Serial Large-volume Paracentesis Research Articles

LVP vs TIPS for Refractory Ascites: Where Do We Stand?

AbstractAscites is the most common complication of end stage liver disease. Refractory ascites is considered a poor prognostic indicator and impacts quality of life, overall survival and contributes significantly to the cost associated with its management. Serial large volume paracentesis (LVP) and transjugular intrahepatic portosystemic shunt (TIPS) placement are the most utilized procedures for the management of refractory ascites and have their advantages and disadvantages. The pathophysiology of ascites in cirrhosis is multifactorial which makes management complex, requiring the consideration of multiple clinical and biochemical variables to guide the appropriate management. This article provides a broad overview of LVP and TIPS, with review of the latest clinical trials and meta-analyses to help guide the management of refractory ascites and improve patient outcomes.

Transjugular intrahepatic portosystemic shunt for the treatment of refractory ascites: A population-based cohort study

BACKGROUND: Randomized trials have shown that transjugular intrahepatic portosystemic shunt (TIPS) improves control of ascites compared with serial large volume paracentesis (LVP) in patients with refractory ascites. However, the effect of TIPS on liver transplant-free (LTF) survival is controversial. Our objective was to compare TIPS versus serial LVP on LTF survival in the general population of patients with refractory ascites. METHODS: This is a retrospective, population-based cohort study using linked administrative health data from Ontario, Canada. Adult patients identified with refractory ascites from January 1, 2008 to December 31, 2016 were included and followed until December 31, 2017. A propensity score was used to match patients treated with serial LVP to those who received TIPS in a 2:1 ratio. LTF survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression with TIPS treated as a time-varying exposure. RESULTS: Overall, 4,935 patients with refractory ascites were identified and 488 patients were matched (325 serial LVP, 163 TIPS). The mean age was 58 years, 70% were male, 50% had viral hepatitis, the median model for end-stage liver disease (MELD) score was 12, 13% received liver transplant and the 1-year LTF survival was 72%. After TIPS, 80 patients (49%) had no further requirement for LVP by 6 months and 61 patients (37%) never required a repeat paracentesis. In survival analysis, there was marginally worse LTF survival in patients receiving TIPS (TIPS HR 1.29, 95% CI 1.00–1.67; p = .052). CONCLUSION: In this population-based study of patients with refractory ascites, TIPS was associated with improved control of ascites but not improved LTF survival.

Use of Peritoneal Catheters for Patients Receiving Palliative Care

Background: Recurrent ascites is a late manifestation of several diseases, including cancer, cirrhosis, and heart failure, invariably associated with very poor prognosis. Hence, every effort must be aimed at reducing discomfort and side effects of its management. Objective: To evaluate if peritoneal catheters (PCs) are a viable alternative treatment approach in palliative patients who fail medical management of ascites. Design: Case study. Results: We report the case of a terminal patient with cirrhosis and hepatocellular carcinoma who presented refractory ascites despite serial large-volume paracentesis. A Tenckhoff percutaneous catheter was inserted, allowing for ascites' control and with no complications noted. Conclusions: PC placement was successful in controlling the patient's symptoms and ultimately improved comfort and well-being during the final stage of his life. This option should be assessed in selected patients to elevate palliative standards of care.

A66 GEOGRAPHIC VARIATION AND INCREASED INVOLVEMENT OF INTERVENTIONAL RADIOLOGISTS IN THE MANAGEMENT OF REFRACTORY ASCITES: A POPULATION BASED STUDY

Abstract 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<.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 <.001) while the proportion performed by GI decreased (50% 1997–2002 vs 33.1% 2013–2017, P<.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)

