Hyponatremia in cirrhosis: From pathogenesis to treatment†

Ginès, Pere; Berl, Tomás; Bernardi, Mauro; Bichet, Daniel G.; Hamon, G; Jiménez, Wladimiro; Liard, J. F.; Martin, Pierre‐Yves; Schrier, Robert W.

doi:10.1002/hep.510280337

Cited by 257 publications

(213 citation statements)

References 142 publications

(183 reference statements)

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“…3 Hyponatremia is a comorbid condition of multiple diseases, occurring in approximately 20% of patients with heart failure, 7,8 and 40% to 57% of patients with advanced cirrhosis. 9,10 The syndrome of the inappropriate release of antidiuretic hormone (SIADH) is additionally a predominant cause of hyponatremia, with a prevalence reported as high as 35% in hospitalized patients. 11 Hyponatremia is not only widespread, but also an independent predictor of mortality.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of incremental healthcare resource burden and readmission rates associated with hospitalized hyponatremic patients in the US

Amin

Deitelzweig

Christian

et al. 2012

Journal of Hospital Medicine

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BACKGROUND:Hyponatremia is a prevalent electrolyte disorder in hospitalized patients indicative of greater morbidity and mortality. A large‐scale retrospective analysis was conducted to evaluate the incremental burden of hospitalized hyponatremic (HN) versus non‐HN patients in terms of hospital resource utilization, costs, and hospital readmissions in the real‐world setting.METHODS:HN patients (≥18 years) were selected from the Premier Hospital Database between January 1, 2007 and March 31, 2010 and matched to a non‐HN control cohort using propensity score matching. Bivariate and multivariate statistics were employed to evaluate the differences in healthcare resource utilization, costs, and hospital readmissions between patient cohorts.RESULTS:Among the matched patient cohorts, length of stay (LOS) (8.8 ± 10.3 vs 7.7 ± 8.5 days, P < 0.001), hospital admission costs ($15,281 ± $24,054 vs $13,439 ± $22,198, P < 0.001), intensive care unit (ICU) LOS (5.5 ± 7.9 vs 4.9 ± 7.1 days, P < 0.001), and ICU costs ($8525 ± $13,342 vs $7597 ± $12,695, P < 0.001) were greater for the HN versus non‐HN cohort, as were hospital readmission rates 30 days postdischarge. Multivariate regressions further demonstrated that hyponatremia was associated with an increase of 10.9% for LOS, 8.2% for total hospitalization costs, 10.2% for ICU LOS, and 8.9% for ICU costs. Additionally, after multivariate adjustment, hyponatremia was associated with a 15.0% increased chance for hospital readmission 30 days postdischarge (P < 0.0001).CONCLUSIONS:Hyponatremia is an independent predictor of increased hospitalization LOS and cost, ICU admission and cost, and 30‐day hospital readmission, and therefore represents a potential target for intervention to reduce healthcare expenditures for a large population of hospitalized hyponatremic patients. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine

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Section: Discussionmentioning

confidence: 99%

Evaluation of incremental healthcare resource burden and readmission rates associated with hospitalized hyponatremic patients in the US

Amin

Deitelzweig

Christian

et al. 2012

Journal of Hospital Medicine

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“…Blood volume expansion follows renal retention of sodium and water, which, in turn, is evoked by secondary hyperaldosteronism, activation of sympathetic nervous system, enhanced secretion of argininevasopressin, and reduced renal perfusion. 3,32,33 The factors responsible for vasodilation are less defined, but an increased production of nitric oxide by endothelial cells likely plays a prominent pathogenetic role. 4,6,34 We explored the relationship between the hyperdynamic circulatory syndrome and the presence of AD as assessed by a battery of well-standardized sympathetic and vagal tests.…”

