Ascitic Fluid Concentrations Research Articles

Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration.

To investigate the long-term probability of the appearance of the first episode of spontaneous bacterial peritonitis in cirrhosis with ascites and to identify predictors of this complication, we closely followed throughout their illness 127 patients consecutively admitted to our unit for the treatment of an episode of ascites without prior spontaneous bacterial peritonitis (follow-up period: 21 +/- 22 mo). Thirteen patients (10%) had the first spontaneous bacterial peritonitis episode during follow-up. The appearance probability of this complication is 11% at 1 yr and 15% at 3 yr. Thirty-three variables obtained at admission (including clinical data, standard liver and kidney function test results, ascitic fluid protein concentrations and hemodynamic parameters) were analyzed in relation to their value in predicting spontaneous bacterial peritonitis development. In univariate analysis (Kaplan-Meier curves) five variables reached statistical significance (p less than 0.05) as predictive factors for the development of the first spontaneous bacterial peritonitis episode. These five variables were poor nutritional status, increased serum bilirubin levels, increased serum AST levels, decreased prothrombin activity and reduced total protein concentration in ascitic fluid. When these five variables were introduced in a multivariate analysis, only the ascitic fluid protein concentration was found to correlate independently with spontaneous bacterial peritonitis development (p = 0.002). The probability of first spontaneous bacterial peritonitis after 3 yr of follow-up was 24% and 4% in patients with ascitic fluid protein content lower than 1 gm/dl and greater than or equal to 1 gm/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascitic fluid and serum cefotaxime and desacetyl cefotaxime levels in patients treated for bacterial peritonitis

Forty-one episodes of ascitic fluid infection were treated with cefotaxime 2 g intravenously every 8 hr, and ascitic fluid and serum were sampled 6, 12, 24, 48, and 96 hr after the first dose of antibiotic. Concentrations of cefotaxime and desacetyl cefotaxime were measured in ascitic fluid and serum by high-performance liquid chromatography. There was essentially 100% penetration of cefotaxime and metabolite from serum into ascitic fluid at all time points. Ascitic fluid was sterilized in 94% of episodes after the first dose of antibiotic. The ascitic fluid concentration of cefotaxime 6 hr after the first dose of antibiotic was greater than 20 times the minimal inhibitory concentration of the drug for 90% of the isolated flora. This rapid ascitic fluid penetration of cefotaxime in high concentration explains the rapid sterilization of ascitic fluid by the drug in the setting of bacterial peritonitis and obviates the need to give a loading dose or intraperitoneal injection.

Ascitic fluid concentrations of fibronectin and cholesterol: comparison of differential diagnostic value with the conventional protein determination

Ascitic fluid concentrations of fibronectin, cholesterol and protein were determined in 95 patients: 38 with cirrhosis of the liver, 10 with miscellaneous nonmalignant diseases, 43 with peritoneal carcinomatosis and 4 with liver metastases or hepatocellular carcinoma. Fibronectin, cholesterol and protein at discrimination values of 7.5 mg/100 ml, 45 mg/100 ml and 3.0 g/100 ml, respectively, separated patients with peritoneal carcinomatosis from patients with cirrhosis with an efficiency of 94%, 90% and 85%, respectively. Thus, ascitic fluid determinations of fibronectin and cholesterol offer good discrimination of cirrhotic ascites from ascites related to peritoneal carcinomatosis, superior to the conventional protein determination. However, the failure of all parameters to distinguish ascites caused by miscellaneous nonmalignant diseases from malignancy-related ascites underscores the importance of highly specific methods to confirm a suspected diagnosis of malignancy-related ascites.

Penetration of cefoperazone into ascites

The pharmacokinetics of cefoperazone was studied in eleven cirrhotic patients with ascites after i.v. administration of a single dose of 15 mg.kg-1 (n = 7) or after three doses of 15 mg.kg-1 given at 12 h intervals (n = 4). The concentrations of cefoperazone in serum and ascitic fluid were determined by HPLC. The peak serum cefoperazone concentration after a single i.v. injection of 15 mg.kg-1 was 96.0 mg.l-1. The serum elimination half-life was longer (5.0 h) than in normal subjects. The penetration of cefoperazone into ascites was satisfactory (32.3% and 58.3% after single and repeated injections, respectively). Ascitic fluid concentrations of cefoperazone exceeded 5.4 mg.ml-1 from 0.5 to 6 h after the single i.v. injection, levels which are well above the MIC of most pathogens found in spontaneous bacterial peritonitis. Adjustment of the dose of cefoperazone in cases of severe hepatic insufficiency does not appear to be necessary provided that renal function is normal.