Cirrhotic ascites: A review of pathophysiology and management

Ascites describes the condition of pathologic fluid accumulation in the peritoneal cavity. Cirrhosis is the most common cause of ascites worldwide, with a half of cirrhotic patients developing ascites within 10 years of diagnosis. The “underfill” and “overflow” theories have traditionally been used to explain the pathogenesis of ascites in cirrhosis. However, with advances in hemodynamic and neurohumoral studies, it has been shown that neither of these theories fully explains the pathophysiologic mechanisms involved. The key roles of portal hypertension and vasodilators such as nitric oxide (NO) in the process of ascites formation have now been recognized. This led to the proposal of the peripheral arterial vasodilatation theory which includes components of both the “underfill” and “overflow” theories. Recently, the role of gut bacteria in the pathogenesis of ascites has been demonstrated. Bacterial translocation is now known to be a key event preceding the onset of ascites. Bacterial DNA and endotoxin have been shown to stimulate NO synthesis. This led to the proposal of a modified version of the vasodilatation hypothesis, “the systemic inflammation hypothesis,” which proposes that translocated bacteria or their products stimulate the release of proinflammatory cytokines which in turn stimulate NO synthesis. Cardiac dysfunction (cirrhotic cardiomyopathy) has also been described in cirrhosis and is believed to contribute to the reduction in effective circulating volume which stimulates renal sodium and water retention. Initial treatment measures include salt restriction and diuretics. Drugs known to reduce glomerular perfusion or directly toxic to the kidneys must be stopped. Initial therapeutic paracentesis should be done in those presenting with tense ascites. There is no need for albumin infusion if the amount of fluid removed is less than 5 liters. For those with refractory ascites, beta-blockers should be stopped. Treatment options include aquaretics; serial large-volume paracentesis with albumin infusion or midodrine in place of albumin; transjugular intrahepatic portosystemic shunt; peritoneovenous shunt; low-flow ascites pump; and liver transplantation.

03:00 PM Abstract No. 268 Comparison of serial large volume paracentesis, TIPS, and peritoneovenous Denver shunt for the treatment of refractory ascites from end-stage liver disease

03:00 PM Abstract No. 268 Comparison of serial large volume paracentesis, TIPS, and peritoneovenous Denver shunt for the treatment of refractory ascites from end-stage liver disease

Central Venous Catheter as Peritoneal Indwelling Catheter for the Management of Recurrent Malignant Ascites: A Case Series.

Background:Malignant ascites is an accumulation of fluid in the peritoneal cavity due to the manifestation of terminal metastatic malignancies. Accumulation of ascitic fluid could cause abdominal distention, early satiety, and shortness of breath. The onset and progression of these symptoms are not only distressing but also cause deterioration of the quality of life. Malignant ascites is associated with poor prognosis with anticipated life expectancy ranging from 1 to 4 months. Therapeutic paracentesis is the mainstay of palliation for malignant ascites. It only provides a temporary relief of symptoms, ascites re-accumulates, and paracentesis has to be repeated.Objectives:The aim of this case series was to evaluate our experiences when treating malignant ascites with placement of central venous catheter in the peritoneal cavity, with special emphasis on patient satisfaction, comfort of caregiver, technical success, and adverse events.Methods:Five patients with advanced disease and recurrent malignant ascites who required multiple paracentesis were selected for placement of 7-FG triple-port Central venous catheter in the peritoneal cavity. Maximum fluids that can be tapped were removed in ward. Patients and their relatives were assessed for satisfaction with the procedure.Results:Out of 5 patients, 3 were female and 2 male (age between 46 and 62 years). Two patients had carcinoma gallbladder and one each of carcinoma ovary, breast, and prostate. All patients were followed up till 1 month from catheter placement. Patients and their relatives were well satisfied in terms of frequent hospital visit for paracentesis.Conclusion:In summary, we suggest that central venous catheter may be used as indwelling peritoneal catheter for the symptom management of recurrent malignant ascites. It provides a relatively safe and cost-effective alternative to serial large-volume paracentesis that requires multiple hospital admissions.

Cost-Effectiveness of Transjugular Intrahepatic Portosystemic Shunt versus Large-Volume Paracentesis in Refractory Ascites: Results of a Markov Model Incorporating Individual Patient-Level Meta-Analysis and Nationally Representative Cost Data

PurposeTo compare relative cost-effectiveness of serial large-volume paracentesis (LVP) and transjugular intrahepatic portosystemic shunt (TIPS) creation for treatment of refractory ascites. Materials and MethodsA decisional Markov model was developed to estimate payer cost and quality-adjusted life-ears (QALYs) associated with LVP and TIPS treatment strategies for cirrhotic patients with refractory ascites. Survival estimates were derived from an individual patient-level meta-analysis of prospective randomized clinical trials. Health utilities for potential health states were derived from a prospective study of patients with cirrhosis. Cost data were derived from national representative claims databases (MarketScan and Medicare) and included reimbursement amounts for relevant procedures, hospitalizations, and outpatient pharmaceutical costs. One-way and probabilistic sensitivity analyses were performed. ResultsLVP resulted in 1.72 QALYs gained at a cost of $41,391, whereas TIPS resulted in 2.76 QALYs gained at a cost of $100,538. Incremental cost-effectiveness ratio of TIPS versus LVP was $57,003/QALY. At a willingness-to-pay ratio of $100,000/QALY, TIPS has a 62% probability of being acceptable compared with LVP. ConclusionsThis study suggests that TIPS should be considered cost-effective in a country that places a relatively high value on health improvements but less so in countries with lower levels of health care resources.

