B. A. Shakhsheer1, J. R. Defazio1, J. N. Luo1, R. Klabbers2, I. D. Fleming1, N. Belogortseva1, A. Zaborin1, O. Zaborina1, J. C. Alverdy1 1Pritzker School Of Medicine, University Of Chicago,Department Of Surgery,Chicago, IL, USA 2Radboud University Nijmegen Medical Centre,Department Of Surgery,Nijmegen, , Netherlands
Introduction: The most dreaded complication after resection of the gastrointestinal tract is anastomotic leak. The effects of opioids on outcomes after gastrointestinal surgery continue to be discovered. Use of patient-controlled analgesia pumps has been associated with increased deep surgical site infection rates by unknown mechanisms. Two findings from our lab may shed light on the mechanisms by which opioids increase anastomotic leak rates: 1. opioids (morphine) directly enhance the virulence of intestinal pathogens and 2. intestinal bacteria play a key causative role in the pathogenesis of leak. Therefore the aim of this study was to examine the effect of opioids on colonic anastomotic leak in a rat model.
Methods: Rats undergoing one-centimeter colectomy at the peritoneal reflection and primary anastomosis were treated with slow release subcutaneous morphine pellets or placebo pellets implanted in the nape of the neck. Rats were sacrificed on post-operative day six and autopsied for gross signs of anastomotic leak. Microbial composition and phenotype (i.e. collagenase production) was investigated via culture of tissues and intraperitoneal lavage. Local anastomotic tissue was subjected to high magnification microscopy and phenotype analysis.
Results: Rats treated with high-dose (15-mg sustained release) subcutaneous morphine pellets developed a 56% leak rate compared with a 3% leak rate in the placebo treated group (n=73, p=0.0045) High powered images of the anastomotic site demonstrated mucosal ulceration in the morphine group with visible disruptions in the anastomotic integrity whereas no such findings were observed in the placebo treated group. Culture of local tissue and intraperitoneal lavage fluid identified the presence of gram-negative bacteria producing high levels of collagenase which may a play role in anastomotic disruption and non-healing.
Conclusion: Morphine significantly increases anastomotic leak rates in rats. The role of microbial composition (i.e. gram negative pathogens) and phenotype (i.e. collagenase productions) remains to be investigated and their predictive value confirmed. Taken together these findings provide a rationale to limit opioid use following colorectal surgery and/or to block their peripheral effects with selective opioid antagonists as a countermeasure to prevent deep organ space infection and anastomotic leak.