A new method of sampling ascitic fluid from rats.

A new method of sampling ascitic fluid from rats over a period of at least 8 h in a reliable and easy way is described. The objective was to determine drug concentrations in ascitic fluid after intraperitoneal chemotherapy. Two silicon tubes were implanted into the abdominal cavity, one for drug administration and regulation of pressure, the other enabled ascitic fluid to be withdrawn.

Appearance of neuropeptides in ascitic fluid after peritoneal therapy with interleukin-2 and lymphokine-activated killer cells for intraabdominal malignancy

Administration of intravenous interleukin-2 (IL-2), followed by intraperitoneal IL-2 and autologous lymphokine-activated killer (LAK) cells to six patients with colonic, ovarian, or endometrial carcinoma restricted to peritoneal spread increased significantly the ascitic fluid concentrations of the neuropeptides substance P (SP) and calcitonin-gene related peptide (CGRP). After intravenous IL-2 alone, the level of SP rose 10- to 140-fold, without a change in that of CGRP. Intraperitoneal IL-2 and LAK cells led to elevations in the concentrations of SP and CGRP to respective maximal means of 319 and 175 pM after 8 hr, which were maintained for 24-48 hr without alterations in the levels of vasoactive intestinal peptide or somatostatin. SP and CGRP from peritoneal fluid were chromatographically indistinguishable from synthetic neuropeptides. The increases in concentrations of SP and CGRP after IL-2 and LAK-cell therapy are the first demonstration of a neural response to a human cellular immunological reaction. The time course and magnitude of the neuropeptide response suggest a role in the vascular side effects of this form of treatment.

Oral pharmacokinetics and ascitic fluid penetration of ofloxacin in cirrhosis.

Plasma and ascitic fluid concentrations of ofloxacin were determined in 12 cirrhotic patients after a single dose and repeated 200 mg oral doses. The single dose kinetics were compared to those obtained in 12 healthy volunteers. Mean plasma elimination half-life was 11.6 h in cirrhotics and 7.0 h in controls. Mean total clearance was 2.3 times lower in patients than in controls, due to a significant decrease of renal clearance of the drug, unrelated to creatinine clearance. Mean apparent volume of distribution was 1.2 l/kg in patients and 1.8 l/kg in controls. Estimated by the ratio of AUC in peritoneal fluid and plasma, ascitic fluid penetration was 80% after the first oral dose. Ascitic fluid concentrations equaled corresponding plasma concentrations after 10 h, without pronounced accumulation of ofloxacin in ascites. We may conclude that, in cirrhotic patients with normal serum creatinine, a significant impairment of renal tubular handling of ofloxacin could be observed and led to a delayed elimination half-life of the drug. Because of its broad spectrum of activity, low side-effect profile, and large ascitic fluid penetration after oral administration, ofloxacin appears to be a new therapeutic approach of severe infections in cirrhotic patients, in particular spontaneous bacterial peritonitis.

Insulin and C-peptide in ascitic fluid and plasma and their relative responses to glucagon in patients with cirrhosis.

