Deleterious Effects of Beta-Blockers on Survival in Patients With Cirrhosis and Refractory Ascites†,‡

Abstract

Beta-blockers may have a negative impact on survival in patients with cirrhosis and refractory ascites. The aim of this study was to evaluate the effect of the administration of betablockers on long-term survival in patients with cirrhosis and refractory ascites. We performed a single-center, observational, case-only, prospective study of patients with cirrhosis and refractory ascites who did or did not receive beta-blockers for the prevention of gastrointestinal bleeding; 151 patients were included. The mean Model for End-Stage Liver Disease score was 18.8 6 4.1. All patients regularly underwent large-volume paracentesis and intravenous albumin administration. Seventy-seven patients (51%) were treated with propranolol (113 6 46 mg/day). The median follow-up for the whole group was 8 months. The median survival time was 10 months [95% confidence interval (CI) 5 8-12 months]. The probability of survival at 1 year was 41% (95% CI 5 33%-49%). The clinical characteristics and laboratory values at enrolment were not significantly different between patients who were receiving propranolol and those who were not. The median survival time was 20.0 months (95% CI 5 4.8-35.2 months) in patients not treated with propranolol and 5.0 months (95% CI 5 3.5-6.5 months) in those treated with propranolol (P 5 0.0001). The 1-year probability of survival was significantly lower in patients who received propranolol [19% (95% CI 5 9%-29%)] versus those who did not [64% (95% CI 5 52%-76%), P < 0.0001]. The independent variables of mortality were Child-Pugh class C, hyponatremia and renal failure as causes of refractory ascites, and beta-blocker therapy. Conclusion: The use of beta-blockers is associated with poor survival in patients with refractory ascites. These results suggest that betablockers should be contraindicated in these patients.

Non-Selective Beta-Blockers in Liver Cirrhosis: Friends or Foes? A Review of the Literature

“…For instance, in early cirrhosis, there is only mild splanchnic and systemic hyperdynamic circulatory state, therefore NSBB are weakly active with some increase in their adverse events as it was shown in the large multicenter clinical trial from Groszmann and colleagues [27] . On the other side, several circulatory changes accompany advanced cirrhosis such as peripheral vasodilation, effective hypovolemia, and arterial hypotension [28][29][30][31] , it is at that time when the maintenance of cardiac output and blood pressure becomes paramount in prolonging overall survival, and the hemodynamic effects of beta-blockers become potentially harmful [26,32,33] .…”

“…After almost three decades of their landmark study in 1981 showing the benefits of NSBB in the prevention of variceal bleeding in patients with cirrhosis [8] , the use of beta-blockers was questioned by Serste et al when they found out that NSBB therapy in patients with refractory ascites was associated with poor survival [32] . In…”

“…Abi Abboud A et al Beta-Blockers in Patients with Cirrhosis their study, 151 patients with cirrhosis and refractory ascites were observed: Patients who were not treated with propranolol had a median survival of 20 months with a 64% probability of survival at 1 year whereas patients who were on propranolol therapy had a dramatically decreased median survival (5 months) with 19% probability of survival at 1 year only [32] . In a subsequent study, Serste and colleagues showed that patients with advanced cirrhosis and refractory ascites who underwent regular large-volume paracentesis had a significantly higher risk of developing paracentesis-induced circulatory dysfunction if they were on NSBB therapy [48] .…”

Commentary: non-haemodynamic effects of beta-blockers in cirrhosis - more than meets the eye? Authors’ reply

“…[3][4][5] The restriction of infectious outcomes to those with hospitalisation results in excluding out-patient infections. However, it can be argued that out-patient episodes would be poorly captured from a coding perspective and have a milder effect on overall prognosis than infections associated with hospitalisation.…”

“…1,2 We agree with the authors that the evidence is split regarding the effects of NSBB on infections and given the poor prognosis of these infections, efforts to improve outcomes are critical. [3][4][5] The restriction of infectious outcomes to those with hospitalisation results in excluding out-patient infections. However, it can be argued that out-patient episodes would be poorly captured from a coding perspective and have a milder effect on overall prognosis than infections associated with hospitalisation.…”