Elsevier

Journal of Hepatology

Volume 55, Issue 4, October 2011, Pages 794-799
Journal of Hepatology

Research Article
Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: A cross-over study

https://doi.org/10.1016/j.jhep.2011.01.034Get rights and content

Background & Aims

In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis-induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis and refractory ascites. A self control cross-over study was performed.

Methods

Patients with cirrhosis and refractory ascites treated with beta-blockers were selected. Heart rate, arterial pressure, and plasma renin concentrations (PRC) were collected before, immediately after and 1 week after large-volume paracentesis associated with intravenous albumin administration. Beta-blocker therapy was progressively discontinued after complete endoscopic eradication of varices. The clinical and biological evaluation was then repeated. The presence of PICD was defined as an increase in PRC of at least 50% above baseline 1 week after paracentesis.

Results

Ten patients were included (nine men, mean age 59.1 ± 10.7 years old). The MELD score was 17.7 ± 4.4 and eight patients were Child–Pugh C. When patients were given beta-blockers, the heart rate did not change immediately after paracentesis while mean arterial pressure significantly decreased; PICD developed in eight patients. After beta-blockers were discontinued, the heart rate significantly increased immediately after paracentesis and mean arterial pressure significantly decreased; PICD only developed in one patient; the difference in the incidence of PICD was significant when these same patients were treated with beta-blockers.

Conclusions

The use of beta-blockers may be associated with a high risk of PICD in patients with cirrhosis and refractory ascites.

Introduction

In patients with cirrhosis, repeated large-volume paracentesis associated with plasma expansion is the first-line treatment of refractory ascites [1], [2]. However, large-volume paracentesis has been shown to trigger a circulatory dysfunction syndrome, characterized by systemic vasodilation and a decrease in effective arterial blood volume despite a compensatory increase in cardiac output [3], [4], [5], [6], [7]. Patients who develop post-paracentesis circulatory dysfunction (PICD) are at risk of developing hyponatremia and renal impairment, and have a low probability of survival [3]. Non-selective beta-blockers are frequently administered to patients with cirrhosis for the prevention of gastrointestinal hemorrhage secondary to portal hypertension [8], [9], [10]. However, in an observational prospective study, we recently reported that beta-blockers were associated with poor survival in these patients, suggesting that this pharmacological treatment has deleterious effects in patients with ascites treated by large-volume paracentesis [11]. Although the mechanism responsible for these deleterious effects is unknown, beta-blockers may play a role in the development of the PICD. Before to evaluate the incidence of PICD in patients randomized into a group that stays under beta-blockers and into a group in whom the beta-blockers are withdrawn, the incidence of PICD was assessed before and after discontinuation of beta-blockers in patients with cirrhosis and refractory ascites. Thus, we decided to perform a prospective cross-over study in these patients.

Section snippets

Patients

Patients with cirrhosis being treated with non-selective beta-blockers, for the prevention of bleeding, and admitted for refractory ascites were consecutively included in this study. The definition of refractory ascites was based on International Ascites Club criteria [12]. Patients were considered to have refractory ascites when they had either diuretic-resistant or diuretic-intractable ascites. Refractory ascites were qualified as diuretic-resistant when ascites could not be stabilized

Patient characteristics

Twenty consecutive patients with cirrhosis, referred to our Liver Unit for large-volume paracentesis, were prospectively evaluated. Ten patients were not included: nine patients refused to provide written consent, and one patient was lost to follow-up. Ten patients were included, six with diuretic-resistant ascites and four with diuretic-intractable ascites. Baseline patient clinical characteristics are summarized in Table 1. There was no significant difference before and after propranolol

Discussion

In this series of patients with cirrhosis and refractory ascites, mean survival and the probability of survival were similar to those observed in previous studies [13], [14]. All patients had at least two paracenteses per month for at least 3 months confirming the diagnosis of refractory ascites and the need for therapeutic or large volume paracentesis associated with plasma expansion [6].

Removal of large volumes of ascites by paracentesis may have deleterious effects on circulatory function

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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These authors contributed equally to this work.

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