Insulin (IRI) and C-peptide dynamics were studied after iv glucagon in 5 nondiabetic patients with ascites due to cirrhosis of the liver. Plasma and ascitic fluid samples for glucose, IRI and C-peptide determinations were obtained before and 6, 10, 15, 20 and 30 min after glucagon injection. Ascitic fluid volumes, estimated by dilution of ip injected PAH, were 6.2 to 20.5 L. The mean fasting plasma glucose [88 +/- 6.7 mg/dl (SE)] and C-peptide (1.40 +/- 0.42 ng/ml) levels were normal; mean plasma insulin was increased (17.4 +/- 3.0 microU/ml). After glucagon injection, there was a subnormal rise in plasma glucose (PG) compared to 5 mild diabetic patients without liver disease (8.4 +/- 3.5 vs 76 +/- 7.4 mg/dl). The plasma C-peptide rise was less than that of plasma IRI (54% vs 192%). The mean basal ascitic fluid concentration of glucose was 86 +/- 9.4 mg/dl, IRI 13.2 +/- 2.9 microU/ml and C-peptide 3.09 +/- 0.49 ng/ml. Total calculated basal ascitic fluid contents of glucose was 5.2-23.3 g, IRI 47, 120-290,000 microU and C-peptide 15,750-66,420 ng. These were 3-10 times the quantity of these substances circulating in the plasma volume. After glucagon injection, there was no significant increase in ascitic fluid glucose or IRI, but there was a 43% increase in C-peptide concentration at 10 min. In ascitic fluid, the molar concentration of IRI was lower and C-peptide higher than plasma, resulting in a C-peptide: IRI molar ratio of 11.31, markedly higher than the published normal plasma ratio of 4.63.(ABSTRACT TRUNCATED AT 250 WORDS)

Low C 3 in cirrhotic ascites predisposes to spontaneous bacterial peritonitis

The risk of developing spontaneous bacterial peritonitis (SBP) in relation to the concentration of C3 in ascitic fluid (AF) has been studied prospectively in 33 patients with cirrhosis of the liver, seven of whom had one or more episodes of SBP during hospitalization. C3 concentrations in the AF of patients who developed infection (9.0 +/- 2.67 mg/dl) were significantly lower than in those who did not (18.26 +/- 8.11 mg/dl) (P less than 0.01). C4 concentrations were similar in both groups. A direct correlation was found between AF C3 and total protein concentrations (P less than 0.001). We conclude that a low C3 concentration in AF may predispose to SBP.

A simple procedure for reliability growth modeling : John Healy. Proc. a. Reliab. Maintainab. Symp., 171 (1987)

The excess and deficit of serotonin can be the cause of somatic and mental disorders. The aim of this study was to evaluate serotonin levels in blood and ascitic fluid as well as excretion of 5-hydroxyindoleacetic acid (5-HIAA) in urine in patients with hepatic encephalopathy (HE).The study included 75 alcoholic cirrhotic patients divided into 3 groups (HE1, HE2, HE3), 25 patients each, with grade 1, 2 and 3 of hepatic encephalopathy according to West-Haven classification. The control group (C) included 25 clinically healthy volunteers. Venous blood and ascitic fluid were collected in fasting. On the same day a 24-hour urine collection was performed. Immunoenzymatic method was used to determine the serotonin level in serum and ascitic fluid, and 5-HIAA in urine (IBL-RE-59121, RE-59131).In the control group, mean serum serotonin level (ng/ml) was 155.5±38.1 and in the 3 study groups: HE1 – 175.2±32.4 (NS), HE2 – 137.2±28.6 (NS), HE3 – 108.3±46.3 (p<0.001). Serotonin concentration in ascitic fluid was on the average about 25% of its level in serum. The excretion of 5-HIAA in urine (mg/24h) in all groups, was: C – 5.9±2.1, HE1 – 5.8±1.8 (NS), HE2 – 4.8±1.2(NS), HE3 – 4.3 ±1.3 (p<0.05).The results of our study indicate that serum and ascitic fluid level of serotonin and urine excretion of 5-HIAA depends on the grade of hepatic encephalopathy. In patients with severe hepatic encephalopathy serotonin concentration in blood is decreased which can affect some clinical manifestation of this disease.

