Systematic review of experimental studies on intestinal anastomosis.

BACKGROUND: The contribution of animal research to a reduction in clinical intestinal anastomotic leakage is unknown, despite numerous experimental studies. In view of the current societal call to replace, reduce and refine animal experiments, this study examined the quality of animal research related to anastomotic healing and leakage. METHODS: Animal studies on intestinal anastomotic healing were retrieved systematically from PubMed and Embase. Study objective, conclusion and animal model were recorded. Reporting quality and internal validity (reporting of randomization and blinding) were assessed. RESULTS: A total of 1342 studies were identified, with a rising publication rate. The objectives of most studies were therapeutic interventions (64·8 per cent) and identification of risk factors (27·5 per cent). Of 350 articles studying experimental therapies, 298 (85·1 per cent) reported a positive effect on anastomotic healing. On average, 44·7 per cent of relevant study characteristics were not reported, in particular details on anastomotic complications (31·6 per cent), use of antibiotics (75·7 per cent), sterile surgery (83·4 per cent) and postoperative analgesia (91·4 per cent). The proportion of studies with randomization, blinding of surgery and blinding of primary outcome assessment has increased in the past two decades but remains insufficient, being included in only 62·4, 4·9 and 8·5 per cent of publications respectively. Animal models varied widely in terms of species, method to compromise healing, intestinal segment and outcome measures used. CONCLUSION: Animal research on anastomotic leakage is of poor quality and still increasing, contrary to societal aims. Reporting and study quality must improve if results are to impact on patients.

Experimental study of diclofenac and its biliary metabolites on anastomotic healing.

BACKGROUND: Diclofenac increases the risk of anastomotic leakage, but the underlying mechanism is unknown. As diclofenac is excreted largely as biliary metabolites, the aim of this study was to determine the effect of these metabolites on intestinal anastomoses. METHODS: This was a randomized controlled blinded experiment using 210 male Wistar rats to assess the effect of 'diclofenac bile' on the anastomotic complication score, leak rate and anastomotic strength following oral and parenteral administration of diclofenac. Bile duct and duodenal catheterization techniques were used for diversion and replacement of bile, and biliary diclofenac metabolites were determined. RESULTS: Replacement of control bile with diclofenac bile resulted in higher anastomotic complication scores (P = 0·006) and leakage in five of 18 animals, compared with one of 18 controls (P = 0·089). In turn, following oral diclofenac administration, replacement of diclofenac bile with control bile reduced anastomotic complications (P = 0·016). The leak rate was seven of 15 versus 13 of 17 without replacement (P = 0·127). After intramuscular administration of diclofenac, the reduction in anastomotic complications was not significant when bile was replaced with control bile (P = 0·283), but it was significant when bile was drained without replacement (P = 0·025). Diclofenac metabolites in bile peaked within 2 h after administration. Administration of diclofenac bile resulted in nearly undetectable plasma levels of diclofenac (mean(s.d.) 0·01(0·01) µg/ml) after 120 min. Following oral diclofenac, bile replacement with control bile did not affect the plasma concentration of diclofenac (0·12(0·08) µg/ml versus 0·10(0·05) µg/ml with diclofenac bile; P = 0·869). CONCLUSION: Altered bile composition as a result of diclofenac administration increases the ileal anastomotic complication rate in rats.