Influence of Prophylactic Probiotics and Selective Decontamination on Bacterial Translocation in Patients Undergoing Pancreatic Surgery: A Randomized Controlled Trial

Abstract

To the Editor: We read with interest the paper by Dr. Diepenhorst et al. (1) entitled "Influence of prophylactic Probiotics and Selective Decontamination On Bacterial Translocation in Patients Undergoing Pancreatic Surgery: A Randomized Controlled Trial." However, we are troubled by the clinical conclusions the authors draw from their small laboratory-based mechanistic study. We are surprised at the low sample size of 30 patients. Expecting a 20% difference in bacterial counts between the group means is optimistic, as is 15% difference in SD, which undoubtedly resulted in the remarkably low numbers needed in this study. Also being satisfied with 80% statistical power is not a very demanding threshold. A 90% statistical power and a 5% SD would require sample size of around 260. This would perhaps have given the conclusions of this study a little more credibility. With only 10 patients in each group, we would suggest not much can be concluded. Much is made in the discussion of the potential importance of probiotics. However, we interpret the animal data, which the authors cite as suggesting selective decontamination of the digestive tract (SDD) to be superior. Furthermore, the authors refer to a German randomized controlled trial (RCT) in liver transplant recipients (2), which demonstrated probiotics to be significantly better than SDD. However, half of the infections in this study were due to enterococci and coagulase-negative staphylococci causing pneumonia and cholangitis in the patients receiving SDD. Pneumonia due to these low-level pathogens is rare, and if excluded from the analysis, then probiotics would not appear to be of such benefit. The same researchers published their first RCT assessing the efficacy of probiotics in acute severe pancreatitis 3 years ago (3). In 298 patients, there was increased mortality in patients with severe pancreatitis given probiotic prophylaxis (16%) compared with placebo (6%). The researchers found that prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. They concluded that probiotic prophylaxis should not be given in severe pancreatitis, although at that time the evidence for bacterial translocation in this disease was overwhelming (4). The researchers confirmed this crucial pathogenetic pathway using clinical end points in their placebo-controlled group (5). In 141 patients with pancreatitis, they concluded organ failure and mortality were all associated with intestinal barrier dysfunction early in the course of acute pancreatitis. The contrasting views on translocation between the two RCTs from the Dutch Acute Pancreatitis Study Group are difficult to reconcile (6). We agree with the authors who caution against drawing any conclusions from their study with only 10 patients per group. We feel that absolutely no comment can be made about intestinal permeability, bacterial translocation, or more importantly the use of probiotics. If the intention of the authors was to show superiority of probiotics over SDD, we believe the design of their RCT was ill conceived both in terms of end point and subset of patient group selected. Andy Petros Pediatric Intensive Care Unit Great Ormond Street Hospital London, United Kingdom Daphne Roos Department of Surgery OLVG Amsterdam, The Netherlands Luciano Silvestri Intensive Care Unit Gorizia Hospital Gorizia, Italy Hans Rommes Intensive Care Unit Gelre Hospitals Apeldorn, The Netherlands Nia Taylor School of Clinical Science University of Liverpool Liverpool, United Kingdom Hendrik van Saene School of Clinical Science University of Liverpool Liverpool, United Kingdom