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Morphine Promotes Colonization of Anastomotic Tissues with Collagenase - Producing Enterococcus faecalis and Causes
Baddr A Shakhsheer1, Luke A Versten1, James N Luo1
1Department of Surgery, Pritzker School of Medicine, University of Chicago, 5841 S Maryland Ave, MC 6040, Chicago, IL, 60605, USA.
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.
Insights
Morphine use in surgery may increase the risk of anastomotic leaks by promoting collagenase-producing Enterococcus faecalis colonization. Limiting opioid use could improve surgical recovery and reduce complications.
Area of Science:
- Gastrointestinal Surgery
- Microbiology
- Pharmacology
Background:
- Anastomotic leaks remain a significant surgical complication despite advances in care.
- Previous research linked leaks to collagenolytic Enterococcus faecalis strains.
- Mechanisms for surgical selection of these strains were unknown.
Purpose of the Study:
- To investigate if morphine, a common surgical analgesic, promotes tissue colonization by collagenolytic E. faecalis.
- To determine if morphine administration contributes to anastomotic leak.
Main Methods:
- Rats received morphine or vehicle in a chronic release formulation.
- Animals were monitored for 6 days before surgical inspection and tissue analysis.
- In vitro experiments assessed morphine's effect on E. faecalis collagenase activity and adherence.
Main Results:
- Morphine-treated rats showed impaired healing and anastomotic leaks correlated with high collagenase-producing E. faecalis.
- Morphine increased E. faecalis adherence and collagenase production in vitro.
- This effect was observed in both low and high baseline collagenase-producing strains.
Conclusions:
- Morphine promotes anastomotic colonization by collagenolytic E. faecalis, contributing to leaks.
- Findings support enhanced recovery after surgery (ERAS) guidelines to limit opioid use.
- Reducing intraoperative opioid exposure may mitigate anastomotic leak risk.
