Effect of Cannabidiol (CBD) on Random Skin Flap Survival in a Rat Model
Skin flap necrosis can be a serious complication after surgical procedures. Currently, the standard of care for threatened skin includes the application of Nitroglycerin ointment, which can have several adverse effects, including headache, dizziness, and hypotension, which may limit its use in certain patient populations. A safe alternative may be cannabidiol (CBD). Recently, the use of cannabis and opinions regarding its safety and potential therapeutic applications have risen to the forefront of American cultural consciousness. It is imperative for the practicing plastic surgeon to understand the effects of cannabis and its active compounds on their patients. The two major active compounds in cannabis are THC and CBD. THC is responsible for the psychotropic effect, while CBD has many physiologic effects in the cardiovascular, hepatic, and central nervous systems. One result of activation of the CBD1 receptor, by CBD, in vascular endothelium is smooth muscle relaxation, resulting in vasodilatation. To date, there have been several studies, in both human and rats, showing the benefit of Nitroglycerin ointment on skin flap necrosis. However, no studies have examined the effect of CBD on skin flap necrosis. Therefore, we aim to assess the effect of topical CBD on a skin necrosis in a caudally based, random pattern skin flap model in rats.
Methods/Technique
:Thirty adult Sprague Dawley rats were block randomized into three groups (N = 10 for each group): control group, topical CBD group, and topical nitroglycerin group. A previously described 3x10cm caudally based, dorsal, random pattern skin flaps were raised on each rat. A barrier was placed between the raised skin flap and the wound bed to prevent healing of the flap to wound bed as a skin graft. For the rats in the nitroglycerin group, 0.5 inch (7.5mg) of 2% nitroglycerin ointment was applied to the skin flap. For the rats in the CBD group, 0.5 inch (10mg) of CBD ointment was applied to the skin flap. For the rats in the control group, 0.5 inch of unmedicated petroleum jelly was applied to the skin flap. The ointments were applied immediately after flap elevation and daily for five days. Skin necrosis was assessed at postoperative day (POD) 1, 3, 5, and 7. Five blinded evaluators assessed the percent of skin necrosis.
Results/Complications
:Percent skin necrosis was similar between the CBD and nitroglycerin groups on POD 1 (32.0% vs. 30.6%, p=0.971). The CBD group demonstrated non-inferiority to the Nitroglycerin group on POD 3 (51.5% vs. 61.3%, p=0.272), POD 5 (52.4% vs. 69.9%, p=0.070), and POD 7 (52.5% vs. 69.5%, p=0.151).
Conclusion
:With more states moving toward legalization of marijuana for medical and recreational use, surgeons are starting to assess the safety and efficacy of cannabinoids in surgical patients. We observed a nonsignificant lower mean percentage of skin necrosis in the CBD cream group on POD 3, 5, and 7 compared to the nitroglycerin group. With a larger powered sample, we believe that CBD ointment may have a larger effect on skin flap survival in rodents than current standard of care Nitroglycerin. Previous studies have demonstrated vasodilatory effect of CBD on vessels. Our study supports the effectiveness of CBD on skin flap survival. The potential use of CBD in enhancing skin flaps survival without the adverse effects of nitroglycerin (headache, dizziness and, hypotension) is promising.