Paracentesis-induced Circulatory Dysfunction Research Articles

Midodrine versus Albumin to Prevent Paracentesis Induced Circulatory Dysfunction in Acute on Chronic Liver Failure Patients in the Outpatient Clinic–a Randomized Controlled Trial

Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5mg thrice daily for three days, 2h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P=0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P= 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P= 0.851). Midodrine was found to be more cost-effective. Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.

Midodrine and albumin as a possible "winning pair" in managing paracentesis-induced circulatory dysfunction: a clinical case report.

Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

Midodrine in Liver Cirrhosis With Ascites: A Systematic Review and Meta-Analysis.

Ascites is the most common complication of liver cirrhosis. Midodrine is a vasoconstrictor that improves splanchnic and systemic hemodynamics, reduces ascites, and improves clinical outcomes. Here, we aimed to examine the role of midodrine in cirrhosis-related ascites.Scopus, Embase, PubMed, and PubMed Central databases were searched for relevant randomized controlled trials comparing midodrine with other interventions in patients with cirrhotic ascites on November 25, 2020, using appropriate keywords like “midodrine”, “ascitic cirrhosis”, “peritoneal paracentesis” and suitable Boolean operators. Odds ratio (OR) and mean difference (MD) were used to analyze pool data as appropriate with a 95% confident interval (CI).A total of 14 studies were included in our analysis including 1199 patients. The addition of midodrine resulted in statistically significant improvement in mean arterial pressure (MAP) (MD, 3.95 mmHg; 95% CI, 1.53-6.36) and MELD (Model for End-Stage Liver Disease) score (MD, -1.27; 95% CI, -2.49 to -0.04) compared to standard medical treatment (SMT). There was also a significant improvement in plasma renin activity and plasma aldosterone concentration. However, there was no significant improvement in mortality or serum creatinine compared to SMT. In addition, there was no statistically significant improvement in MAP, plasma renin activity, plasma aldosterone concentration, MELD score, overall mortality, and paracentesis-induced circulatory dysfunction comparing midodrine with albumin.Midodrine alone leads to significant improvement in various clinical parameters in patients with cirrhotic ascites compared to standard medical care. At the same time, it was found to be non-inferior to albumin. Therefore, further well-designed studies need to be carried out on midodrine in addition to albumin for optimal clinical benefits among patients with ascites due to cirrhosis.

Management of refractory ascites.

The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.

The challenges of ascites management: An Indian perspective.

Content available: Author Interview and Audio Recording.

IMPACT OF REFRACTORY ASCITES ON THE SURVIVAL OF PATIENTS WITH CIRRHOSIS

Refractory ascites is an infrequent complication in patients with cirrhosis; it is considered in those who do not respond to diuretics or who have adverse effects with diuretics. Treatment is large-volume paracentesis, followed by plasma volume expansion to prevent paracentesis-induced circulatory dysfunction (PICD) to avoid deterioration in renal function and hyponatremia. Intermittent paracentesis could increase morbidity and mortality in these patients. Perhaps the classic prognostic scales, such as MELD, undervalue this factor that is not usually considered for prioritizing transplantation. The objective of this study is to assess the survival of patients with cirrhosis with refractory ascites. Observational, retrospective, descriptive and analytical study. Patients with cirrhosis and refractory ascites were included, who were subjected to intermittent paracentesis on several occasions from February 2019 to June 2021. Descriptive statistics were performed with central tendency and dispersion measures, baseline and final MELD were calculated, and mortality was evaluated. Eleven patients were included, six men (54.5%) and five women (45.5%), aged 54 ± eight years. The patients had a range of paracentesis performed from 3 to 30 occasions (median five interventions), with a follow-up of 1 to 40 months (median of 8 months). The etiology of cirrhosis was alcoholic 63.6%, MALFD 9.1%, and 27.3% other causes. The total amount of fluid drained per patient was 37 to 439 L, 90% of the patients classified as Child-Pugh grade C, and 10% B. The median of the initial MELD was 15 (range = 13), and the median of the final MELD was 22 (range=17). There was no significant difference according to the Wilcoxon test p = 0.317. The renal function between the first and the last paracentesis decreased mildly by 24% and from 36% to 45% severely. Overall mortality was six patients (54.5%). The causes of death were spontaneous bacterial peritonitis (SBP) 9%, ACLF (Acute on Cronic Liver Failure) 27%, infarction 9%, and sepsis 9%. Median survival was 18 months (range 13-23) Patients with refractory ascites have very high mortality (59%); Despite the amount of fluid drained, up to 439L in one patient (for example), it did not seriously affect kidney function overall. We found no statistically significant difference between the initial and final MELD values (Figure 1). However, the MELD score does not make them candidates for liver transplantation; therefore, refractory ascites should be considered with an additional score to enter them on the transplant list. Refractory ascites is uncommon, but it has high mortality; the MELD scale may not accurately predict the possibility of death, so they should be entered with an additional score to consider them candidates for liver transplantation. The authors declare that there is no conflict of interest

