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Intravenous albumin infusion prevents renal impairment (RI) and improves hospital survival in patients with spontaneous bacterial peritonitis (SBP)
4.5 GENERAL 1
GS3/13
SESSION
3
1
EVIDENCE OF REDUCED EFFECTIVENESS OF AN OTHERWISE ACTMTY IN DGPAMINERGIC ENDGGENOUS INCREASED COMPENSATED CIRRHOSIS. G Sansot?. A Fenwi. E. Liamldi*. CN Castellana**, G Termnova, M Ghidoni. E Villa, F Manenti. Chairs of Gastmenterologv, Universi@ of Modena, Imly. Pharmacolqy,
‘Endocrinology
and **Clinical
Endogenous dopamine exerts a combined adrenal and renal mediation of the natriuretic response to central fluid volume expansion. Plasma dopamine levels rise in association with the natriuretic response to volume expansion produced by head-out water immersion. Aldosterone secretion both in rat and in man is inhibited by dopamine. Dopamine inhibits Na’-K’ATPase activity in proximal convoluted and straight tubule segments. In this manner dopamine increases sodium delivery to the distal nephron and natriuresis. We studied 12 patients with Child-Pugh class A cirrhosis without history of previous ascites or diuretic consumption (after an equilibration period of five days on a normocaloric diet with a daily sodium intake of 120 mEq) and compared them to 9 control subjects, on the basis of the evaluation of a) the degree of dopaminergic activity, as measured by the incremental aldosterone responses 30 and 60 min min atler metoclopramide (h4TC) 10 mg i.v. administration; b) basal morning levels of active renin and aldosterone while reclining ; c) 4 h renal clearances of lithium (C-Li) (an index of fluid and sodium delivery to the distal tubule) and creatinine (C-Cr), d) 4 h urinary excretion parameters of sodium and potassium. With respect to controls, patients showed signiticantly greater incremental aldosterone responses both 30 and 60 min atler MTC (respectively, +30 mitt: 160.2 f 68.8 v. 83.6 f 35.2 pg/ml, ~4.01; +60 min: 140.5 f 80.3 v 36.8 i 39.0 pg/ml, p
HEPATIC BLOOD FLOW AND SPLANCHNIC (IXPGEN CONSUMPTION IN PATIENTS WITH HEPATIC ENCEPHALOPATHY BEFORE AND AFTER HIGH-VOLUME PLASMAPHERESIS. JO. Clemmesen. FS. Larsen. BA Hansen P. Ott. Department Hepatology A-2101, Rigshospitalet, Copenhagen, Denmark.
of
It is not known whether an oxygen dept is present in the splanchnic region in patients with hepatic encephalopathy (HE). Earlier studies has shown that high-volme plasmapheresis @VP) decreases a high cardiac output (CO) in patients with acute liver (ALF) but increases CO in patients with chronic liver failure (CLF). Further, HVP increases cerebral oxygen consumption in patients with ALF. We studied splanchnic hemodynamics and splanchnic oxygen consumption in 11 patients with ALF and 7 patients with CLF before and after HVP. Hepatic blood flow was estimated by use of Fick’s principle with constant infusion of D-sorbitol and liver vein catheterisation. All patients had HE grade 2-4. Results: In m with ALF hepatic blood flow (HElF) increased from 1.67 f 0.72 L/mm before HVP to 2.07 l 1.11 L/mm after HVP (p = 0.04). Splanchnic oxygen consumption was not changed statistically significantly (2.98 f 0.68 mmol/min vs 3.44kl.03 mmol/min, p = 0.10). CO was unchanged (6.7 f 2.5 L/min vs 6.6 f 2.2 L/min (p-0.75) while systemic vascular resistance index (SVRI) increased from 1587*650 to 202&806 dyn s cm*’ m* (p=O.O06). In patients with CLF, EHBF increased from 1.89 f 1.32 L/mm to 2.34 f 1.54 L/mm @ = 0.04). Splanchnic oxygen consmnption remained unchanged (3.13 f 2.14 mmol/min vs 2.89 f 1.35 mmol/min, p = 0.56). In this-group CO increased from 9.1 f 2.8 L/min to 10.1 f 2.9 Wmin @=0.006) while SVIU was unchanged (972*288 vs 1106i540 dyn s cm“ m* ;NS). Conclusion: In ALF, HVP increased HBF by increasing SVRl so that a larger fraction of CO was directed to the splanchnic organs. In CLF, HBF increased as a fixed fraction of CO. These data support the hypothesis that the vasodilatation in CLF is of mor chronic nature. While HBF increased after HVP in both groups splanchnic oxygen consumption was unchanged. These data indicate that a tissue hypoxia is not present in the splanchnic region in patients with HE.
