Akkermans, Louis M.

Besselink, Marc G.

Buskens, Erik

Gooszen, Hein G.

van Santvoort, Hjalmar C.

University of Groningen

   University of GroningenProbiotic prophylaxis in predicted severe acute pancreatitis - ReplyBesselink, Marc G.; van Santvoort, Hjalmar C.; Buskens, Erik; Akkermans, Louis M.;Gooszen, Hein G.; Dutch Acute Pancreatitis Study GrpPublished in:LANCETIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2008Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Besselink, M. G., van Santvoort, H. C., Buskens, E., Akkermans, L. M., Gooszen, H. G., & Dutch AcutePancreatitis Study Grp (2008). Probiotic prophylaxis in predicted severe acute pancreatitis - Reply.LANCET, 372(9633), 114-114.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019Correspondence114 www.thelancet.com   Vol 372   July 12, 2008On the basis of all of the above points, one cannot conclude that pro biotics in general present a risk in enteral feeding.I declare that I have no conﬂ ict of interest.Philippe Marteauphilippe.marteau@lrb.aphp.frAP-HP, Medico-surgical Department of Digestive Diseases, Lariboisière Hospital, 2 rue Ambroise Paré 75010 Paris, France1 Besselink MGH, van Santvoort HC, Buskens E, et al, for the Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 2008; 371: 651–59.2 van Minnen LP, Timmerman HM, Lutgendorﬀ  F, et al. Modiﬁ cation of intestinal ﬂ ora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis. Surgery 2007; 141: 470–80.3 Marteau P,  Shanahan F. Basic aspects and pharmacology of probiotics: an overview of pharmacokinetics, mechanisms of action and side-eﬀ ects. Best Pract Res Clin Gastroenterol 2003; 17: 725–40.4 Alfaleh K, Bassler D. Probiotics for prevention of necrotizing enterocolitis in preterm infants.Cochrane Database Syst Rev 2008; 1: CD005496.Authors’ replyGregor Reid and colleagues cor rectly cite the deﬁ nition of a pro biotic provided by the Food and Agriculture Organiza-tion and WHO: “Live micro organ isms which when administered in ade quate amounts confer a health beneﬁ t on the host”. This does not mean that if such a product shows negative eﬀ ects in a new study in a diﬀ erent popula tion, the product should no longer qualify as a probiotic. From now on we will refer to the product used as a “combina-tion of probiotic strains” or “the com bination” because the individual strains have shown beneﬁ cial eﬀ ects in previous studies. Contrary to Reid and colleagues’ sug gestion, our combination was designed after rigorous selection studies.1 In several animal studies and smaller clini cal studies, no negative eﬀ ects of the com bination were detected. As a con sequence, we feel that it was probably not the com bination but the administration of the combination together with the severity of the disease that was largely responsible for the eﬀ ects obtained.The implication that the increased mortality rate in the probiotics group was caused by a higher rate of organ failure on the day of randomisation in the study product group is incorrect. None of the baseline characteristics diﬀ ered signiﬁ cantly between the groups. Furthermore, in a post-hoc sub group analysis, having excluded patients with organ failure on the day of randomisation, mortality was still twice as high and bowel ischaemia was signiﬁ cantly more frequent in the group receiving the study product.Bala Reddy and John MacFie pro pose “hypercaloric feeding” as a potential cause of bowel ischaemia. This was a post-hoc, quite heterogeneous, end-point and whether it was initiated by organ failure, inﬂ ammation, or other unknown factors is unclear. It is, how-ever, unlikely that it was related to hypercaloric feeding as such, because the feeding regimen—jejunal infu sion of multiﬁ bre nutrition—was identical in both groups and the admin istra tion of the study product, with a negligible caloric load, was the only diﬀ erence.Philippe Marteau raises concerns about the dose of probiotics, and we agree that studies on doses are in-deed lacking. However, several trials, in patients with acute pancreatitis and pa-tients scheduled for elective ab dom inal surgery, have used even higher doses of probiotics with a similar route of intrajejunal (bolus) admin istration.2–4As for our alleged conclusion that pro biotics in general present a risk in en ter al feeding, we feel that this does not accurately reﬂ ect our cautious inter-pretation that probiotics can no longer be considered harmless under all con-ditions, especially in critically ill patients.We declare that we have no conﬂ ict of interest.Marc G Besselink, Hjalmar C van Santvoort, Erik Buskens, Louis M Akkermans, *Hein G Gooszen, on behalf of the Dutch Acute Pancreatitis Study Grouph.gooszen@umcutrecht.nlUniversity Medical Center Utrecht, PO Box 85500, HP G04.228, 3508 GA Utrecht, Netherlands (MGB, HCvS, LMA, HGG); and University Medical Center Groningen, Groningen, Netherlands (EB)1 Timmerman HM, Niers LE, Ridwan BU, et al. Design of a multispecies probiotic mixture to prevent infectious complications in critically ill patients. Clin Nutr 2007; 26: 450–59.2 Rayes N, Seehofer D, Theruvath T, et al. Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation—a randomized, double-blind trial. Am J Transplant 2005; 5: 125–30.3 Rayes N, Seehofer D, Theruvath T, et al. Eﬀ ect of enteral nutrition and synbiotics on bacterial infection rates after pylorus-preserving pancreatoduodenectomy: a randomized, double-blind trial. Ann Surg 2007; 246: 36–41.4 Olah A, Belagyi T, Issekutz A, Gamal ME, Bengmark S. Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis. Br J Surg 2002; 89: 1103–07.According to Marc Besselink and colleagues, the increase in mortality in patients with pancreatitis treated with probiotics was due to bowel ischaemia.1It has been suggested that most small-bowel diseases have a com mon ﬁ nal pathogenic path way.2 Ac cord-ingly, entero cytic damage by various assaults (bio chemi cal, im muno logical, micro bio logi al, vas cular, etc) leads to an increase in intestinal permeability. This in creased permeability results in a tissue reaction as luminal sub-stances gain access to the mucosa where bac teria are the main neutro-phil chemo attractant.2The prototype of this damage is enteropathy caused by non-steroidal anti-inﬂ ammatory drugs,3 but there are more than 30 situa tions in human beings in which an increase in intes-tinal permeability leads to a uniform-ly prevalent and severe entero pathy.2 These entero pathies cannot easily be distinguished from each other, even by entero scopy or histological-ly (on which the changes resemble ischaemia). The in ﬂ ammation can respond to antimicrobials (metro-nidazole), im pli cat ing resident com-men sal anaerobic bac teria in the patho genesis.4The patients described by Besselink and colleagues had pancreatitis, and 

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Probiotic prophylaxis in predicted severe acute pancreatitis - Reply

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