Oral pharmacokinetics and ascitic fluid penetration of pefloxacin in cirrhosis

Plasma and ascitic fluid concentrations of pefloxacin in 10 cirrhotic patients and 8 healthy volunteers were determined following administration of a single oral dose of 400 mg. The mean elimination half-life was significantly increased in the patients (29.0 h) compared to in 8 healthy volunteers (12.3 h). In patients, the total plasma clearance (2.71 vs 6.85 l/h) and volume of distribution (1.12 vs 1.67 l/kg) were decreased. Estimated by the ratio of the AUC in peritoneal fluid and plasma, ascitic fluid penetration was 68% after one oral dose, and pronounced accumulation of pefloxacin in ascites was found after repeated doses. Oral pefloxacin would seem to be a convenient and useful treatment of spontaneous, gram-negative, bacterial peritonitis in cirrhosis. However, the decreased hepatic metabolism of the drug leads to a marked accumulation in plasma and ascites after repeated doses, and a reduced dose is required in these patients.

Opsonic activity of human ascitic fluid: a potentially important protective mechanism against spontaneous bacterial peritonitis.

The opsonic activity of 60 ascitic fluids from 47 patients was measured using a standard opsonophagocytic assay. Curve analysis of the opsonic activity compared to the ascitic fluid concentration of total protein, total hemolytic complement, C3 and C4 yielded correlation coefficients of 0.84 (p less than 0.001), 0.84 (p less than 0.001), 0.94 (p less than 0.001) and 0.92 (p less than 0.001), respectively. There appeared to be a threshold of concentration for each protein below which there was no killing of bacteria. Cirrhotic ascites had significantly (all p less than 0.001) lower concentrations of total protein and complement and less opsonic activity than noncirrhotic ascites (including malignant, cardiac and miscellaneous types). Perhaps it is the dilution of crucial antimicrobial proteins below a threshold which predisposes to spontaneous bacterial peritonitis.

Clinical pharmacology of intraperitoneal cisplatin

The clinical pharmacology of cisplatin was determined in six patients with malignant ascites secondary to ovarian cancer, and in one patient with peritoneal mesothelioma, following intraperitoneal administration of cisplatin (25–60 mg/m 2). The drug was administered in 1 liter of normal saline as a 15- to 30-min infusion. Total, and in some patients free (ultrafilterable), platinum concentrations were determined in plasma, urine, and ascitic fluid by flameless atomic absorption spectrometry. The peak total platinum concentrations in ascitic fluid at the end of infusion were related to dose, a 50 mg/m 2 dose producing a 20 to 80 μg cisplatin/ml concentration. Filterable platinum represented between 3 and 59% of total platinum in the peritoneum at 4 to 6.5 hr following its administration. Plasma platinum concentrations ranged between 0.2 to 1.6 μg/ml 4 hr following administration, and reached a plateau for the next 24 to 48 hr largely in the form of protein-bound platinum. The urinary excretion of cisplatin was consistent with variation in absorption from the peritoneum. Minimal gastrointestinal, bone marrow, and renal toxicities during therapy suggest that sustained free platinum concentrations in ascites may be obtained without significant toxicity and support the intraperitoneal route of administration as an effective strategy for cisplatin therapy of intrabdominal malignancies.

The presence of glucagon in ascitic fluid in cirrhotic patients.

Glucose, insulin, glucagon, and liver profiles were determined simultaneously in plasma and ascitic fluid after an overnight fast in ten cirrhotic patients to assess the role of ascites in hyperglucagonemia and hyperinsulinemia of hepatic cirrhosis and to investigate if glucagon and insulin diffuse freely across the peritoneum. Plasma in ten normal subjects was studied as well. Glucose levels in plasma were normal in all patients; in ascitic fluid they were higher than in plasma in 7 cases and lower in 3 cases. Plasma glucagon was raised in seven patients with advanced liver dysfunction as documented by the presence of jaundice and reversed albumin/ globulin ratio. Plasma insulin was elevated in patients with hepatic dysfunction and/or esophageal varices. In the absence of jaundice and varices, glucagon and insulin concentrations were normal. Ascitic fluid glucagon was always lower than the plasma with a significant correlation. Ascitic fluid insulin was undetectable in three patients. In the remaining patients, the realtionship between plasma and ascitic fluid insulin levels was not significant. No relationship were observed between liver dysfunction and hormonal concentrations in ascitic fluid. These studies suggest that, (1) both glucagon.and insulin may diffuse freely across the peritoneum into the peritoneal cavity, with a consistent glucagon gradient between plasma and ascitic fluid. The apparent lack of such a relationship for insulin is unexplained and may need further evaluation, and (2) in hepatic cirrhosis the presence of ascites may not influence plasma glucagon or insulin concentrations unless accompanied by jaundice and a reversal of albumin/globulin ratio, both indices of advanced liver dysfunction and the presence of esophageal varices, a sign of moderately severe portosystemic shunting.

