Renal failure with cirrhosis. Observations on the role of diuretics.
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Biomedical subjects
Publications and source records attributed to T B Reynolds.
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Explore the source record for details and available documents.
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The effect of inhibitors of prostaglandin synthesis on diuretic action was examined in patients with ascites due to chronic liver disease and in normal subjects. In patients with ascites, natriuresis after 80 mg i.v. furosemide was reduced 82% by pretreatment with indomethacin. Creatinine clearance was reduced only 16%. These effects were likely due to inhibition of renal prostaglandin synthesis, since urinary prostaglandin E2 fell and there was also reduction in natriuresis with naproxen (52%). The effects were not specific for furosemide since spironolactone-induced natriuresis was also reduced by indomethacin (82%), naproxen (52%), and aspirin (33%). In normal subjects, indomethacin reduced furosemide natriuresis by only 14% while creatinine clearance was not affected. The mechanisms of these drug interactions are uncertain but probably involve renal hemodynamics which appear to be supported importantly by renal prostaglandins in patients with ascites due to liver disease.
We examined beta 2-microglobulin (B2MG) excretion, an index of tubular function, in patients with hepatorenal syndrome, in whom tubular function is generally regarded as normal. Urine B2MG was significantly higher in these patients than in control patients with normal serum creatinine concentration. Patients with high urine B2MG concentration had markedly higher serum bilirubin than did patients with normal values (31 +/- 3 vs. 10 +/- 8 mg%, p less than 0.001), whereas prothrombin activity, serum albumin and serum B2MG concentration were similar. A "threshold" serum bilirubin concentration of about 23 mg% differentiated patients with normal and high urine B2MG values. Renal morphology at autopsy was unremarkable in both groups. Tubular dysfunction, manifested by increased urinary excretion of B2MG, occurs in patients with hepatorenal syndrome and deep jaundice. This measurement cannot, therefore, be used to make a diagnosis of acute tubular injury, as due to aminoglycosides, in such patients.
Large volume paracentesis, while effectively relieving symptoms in patients with tense ascites, has been generally avoided due to reports of complications attributed to an acute reduction in intravascular volume. Measurements of plasma volume in these subjects have been by indirect methods and have not uniformly confirmed hypovolemia. We have prospectively evaluated 18 patients (20 paracenteses) with tense ascites and peripheral edema due to chronic liver disease undergoing 5 liter paracentesis for relief of symptoms. Plasma volume pre- and postparacentesis was assessed by a 125I-labeled human serum albumin dilution technique as well as by the change in hematocrit and postural blood pressure difference. No significant change in serum sodium, urea nitrogen, hematocrit or postural systolic blood pressure difference was noted at 24 or 48 hr after paracentesis. Serum creatinine at 24 hr after paracentesis was unchanged but a small but statistically significant increase in serum creatinine (+0.1 +/- 0.3 mg per dl, p less than 0.01) was noted at 48 hr postparacentesis. Plasma volume changed -2.7% (n = 6, not statistically significant) during the first 24 hr and -2.8% (n = 12, not statistically significant) during the 0- to 48-hr period. No complications from paracentesis were noted. These results suggest that 5 liter paracentesis for relief of symptoms is safe in patients with tense ascites and peripheral edema from chronic liver disease.
A urinary sodium concentration [U(Na)] of less than 10 mmoles per liter is considered important in differentiating hepatorenal syndrome from other causes of progressive renal impairment in patients with liver disease. However, occasionally, patients with hepatorenal syndrome have been recognized in whom the U(Na) is consistently greater than 10 mmoles per liter. Eight such patients, in all of whom there was no clinical or laboratory evidence to implicate other causes of progressive renal impairment, were identified. The clinical features, hepatic and renal status and hospital course were compared with eight other patients who had hepatorenal syndrome and a U(Na) consistently less than 10 mmoles per liter. The mean U(Na) was 24 +/- 4 mmoles per liter in the high U(Na) group and 3.7 +/- 1.8 mmoles per liter in the low U(Na) group. All patients in both groups had acutely decompensated alcoholic hepatitis of similar severity and activity. The high U(Na) group had significantly less clinical ascites and peripheral edema and higher serum levels of sodium and chloride both at the onset of the hepatorenal syndrome and throughout the clinical course. Significant differences in the serum potassium and blood urea nitrogen levels became apparent between the two groups of patients as renal failure progressed, and the mean average blood urea nitrogen to serum creatinine ratio was significantly higher (p less than 0.025) in the low U(Na) group (13.8 +/- 0.9 vs. 10.1 +/- 1.1). Mean urinary potassium concentration was significantly higher in the high U(Na) patients but urinary creatinine concentrations, specific gravity and sediment were similar in both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
In patients with portal hypertension and tense ascites, large-volume paracentesis improves patient comfort and may improve systemic hemodynamics. However, it has been avoided in nonedematous patients because of concern for complications, including intravascular volume depletion. In this study, 12 nonedematous patients with chronic liver disease, portal hypertension and tense ascites underwent 14 large-volume (5-liter) paracenteses for the relief of discomfort and/or respiratory distress. Plasma volume was measured directly by a dilution method with 125I-labeled human serum albumin prior to and at 24 or 48 hr after 13 of the paracenteses. All patients felt better postparacentesis. No dizziness, hypotension, tachycardia, encephalopathy or change in mean serum sodium, creatinine or blood urea nitrogen occurred. Two patients experienced a decrease in hematocrit, which was not explained by blood loss or increase in plasma volume. Mean plasma volume was 3,713 +/- 129 ml (55.1 +/- 1.5 ml per kg ideal body weight) preparacentesis and 3,684 +/- 136 ml postparacentesis, the difference being -0.78% (p = 0.48, NS). Our results suggest that 5-liter paracentesis in nonedematous patients with tense portal hypertension-related ascites improves patient comfort and is not associated with a decrease in measured plasma volume.
We prospectively studied 51 consecutive bacteremic patients with chronic liver disease in order to evaluate their clinical presentation and to assess the relationship of various clinical parameters to mortality. Forty-two patients had alcoholic liver disease and 40 were in Class C, by the Pugh modification of Child's criteria. Soft tissue infections were the most common source of bacteremia, followed by pneumonia, spontaneous bacterial peritonitis and urinary tract infection. Gram positive organisms were isolated in 69% of cases, and Gram negative ones in 31%. In nine patients, no source of bacteremia was detected. Leukocytosis occurred in 59% of patients and bandemia in only 41%. Although appropriate antibiotic therapy was begun in all cases on admission, 17 patients (33%) died in the hospital. Of 38 clinical parameters evaluated, multivariate analysis revealed that the three variables contributing the most independent information toward predicting in-hospital mortality were the absence of a history of fever, an elevated serum creatinine and marked leukocytosis. Improved understanding of the pathophysiologic relationship between these parameters and patient outcome may enable us to improve the therapy of bacteremic patients with chronic liver disease.
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