Low Incidence of Bleeding Events With a Restrictive Platelet Transfusion Protocol in Patients With Cirrhosis and Concomitant End Stage Renal Disease

Introduction: Management of ascites in cirrhosis with concomitant end-stage renal disease (ESRD) presents a challenge as diuretic titration and transjugular portosystemic shunt (TIPS) effectiveness are limited. Patients are often managed with serial large volume paracentesis (LVPs); both quantitative and qualitative platelet dysfunction may increase LVP bleed risk. Society guidelines differ with respect to minimum platelet thresholds for safe LVP. The primary aim of this study was to characterize rate of bleeding in a population with cirrhosis and ESRD receiving LVP with a restrictive platelet transfusion strategy. Methods: Retrospective study of consecutive inpatients LVP at a tertiary medical center between January 2016 and December 2017. Institutional clinical census developed a protocol in which no patients received fresh frozen plasma (FFP), platelets or desmopressin prior to ultrasound guided LVP. Records tabulated: date/time of LVP, complete blood profile (CBC), INR and model for end stage liver disease (MELD score) on day of procedure, any blood products transfused during inpatient stay, and any angiogram procedures performed. Details of any secondary hospital encounter within 2 weeks of LVP reviewed. Results: 757 inpatients underwent usLVP. Mean INR, platelet count and MELD was 2.1 (1.7-2.8), 124 (11-157k) and 24 (21-36) respectively. 35% of patients had INRs > 2.0. 131 patients (17%) had platelet counts < 50k and 32 patients (4%) had < 30k. 260 patients (34%) were on renal replacement therapy RRT) at the time of usLVP. An additional 52 patients had Cr >2.0 (7%). Only 1 of 757 patients (0.13%) had post-LVP bleeding requiring transfusion of 2 units of packed red blood cells. No patient required angiogram intervention for bleeding and no patient died from LVP related complications. Conclusion: Incidence of bleeding with ultrasound guided LVP is very rare, even in a high risk patient population with severe renal dysfunction and thrombocytopenia. Prophylactic product transfusion or desmopressin do not appear warranted in this high risk population.

Cost Effectiveness of Early Insertion of Transjugular Intrahepatic Portosystemic Shunts for Recurrent Ascites

Treatment options for recurrent ascites resulting from decompensated cirrhosis include serial large-volume paracentesis and albumin infusion (LVP+A) or insertion of a transjugular intrahepatic portosystemic shunt (TIPS). Insertion of TIPSs with covered stents during early stages of ascites (early TIPS, defined as 2 LVPs within the past 3 weeks and <6 LVPs in the prior 3 months) significantly improves chances of survival and reduces complications of cirrhosis compared with LVP+A. However, it is not clear if TIPS insertion is cost effective in these patients. We developed a Markov model using the payer perspective for a hypothetical cohort of patients with cirrhosis with recurrent ascites receiving early TIPSs or LVP+A using data from publications and national databases collected from 2012 to 2018. Projected outcomes included quality-adjusted life-year (QALY), costs (2017 US dollars), and incremental cost-effectiveness ratios (ICERs; $/QALY). Sensitivity analyses (1-way, 2-way, and probabilistic) were conducted. ICERs less than $100,000 per QALY were considered cost effective. In base-case analysis, early insertion of TIPS had a higher cost ($22,770) than LVP+A ($19,180), but also increased QALY (0.73 for early TIPSs and 0.65 for LVP+A), resulting in anICER of $46,310/QALY. Results were sensitive to cost of uncomplicated TIPS insertion andtransplant, need for LVP+A, probability of transplant, and decompensated QALY. In probabilistic sensitivity analysis, TIPS insertion was the optimal strategy in 59.1% of simulations. Based on Markov model analysis, early placement of TIPSs appears to be a cost-effective strategy for management of specific patients with cirrhosis and recurrent ascites. TIPS placement should be considered early and as a first-line treatment option for select patients.

