Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites

The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be effective in the control of refractory or recidivant ascites. However, the effect of TIPS on survival as compared with that of large-volume paracentesis plus albumin is uncertain. A multicenter, prospective, clinical trial was performed in 66 patients with cirrhosis and refractory or recidivant ascites (16 Child-Turcotte-Pugh class B and 50 Child-Turcotte-Pugh class C) randomly assigned to treatment with TIPS (n = 33) or with large-volume paracentesis plus human albumin (n = 33). The primary endpoint was survival without liver transplantation. Secondary endpoints were treatment failure, rehospitalization, and occurrence of complications. Thirteen patients treated with TIPS and 20 patients treated with paracentesis died during the study period, 4 patients in each group underwent liver transplantation. The probability of survival without transplantation was 77% at 1 year and 59% at 2 years in the TIPS group as compared with 52% and 29% in the paracentesis group (P = .021). In a multivariate analysis, treatment with paracentesis and higher MELD score showed to independently predict death. Treatment failure was more frequent in patients assigned to paracentesis, whereas severe episodes of hepatic encephalopathy occurred more frequently in patients assigned to TIPS. The number and duration of rehospitalizations were similar in the two groups. In conclusion, compared to large-volume paracentesis plus albumin, TIPS improves survival without liver transplantation in patients with refractory or recidivant ascites.     

Total paracentesis associated with intravenous albumin management of patients with cirrhosis and ascites

Repeated large-volume paracentesis (4-6 L/day) is an effective and safe therapy of ascites in patients with cirrhosis provided albumin is infused intravenously. To investigate whether ascites can be safely mobilized in only one paracentesis session ("total paracentesis"), 38 cirrhotic patients with tense ascites were treated with total paracentesis plus intravenous albumin (6-8 g/L ascites removed). Standard liver tests and renal function tests, glomerular filtration rate, free water clearance, plasma volume, plasma renin activity, and plasma aldosterone and norepinephrine concentrations were measured before and after treatment. Total paracentesis was effective in mobilizing ascites in all but 1 patient and did not impair any of the parameters studied. The volume of ascitic fluid removed and the duration of the procedure were 10.7 +/- 0.5 L (mean +/- SEM) and 60 +/- 3 min, respectively. Five of the 38 patients (13%) developed complications during the first hospital stay (hepatic encephalopathy and gastrointestinal hemorrhage in 2 patients each and culture-negative bacterial peritonitis in 1). No patient developed renal impairment. This complication rate, as well as the clinical course of the disease during follow-up, estimated by the probability of readmission to hospital, causes of readmission, and survival probability after treatment, was similar to that reported in patients treated with repeated large-volume paracentesis. These results indicate that total paracentesis associated with intravenous albumin can be safely performed in cirrhotic patients with tense ascites and suggest that these patients could be treated in a single-day hospitalization regime.     

Randomized comparative study of hemaccel vs. albumin infusion after total paracentesis in cirrhotic patients with refractory ascites.

Fifty-four cirrhotic patients with refractory ascites were treated with one-session large-volume paracentesis and randomly assigned to two groups. The first group was infused with human albumin, and the second group was infused with hemaccel at doses with comparable oncotic power. The two groups were compared for incidence of complications, recurrence of massive ascites after hospital dismissal and survival rate. The incidence of complications traditionally related to paracentesis, the probability of requiring readmission to the hospital for ascites (p = 0.48) and the probability of survival after entry into the study (p = 0.85) were the same for the two groups. A multivariate analysis of 16 parameters, including treatment modality, identified absolute unresponsiveness to diuretics as the only independent predictor of mortality. These results indicate that hemaccel infusion may safely replace albumin infusion after total paracentesis for cirrhotic patients with refractory ascites.     

