SLR - December 2014 - Zachary Flynn

Opioid Analgesics Stop the Development of Clostridial Gas Gangrene

Reference: Chakravorty A, Awad MM, Hiscox TJ, Cheung JK, Choo JM, Lyras D, Rood JI. Opioid Analgesics Stop the Development of Clostridial Gas Gangrene. J Infect Dis. 2014 Aug 1;210(3):483-92.

Scientific Literature Review

Reviewed By: Zachary Flynn, DPM
Residency Program: St. Francis Hospital & Medical Center: Hartford CT

Podiatric Relevance: Gas gangrene is one of the most common causes of limb loss in the podiatric realm. Rapid progression of gas gangrene limits treatment options and increases the rate of limb loss. Current treatment protocols include intravenous antibiotics and rapid serial debridements or amputation. New or advanced treatment options are needed to help delay or slow disease progression and increase chances of limb salvage.

Methods: C. perfringens bacteria were grown on agar overnight. They were then placed in Dulbecco’s phosphate-buffered saline. Buprenorphine (0.1mg/kg) and Morphine sulfate (5mg/kg) were diluted with saline and injected subcutaneously into the rear left leg of mice 15 minutes before infection. They were continually injected every four hours with the same suspension. Mice were injected with 50uL of the bacterial cell suspension into the right rear leg. They were then monitored every 30 minutes for 12 hours for signs of infection and tissue necrosis. They were humanely euthanized if toxicity or severe necrosis occurred. All mice were euthanized at the end of the monitoring period.

Results: Results unexpectedly showed that pretreatment of mice with buprenorphine was protective against C. perfringens infection, not C. septicum. Mice had a mean survival of 6.5 hours without pretreatment with opioids and 11.5 hours with pretreatment of Buprenorphine. In those mice pretreated with morphine, it also showed protective properties from clostridial infection with mean survival times of 10.6 hours and 5.4 hours respectively. Testing was then repeated with the infection allowed to progress for 3.5 hours, at which time surviving mice were then injected with Buprenorphine. Mean survival times were 9.8 hours with opioid treatment, compared to 4.8 hours without treatment, confirming protective properties of opioid treatment after infection progression.
 
Conclusion: Buprenorphine appears to alter the balance of cellular trafficking by modulating the chemokine and cytokine content of the infected region, thereby allowing effective and efficient bacterial clearance and sustained blood flow. This prevents the establishment of an ischemic environment that fosters the growth of C. Perfringens. Timing appears to be critical in the administration. The drug must reach the site of infection before ischemia and necrosis prevents it from providing these therapeutic effects. Therefore, topical and direct infusion options offer highest yield. This is particularly vital to the field of podiatry, specifically limb salvage situations from gas gangrene infections resulting from Clostridial species. Further studies would be needed to test against other strains of gas causing bacteria.

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