Abstracts
1998 Digestive Disease Week

#2320

EARLY FAILURE OF INTESTINAL BARRIER FUNCTION AND ENDOTOXEMIA IN SEVERE ACUTE PANCREATITIS. BJ Ammori, PG Leeder, RFG King, *GR Barclay, IG Martin, M Larvin, MJ McMahon. University of Leeds Academic Surgical Unit, The General Infirmary, Leeds UK, and *Blood Transfusion Service, Royal Infirmary, Edinburgh, UK.

The most life-threatening developments in acute pancreatitis are multiple organ-system failure (MOSF) and infected pancreatic necrosis. The pathogenesis of these complications remains unclear, but experimental studies suggest that translocation of bacteria and toxins via a 'leaky' intestinal mucosal barrier may contribute. The present study investigated intestinal permeability in healthy controls and patients with acute pancreatitis,
its relationship with severity, and evidence for endotoxemia.

Polyethylene glycol (PEG) 400 and PEG 3350 were selected to determine micromolecular and macromolecular intestinal permeability. PEG 400 (5g) and PEG 3350 (40g) were administered orally or nasogastrically. Urinary PEG 400 and 3350 were measured by high-performance liquid chromatography. Samples were completed within 72 hours of symptom onset. Attacks were classified as mild or severe by the Atlanta Criteria. APACHE-II scores and C-reactive protein (CRP) levels were measured daily, and endotoxin and anti-endotoxin antibodies determined at admission. There were 75 subjects: 23 healthy controls; 36 mild and 16 severe attacks. Groups were comparable for age and sex distribution, and mild and severe attacks for aetiology. Median admission APACHE-II was 10 (range 4-16) in severe and 5 (range 1-13) in mild attacks, median peak CRP 279 (range 99-379) mg/l in severe and 90 (range 11-237) mg/l in mild attacks.

Urinary recovery of PEG 400 was similar in all groups, but that of PEG 3350 was significantly greater in severe attacks (median 0.46%, range 0.04-10.8%) compared with mild attacks (median 0.08%, range 0.05-0.26%) and controls (median 0.12%, range 0.05-0.22%) (both p<0.001), as was the ratio of recovery of PEG 3350 to 400. Endotoxemia was detected more frequently in severe compared with mild attacks (50% vs. 22%), and at greater levels (median 0.035 EU/ml vs. 0.01 EU/ml), but these differences were not statistically significant. However, IgG anti-endotoxin levels were significantly lower in severe compared with mild attacks (median 65.8 vs. 111 GMU, p<0.01), indicating greater prior exposure to endotoxin.

The results suggest that intestinal permeability to macromolecules increases early in the course of severe attacks. Thus, translocation of bacteria and bacterial toxins may contribute both to the pathogenesis of MOSF, and to superinfection of pancreatic necrosis in acute pancreatitis.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.