A Case of Decompensated Cirrhosis Successfully Managed with Large-Volume Paracentesis and Albumin Infusion, Enabling Waiting for Deceased Donor Liver Transplant

Introduction: Spontaneous bacterial peritonitis (SBP) is the most common bacterial infection in cirrhosis with high mortality. Antibiotics are the mainstay of treatment. Moreover, albumin infusion in SBP improves survival by 60% and decreases the risk of acute renal impairment. Large volume paracentesis (LVP) is the standard treatment for tense ascites. LVP is historically avoided in patients with SBP due to the potential risk of circulatory dysfunction. These are based on presumed physiologic mechanisms and have not been adequately studied with robust clinical outcomes. We decided to determine whether or not LVP can be safely used in SBP patients, especially in the era where albumin infusion, regardless of performing LVP or not, is part of SBP management. Potential benefits of LVP in SBP include: improved patients’ abdominal discomfort, decreased ascites microbial load, decreased intra-abdominal pro-inflammatory cytokines, and bacterial vasoactive peptides. Methods: We conducted a systematic review of randomized controlled clinical trials (RCTs). We searched Medline, EMBASE, Cochrane CENTRAL, and Clinicaltrials.gov databases using controlled vocabularies (MeSH, EMTREE), and key word searching for large volume/therapeutic paracentesis, spontaneous bacterial peritonitis, and refractory/tense ascites. We also screened all SBP trials as well as all LVP trials. We also performed hand searching and cross referencing of clinical guidelines and major reviews. Results: Our comprehensive search retrieved 189 trials in Medline, 147 in Cochrane CENTRAL, 91 in EMBASE, and 28 in Clinicaltrials.gov in English. After removing the duplicates there was only randomized controlled clinical trial that studied LVP in SBP patients. All other LVP trials had excluded SBP patients from their studies. Similarly, all SBP trials did not include LVP in their management. The AASLD clinical guidelines did not provide recommendations regarding whether or not LVP can be considered in SBP. The only available RCT of LVP in SBP randomized 42 SBP patients to receive LVP (group 1) vs. no LVP (group 2). Twelve months survival was not statistically significantly different between 2 groups (11.1% vs. 14.3%; p>0.05), however symptoms resolved faster with LVP (p=NS) but with slightly higher rate of renal impairment (p=NS ). Conclusion: There is an extreme paucity of evidence with regard to role and safety of LVP in tense ascites in SBP. The current clinical guidelines do not provide recommendations on whether or not LVP can be considered in SBP. The only retrieved small RCT showed no worse outcomes with LVP, whereas LVP may cause faster symptom relief. Further investigations are warranted to delineate clinical risks and benefits of LVP in SBP.

Effect of Paracentesis and Albumin on Non-azotemic Renal Dysfunction in Children With Cirrhosis

Current guidelines for clinical practice recommend the infusion of human albumin after large volume paracentesis. After inspecting the current evidence behind this recommendation, we decided to conduct a systematic review and meta-analysis in order to address the effect of albumin on mortality and morbidity in the context of large volume paracentesis. We performed a comprehensive search of large databases and abstract books of conference proceedings up to March 15th 2016 for randomized controlled trials, testing the infusion of human albumin against alternatives (vs no treatment, vs plasma expanders; vs vasoconstrictors) in HCC-free patients suffering from cirrhosis. We analyzed these trials with regard to mortality, changes in plasma renin activity (PRA), hyponatremia, renal impairment, recurrence of ascites with consequential re-admission into hospital and additional complications. We employed trial sequential analysis in order to calculate the number of patients required in controlled trials to be able to determine a statistically significant advantage of the administration of one agent over another with regard to mortality. We were able to include 21 trials totaling 1277 patients. While the administration of albumin prevents a rise in PRA as well as hyponatremia, no improvement in strong clinical endpoints such as mortality could be demonstrated. Trial sequential analysis showed that at least 1550 additional patients need to be recruited into RCTs and analyzed with regard to this question in order to detect or disprove a 25% mortality effect. There is insufficient evidence that the infusion of albumin after LVP significantly lowers mortality in HCC-free patients with advanced liver disease.

