ArticlesProbiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial
Introduction
The incidence of acute pancreatitis in Europe and the USA is increasing by about 5% per year, mainly owing to an increase in biliary pancreatitis.1, 2, 3 About a fifth of patients will develop necrotising pancreatitis, which is associated with a 10–30% mortality rate, mostly attributed to infectious complications and infection of (peri)pancreatic necrotic tissue in particular.1 These infections are thought to be the sequelae of a cascade of events starting with small-bowel bacterial overgrowth, mucosal barrier failure, and a proinflammatory response leading to bacterial translocation of intestinal bacteria.4, 5, 6 Systemic antibiotic prophylaxis has long been studied as a measure to prevent secondary infection in acute pancreatitis.1 However, two double-blind, placebo-controlled trials7, 8 and two meta-analyses9, 10 have failed to show a beneficial effect, and many clinicians have abandoned this strategy. In the two antibiotic trials, the incidence of extrapancreatic infections (eg, bacteraemia, pneumonia) and pancreatic infection remained high.7, 8 Consequently, there is a clear need for other strategies to prevent infectious complications in patients with acute pancreatitis.
Probiotics, as an adjunct to enteral nutrition, have raised high expectations and are currently gaining worldwide popularity for their presumed health-promoting effects.11, 12 Certain strains of probiotic bacteria might prevent infectious complications by reducing small-bowel bacterial overgrowth, restoring gastrointestinal barrier function, and modulating the immune system.11, 12 A reduction of infectious complications has been reported in several clinical studies with probiotics in patients undergoing elective abdominal operations13, 14 and in patients with acute pancreatitis.15 However, because of their small size and methodological quality, these studies do not justify global implementation of probiotics as a preventive measure in acute pancreatitis. Accordingly, we embarked on a nationwide multicentre randomised, double-blind, placebo-controlled trial—the PRObiotics in PAncreatitis TRIAl (PROPATRIA)—to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis.
Section snippets
Patients
The design and rationale of the study have been described in detail elsewhere.16 Adult patients admitted with a first episode of acute pancreatitis were enrolled in eight university medical centres and seven major teaching hospitals in the Netherlands. Acute pancreatitis was defined as abdominal pain in combination with serum amylase or lipase concentrations that were raised to at least three times the institutional upper limit of normal. Patients were not enrolled in the study if any of the
Results
732 consecutive patients with a first episode of acute pancreatitis were registered prospectively between March, 2004, and March, 2007 (figure 1). 298 patients were predicted to have a severe disease course (135 patients with APACHE II score ≥8, 204 with Imrie score ≥3, 252 with C-reactive protein >150 mg/L), and were randomly assigned treatment with probiotics or with placebo (figure 1). Two patients—one in each group—were excluded from the final analysis because of an incorrect diagnosis of
Discussion
This randomised, double-blind, placebo-controlled trial in patients with predicted severe acute pancreatitis showed no beneficial effect of probiotic prophylaxis on the occurrence of infectious complications. However, mortality in the probiotics group was about twice as high as in the placebo group. Thus, this combination of probiotics should not be administered routinely in patients with predicted severe acute pancreatitis, and such preparations can no longer be considered to be harmless
References (40)
- et al.
Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality
J Gastrointest Surg
(1999) - et al.
Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial
Gastroenterology
(2004) - et al.
Randomized controlled trials of antibiotic prophylaxis in severe acute pancreatitis: relationship between methodological quality and outcome
Pancreatology
(2007) - et al.
Gut flora in health and disease
Lancet
(2003) - et al.
Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation—a randomized, double-blind trial
Am J Transplant
(2005) - et al.
Useful markers for predicting severity and monitoring progression of acute pancreatitis
Pancreatology
(2003) - et al.
Design of a multispecies probiotic mixture to prevent infectious complications in critically ill patients
Clin Nutr
(2007) - et al.
Influence of synbiotic containing Lactobacillus acidophilus La5, Bifidobacterium lactis Bb 12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose on gut barrier function and sepsis in critically ill patients: a randomised controlled trial
Clin Nutr
(2004) - et al.
Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis
Surgery
(2007) - et al.
Non-occlusive mesenteric ischaemia: a common disorder in gastroenterology and intensive care
Best Pract Res Clin Gastroenterol
(2003)