Journal of Gastrointestinal Surgery

, Volume 20, Issue 10, pp 1744–1751 | Cite as

Morphine Promotes Colonization of Anastomotic Tissues with Collagenase - Producing Enterococcus faecalis and Causes Leak

  • Baddr A. Shakhsheer
  • Luke A. Versten
  • James N. Luo
  • Jennifer R. Defazio
  • Robin Klabbers
  • Scott Christley
  • Alexander Zaborin
  • Kristina L. Guyton
  • Monika Krezalek
  • Daniel P. Smith
  • Nadim J. Ajami
  • Joseph F. Petrosino
  • Irma D. Fleming
  • Natalia Belogortseva
  • Olga Zaborina
  • John C. Alverdy
Original Article

Abstract

Background

Despite ever more powerful antibiotics, newer surgical techniques, and enhanced recovery programs, anastomotic leaks remain a clear and present danger to patients. Previous work from our laboratory suggests that anastomotic leakage may be caused by Enterococcus faecalis strains that express a high collagenase phenotype (i.e., collagenolytic). Yet the mechanisms by which the practice of surgery shifts or selects for collagenolytic phenotypes to colonize anastomotic tissues remain unknown.

Methods

Here, we hypothesized that morphine, an analgesic agent universally used in gastrointestinal surgery, promotes tissue colonization with collagenolytic E. faecalis and causes anastomotic leak. To test this, rats were administered morphine in a chronic release form as would occur during routine surgery or vehicle. Rats were observed for 6 days and then underwent exploratory laparotomy for anastomotic inspection and tissue harvest for microbial analysis. These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery.

Results

Results demonstrated that compared to placebo-treated rats, morphine-treated rats demonstrated markedly impaired anastomotic healing and gross leaks that correlated with the presence of high collagenase-producing E. faecalis adherent to anastomotic tissues. To determine the direct role of morphine on this response, various isolates of E. faecalis from the rats were exposed to morphine and their collagenase activity and adherence capacity determined in vitro. Morphine increased both the adhesiveness and collagenase production of four strains of E. faecalis harvested from anastomotic tissues, two that were low collagenase producers at baseline, and two that were high collagenase producers at baseline.

Conclusion

These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery.

Keywords

Anastomotic leak Enterococcus faecalis Morphine 

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Copyright information

© The Society for Surgery of the Alimentary Tract 2016

Authors and Affiliations

  • Baddr A. Shakhsheer
    • 1
  • Luke A. Versten
    • 1
  • James N. Luo
    • 1
  • Jennifer R. Defazio
    • 1
  • Robin Klabbers
    • 2
  • Scott Christley
    • 1
  • Alexander Zaborin
    • 1
  • Kristina L. Guyton
    • 1
  • Monika Krezalek
    • 1
  • Daniel P. Smith
    • 3
  • Nadim J. Ajami
    • 3
  • Joseph F. Petrosino
    • 3
  • Irma D. Fleming
    • 1
  • Natalia Belogortseva
    • 1
  • Olga Zaborina
    • 1
  • John C. Alverdy
    • 1
  1. 1.Department of Surgery, Pritzker School of MedicineUniversity of ChicagoChicagoUSA
  2. 2.Department of SurgeryRadboud University Nijmegen Medical CentreNijmegenNetherlands
  3. 3.Center for Metagenomics and Microbiome ResearchBaylor College of MedicineHoustonUSA

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