Quality of Life of Patients with Decompensated Cirrhosis Who Undergoing Serial Large Volume Paracentesis

Introduction: Serial large volume paracentesis is the most common treatment option for refractory ascites in patients with decompensated cirrhosis. This treatment aims to relieve symptoms and maximize the functionality of the individual’s everyday life, and to generally improve patient’s QoL to any extent, considering the limits imposed by the course of the diseases and patients health status. Purpose of this study is to assess the QoL of patients with decompensated cirrhosis undergoing serial large volume paracentesis. Material and Method: A cohort of 60 patients attending the 2nd Department of Medicine, Medical School of Athens, Hippokration Hospital was recruited. The data were collected with the help of a two-part anonymous self-reported questionnaire consisting of a sheet containing clinical and demographic information and the SF-36 scale. Mean and standard deviation for continuous data and frequencies, and percentages for categorical data were calculated. Non parametric tests such were applied. For the analysis of the data, the statistical package SPPS20 was employed. Results: Out of the total number of participants in the study, 64.41% were men and 35.59% were women. The average age of the respondents was 70.8, with a standard deviation of 10.9 years. More than half (56.14%) were past smokers, 31.58% were current smokers and the remaining 12.28% were non-smokers. The statistical analysis revealed that patients with higher education (p <0.05) reported better scores in QoL on the scales mental health, functionality, and vitality. Women, according to the results of our research, experienced a better QoL on the scale of physical activity than men (p <0.05). Also, those who were not suffering from another disease and were not smokers had a better QoL. Conclusions: Based on the findings of the present study, it appears that factors such as educational level, marital status, age, gender, hospital readmissions can affect the QoL of patients subject to large volume paracentesis. Implementation and evaluation of health education programs aimed at improving the QoL of these patients and their families is of vital importance.

Refractory Ascites: How to Establish the Diagnosis and What Can Be Done?

Refractory ascites accounts for 5-10 % of all ascites and portends a very poor prognosis. Refractory ascites can be diuretic-resistant (unresponsive to maximal dose of diuretics) or diuretic-intractable (inability to use an effective dose of diuretics due to development of complications). Management is challenging as therapeutic options are limited. Available options include serial large volume paracentesis or placement of transjugular intrahepatic portosystemic shunt. A novel device involving an automated low flow ascites pump and a peritoneo-vesical shunt has been recently developed but long term safety and efficacy data are awaited. Liver transplantation is the only modality proven to improve long-term survival.

To Drain or Not Drain: PleurX Indwelling Drainage Catheters for Non-Malignant Refractory Ascites or Hepatic Hydrothorax

Purpose: The insertion of chronic indwelling drainage catheters for treatment of refractory ascites or hepatic hydrothorax in cirrhotic patients is controversial due to concerns related to infectious complications. PleurX drainage catheters are reported to have low infection rates due to their design and polyester cuff that promotes tissue ingrowth. The aim of the current study was to determine the 30 and 90-day mortality in cirrhotic patients with refractory non-malignant ascites or hepatic hydrothorax after placement of PleurX catheter. Methods: An interventional radiology database was queried for patients who underwent a PleurX catheter for indication of non-malignant refractory ascites or hepatic hydrothorax between the dates of January 1st, 2005 to January 1st, 2011 at a single transplant center. Medical records including the transplant database were reviewed by two of the study investigators. Demographics, laboratories, catheter related infectious morbidity, and mortality were collected. Results: A total of 26 patients with non-malignant ascites (n=16) and hepatic hydrothorax (n=10) underwent PleurX catheter insertion during the study period. The mean age was 57.1 ± 7.5 years and 61.5% were male. The mean MELD score was 21.7 ± 7.7 with majority of patients belonging to Child's - Pugh class C (69%). Follow up data was available for all the patients. The 30 and 90-day mortality in the study cohort was 30.8% and 61.5%, respectively. Two catheter related infections (8%) occurred within 30 days of insertion (Candida glabrata peritonitis and E. Coli sepsis). 69% (n=18) of the patients in the study cohort were transplant eligible and were being followed in the pretransplant clinic. The 30 and 90-day mortality in the study cohort was 27.8% and 66.7%, respectively. 11.1% of the patients were transplanted after insertion with an time to transplant of 107 ± 79.2 days. The two above-mentioned infections were within this group. In the remaining transplant non-eligible patients (n=8), PleurX was performed for palliation. The 30 and 90-day mortality was 37.5% and 50.0%, respectively. No catheter related infections were found in this subgroup. 4 patients survived to the end of the study period with average length of follow-up of 607 ± 128 days. Conclusion: Patients undergoing PleurX catheter drainage placement for refractory ascites and hepatic hydrothorax have high 30 day and 90-day mortality presumably from underlying liver disease. Due to low incidence of infectious complications, PleurX catheter could be an option when serial large volume paracentesis or transjugular intrahepatic shunts are not an option.