Total therapeutic paracentesis (TTP) with and without intravenous albumin in the treatment of cirrhotic tense ascites: a randomized controlled trial

ABSTRACT— We studied 35 cirrhotic patients with tense ascites assigned at random into two groups: Group I consisted of 17 patients treated by total therapeutic paracentesis (TTP) (6–15 1) plus i.v. albumin (5 g/l of fluid) and Group II consisted of 18 patients treated by TTP (5.5–15.5 1) without albumin. On 19 patients we performed a sequential assessment of cardiac output (CO), plasma renin activity (PRA) and plasma aldosterone (PA). Both groups were similar in age, sex, and etiology of cirrhosis. CO, PRA and PA values were expressed as mean changes occurring in relation to their respective baseline values. CO changes after TTP (1/min): Group I: 2.5 after 6 h and 2.2 after 12 h; Group II: 2.2 after 6 h and –0.4 after 12 h, (p<0.05 comparing values after 12 h between the two groups). PRA changes after TTP (ng/dl/h): Group I: –7.4 after 1 h, –7.8 after 6 h and –3.2 after 24 h; Group II: –2.4 after 1 h, –0.8 after 6 h and 3.9 after 24 h (p<0.05 comparing values between both groups after 6 and 24 h). PA changes after TTP (ng/dl): Group I: –50.5 after 1 h, –36.7 after 6 h and –34.6 after 24 h; Group II: –18.2 after 1 h, –2.2 after 6 h and 20 after 24 h, (p < 0.05 comparing values between both groups after 1 and 6 h). Complications were minimal in both groups. In conclusion, there was an increase of CO and a decrease of PRA and PA in all patients early after TTP. However, after 6 h there was a decrease of CO and an increase of PRA and PA, suggesting hypovolemia, only in patients without albumin. The frequency of complications after 24 h was similar in both groups. Since we do not exclude the possibility of complications over a longer period of time, we recommend the use of plasma expanders until their impact on morbidity and mortality in the long term is well established. The best time to infuse them is about 6 h after the procedure.     

Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites : Results of a randomized study

Forty-one patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g for each 1000 ml of ascites removed) (group I = 20 patients) or paracentesis with albumin (6 g for each 1000 ml of ascites) (group II = 21 patients). The basal clinical features, laboratory data, and plasma renin activity were similar in both groups. The volume of ascites removed was 12.9 +/- 4.4 and 10.9 +/- 3.7 liters in group I and II, respectively (n.s.). No significant changes were observed in liver and renal function tests, KPTT, platelet count, factor VIII, serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups, except for a decrease in bilirubin in group I and a transient increase of serum albumin in group II. Four patients developed complications in each group, mainly hyponatremia, while one patient in each group developed renal impairment. One patient from group I died with hepatic encephalopathy. Moreover, the probability of survival and readmission to the hospital because of tense ascites were similar in both groups of patients during the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient treated. These results indicate that repeated large volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites. However, due to its reduced cost, paracentesis with Dextran 70 may be considered the treatment of choice in cirrhotic patients with tense ascites without liver cancer and renal failure.     

Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis

Extracorporeal albumin dialysis (ECAD) may improve severe hepatic encephalopathy (HE) in patients with advanced cirrhosis via the removal of protein or non-protein-bound toxins. A prospective, randomized, controlled, multicenter trial of the efficacy, safety, and tolerability of ECAD using molecular adsorbent recirculating system (MARS) was conducted in such patients. Patients were randomized to ECAD and standard medical therapy (SMT) or SMT alone. ECAD was provided daily for 6 hours for 5 days or until the patient had a 2-grade improvement in HE. HE grades (West Haven criteria) were evaluated every 12 hours using a scoring algorithm. The primary endpoint was the difference in improvement proportion of HE between the 2 groups. A total of 70 subjects [median age, 53; 56% male; 56% HE grade 3; 44% HE grade 4; median model for end-stage liver disease (MELD) 32 (11-50) and CPT 13 (10-15)] were enrolled in 8 tertiary centers. Patients were randomized to ECAD + SMT (n = 39) or SMT alone (n = 31). Groups were matched in demographics and clinical variables. The improvement proportion of HE was higher in ECAD (mean, 34%; median, 30%) versus the SMT group (mean, 18.9%; median, 0%) (P = 0.044) and was reached faster and more frequently than in the SMT group (P = 0.045). Subjects receiving ECAD tolerated treatment well with no unexpected adverse events. Conclusion: The use of ECAD may be associated with an earlier and more frequent improvement of HE (grade 3/4). Because this 5-day study was not designed to examine the impact of MARS on survival, a full assessment of the role of albumin dialysis awaits the results of additional controlled trials.     