INTRAVENOUS ALBUMIN INFUSION PREVENTS RENAL IMPAIRMENT (RI) AND IMPROVES HOSPITAL SURVIVAL IN PATIENTS WITH SPONTANEOUS BACTERIAL PERITONITIS (SBP). P.Sort*. M. Navasa* and Soanish aroup for the studv of bacterial infections in cirrhosis. *Hosoital Clinic i Provincial. Barcelona. Soain. One third of patients with SBP develop RI in relation with a deterioration of circulatory function, as reflected by an increase in plasma renin activity (PRA). The development of RI is the most important predictor of hospital mortality in SBP. This study assesses whether plasma volume expansion prevents the impairment in circulatory and renal function and improves hospital survival in these patients. 119 patients with SBP were randomized to receive albumin infusion (1.5 g/Kg body wt. on the 1’ day and 1 g/Kg of body wt. on the 3rd day) plus cefotaxime (n=59) or cefotaxime alone (n=60). At diagnosis, hepatic and renal function, PRA and incidence of hepatocarcinoma were similar in both groups. The incidence of circulatory dysfunction (increase of 50% in PRA above baseline levels at the sixth day of inclusion) (4% vs 30% , p
CRITICAL ROLE OF DISTAL TUBULAR HANDLING OF SODIUM lN THE REGULATION OF EXTRACELLULAR FLUID VOLUME IN COMPENSATED clRRH0s1s. G Sanso&. A Fermn’, E. Bamldi’. CN CastelImo**, M Ghidoni. E Villa, F Chairs of Gastroenterologv. Manmti. Phannocologv, University of Modem, Italy.
*Endocrinology
and
‘*Clinical
For any given value of plasma aldosterone concentration cirrhotic patients without ascites excrete significantly less sodium with respect to healthy controls. In compensated cirrhosis a direct study of the distribution of sodium reabsorption along the different segments of the renal tubule is still lacking, especially if evaluated in conjunction with markers of the central fluid volume. We studied 12 patients with Child-Pugh class A cirrhosis and 9 healthy subjects (both groups following a diet with a daily sodium intake of 120 mEq), on the basis of the evaluation of 1) the degree of dopaminergic activity, as measured by the mcremental aldosterone responses 30 and 60 mitt mitt atler metoclopramide (MTC) 10 mg i.v. administration; 2) basal morning levels of active renin and aldosterone while reclining 3) 4 h renal clearances of lithmm (an index of fluid delivery to the distal tubule) and creatinine, both measured in recumbency; 4) urinary excretion parameters of sodium and potassium With respect to controls, the patients showed significantly greater incremental aldosterone responses both 30 and 60 min atter i.v. MTC (respectively, +30 mitt: 160.2 f 68.8 v. 83.6 f 35.2 pg/ml, pa.01; +60 mm: 140.5 * 80.3 v. 36.8 f 39.0 pg/ml, pQ).Ol), displaying increased endogenous dopaminergic activity. The patients showed not significantly lower plasma levels of active renin and aldosterone but significant higher values of distal fractional sodium reabsorption I with respect to controls (respectively, 21.09 f 6.7 % v. 12.58 f 4.8 % of the filtered sodium load; pa.02). In the patients’ group, we found significant negattve correlations between: A) absolute distal sodium reabsorption and active renin (r:-O.59, pcO.05); B) active renin and dopaminergic activity (expressed as plasma aldosterone incremental values 30 mitt atbar i.v. h4TC) (r: -0.64; p~l.05); C) active renin and absolute distal delivery of sodium (r: -0.58, pa3.05). In summary, correlation A suggests that in patients with compensated cirrhosis the distal tubular reabsorption of sodium is critical in regulating central fluid volume. Correlations B and C demonstrate that in the presence of expanded fluid volume there is a compensatory tendence of the proximal tubule to &liver more sodium to the distal nephron, paralleled by an mcrease of dopaminergic activity. Finally, the inverse correlation between acttve renin and dopaminergic activity contiis this last parameter as a reliable marker of the state of central fluid volume replenishment.