Section: Discussionmentioning

confidence: 99%

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites

et al. 1999

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Patients with advanced cirrhosis frequently show hemodynamic abnormalities. Autonomic dysfunction (AD) is also common and, owing to the importance of autonomic function in cardiovascular homeostasis, it may be involved in the pathogenesis of the hyperdynamic circulation. We, therefore, evaluated the hemodynamic status and autonomic function in 30 patients with cirrhosis, most of them with an advanced stage of the disease. Autonomic function was assessed with 7 cardiovascular tests exploring the vagal or sympathetic function. Each test was scored from 1 to 3 (normal, borderline, altered). Cardiac index (CI) was measured by an echocardiogram. Twenty-four (80%) patients showed an AD, this being definite in 14 (47%) patients. A vagal dysfunction (VD) was found in 19 patients (63%), this being definite in 11 patients (37%), and a sympathetic dysfunction (SD) in 7 patients (definite in 3 [10%] patients). The patients with AD showed a faster heart rate (P ‫؍‬ .021), lower indicized peripheral vascular resistance (P ‫؍‬ .013), and increased CI (P ‫؍‬ .004) than patients without AD whereas mean arterial pressure did not differ. Similar results were seen by grouping patients according to the VD. AD score was directly correlated with heart rate (r ‫؍‬ 0.53; P ‫؍‬ .002) and CI (r ‫؍‬ 0.45; P ‫؍‬ .016), and inversely correlated with peripheral vascular resistance (r ‫؍‬ 0.46; P ‫؍‬ .013). Even closer correlations were found with vagal score. AD (mainly VD) may be involved in the pathogenesis of the hyperdynamic circulatory syndrome of patients with advanced cirrhosis. (HEPATOLOGY 1999;30:1387-1392.)Hyperdynamic circulation is a common and long-recognized feature of patients with advanced cirrhosis, 1 consisting of elevated cardiac rate and output and reduced peripheral vascular resistance, so that arterial pressure is tendentially or frankly reduced. The clinical importance of this disorder was shown by subsequent studies, showing that the alterations of systemic hemodynamics, renal function, and vasoactive systems are prognostic indicators even more accurate than the tests exploring liver function. 2 The setting of the hyperdynamic circulatory syndrome is the pathogenetic background of complications such as renal sodium and water retention and hepatorenal syndrome. 3 Splanchnic blood pooling, opening of portal-systemic collaterals, and arterial vasodilation, as well as a compensatory increase in blood volume, are the causative events of the hyperdynamic circulatory syndrome. 4,5 The pathogenesis of arterial vasodilation is still debated. It has been proposed that an overproduction of a variety of vasorelaxant agents, such as histamine, adenosine, gut-derived peptides and endothelial cell-derived vasodilators, and bile acid retention reduce the responsiveness of the vascular bed to endogenous vasoconstrictor stimuli. 4,6 The autonomic nervous system plays a central role in modulating cardiac performance and vasomotor activity. The presence of an autonomic dysfunction (AD) in cirrhosis has been clearly shown through different...

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“…2,3 The inability of these patients to excrete an appropriate amount of free water is related to many factors, the most important of which is the nonosmotic stimulation of vasopressin release. [4][5][6] Plasma vasopressin levels are increased despite low plasma osmolality, 7 reflecting the resetting of the osmostat to a lower osmolar threshold for vasopressin suppression. 8 Vasopressin exerts its effects on water metabolism through the activation of specific V 2 receptors, which are expressed on the cells of the ascending limb of the loop of Henle and on the cells of the collecting duct of the nephron.…”

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A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial

et al. 2003

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for The North American VPA-985 Study Group Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V 2 receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V 2 receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P < .05) and serum sodium (P < .05), without significant changes in orthostatic blood pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use. (HEPATOLOGY 2003;37:182-191.)See Editorial on Page 13 P atients with advanced cirrhosis and ascites or with congestive heart failure (CHF) have a disturbance in water metabolism, resulting in decreased renal free water excretion and dilutional hyponatremia. 1 The presence of hyponatremia in hospitalized patients with alcoholic cirrhosis or CHF is associated with a significantly increased mortality. 2,3 The inability of these patients to excrete an appropriate amount of free water is related to many factors, the most important of which is the nonosmotic stimulation of vasopressin release. [4][5][6] Plasma vasopressin levels are increased despite low plasma osmolality, 7 reflecting the resetting of the osmostat to a lower osmolar threshold for vasopressin suppression. 8 Vasopressin exerts its effects on water metabolism through the activation of specific V 2 receptors, which are expressed on the cells of the ascending limb of the loop of Henle and on the cells of the collecting duct of the nephron. 9 In the collecting duct, the activation of the V 2 receptor increases water reabsorption directly through the insertion of water channels into the otherwise water-impermeable collecting duct cells. 10 V 2 receptor antagonists, by competitive binding to the V 2 receptor, can displace vasopressin and, the...

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Hyponatremia in cirrhosis: From pathogenesis to treatment†

Cited by 257 publications

References 142 publications

Evaluation of incremental healthcare resource burden and readmission rates associated with hospitalized hyponatremic patients in the US

Evaluation of incremental healthcare resource burden and readmission rates associated with hospitalized hyponatremic patients in the US

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites

A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial

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