A randomised prospective trial comparing daily paracentesis and intravenous albumin with recirculation in diuretic refractory ascites

We report a randomised trial in 40 consecutive patients with diuretic refractory ascites comparing our standard therapy of ascites recirculation (Rhodiascit apparatus) with the newly proposed method of daily paracentesis (3-4 litre) and intravenous albumin infusion. A mean of five (range 2-13) paracenteses removed 13.3 (2.0-36.0) l of ascites. 12 (5-32) h of recirculation produced 6.0 (2.0-12.0) l of waste. A significant diuresis occurred in 14 recirculation patients compared to four treated by paracentesis. No significant changes in electrolyte levels or renal function occurred. Complications were commoner with paracentesis (12) than with recirculation (5). Following recirculation, 18 patients were discharged after 7 (2-21) days; significantly (p less than 0.04) shorter than after paracentesis (11 (4-34) days, 16 discharges). Ascites reaccumulation and survival were identical in both groups. Fewer complications, shorter hospital stay and lower consumables costs (recirculation 240 pounds, paracentesis 400 pounds) make ascites recirculation an attractive therapeutic option to daily paracentesis and intravenous albumin in diuretic refractory ascites.     

Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis

BACKGROUND & AIMS: The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be more effective than repeated paracentesis plus albumin in the control of refractory ascites. However, its effect on survival and healthcare costs is still uncertain. METHODS: Seventy patients with cirrhosis and refractory ascites were randomly assigned to TIPS (35 patients) or repeated paracentesis plus intravenous albumin (35 patients). The primary endpoint was survival without liver transplantation. Secondary endpoints were complications of cirrhosis and costs. RESULTS: Twenty patients treated with TIPS and 18 treated with paracentesis died during the study period, whereas 7 patients in each group underwent liver transplantation (mean follow-up 282 +/- 43 vs. 325 +/- 61 days, respectively). The probability of survival without liver transplantation was 41% at 1 year and 26% at 2 years in the TIPS group, as compared with 35% and 30% in the paracentesis group (P = 0.51). In a multivariate analysis, only baseline blood urea nitrogen levels and Child-Pugh score were independently associated with survival. Recurrence of ascites and development of hepatorenal syndrome were lower in the TIPS group compared with the paracentesis group, whereas the frequency of severe hepatic encephalopathy was greater in the TIPS group. The calculated costs were higher in the TIPS group than in the paracentesis group. CONCLUSIONS: In patients with refractory ascites, TIPS lowers the rate of ascites recurrence and the risk of developing hepatorenal syndrome. However, TIPS does not improve survival and is associated with an increased frequency of severe encephalopathy and higher costs compared with repeated paracentesis plus albumin.     

Long-term clinical outcome of large volume paracentesis with intravenous albumin in patients with spontaneous bacterial peritonitis: a randomized prospective study

BACKGROUND AND AIM: Large volume paracentesis (LVP) with plasma volume expansion has been used for tense or refractory ascites. However, still in question is whether it is safe and effective for the treatment of spontaneous bacterial peritonitis (SBP). We addressed this issue and conducted a study to assess safety and long-term outcome of LVP in cirrhotic patients with SBP. METHODS: Forty-two randomly assigned cirrhotic patients with SBP were classified into two groups; Group 1 included 21 patients who were treated with LVP and intravenous albumin; and Group 2 included 21 patients who were treated with diuretics and intravenous albumin. RESULTS: The overall cumulative survival rate was poor in patients with SBP (42.5% and 22.5% at 6 and 12 months, respectively). At 7 days after treatment, the blood tests were similar between the two groups. In the ascitic fluid, the white blood cell counts decreased significantly and the protein concentrations tended to increase in both groups. In-hospital days, resolution rate of SBP, and in-hospital mortality rate were similar between the two groups. Although complication rates tended to be slightly higher in Group 1, long-term cumulative survivals were similar between Group 1 and Group 2. LVP was effective in removing abdominal discomfort in patients with tense ascites without serious complication. CONCLUSIONS: LVP with intravenous albumin was as effective as diuretics with intravenous albumin for the treatment of SBP with similar mortality. LVP with intravenous albumin might be feasible for the treatment of tense or refractory ascites in cirrhotic patients with SBP.     

