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Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V₂-receptor antagonist tolvaptan.

Gaglio P, Marfo K, Chiodo J - Dig. Dis. Sci. (2012)

Bottom Line: Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance.The primary cause is increased release of arginine vasopressin.Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant.

View Article: PubMed Central - PubMed

Affiliation: Division of Hepatology, Montefiore Medical Center and Albert Einstein College of Medicine, 111 East 210th Street, Rosenthal 2 Red Zone, Bronx, NY 10467, USA. eric.justice@bioscicom.net

ABSTRACT
Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.

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Six-month survival among 126 critically ill patients with cirrhosis. From Jenq et al. [13], reproduced with permission
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Fig1: Six-month survival among 126 critically ill patients with cirrhosis. From Jenq et al. [13], reproduced with permission

Mentions: In their study of 126 cirrhotic patients in an ICU, Jenq et al. found that hyponatremia was associated with increased frequency of ascites (OR 4.57, P < .001), hepatic encephalopathy (OR 2.38, P = .027), sepsis (OR 2.08, P = .048), and renal failure (OR 3.74, P = .001), as well as higher illness severity scores (based on MELD [model for end-stage liver disease], SOFA [Sequential Organ Failure Assessment], APACHE II [Acute Physiology and Chronic Health Evaluation II], and APACHE III rankings) [13]. It was also an independent predictor for both in- and out-of-hospital mortality, with in-hospital (73 vs. 56 %, P = .043) and 6-month mortality rates being significantly increased in hyponatremic versus normonatremic patients (Fig. 1). Most patients in this series had gastrointestinal bleeding, and hyponatremia was also significantly associated with mortality in this subgroup.Fig. 1


Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V₂-receptor antagonist tolvaptan.

Gaglio P, Marfo K, Chiodo J - Dig. Dis. Sci. (2012)

Six-month survival among 126 critically ill patients with cirrhosis. From Jenq et al. [13], reproduced with permission
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3472061&req=5

Fig1: Six-month survival among 126 critically ill patients with cirrhosis. From Jenq et al. [13], reproduced with permission
Mentions: In their study of 126 cirrhotic patients in an ICU, Jenq et al. found that hyponatremia was associated with increased frequency of ascites (OR 4.57, P < .001), hepatic encephalopathy (OR 2.38, P = .027), sepsis (OR 2.08, P = .048), and renal failure (OR 3.74, P = .001), as well as higher illness severity scores (based on MELD [model for end-stage liver disease], SOFA [Sequential Organ Failure Assessment], APACHE II [Acute Physiology and Chronic Health Evaluation II], and APACHE III rankings) [13]. It was also an independent predictor for both in- and out-of-hospital mortality, with in-hospital (73 vs. 56 %, P = .043) and 6-month mortality rates being significantly increased in hyponatremic versus normonatremic patients (Fig. 1). Most patients in this series had gastrointestinal bleeding, and hyponatremia was also significantly associated with mortality in this subgroup.Fig. 1

Bottom Line: Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance.The primary cause is increased release of arginine vasopressin.Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant.

View Article: PubMed Central - PubMed

Affiliation: Division of Hepatology, Montefiore Medical Center and Albert Einstein College of Medicine, 111 East 210th Street, Rosenthal 2 Red Zone, Bronx, NY 10467, USA. eric.justice@bioscicom.net

ABSTRACT
Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.

Show MeSH
Related in: MedlinePlus