Terlipressin has stood the test of time: Clinical overview in 2020 and future perspectives.

Vasoactive drugs form the mainstay of therapy for two of the most important complications of liver disease: hepatorenal syndrome (HRS) and acute variceal bleed (AVB). With cumulative evidence supporting the use in cirrhosis, terlipressin has been recommended for the management of HRS and AVB. However, owing to the safety concerns, terlipressin was not approved by food and drug administration (FDA) until now. In this review, we discuss the pharmacology and the major practice-changing studies on the safety and efficacy of terlipressin in patients with cirrhosis particularly focusing on existing indications like AVB and HRS and reviewing new data on the expanding indications in liver disease. The references for this review were identified from PUBMED with MeSH terms such as "terlipressin," "hepatorenal syndrome," "varices, esophagal and gastric," "ascites" and "cirrhosis." Terlipressin, a synthetic analogue of vasopressin, was introduced in 1975 to overcome the adverse effects of vasopressin. Terlipressin is an effective drug for HRS reversal in patients with liver cirrhosis and acute-on-chronic liver failure. There is documented mortality benefit with terlipressin therapy in HRS and AVB. Adverse effects are common with terlipressin and need to be monitored strictly. There is some evidence to support the use of this drug in refractory ascites, hepatic hydrothorax, paracentesis-induced circulatory dysfunction and perioperatively during liver transplantation. However, terlipressin is not yet recommended for such indications. In conclusion, terlipressin has stood the test of time with expanding indications and clear prerequisites for clinical use. Our review warrants a fresh perspective on the efficacy and safety of terlipressin.

Paracentesis-Induced Circulatory Dysfunction With Modest-Volume Paracentesis Is Partly Ameliorated by Albumin Infusion in Acute-on-Chronic Liver Failure.

Paracentesis-induced circulatory dysfunction (PICD) is a serious complication of large-volume (>5L) paracentesis in cirrhosis and is reduced with albumin infusion. There is a lack of data on PICD in acute-on-chronic liver failure (ACLF). Because ACLF patients have greater hemodynamic derangements than patients with decompensated cirrhosis, we investigated whether PICD could develop with modest-volume paracentesis (MVP) and the role of albumin infusion. A total of 80 ACLF patients undergoing <5L paracentesis were randomized to receive albumin (8 g/dL of ascitic fluid; n=40) or no albumin (n=40) and serially followed to detect PICD. Baseline characteristics were comparable between groups, including volume of ascitic tap (4.16±0.23 versus 4.14±0.27 L; P=0.72) and plasma renin activity (PRA; 20.5±7.03 versus 23.2±8.24ng/mL/hour; P=0.12). PICD was more frequent in the no-albumin group than the albumin group (70% versus 30%; P=0.001), with higher incidence of hepatic encephalopathy (50% versus 27.5%; P=0.04), hyponatremia (67.5% versus 22.5%; P<0.001), acute kidney injury (62.5% versus 30%; P=0.001), and in-house mortality (62.5% versus 27.5%; P=0.003). PRA of 25.15ng/mL at day 3 had sensitivity and specificity of 71% and 68%, respectively, for development of PICD at day 6. Albumin infusion decreased the incidence of PICD at day 6 (odds ratio, 0.068; 95% confidence interval, 0.011-0.43; P=0.005). PICD is common and develops even with MVP in ACLF patients. Albumin infusion decreases the incidence of PICD and mortality in patients with ACLF. Clinical trial identifier: NCT02467348.

