P: 72 Hyponatremia Correction in Cirrhosis May Increase the Speed of Complex Information Processing

Abstract

BACKGROUND: Hyponatremia is frequent in patients with advanced cirrhosis and ascites. A decrease in plasma osmolality exacerbates astrocyte swelling and through this mechanism may worsen cognitive function. Our objective was to determine whether, in patients with cirrhosis and ascites, an increase in plasma sodium (spontaneous or induced by an aquaretic) leads to an improvement in cognitive function. METHODS: 250 patients with liver cirrhosis and ascites were included in two double-blind, randomised, multicentre clinical studies of satavaptan (a vasopressin V2 antagonist). Patients were included after a "wash-out period" (one week on controlled sodium intake and spironolactone 100 mg/d) and received either placebo (n = 61) or satavaptan (n = 189) at three different doses (5, 12.5, 25 mg/d). Patients completed the trail-making test (TMT) at baseline and at 5–7 and 14–28 days of follow-up. The TMT (scored in seconds) assesses speed of information processing and is considered a test of simple (part A) and complex attention (part B). Improvement of hyponatraemia was defined as an increase in plasma sodium >5 mmol/l or to a value >135 mmol/l. RESULTS: At inclusion into the studies, patients with normonatremia exhibited better results on the TMT-A and TMT-B that could not be explained by differences on age. This group also exhibited better parameters of liver function (Table 1). Improvement of hyponatremia was associated with shortening on the time needed to complete TMT-B: −20 s vs −6.5 s (P = 0.02), but not TMT-A: −10 s vs −5 s (P = 0.16). Increase in serum osmolality was also associated with better TMT-B scores (P < 0.001 at Day 5-7 and P = 0.033 at Day 14–28), but this was not shown for TMT-A. Liver function parameters remained stable in both groups of patients. Improvement of hyponatremia at Day 5 was most commonly seen in patients that received satavaptan (59.7%, n = 82) than in those treated with placebo (18.5%, n = 28). Median changes in TMT scores with satavaptan (all doses pooled) compared to placebo were: TMT-A −10 s vs 0 s (P = 0.08) and TMT-B −20 s vs −7.5 s (P = 0.12). CONCLUSIONS: Improvement of hyponatremia in cirrhosis was associated with an increase in the speed of complex information processing. Improvement of hyponatremia was achieved more frequently with satavaptan treatment, which showed a trend towards better results on cognitive function.