See the Original "The impact of paracentesis flow rate in patients with liver cirrhosis on the development of paracentesis induced circulatory dysfunction" on page 365.

Cell-free and concentrated ascites reinfusion therapy versus large-volume paracentesis for the treatment of cirrhotic patients with refractory ascites: A multicenter prospective observational study.

To the Editor: We read with interest Kramer et al.'s article, “Large-volume paracentesis in the management of ascites in children.” The authors reviewed their experience with large-volume paracentesis (LVP) in a pediatric population and concluded that the procedure is safe and effective for managing tense abdominal ascites in children. We would like to contribute to Kramer et al.'s work with our experience in pediatric liver transplant recipients with tense abdominal ascites. Between January 1998 and September 2002, we evaluated 13 children with medically unresponsive tense ascites who underwent large-volume paracentesis before and/or after orthotopic liver transplantation (median age, 6.8 years; range, 0.6–16 years). LVP is defined as removal of 50 mL or more of ascitic fluid per kilogram of dry body weight. Forty-one LVP sessions were performed in 13 children. All of the patients had tense ascites with abdominal discomfort accompanied either by poor appetite or respiratory compromise. All patients were treated with 1 to 3 mg/kg per day of furosemide and 0.2 to 2 mg/kg per day of spironolactone. The LVP procedure was performed with the patient in the supine position. Blood products were administered if the prothrombin time was prolonged more than 3 seconds above the normal and if the platelet count was less than 30,000/mm3. We used either a 16- or 18-gauge radiopaque catheter (Abbocath™-T, Abbott Ireland, Sligo, Republic of Ireland) inserted by the Z technique. The physician or assistant observed the patient during drainage. We did not use albumin infusion during drainage because our patients were routinely receiving albumin 1 g/kg per day. The mean volume removed was 1,387 ± 820 mL. In eight sessions, the neutrophil count of the ascitic fluid was greater than 250/mm3, which was considered diagnostic for bacterial peritonitis. However, bacterial cultures in these cases were negative. Ascitic albumin concentration and LDH levels ranged from 1.2 to 2.8 g/dL (mean, SDS 1.8 ± 0.8) and 106 to 298 (mean, SDS 134.6 ± 73.8), respectively, whereas ascitic sodium concentration ranged from 98 to 132 mEq/L (mean and SDS, 17.8 ± 12.5 mEq/L). Duration of drainage ranged from 0.8 to 1 hour. All procedures were well tolerated. During drainage we did not encounter any signs of respiratory or hemodynamic instability such as hypotension, tachypnea, or decreased urine output. No significant changes in serum electrolytes, liver and renal function, or coagulation profiles were observed after LVP. Neither bacteremia nor sepsis developed as a complication of the procedure. In one patient, intraperitoneal bleeding occurred, possibly from the abdominal wall. The patient received a blood transfusion and was monitored in the intensive care unit. We did not encounter any evidence of leakage complicating any of the procedures. After LPV, improved appetite and oral intake was observed, with improved quality of life and social activity. Moreover the anxiety of parents diminished as the distension of the abdomen decreased. The role of LVP in the pediatric patient with ascites is still not clear. Although LVP is frequently used in adults for the management of tense ascites, there has been only one report of this technique in pediatric patients (1). Our experience also indicated that LVP was safe and effective in pediatric patients. After LVP, there appeared to be an increase in appetite and activity among our patients. Bhatia et al. studied esophageal body motility and LES pressures in 13 patients with cirrhosis with tense ascites in the basal state and after paracentesis (2). They demonstrated that the duration of esophageal contractions was increased in the presence of ascites and decreased after control of ascites. We speculate that improved esophageal motility could be one factor in the improved appetites of our treated patients. Although we did not assess pulmonary function in all patients, the respiratory rate of all decreased after LVP. In a recent adult study, it was suggested that LVP resulted in improved pulmonary function (3). Ascitic fluid can be removed effectively with minimal complication (1,4,5). Intraperitoneal hemorrhage is a well-known and potentially hazardous complication of paracentesis, which occurred in one patient in our series (5). The mortality of intraperitoneal hemorrhage is reported to be as high as 70% in adults, and recent studies show that severity of thrombocytopenia or coagulopathy did not increase the risk of hemorrhage in LVP (6,7). In children it is uncertain whether correction of coagulopathy would decrease the risk of hemorrhage. Kramer et al. speculate that correction of coagulopathy in children undergoing LVP may not be required (1). This issue clearly requires further study in the pediatric population. Çiğdem Arikan Funda Özgenç Sezin Aşik Akman Raşit Vural Yağci Yaman Tokat Sema Aydoğdu