Preservation of nutritional‐status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis

Refractory ascites in liver-cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritional-support could improve outcomes in cirrhotic patients. Cirrhotic patients undergoing serial large-volume paracentesis for refractory-ascites were enrolled and randomized into three groups. Group A received post-paracentesis intravenous nutritional-support in addition to a balanced oral diet and a late-evening protein snack, group B received the same oral nutritional-protocol as the first group but without parenteral support, and group C (the control group) received a low-sodium or sodium-free diet. Clinical, anthropometric and laboratory nutritional parameters and biochemical tests of liver and renal function were reported for 12 months of follow-up. We enrolled 120 patients, who were randomized into three groups of equal size. Patients on the nutritional-protocol showed better preservation of clinical, anthropometric and laboratory nutritional parameters that were associated with decreased deterioration of liver function compared with patients on the low-sodium or sodium-free diet (group C). Groups A and B had lower morbidity and mortality rates than the control group (C). Mortality rates were significantly better in patients who were treated with parenteral-nutritional-support than for the other two groups. In patients who were on the nutritional-protocol, there was a reduction in the requirement of taps for the treatment of refractory ascites. Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites.

Evaluation and management of patients with refractory ascites

Some patients with ascites due to liver cirrhosis become no longer responsive to diuretics. Once other causes of ascites such as portal vein thrombosis, malignancy or infection and non-compliance with medications and low sodium diet have been excluded, the diagnosis of refractory ascites can be made based on strict criteria. Patients with refractory ascites have very poor prognosis and therefore referral for consideration for liver transplantation should be initiated. Search for reversible components of the underlying liver pathology should be undertaken and targeted therapy, when available, should be considered. Currently, serial large volume paracentesis (LVP) and transjugular intrahepatic portasystemic stent-shunt (TIPS) are the two mainstay treatment options for refractory ascites. Other treatment options are available but not widely used either because they carry high morbidity and mortality (most surgical options) rates, or are new interventions that have shown promise but still need further evaluation. In this comprehensive review, we describe the evaluation and management of patients with refractory ascites from the prospective of the practicing physician.

The transjugular intrahepatic portosystemic shunt for the management of cirrhotic refractory ascites

Cirrhotic ascites results from sinusoidal hypertension and sodium retention, which is secondary to a decreased effective arterial blood volume. Transjugular intrahepatic portosystemic shunt (TIPS) placement is currently indicated in cirrhotic patients with refractory ascites who require large-volume paracentesis (LVP) more than two or three times per month. TIPS placement is associated with normalization of sinusoidal pressure and a significant improvement in urinary sodium excretion that correlates with suppression of plasma renin activity, which is, itself, indicative of an improvement in effective arterial blood volume. Compared with serial LVP, placement of an uncovered TIPS stent is more effective at preventing ascites from recurring; however, increased incidence of hepatic encephalopathy and shunt dysfunction rates after TIPS placement are important issues that increase its cost. Although evidence suggests that TIPS placement might result in better patient survival, this needs to be confirmed, particularly in light of the development of polytetrafluoroethylene-covered stents. Favorable results apply to centers experienced in placing the TIPS, with the aim being to decrease the portosystemic gradient to <12 mmHg but >5 mmHg. This article reviews the pathophysiologic basis for the use of a TIPS in patients with refractory ascites, the results of controlled trials comparing TIPS placement (using uncovered stents) versus LVP, and a systematic review of predictors of death after TIPS placement for refractory ascites.