Role of Terlipressin in Cirrhotic Patients with Ascites and without Hepatorenal Syndrome: A Systematic Review of Current Evidence.

Ascites, a common complication in cirrhosis, is prone to the development of acute kidney injury or hepatorenal syndrome and can be complicated by circulatory dysfunction after paracentesis. Terlipressin has not been considered as the mainstay treatment option for ascites in cirrhosis yet. The present work aimed to systematically review the current evidence regarding the use of terlipressin in cirrhosis with ascites and without hepatorenal syndrome. PubMed, EMBASE, and Cochrane Library databases were searched for relevant studies. Twelve studies were eligible. In 3 studies (1 randomized controlled trial and 2 single-arm studies without controls) involving 32 patients who received terlipressin for nonrefractory ascites, terlipressin improved hemodynamics by decreasing the heart rate and cardiac output and increasing the mean arterial pressure and systemic vascular resistance. In 5 studies (1 randomized controlled trial, 2 single-arm studies without controls, and 2 comparative studies with controls) involving 67 patients who received terlipressin for refractory ascites, terlipressin improved renal function by increasing the glomerular filtration rate, renal blood flow, urinary sodium, and urine output and decreasing serum creatinine. In 4 studies (4 randomized controlled trials) involving 71 patients who received terlipressin for preventing from paracentesis-induced circulatory dysfunction, terlipressin prevented from paracentesis-induced circulatory dysfunction by increasing the mean arterial pressure and systemic vascular resistance and decreasing plasma renin. Terlipressin may improve hemodynamics, severity of ascites, and renal function and prevent from paracentesis-induced circulatory dysfunction in cirrhosis with ascites and without hepatorenal syndrome. However, no study has evaluated the effect of terlipressin for prevention of acute kidney injury.

High efficacy of low-dose albumin infusion in the prevention of paracentesis-induced circulatory dysfunction

BackgroundLarge-volume paracentesis (LVP) is a main pillar in treating patients with tense ascites. Without plasma expanders use, paracentesis-induced circulatory dysfunction (PICD) is a common complication with decreased survival. The aim was to compare low-dose albumin (2 g/L ascitic fluid removed n = 85) with standard-dose albumin (6 g/L ascitic fluid removed, n = 25) for prevention of PICD. Liver function tests, urea, creatinine, CBC, and abdominal ultrasonography were done. Plasma renin activity (PRA) was measured at baseline and on the 6th day post-LVP. The delta change (Δ) = day 6 variable minus baseline variable value. PICD was defined as increase in PRA of > 50% of the baseline value.ResultsPatients in low-dose albumin group were mainly Child B compared with Child C (85.9% vs. 52%; p = 0.001), underwent less paracentesis volume (9.78 ± 3.56 vs. 12.52 ± 3.6 L; p = 0.001), but had higher baseline PRA (859.62 ± 1151.34 vs. 165.93 ± 95.34 pg/mL; p = 0.001). In both groups, the PRA increased at day 6 compared with the baseline (1141.57 ± 1433.01 vs. 859.62 ± 1151.34 pg/mL; p = 0.01) and (192.21 ± 80.99 vs. 165.93 ± 95.34 pg/mL; p = 0.01) respectively. Both groups were comparable for Δ PRA (281.95 ± 851.4 vs. 26.28 ± 30.2 pg/mL; p = 0.102) and PRA percent increase (10.97 ± 30.77 vs. 12.57 ± 14.87; p = 0.844). They had comparable PICD incidence (24.7% vs. 12%; p = 0.27). Females were more liable for PICD occurrence than males (OR 2.91, 95% CI 1.125–7.547, p = 0.028) and so Child B patients than Child C (OR 8.4, 95% CI 1.072–65.767, p = 0.043).ConclusionLow-dose albumin infusion is comparable to the standard-dose albumin for the prevention of PICD.

Pathophysiology and Prevention of Paracentesis-induced Circulatory Dysfunction: A Concise Review.

