title: Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial.
abstract: 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.
  
  
  
  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 > or =8, Imrie score > or =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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Marc Gh
authors.initials: MG
authors.lastname: Besselink
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Hjalmar C
authors.initials: HC
authors.lastname: van Santvoort
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Department of Epidemiology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Buskens
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Marja A
authors.initials: MA
authors.lastname: Boermeester
authors.affiliation: Department of Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Harro M
authors.initials: HM
authors.lastname: Timmerman
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Nieuwenhuijs
authors.affiliation: Department of Radiology, St Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Bollen
authors.affiliation: Department of Surgery, St Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: van Ramshorst
authors.affiliation: Department of Gastroenterology, Gelderse Vallei Hospital, Ede, Netherlands.
authors.forename: Ben Jm
authors.initials: BJ
authors.lastname: Witteman
authors.affiliation: Department of Surgery, Canisius Wilhelmina Hospital, Nijmegen, Netherlands.
authors.forename: Camiel
authors.initials: C
authors.lastname: Rosman
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Ploeg
authors.affiliation: Department of Gastroenterology, Meander Medical Center, Amersfoort, Netherlands.
authors.forename: Menno A
authors.initials: MA
authors.lastname: Brink
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Alexander Fm
authors.initials: AF
authors.lastname: Schaapherder
authors.affiliation: Department of Surgery and NUTRIM, University Hospital Maastricht, Maastricht, Netherlands.
authors.forename: Cornelis Hc
authors.initials: CH
authors.lastname: Dejong
authors.affiliation: Department of Gastroenterology, Rijnstate Hospital, Arnhem, Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wahab
authors.affiliation: Department of Surgery, St Elisabeth Hospital, Tilburg, Netherlands.
authors.forename: Cees Jhm
authors.initials: CJ
authors.lastname: van Laarhoven
authors.affiliation: Department of Surgery, Medical Center Rijnmond Zuid, Rotterdam, Netherlands.
authors.forename: Erwin
authors.initials: E
authors.lastname: van der Harst
authors.affiliation: Department of Surgery, Erasmus Medical Center, Rotterdam, Netherlands.
authors.forename: Casper Hj
authors.initials: CH
authors.lastname: van Eijck
authors.affiliation: Department of Surgery, Vrije Universiteit Medical Center, Amsterdam, Netherlands.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cuesta
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Louis Ma
authors.initials: LM
authors.lastname: Akkermans
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands. Electronic address: h.gooszen@umcutrecht.nl.
authors.forename: Hein G
authors.initials: HG
authors.lastname: Gooszen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010195:Pancreatitis / Q000150:complications / Q000517:prevention & control*; D010919:Placebos; D019936:Probiotics / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D010919:Placebos