 56: 390-394.
  • 4
    Krag A, Hobolth L, Møller S, Bendtsen F. Hyponatraemia during terlipressin therapy. Gut 2010; 59: 417-418.
  • 5
    Krag A, Møller S, Henriksen JH, Holstein-Rathlou NH, Larsen FS, Bendtsen F. Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome. HEPATOLOGY 2007; 46: 1863-1871.
  • 6
    Lo GH, Chen WC, Wang HM, Lin CK, Chan HH, Tsai WL, et al. Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices. Gut 2009; 58: 1275-1280.

Aleksander Krag M.D., Ph.D.*, Søren Møller Dm.Sci.†, Flemming Bendtsen Dm.Sci.*, * Departments of Gastroenterology, Hospital Hvidovre, Copenhagen University, Copenhagen, Denmark, † Departments of Clinical Physiology, Hospital Hvidovre, Copenhagen University, Copenhagen, Denmark.