肝硬变患者放腹水输注白蛋白对血浆ANF RAAS的影响

目的探讨排放腹水静输白蛋白对肝硬变患者血浆ＡＮＦ，ＲＡＡＳ的影响．方法肝硬变腹水患者１２例，男１０例，女２例，年龄２０岁～６７岁，平均４８岁．经内科联合利尿治疗无效．在６０ｍｉｎ内排腹水２５Ｌ～５Ｌ后３０ｍｉｎ静脉输注白蛋白２０ｇ，６０ｍｉｎ输完．分别测排放腹水前后，输白蛋白前后及次晨０８∶００血浆ＡＮＦ，ＲＡＡＳ，电解质，白蛋白，ＢＵＮ，Ｃｒ等浓度和尿量、血压、脉搏变化．结果血浆ＡＮＦ值从１６０１ｎｇ／Ｌ±５１５ｎｇ／Ｌ升至３２０８ｎｇ／Ｌ±１０３２ｎｇ／Ｌ，上升了２倍，其效应持续至次日晨，同时血浆ＲＡＡＳ下降〔（２１４±０４４）μｇ／Ｌ·ｈ〕→〔（０９９±１２１）μｇ／Ｌ·ｈ〕，较单纯放腹水为强〔（２１４±０４４）μｇ／Ｌ·ｈ〕→〔（１２８±０９９）μｇ／Ｌ·ｈ〕，时间亦长．血浆钠、钾、氯、白蛋白、ＢＵＮ、Ｃｒ、心率、血压无明显改变，尿钠、尿钾、Ｃｃｒ排泄量增加．尿量增加（３７５９ｍｌ／ｈ±２３７３ｍｌ／ｈ至９１３８ｍｌ／ｈ±４７９４ｍｌ／ｈ），并恢复对利尿剂反应．结论排放腹水静输白蛋白是治疗肝硬变腹水的安全有效方法．     

Timing of paracentesis and outcomes in hospitalized patients with decompensated cirrhosis

BACKGROUNDAscites is one of the most common complications of cirrhosis, placing a significant burden on the healthcare system. Data regarding the optimal time of paracentesis and outcomes among patients with cirrhosis and ascites are scarce.AIMTo assess the outcomes of patients who underwent paracentesis within 12 h after admission compared to patients who underwent paracentesis later than 12 h.METHODSThe study included 185 patients with cirrhosis and ascites who underwent paracentesis. The early paracentesis group was defined as paracentesis performed < 12 h after admission (65 patients) and the delayed paracentesis group was defined as paracentesis performed > 12 h after admission (120 patients). New-onset complications of cirrhosis, length of hospital stay, weekday or weekend admission, in-hospital mortality rate, and 90-d readmission rates were assessed and compared between the groups.RESULTSSignificantly more patients in the delayed paracentesis group than in the early paracentesis group developed hepatic encephalopathy (45% vs 21.5%, P < 0.01), hepato-renal syndrome (21.6% vs 9.2%, P = 0.03) and infections (25% vs 10.7%, P = 0.02) during hospitalization. There were no statistically significant differences in the occurrence of spontaneous bacterial peritonitis and upper gastrointestinal bleeding between the two groups. Length of stay was shorter in the early paracentesis group than in the delayed paracentesis group (6.7 d vs 12.2 d) and in-hospital mortality was lower among patients in the early paracentesis group. Patients in the delayed paracentesis group had a higher risk of developing complications during hospitalization. CONCLUSIONEarly paracentesis (within 12 h after admission) could be a new inpatient quality metric among patients hospitalized with cirrhosis and ascites as it is associated with fewer complications of cirrhosis, lower in-hospital mortality and shorter length of stay.     

Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study.

BACKGROUND: Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. AIMS: To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. METHODS: Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. RESULTS: Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. CONCLUSIONS: This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.