Annually, 10% of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis (LVP) is a frequently used therapeutic procedure. LVP, although a safe method, is associated with circulatory dysfunction in a significant percentage of patients, which is termed paracentesis-induced circulatory dysfunction (PICD). PICD results in faster reaccumulation of ascites, hyponatremia, renal impairment, and shorter survival. PICD is diagnosed through laboratory results, with increases of >50% of baseline plasma renin activity to a value ≥4 ng/mL/h on the fifth to sixth day after paracentesis. In this review, we discuss the pathophysiology and prevention of PICD.

Refractory Ascites in Liver Cirrhosis.

Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.

An update on the pathogenesis and clinical management of cirrhosis with refractory ascites

ABSTRACTIntroduction: Ascites commonly complicates cirrhosis, becoming refractory to treatment with diuretics and sodium restriction in approximately 10% of patients. Pathogenesis of refractory ascites (RA) is multifactorial, the common final pathway being renal hypoperfusion and avid sodium retention. Refractory ascites has a negative prognostic implication in the natural history of cirrhosis. Management of RA include sodium restriction and regular large volume paracentesis (LVP) with albumin infusions, preventing paracentesis-induced circulatory dysfunction. In appropriate setting, transjugular intrahepatic porto-systemic shunt (TIPS) can be considered. Ascites clearance with TIPS can lead to nutritional improvement, avoiding sarcopenia. Liver transplantation (LT) remains the definitive treatment for eligible candidates.Areas covered: Our review summarizes current updates on pathogenesis and clinical management of RA including potential future therapeutic options such as the automated slow-flow ascites pump, chronic outpatient albumin infusion and cell-free and concentrated ascites reinfusion therapy.Expert commentary: Standard of care in patients with RA include LVP with albumin replacement and prompt referral for LT where indicated. Other novel therapeutic options on the horizon include automated low-flow ascites pump and cell-free, concentrated albumin reinfusion therapy.

Standardizing the Use of Albumin in Large Volume Paracentesis

Background Albumin after large volume paracentesis (LVP) reduces paracentesis-induced circulatory dysfunction (PICD). The most efficacious dose of albumin for LVP is unclear. Objective To evaluate the impact of implementing a standardized LVP order set on albumin utilization and patient outcomes. Methods This is a retrospective review of patients with ascites due to cirrhosis who received a therapeutic paracentesis at a large, academic institution. Primary outcome was amount of albumin used prior to and after order set implementation. Albumin doses were standardized in the order set to 25 g (5-6 L removed), 50 g (7-10 L), and 75 g (>10 L). Patient outcomes were rates of hyponatremia, renal impairment, and hypotension. Results There were 100 patients included in each arm of the final analysis. Patients prior to order set implementation received a higher amount of albumin per liter removed compared to those post-implementation (8.3 g/L vs 6.5 g/L, respectively; P < .01). There were no significant differences between groups in absolute changes in serum sodium (0 mEq/L vs −1 mEq/L, P = .64), serum creatinine (0.06 mg/dL vs 0.05 mg/dL, P = .94), or systolic blood pressure (−4 mm Hg vs −3 mm Hg, P = .96). There were no differences between groups in rates of hyponatremia (1.6% vs 6.6%, P = .21), renal impairment (11.3% vs 11.5%, P = .97), or hypotension (17.4% vs 17.6%, P = .97). Conclusions Use of an order set to guide albumin dosing based on amount of ascitic fluid removed during LVP resulted in a significant reduction in the amount of albumin given with no difference in adverse effects.

Hemodynamic Evaluation of Nonselective β-Blockers in Patients with Cirrhosis and Refractory Ascites.

