Editorial: spontaneous bacterial peritonitis--bacteriology, diagnosis, treatment, risk factors and prevention. Authors' reply.

Abstract

We kindly thank Drs Lachlan and Fallowfield for their commentary on our paper,1, 2 and in regard to nonselective beta-blocker (NSBB) therapy in patients with resistant ascites, agree that definitive conclusions about its detrimental effect cannot be drawn at this time, nor are expected in the near future. Nonselective beta-blocker therapy (propranolol and nadolol) remains cornerstone therapy in primary and secondary prophylaxis of variceal bleeding and is the only medication shown to improve survival in patients with cirrhosis and medium to large varices.3 In the original research demonstrating this effect, including Pascal et al.,4 Groszmann et al.5 and Poynard et al.'s meta-analysis,6 patients with refractory ascites were not studied or were excluded from analysis. Nonselective beta-blocker therapy is not without caveats, and the ‘window hypothesis’ as proposed by Krag et al.7 has strong legitimacy. In a large, multicenter, double-blinded, placebo-controlled trial, NSBB therapy was found to have no role in pre-primary prophylaxis of varices, and serious adverse events such as bradycardia (<50 beats per min) and syncope occurred in 20 patients (18%) in the timolol group and in six patients (6%) in the placebo (P = 0.006).8 Furthermore, patients with cirrhosis, ascites, and low cardiac index (<1.5 L/min/m2) have significantly poorer survival compared to similar patients with a higher cardiac index.9 As such, there is baseline hypotension in patients with end-stage liver disease (ESLD). NSBBs decrease cardiac output and further impair cardiac compensatory reserve making these patients increasingly susceptible to hemodynamic instability, azotemia and end-organ damage. Lastly, there are three retrospective studies demonstrating potential harm including SBP and/or decreased survival with NSBB therapy in patients with resistant ascites,10-12 and one recent retrospective study demonstrating improved survival for patients listed for liver transplantation.13 While the hepatology community awaits outcomes of well conducted studies, we advise that existing NSBB use should be tapered and discontinued in patients with ESLD and resistant ascites. The authors’ declarations of personal and financial interests are unchanged from those in the original article.2