Efficacy of a twelve-hourly ceftriaxone regimen in the treatment of serious bacterial infections.

Eighteen patients with 21 serious infections were treated with ceftriaxone, 1 g intravenously every 12 h, for a mean duration of 8 days. Eighteen gram-negative and two gram-positive organisms were isolated. Sites of infection included blood (three patients), urinary tract (six patients), respiratory tract (seven patients), biliary tract (three patients), ascitic fluid (one patient), and skin (one patient). Serum, bile, and ascitic fluid concentrations of ceftriaxone were in excess of the minimal bactericidal concentration required for the infecting organism in all cases. A bacteriological response was demonstrated in 94% of the infections. A clinical response occurred in four infections from which no pathogens were recovered. In one patient, ceftriaxone failed to eradicate a peritoneal infection due to Bacteroides fragilis. In two patients, superinfection with enterococci developed both during and after therapy. Systemic tolerance to ceftriaxone was excellent.

Carcinoembryonic antigen in ovarian cancer: correlation of concentrations in tumour tissue, cyst fluid, ascitic fluid and peripheral blood.

Summary: The interpretation of CEA levels in patients with malignant disease is still difficult in some instances because of lack of knowledge of the factors which influence the concentrations of CEA in peripheral blood. In the present study of patients with advanced ovarian cancer, CEA was measured in extracts of the tumour, in cyst fluid, in ascitic fluid, as well as in serum. A gradient in CEA level was found in the various compartments, highest values being found in the primary tumour and cyst fluid, intermediate values in the surrounding ascitic fluid, and the lowest values in peripheral blood. A significant correlation was found between CEA concentrations in tumour and cyst fluid or ascitic fluid, but not between CEA concentrations in tumour and serum. CEA was more frequently detected in the ascitic fluid than the corresponding serum; it increased the CEA positivity rate from 57% to 78%.

Intraperitoneal pressure: ascitic fluid and splanchnic vascular pressures, and their role in prevention and formation of ascites.

Seventeen patients with ascites due to cirrhosis underwent hepatic venous catheterization and pressure measurement in the ascitic fluid. Intraperitoneal fluid hydrostatic pressure (IFP) ranged 3.5-22, mean 11.2 mm Hg, and correlated closely to the pressure in the inferior vena cava (r = 0.97, P < 0.001), which was on average 1.8 mmHg above that of ascitic fluid (P < 0.005). Wedged hepatic venous pressure (WHVP) (range 19-43, mean 32 mmHg) correlated directly to IFP (0.89, P < 0.001) and was significantly higher than that of ten cirrhotic patients without ascites (range 12-27, mean 20 mmHg, P < 0.005). After diuretic therapy WHVP decreased to an average of 20 mmHg. Mean plasma colloid osmotic pressures were 20 mmHg (range 18-24 mmHg)( and 23 mmHg (range 19-29 mmHg) in patients with and without ascites, the values being significantly different (P < 0.05). Colloid osmotic pressure of ascitic fluid ranged 1-14, mean 4.9 mmHg. Mean ratio between albumin concentration in ascitic fluid and plasma was 0.31 (range 0.12-0.77). In five pigs portal venous pressure (PVP) increased during infusion of fluid into the peritoneal cavity. The increase in PVP was smaller than that of IFP (P < 0.02), indicating that ascitic fluid stems the pressures in the splanchnic venous vascular bed up to a higher level, but that the transmural hydrostatic pressure difference decreases simultaneously. The results are discussed in relation to the local 'oedema-preventing' mechanisms: (a) increased interstitial hydrostatic fluid pressure, (b) decreased interstitial fluid colloid osmotic pressure, (c) increased lymph flow, and it is concluded that the peritoneal space can be considered as a special part of the interstitium in which IFP is considered to play an important role in regulation of ascitic fluid.

