Gastroenterology

Gastroenterology

Volume 146, Issue 7, June 2014, Pages 1680-1690.e1
Gastroenterology

Original Research
Full Report: Clinical—Liver
Nonselective β Blockers Increase Risk for Hepatorenal Syndrome and Death in Patients With Cirrhosis and Spontaneous Bacterial Peritonitis

https://doi.org/10.1053/j.gastro.2014.03.005Get rights and content

Background & Aims

Nonselective β blockers (NSBBs) reduce portal pressure and the risk for variceal hemorrhage in patients with cirrhosis. However, development of spontaneous bacterial peritonitis (SBP) in these patients could preclude treatment with NSBBs because of their effects on the circulatory reserve. We investigated the effects of NSBBs in patients with cirrhosis and ascites with and without SBP.

Methods

We performed a retrospective analysis of data from 607 consecutive patients with cirrhosis who had their first paracentesis at the Medical University of Vienna from 2006 through 2011. Cox models were calculated to investigate the effect of NSBBs on transplant-free survival time and adjusted for Child-Pugh stage and presence of varices.

Results

NSBBs increased transplant-free survival in patients without SBP (hazard ratio = 0.75; 95% confidence interval: 0.581–0.968; P = .027) and reduced days of nonelective hospitalization (19.4 days/year for patients on NSBBs vs 23.9 days/year for patients not taking NSBBs). NSBBs had only moderate effects on systemic hemodynamics at patients' first paracentesis. However, at the first diagnosis of SBP, the proportion of hemodynamically compromised patients with systolic arterial pressure <100 mm Hg was higher among those who received NSBBs (38% vs 18% of those not taking NSBBs; P = .002), as was the proportion of patients with arterial pressure <82 mm Hg (64% of those taking NSBBs vs 44% of those not taking NSBBs; P = .006). Among patients with SBP, NSBBs reduced transplant-free survival (hazard ratio = 1.58; 95% confidence interval: 1.098–2.274; P = .014) and increased days of nonelective hospitalization (29.6 days/person-year in patients on NSBBs vs 23.7 days/person-year in those not taking NSBBs). A higher proportion of patients on NSBBs had hepatorenal syndrome (24% vs 11% in those not taking NSBBs; P = .027) and grade C acute kidney injury (20% vs 8% for those not taking NSBBs; P = .021).

Conclusions

Among patients with cirrhosis and SBP, NSBBs increase the proportion who are hemodynamically compromised, time of hospitalization, and risks for hepatorenal syndrome and acute kidney injury. They also reduce transplant-free survival. Patients with cirrhosis and SBP should not receive NSBBs.

Section snippets

Study Design

A total of 607 consecutive patients with cirrhosis who underwent their first paracentesis at the Medical University of Vienna between 2006 and 2011, had bacterial cultures from ascites, and did not display any exclusion criteria, were included in this retrospective study. Patients with other causes of ascites, such as severe cardiovascular disease, renal insufficiency, extrahepatic malignancies, and noncirrhotic portal hypertension, were excluded from the study.

Assessed Parameters

Epidemiological characteristics,

Patient Characteristics and Systemic Hemodynamics at the First Paracentesis

Except for a higher proportion of female subjects (NSBB: 34% vs no-NSSB: 27%; P = .048) and patients with varices (NSBB: 90% vs no-NSBB: 62%; P < .001) in the NSBB group, no statistically significant differences in patient characteristics between patients with NSBB treatment, and without, were observed (Table 1).

Although the mean heart rate (NSBB: 77.5 ± 16.5 beats/min vs no-NSBB: 83.9 ± 15.5 beats/min; P < .001) and systolic arterial pressure (SAP) (NSBB: 114 ± 18 vs no-NSBB: 117 ± 18 mm Hg; P

Discussion

A recent landmark study by Serste et al12 demonstrated reduced survival in patients with refractory ascites who were treated with NSBBs and has initiated a lively debate among gastroenterologists on the appropriate use of NSBBs in patients with advanced cirrhosis. In summary, the editorial30 and various other responses to this study brought up concerns about the unequal distribution of esophageal varices between the NSBB and no-NSBB group. In addition, the trends toward a higher prevalence of

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    This article has an accompanying continuing medical education activity on page e14. Learning Objective: Upon completion of this exam, successful learners will be able to identify patients with cirrhosis and ascites that no longer benefit from non-selective β blocker treatment since the development of spontaneous bacterial peritonitis indicates an event when non-selective beta-blockers can compromise the circulatory reserve.

    Conflicts of interest The authors disclose no conflicts.

    Author names in bold designate shared co-first authors.

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