IntroductionPatients with end-stage liver disease (ESLD) and refractory ascites (RA) have a median transplant-free survival of 6 months. Large volume paracentesis (LVP) is the first-line treatment recommended by the current...

Introduction: Ascites is the leading cause of hospitalization in cirrhotic patients. The American Association for the Study of Liver Diseases (AASLD) provides guidelines regarding paracentesis. While many providers give platelets and fresh frozen plasma (FFP) prior to paracentesis, AASLD discourages this as its evidence in reducing bleeds or morbidity is lacking. Regarding albumin infusion, AASLD reports survival benefit if given after large volume paracentesis (LVP), fluid removal greater than 4-5L. Nonadherence to these recommendations may result in poor outcomes, such as volume overload and acute kidney injury (AKI). We describe the results of adherence to guidelines for LVP in cirrhotic patients at a tertiary care center in the hopes of providing quality improvement and improving overall survival. Methods: We retrospectively constructed an inpatient cohort of consecutive patients eligible for paracentesis admitted to MGUH from Jan 2011-Sept 2015 (Table 1). Eligible patients had 1 of 3 primary diagnoses- ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy (HE)- and a secondary diagnosis of cirrhosis. Cases of HE required ascites as a secondary diagnosis. The independent variable was chart reviewed, verifying receipt of any LVP during hospitalization. The primary outcome variable was receipt of IV albumin. Secondary outcomes included receipt of FFP or platelets; AKI; and inpatient mortality. The chi square test was employed for all analyses.Table: Table. Patient DemographicsResults: Of the 280 cases that met eligibility criteria, 177 had any paracentesis--119 were diagnostic and 58 were LVPs. When compared with diagnostic paracentesis, receipt of LVP was associated with receipt of IV albumin (p<0.001). However, only 64% of patients undergoing LVPs received albumin. LVP was not associated with receipt of blood products. Of patients undergoing LVP, 22.2% and 17.3% received FFP and platelets respectively (Table 2).Table: No Caption availableConclusion: Our preliminary data shows room for improvement with regard to paracentesis and adherence to AASLD guidelines. IV albumin is not universally administered for LVPs; and potentially unnecessary blood products are being administered in a minority of patients undergoing paracentesis. Improved adherence to guidelines could result in fewer cases of volume overload and post-LVP AKI. Future safety interventions aimed at optimizing inpatient paracentesis practice can utilize these data as baseline to which post-intervention data can be compared.

This study compared the changes in serum albumin, globulin, and colloid osmotic pressure (COP) before and after transjugular intrahepatic portosystemic shunt (TIPS) or large volume paracentesis (LVP) in patients with ascites. Of 23 patients with refractory ascites, 17 had TIPS and 6 had LVP with infusion of albumin. Colloid osmotic pressure measurements were calculated, using the formula previously proposed by Hoefs: COP = A (1.058G + 0.163A + 3.11) where A = serum albumin and G = serum globulin. After 1 month, ascites resolved in 9 of the 17 patients who had TIPS and in none of the 6 who had LVP. Colloid osmotic pressure increased significantly in patients whose ascites resolved after TIPS. Colloid osmotic pressure did not change in the patients whose ascites did not resolve after TIPS, and COP decreased significantly in the LVP group. A statistically significant difference was found in the pre-TIPS COP measurements between those patients who had resolution of ascites and those who did not. A pre-TIPS COP of < or =20 mm Hg predicted resolution of ascites with an 88% sensitivity and a 78% specificity. Serum COP increased significantly in patients with resolution of ascites but remained unchanged in patients with persistent ascites after TIPS. Serum COP decreased after LVP. A statistically significant difference in the pre-TIPS COP was found between patients whose ascites resolved and patients having persistent ascites.