Background Nonselective β-blockers (NSBB) have been associated with increased incidence of paracentesis-induced circulatory dysfunction (PICD) and reduced survival in patients with cirrhosis and refractory ascites. Aim To prospectively evaluate a hemodynamic response to NSBB in cirrhotics listed for liver transplantation with refractory ascites undergoing large volume paracentesis (LVP). Methods Patients with cirrhosis and refractory ascites, with an indication to start NSBB in primary prophylaxis for variceal bleeding, were enrolled. During two consecutive LVP, while being, respectively, off and on NSBB, cardiac output (CO), systemic vascular resistances (SVR), peripheral vascular resistances (PVR), and plasma renin activity (PRA) were noninvasively assessed. Results Seventeen patients were enrolled, and 10 completed the study. Before NSBB introduction, SVR (1896 to 1348 dyn·s·cm−5; p = 0.028) and PVR (47 to 30 mmHg·min·dl·ml−1; p = 0.04) significantly decreased after LVP, while CO showed an increasing trend (3.9 to 4.5 l/m; p = 0.06). After NSBB introduction, LVP was not associated with a significant increase in CO (3.4 to 3.8 l/m; p = 0.13) nor with a significant decrease in SVR (2002 versus 1798 dyn·s·cm−5; p = 0.1). Incidence of PICD was not increased after NSBB introduction. Conclusion The negative inotropic effect of NSBB was counterbalanced by a smaller decrease of vascular resistances after LVP, probably due to splanchnic β2-blockade. This pilot study showed that NSBB introduction may be void of detrimental hemodynamic effects after LVP in cirrhotics with refractory ascites.

Albumin May Prevent the Morbidity of Paracentesis-Induced Circulatory Dysfunction in Cirrhosis and Refractory Ascites: A Pilot Study.

Large-volume total paracentesis may result in paracentesis-induced circulatory dysfunction, which is associated with poor outcomes. To explore the short- and long-term effects of paracentesis-induced circulatory dysfunction on systemic hemodynamics, renal function and other cirrhosis-related complications in patients with refractory ascites, following subtotal large-volume paracentesis. Patients with cirrhosis and refractory ascites without renal dysfunction had systemic hemodynamics, renal function, and neurohormones (plasma active renin, aldosterone, norepinephrine and angiotensin II) measured pre- and 6days post-paracentesis. Paracentesis was limited to ≤8L with 6-8g of albumin per liter ascites drained. Patients were followed up until transjugular intrahepatic portosystemic shunt insertion, liver transplantation, or death. Paracentesis-induced circulatory dysfunction was defined as >50% increase in plasma active renin 6days post-paracentesis. Fifty-seven patients (mean age 59.0±9.4years) had mean 6.8±1.8L of ascites removed with 9±3g of albumin given/L of ascites drained. Patients were followed up for 715±104days. Twenty-three patients (40.4%) developed paracentesis-induced circulatory dysfunction with unchanged serum creatinine on day six, despite worsening of hemodynamics (mean arterial pressure 90±10mmHg at baseline vs. 84±8mmHg on day six, p<0.05). Similar hemodynamic changes were observed among patients without paracentesis-induced circulatory dysfunction. There was no significant difference in the long-term renal function or cirrhosis-related complications between the groups. The occurrence of paracentesis-induced circulatory dysfunction, as defined by plasma active renin, may not have a significant short- and long-term impact on renal function or cirrhosis-related complications in patients with refractory ascites who undergo subtotal paracentesis with albumin infusion.

Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis.

Midodrine has been reported to improve systemic and renal hemodynamics in patients with cirrhotic ascites. However, the results of clinical trials are conflicting. The aim of this study is to evaluate the effects of midodrine on cirrhotic ascites through a meta-analysis and systematic review. We searched PubMed (January 1966-December 2014), EMBASE (January 1966-December 2014), the Cochrane Library (Issue 11, 2014), ScienceDirect (January 1966-December 2014), and the China National Knowledge Infrastructure (January 1979-December 2014) databases using the terms 'midodrine' AND 'cirrhosis' AND 'ascites' AND 'paracentesis' for all relevant randomized controlled trials using midodrine for treatment of cirrhotic ascites. In all, 10 trials with a total of 462 patients were included. As a novel therapy for cirrhotic ascites, midodrine was not found to improve survival [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.23-2.91]; although it might improve response rates (OR 3.36, 95% CI 1.47-7.69) and reduce plasma renin activity (MD -3.10, 95% CI -5.37 to -0.84). When midodrine was used as an alternative to albumin in large-volume paracentesis, the mortality was higher for midodrine than for albumin (OR 10.76, 95% CI 1.35-85.97). However, there was no statistically significant difference in the development of paracentesis-induced circulatory dysfunction between midodrine group and albumin group (OR 1.69, 95% CI 0.43-6.72). Midodrine may have treatment effects on cirrhotic ascites. Better powered and well-designed trials are required to assess the extent of the efficacy of midodrine in specifically targeted patients.

