Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial

Besselink, M. G. H., van Santvoort, H. C., Buskens, E., Boermeester, M. A., van Goor, H., Timmerman, H. M., Nieuwenhuijs, V. B., Bollen, T. L., van Ramshorst, B., Witteman, B. J. M., Rosman, C., Ploeg, R. J., Brink, M. A., Schaapherder, A. F. M., Dejong, C. H. C., Wahab, P. J., van Laarhoven, C. J. H. M., van der Harst, E., van Eijck, C. H. J., Cuesta, M. A., Akkermans, L. M. A., Gooszen, H. G. & Dutch Acute Pancreatitis Study Grp, 23-Feb-2008, In : LANCET. 371, 9613, p. 651-659 9 p.

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  • Marc G. H. Besselink
  • Hjalmar C. van Santvoort
  • Erik Buskens
  • Marja A. Boermeester
  • Harry van Goor
  • Harro M. Timmerman
  • Vincent B. Nieuwenhuijs
  • Thomas L. Bollen
  • Bert van Ramshorst
  • Ben J. M. Witteman
  • Camiel Rosman
  • Rutger J. Ploeg
  • Menno A. Brink
  • Alexander F. M. Schaapherder
  • Cornelis H. C. Dejong
  • Peter J. Wahab
  • Cees J. H. M. van Laarhoven
  • Erwin van der Harst
  • Casper H. J. van Eijck
  • Miguel A. Cuesta
  • Louis M. A. Akkermans
  • Hein G. Gooszen
  • Dutch Acute Pancreatitis Study Grp

Background Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis.

Methods In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score >= 8, Imrie score >= 3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications-ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites-during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949.

Findings One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1.06, 95% CI 0.75-1.51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2.53, 95% CI 1.22-5.25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0.004).

Interpretation In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic: strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.

Original languageEnglish
Pages (from-to)651-659
Number of pages9
Issue number9613
Publication statusPublished - 23-Feb-2008



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