Background The disease burden from cirrhosis is increasing worldwide. Refractory ascites (RA) is a complication of cirrhosis associated with poor prognosis if liver transplant is not an option. Serial large volume paracentesis (LVP) is the standard of care in the management of refractory ascites (RA) and outpatient LVP has been shown to be safe and cost effective. Epidemiologic data is lacking regarding the incidence of RA, or how patients with RA are managed in routine clinical practice. Aims To describe secular trends in the incidence of RA in Ontario from 2000–2017, and to describe physician provider types performing LVPs in the RA population in Ontario. Methods This retrospective, population-based cohort study uses routinely collected healthcare data from Ontario, Canada, housed at ICES. From January 1, 2000 to Dec 31, 2017 all adult patients with cirrhosis were identified using a validated case definition, and those with RA were identified based on the need for serial LVP. All LVP procedures were described based on patient demographics, local health integration network (LHIN), physician type (Gastroenterology [GI], Internal Medicine [IM], Interventional Radiology [IR], Emergency Medicine [ER], other) and albumin administration. Annual incidence rates (IR) of RA in patients with cirrhosis were calculated and compared using Poisson regression to calculate incident rate ratios (IRRs). Annual LVP volume by provider type and LHIN were calculated and differences were compared using chi-squared analysis. Results The overall incidence of RA in patients with cirrhosis remained relatively stable over the study period (IRR 1.01, 95% CI 1.00–1.02 P&amp;lt;.001). The highest incidence of RA was in those with viral hepatitis and alcohol-related cirrhosis. A total of 90,126 LVPs were identified (median age 61 years [IQR 53–70], 69% male, median LVP per patient 24 [IQR 11–48], 15.8% received albumin infusion). The absolute numbers of LVPs more than tripled over the study period (12,047 in 1997–2002 vs. 37,437 in 2013–2017). GI performed the majority of LVPs (40.1%) followed by IR (22.4%), and IM (8.4%), but there was substantial variation based on location (Fig 1). Overall, the proportion performed by IR increased during the study (7.8% in 1997–2002 vs 30.8% in 2013–2017, P &amp;lt;.001) while the proportion performed by GI decreased (50% 1997–2002 vs 33.1% 2013–2017, P&amp;lt;.001). Conclusions The number of LVPs performed for RA have increased dramatically in Ontario over the past two decades, with the proportion being performed by GI physicians decreasing, while IR is increasing. Substantial variability exists across LHINs on the use of LVP, which may reflect differences in access to resources for LVP, or physician practice. Appropriate albumin use with LVP remains an area for potential quality improvement initiatives in the future. Funding Agencies AASLD Foundation Clinical Translational and Outcomes Research Award in Liver Disease (for supervisor JF)

Treatment of cirrhotic tense ascites with Dextran-40 versus albumin associated with large volume paracentesis: a randomized controlled trial.

Background and aim: Ascites in liver cirrhosis is associated with a poor prognosis and impairment of the quality of life. The clinical efficacy and safety of large-volume paracentesis in comparison to dialytic peritoneal ultrafiltration in the treatment of marked ascites were evaluated. Patients and methods: A total of 96 cirrhotic patients with marked ascites were divided into two groups: group I 48 patients treated with dialytic ultrafiltration group IIa 31 patients treated with LVP without albumin and IIb 17 patients treated with LVP plus albumin infusion. Results: Mean arterial pressure of patients in the studied groups show significant decrease immediately after the different procedures and start to rise within 24 hours and reach readings similar to those before ascites drainage especially with peritoneal ultrafiltration. Improvement in plasma albumin concentration has been reported after dialytic ultrafiltration. There is statistically significant decrease in serum creatinine after 48 hours of the different treatments. The average volume of ascites removed was (9.04 ± .04) in the dialytic ultrafiltration group versus (4.45 ± 0.51) in large volume paracentesis without albumin group and (6.06 ± 0.83) in large-volume paracentesis plus albumin infusion. After treatment all patients experienced a relief of ascites which is better with larger amounts of fluids removed as occurred in dialytic ultrafiltration group. Conclusion: Dialytic ultrafiltration is an effective and relatively safe alternative to large-volume paracentesis in the treatment of marked ascites in cirrhotic patients. Blood pressure is well maintained, kidney functions are preserved. Dialytic ultrafiltration has the advantages of cost and time saving and avoidance of blood-borne infection associated with intravenous transfusion of blood products such as albumin.