Relationship between endotoxaemia and protein concentration of ascites in cirrhotic patients.

Endotoxaemia was investigated by the Limulus assay in 42 cirrhotic patients with ascites and in 33 without ascites. The incidence of endotoxaemia in the former group (59.5%) was significantly (P less than 0.05) higher than in the latter (36.4%). Correlation between endotoxaemia and specific gravity and concentrations of total protein, albumin, and globulin in ascitic fluid was studied in the group with ascites. The specific gravity of ascites in 25 patients with endotoxaemia was significantly greater than that in 17 patients without endotoxaemia (P less than 0.01). The concentration of total protein in patients with endotoxaemia (13.95 +/- 7.18 milligram, mean +/- SD) was nearly twice as high (P less than 0.01) as in patients without endotoxaemia (7.49 +/- 3.60 milligram). The protein content of those who showed reactions greater or equal to 2(+) in the Limulus assay (16.78 +/- 7.14 milligram) was a significantly (P less than 0.05) higher than in those with 1(+) reaction (11.26 +/- 6.33 milligram). Moreover, the concentration of albumin in patients with endotoxaemia (7.68 +/- 4.60 milligram) was more than twice that of the patients without endotoxaemia (3.39 +/- 1.58 milligram, P less than 0.01). On the other hand, globulin concentration in patients with endotoxaemia was 1.6 times that of patients without endotoxaemia (P less than 0.01). Similar differences were noted between endotoxaemic and non-endotoxaemic patients in the ascites-to-serum ratio in protein, albumin, and globulin. These results suggest that in liver cirrhosis endotoxaemia may cause an increase in protein concentrations in ascitic fluid, and that it may be a precipitating factor in the formation of ascites.

Prediction of the concentration of penicillins in ascitic fluid from serum kinetics and protein binding of the antibiotics in serum and ascitic fluid of dogs.

Ascites was induced in dogs by partial ligation of the inferior vena cava. Concentrations of ampicillin, penicillin G, oxacillin, cloxacillin, dicloxacillin, nafcillin, and methicillin in ascitic fluid and serum were each determined in three animals. All antibiotics were administered intramuscularly in a dose of 15 mg/kg (dry weight) for both single-dose and multiple-dose (eight doses at 4-hr intervals) studies. Binding of antibiotics to serum and ascitic fluid proteins was measured by ultracentrifugation. After single doses the highly protein-bound drugs (oxacillin, cloxacillin, dicloxacillin, and nafcillin) had lower percentages of penetration (ratio of peak in ascitic fluid to that in serum, multipled by 100) than did methicillin, ampicillin, and penicillin G, which have a lower degree of protein binding. The effect was partially overcome by repetitive doses, but five to six doses were usually required to reach equilibrium. In addition to protein binding, serum kinetics (particularly the log mean total concentration of drug in serum after multiple doses) were important determinants of antibiotic concentrations in ascitic fluid. The total antibiotic concentration in ascitic fluid at equilibrium can be accurately calculated from the log mean serum concnetration and the percentages of protein binding in serum and ascitic fluid.

Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis.

Thirty-six paired specimens of serum and ascitic fluid from 21 patients with peritonitis and ascites, most with sponetaneous bacterial peritonitis and alcoholic cirrhosis, were assayed for antibiotic content. Antibiotics assayed and number of determinations were gentamicin, 14; tobramycin, 7; ampicillin, 5; clindamycin, 3; penicillin G, 2; cephalothin, 2; chloramphenico, 2; and cefazolin, 1. In 31 pared specimens the ascitic fluid antibiotic concentration was about one half or more of the simultaneous serum level and in 17 assays exceeded 90% of the serum level. All antibiotics studied penetrated ascitic fluid equally well. Clinical response to antibiotic therapy was good in 12 of 16 patients with culture-proven bacterial peritonitis. Antibiotic levels in ascitic fluid exceeded the minimal inhibitory concentration of the infecting organisms in all but one patient who responded. Direct intraperitoneal instillation of antibiotics does not appear to be necessary routinely; however, there may be an initial lag of several hours before antibiotic concentrations is ascites achieve therapeutic levels.