GS3/13
SESSION
3
1
EVIDENCE OF REDUCED EFFECTIVENESS OF AN OTHERWISE ACTMTY IN DGPAMINERGIC ENDGGENOUS INCREASED COMPENSATED CIRRHOSIS. G Sansot?. A Fenwi. E. Liamldi*. CN Castellana**, G Termnova, M Ghidoni. E Villa, F Manenti. Chairs of Gastmenterologv, Universi@ of Modena, Imly. Pharmacolqy,
‘Endocrinology
and **Clinical
Endogenous dopamine exerts a combined adrenal and renal mediation of the natriuretic response to central fluid volume expansion. Plasma dopamine levels rise in association with the natriuretic response to volume expansion produced by head-out water immersion. Aldosterone secretion both in rat and in man is inhibited by dopamine. Dopamine inhibits Na’-K’ATPase activity in proximal convoluted and straight tubule segments. In this manner dopamine increases sodium delivery to the distal nephron and natriuresis. We studied 12 patients with Child-Pugh class A cirrhosis without history of previous ascites or diuretic consumption (after an equilibration period of five days on a normocaloric diet with a daily sodium intake of 120 mEq) and compared them to 9 control subjects, on the basis of the evaluation of a) the degree of dopaminergic activity, as measured by the incremental aldosterone responses 30 and 60 min min atler metoclopramide (h4TC) 10 mg i.v. administration; b) basal morning levels of active renin and aldosterone while reclining ; c) 4 h renal clearances of lithium (C-Li) (an index of fluid and sodium delivery to the distal tubule) and creatinine (C-Cr), d) 4 h urinary excretion parameters of sodium and potassium. With respect to controls, patients showed signiticantly greater incremental aldosterone responses both 30 and 60 min atler MTC (respectively, +30 mitt: 160.2 f 68.8 v. 83.6 f 35.2 pg/ml, ~4.01; +60 min: 140.5 f 80.3 v 36.8 i 39.0 pg/ml, p
HEPATIC BLOOD FLOW AND SPLANCHNIC (IXPGEN CONSUMPTION IN PATIENTS WITH HEPATIC ENCEPHALOPATHY BEFORE AND AFTER HIGH-VOLUME PLASMAPHERESIS. JO. Clemmesen. FS. Larsen. BA Hansen P. Ott. Department Hepatology A-2101, Rigshospitalet, Copenhagen, Denmark.
of
It is not known whether an oxygen dept is present in the splanchnic region in patients with hepatic encephalopathy (HE). Earlier studies has shown that high-volme plasmapheresis @VP) decreases a high cardiac output (CO) in patients with acute liver (ALF) but increases CO in patients with chronic liver failure (CLF). Further, HVP increases cerebral oxygen consumption in patients with ALF. We studied splanchnic hemodynamics and splanchnic oxygen consumption in 11 patients with ALF and 7 patients with CLF before and after HVP. Hepatic blood flow was estimated by use of Fick’s principle with constant infusion of D-sorbitol and liver vein catheterisation. All patients had HE grade 2-4. Results: In m with ALF hepatic blood flow (HElF) increased from 1.67 f 0.72 L/mm before HVP to 2.07 l 1.11 L/mm after HVP (p = 0.04). Splanchnic oxygen consumption was not changed statistically significantly (2.98 f 0.68 mmol/min vs 3.44kl.03 mmol/min, p = 0.10). CO was unchanged (6.7 f 2.5 L/min vs 6.6 f 2.2 L/min (p-0.75) while systemic vascular resistance index (SVRI) increased from 1587*650 to 202&806 dyn s cm*’ m* (p=O.O06). In patients with CLF, EHBF increased from 1.89 f 1.32 L/mm to 2.34 f 1.54 L/mm @ = 0.04). Splanchnic oxygen consmnption remained unchanged (3.13 f 2.14 mmol/min vs 2.89 f 1.35 mmol/min, p = 0.56). In this-group CO increased from 9.1 f 2.8 L/min to 10.1 f 2.9 Wmin @=0.006) while SVIU was unchanged (972*288 vs 1106i540 dyn s cm“ m* ;NS). Conclusion: In ALF, HVP increased HBF by increasing SVRl so that a larger fraction of CO was directed to the splanchnic organs. In CLF, HBF increased as a fixed fraction of CO. These data support the hypothesis that the vasodilatation in CLF is of mor chronic nature. While HBF increased after HVP in both groups splanchnic oxygen consumption was unchanged. These data indicate that a tissue hypoxia is not present in the splanchnic region in patients with HE.