Reduced Albumin Dosing During Large-Volume Paracentesis Is Not Associated with Adverse Clinical Outcomes

LVP is used to manage diuretic-resistant ascites in cirrhotic patients. Albumin administration prevents complications including acute kidney injury and paracentesis-induced circulatory dysfunction, but the optimal dose is unclear. We sought to assess adherence to guidelines enacted in July 2011 at our center for reducing the albumin dose administered at large-volume paracentesis (LVP) and evaluate the cost and rate of complications of LVPs before and after guideline enactment. All LVPs performed on cirrhotic patients in our center's Department of Radiology between July 2009 and January 2014 were studied. Outcomes included adherence to guidelines, LVP complications, and administered albumin cost. Groups were compared using Student's t tests for continuous data and Chi-square or Fisher's exact tests for categorical data. A repeated measurements model accounted for patients with multiple LVPs. Of the 935 LVPs, 288 occurred before guideline implementation (group 1) and 647 occurred after (group 2). The mean dose of albumin administered was 13.7 g/L of ascites removed in group 1 versus 10.3 g/L in group 2 (p < 0.0001). Of the group 2 LVPs, 235 (36.3 %) adhered to guidelines. There were no significant differences in LVP complications. Guidelines were followed in one-third of LVPs. Despite this limited adherence, a reduction in albumin administration and associated cost savings was still observed. There was no increase in LVP-related complications after guideline implementation or in the adherent group, suggesting that albumin dose can be safely reduced. Future efforts should be directed at enhancing guideline adherence and potentially further reducing albumin dosing.

The impact of paracentesis flow rate in patients with liver cirrhosis on the development of paracentesis induced circulatory dysfunction.

Background/AimsAscites is a dreadful complication of liver cirrhosis associated with short survival. Large volume paracentesis (LVP) is used to treat tense or refractory ascites. Paracentesis induced circulatory dysfunction (PICD) develops if no plasma expanders are given with ominous complications. To study the effect of ascites flow rate on PICD development.MethodsSixty patients with cirrhosis and tense ascites underwent LVP of 8 L were randomized into 3 equal groups of different flow rate extraction; group I (80 mL/minute), group II (180 mL/minute) and group III (270 mL/minute). Plasma renin activity (PRA) was measured baseline and on day six. PICD was defined as increase in PRA >50% of the pretreatment value.ResultsIn group I through 3; the mean age was (52.5±9.4 vs. 56.4±8.5 vs. 55.8±7.1 years; P>0.05), mean arterial pressure (81.4±5.6 vs. 81.5±7 vs. 79.5±7.2 mmHg; P>0.05), MELD (17.6±4.1 vs. 15.8±4.1 vs. 14.7±4.5). Baseline PRA was comparable (1,366.0±1244.9 vs. 1,151.3±1,444.8 vs. 951.9±1,088 pg/mL; P>0.05). There was no statistically significant (P>0.05) flow mediated changes (Δ) of creatinine (0.23±0.27 vs. 0.38±0.33 vs. 0.26±0.18 mg/dL), MELD (1.25±5.72 vs. 1.70±2.18 vs. 1.45±2.21) or PRA (450.93±614.10 vs. 394.61±954.64 vs. 629.51±1,116.46 pg/mL). PICD was detected in a similar frequency in the three groups (P>0.05). On univariate logistic analysis only female sex was a fairly significant PICD predictor (Wald 3.85, odds ratio 3.14; P=0.05).ConclusionsThe ascites flow rate does not correlate with PICD development.

Effects of non-selective β-blockers on hemodynamics and paracentesis induced circulatory dysfunction in patients with cirrhosis undergoing large volume paracentesis

Background and aims: Non-selective β-blockers (NSBBs) have been associated with increased incidence of paracentesis induced circulatory dysfunction (PICD) and reduced survival in patients with cirrhosis and refractory ascites. We have prospectively evaluated intra-individual central and peripheral hemodynamic effects produced by NSBBs introduction and the incidence of PICD in patients undergoing large volume paracentesis (LVP).