Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial.
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.
Besselink
Marc Gh
MG
Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
van Santvoort
Hjalmar C
HC
Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
Buskens
Erik
E
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Department of Epidemiology, University Medical Center Groningen, Groningen, Netherlands.
Boermeester
Marja A
MA
Department of Surgery, Academic Medical Center, Amsterdam, Netherlands.
van Goor
Harry
H
Department of Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
Timmerman
Harro M
HM
Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
Nieuwenhuijs
Vincent B
VB
Department of Surgery, University Medical Center Groningen, Groningen, Netherlands.
Bollen
Thomas L
TL
Department of Radiology, St Antonius Hospital, Nieuwegein, Netherlands.
van Ramshorst
Bert
B
Department of Surgery, St Antonius Hospital, Nieuwegein, Netherlands.
Witteman
Ben Jm
BJ
Department of Gastroenterology, Gelderse Vallei Hospital, Ede, Netherlands.
Rosman
Camiel
C
Department of Surgery, Canisius Wilhelmina Hospital, Nijmegen, Netherlands.
Ploeg
Rutger J
RJ
Department of Surgery, University Medical Center Groningen, Groningen, Netherlands.
Brink
Menno A
MA
Department of Gastroenterology, Meander Medical Center, Amersfoort, Netherlands.
Schaapherder
Alexander Fm
AF
Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
Dejong
Cornelis Hc
CH
Department of Surgery and NUTRIM, University Hospital Maastricht, Maastricht, Netherlands.
Wahab
Peter J
PJ
Department of Gastroenterology, Rijnstate Hospital, Arnhem, Netherlands.
van Laarhoven
Cees Jhm
CJ
Department of Surgery, St Elisabeth Hospital, Tilburg, Netherlands.
van der Harst
Erwin
E
Department of Surgery, Medical Center Rijnmond Zuid, Rotterdam, Netherlands.
van Eijck
Casper Hj
CH
Department of Surgery, Erasmus Medical Center, Rotterdam, Netherlands.
Cuesta
Miguel A
MA
Department of Surgery, Vrije Universiteit Medical Center, Amsterdam, Netherlands.
Akkermans
Louis Ma
LM
Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
Gooszen
Hein G
HG
Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands. Electronic address: h.gooszen@umcutrecht.nl.
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
D010919:Placebos