INTRAVENOUS ALBUMIN INFUSION PREVENTS RENAL IMPAIRMENT (RI) AND IMPROVES HOSPITAL SURVIVAL IN PATIENTS WITH SPONTANEOUS BACTERIAL PERITONITIS (SBP). P.Sort*. M. Navasa* and Soanish aroup for the studv of bacterial infections in cirrhosis. *Hosoital Clinic i Provincial. Barcelona. Soain. One third of patients with SBP develop RI in relation with a deterioration of circulatory function, as reflected by an increase in plasma renin activity (PRA). The development of RI is the most important predictor of hospital mortality in SBP. This study assesses whether plasma volume expansion prevents the impairment in circulatory and renal function and improves hospital survival in these patients. 119 patients with SBP were randomized to receive albumin infusion (1.5 g/Kg body wt. on the 1’ day and 1 g/Kg of body wt. on the 3rd day) plus cefotaxime (n=59) or cefotaxime alone (n=60). At diagnosis, hepatic and renal function, PRA and incidence of hepatocarcinoma were similar in both groups. The incidence of circulatory dysfunction (increase of 50% in PRA above baseline levels at the sixth day of inclusion) (4% vs 30% , p
CRITICAL ROLE OF DISTAL TUBULAR HANDLING OF SODIUM lN THE REGULATION OF EXTRACELLULAR FLUID VOLUME IN COMPENSATED clRRH0s1s. G Sanso&. A Fermn’, E. Bamldi’. CN CastelImo**, M Ghidoni. E Villa, F Chairs of Gastroenterologv. Manmti. Phannocologv, University of Modem, Italy.
*Endocrinology
and
‘*Clinical
For any given value of plasma aldosterone concentration cirrhotic patients without ascites excrete significantly less sodium with respect to healthy controls. In compensated cirrhosis a direct study of the distribution of sodium reabsorption along the different segments of the renal tubule is still lacking, especially if evaluated in conjunction with markers of the central fluid volume. We studied 12 patients with Child-Pugh class A cirrhosis and 9 healthy subjects (both groups following a diet with a daily sodium intake of 120 mEq), on the basis of the evaluation of 1) the degree of dopaminergic activity, as measured by the mcremental aldosterone responses 30 and 60 mitt mitt atler metoclopramide (MTC) 10 mg i.v. administration; 2) basal morning levels of active renin and aldosterone while reclining 3) 4 h renal clearances of lithmm (an index of fluid delivery to the distal tubule) and creatinine, both measured in recumbency; 4) urinary excretion parameters of sodium and potassium With respect to controls, the patients showed significantly greater incremental aldosterone responses both 30 and 60 min atter i.v. MTC (respectively, +30 mitt: 160.2 f 68.8 v. 83.6 f 35.2 pg/ml, pa.01; +60 mm: 140.5 * 80.3 v. 36.8 f 39.0 pg/ml, pQ).Ol), displaying increased endogenous dopaminergic activity. The patients showed not significantly lower plasma levels of active renin and aldosterone but significant higher values of distal fractional sodium reabsorption I with respect to controls (respectively, 21.09 f 6.7 % v. 12.58 f 4.8 % of the filtered sodium load; pa.02). In the patients’ group, we found significant negattve correlations between: A) absolute distal sodium reabsorption and active renin (r:-O.59, pcO.05); B) active renin and dopaminergic activity (expressed as plasma aldosterone incremental values 30 mitt atbar i.v. h4TC) (r: -0.64; p~l.05); C) active renin and absolute distal delivery of sodium (r: -0.58, pa3.05). In summary, correlation A suggests that in patients with compensated cirrhosis the distal tubular reabsorption of sodium is critical in regulating central fluid volume. Correlations B and C demonstrate that in the presence of expanded fluid volume there is a compensatory tendence of the proximal tubule to &liver more sodium to the distal nephron, paralleled by an mcrease of dopaminergic activity. Finally, the inverse correlation between acttve renin and dopaminergic activity contiis this last parameter as a reliable marker of the state of central fluid volume replenishment.