To study whether circulatory changes during large volume paracentesis (LVP) in patients with liver cirrhosis and tense ascites as assessed by novel non-invasive haemodynamic measuring technology are reversed by subsequent albumin infusion. Eleven patients with portal hypertensive ascites secondary to liver cirrhosis of Child's class B or C were studied during LVP (10.7 +/- 4.4 l) and subsequent infusion of albumin. Digital arterial pulse waves were continuously measured by vascular unloading technique providing data for beat-to-beat values of systolic (P(s)), diastolic (P(d)) and mean arterial pressures (P(m)), respectively, as well as for heart rate (F(h)), stroke volume (V(s)), cardiac output (Q(co)) and peripheral resistance (R). Data extrapolated to the end of paracentesis, albumin infusion and follow-up phases were compared with the end of the equilibration phase. At the end of paracentesis, P(s), P(m) and P(d) changed by -14 +/- 15% (p < 0.05), -16 +/- 11% (p < 0.01) and -17 +/- 11% (p < 0.001), respectively, whereas Q(co) and F(h) did not change substantially. There was a highly significant increase in V(s) by +21 +/- 25% (p < 0.01). The largest change was seen in R which significantly decreased by -29 +/- 24% (p < 0.01). This change was not reversed by infusion of albumin and persisted up to the end of follow-up. The haemodynamic changes following LVP appear to be first and foremost controlled by changes in peripheral resistance with insufficient cardiac compensation. Further studies combining albumin with vasopressors for prevention of paracentesis-induced circulatory changes are needed.

Published literature on renal dysfunction (RD) in pediatric cirrhosis are limited. We aimed to detect early RD in cirrhotic children by renal resistive index (RI) and plasma aldosterone (PA). We evaluated the effects of large-volume paracentesis (LVP) and albumin infusion on the same. Non-azotemic cirrhotic children with tense ascites (undergoing LVP with albumin infusion) were prospectively enrolled. Blood biochemistry and doppler ultrasonography for RI and PA were measured at regular intervals. RI >0.7 was considered as RD. Outcomes were noted at D90 and 1 year. Chronic liver disease children without ascites were included as controls. Of the 99 cirrhotic children, tense ascites (n=51) had higher baseline RI than controls (n=48) (p<0.001). Overall, baseline RD was observed in 32% and was significantly higher in tense ascites compared to controls (59% vs. 4%, p<0.001). Tense ascites with RD at admission had higher chances of acute kidney injury (AKI) (p=0.009), ascites recurrence (p=0.043), hospital readmission (p=0.048), and mortality (p=0.009) compared to patients without RD by D90. Significant reduction in RI was noted at 48 h, D7, D30, and D90 compared to baseline after LVP with albumin. Pediatric End-stage Liver Disease (PELD) score and PA had a strong positive correlation with baseline RI (R2=0.51, R2=0.47). Using multivariate analysis, PELD score and PA were predictors of AKI (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.04-1.24; p=0.003) and mortality (OR: 1.82; 95% CI: 1.22-2.72; p=0.004), respectively. Abnormal baseline RI can be used as an early predictor of RD and predict long-term renal ouctomes in pediatric cirrhosis. Baseline RI correlated well with the severity of liver disease and PA. Paracentesis and albumin infusion effectively reduced RI.

Prevention of paracentesis-induced circulatory dysfunction in cirrhosis: Standard vs half albumin doses. A prospective, randomized, unblinded pilot study