Cold atmospheric plasma therapy improves wound healing in diabetic foot ulcers

The application of cold atmospheric plasma (CAP) therapy to diabetic foot ulcers (DFUs) led to significant acceleration of wound healing process compared with placebo treatment, the German KaltplasmaWund trial has shown.

A common complication of diabetes, DFUs entail increased risk of hospitalization, lower limb amputation, quality of life impairment, and death. [Lancet 2005;366:1719-1724; Int J Mol Sci 2016;17:917; Diabet Med 2020;37:211-218] “CAP therapy resulted in beneficial effects in chronic wound treatment in terms of wound surface reduction … [This] could potentially result in earlier transition to ambulatory treatment and discharge from the hospital,” said the researchers.

DFUs were classified according to the combined Wagner-Armstrong scale – patients with superficial or infected (but without signs of ischemia) DFUs extending to tendons/articular capsules were eligible. A patient with ≥1 wound could participate. Sixty-five DFUs from 45 participants (mean age 68.5 years) were randomized 1:1 to eight applications of either CAP therapy generated from argon gas in an atmospheric pressure plasma jet, or standard placebo treatment. [JAMA Network Open 2020;doi:10.1001/jamanetworkopen.2020.10411]

Wound healing rate was more pronounced with CAP vs placebo in terms of total mean area reduction (remaining wound area, 30.5 percent vs 55.2 percent; p=0.03).

However, no significant difference was observed in terms of reduction of infection and microbial load between CAP and placebo (53 percent vs 50 percent; p=0.59). Even after limiting to wounds with an area of at least 1 cm², the difference in microbial load reduction was not significant (−1.16 vs −0.42; p=0.18).

This effect could be attributed to procedural issues such as regular wound debridement, local disinfection, off-loading, moist wound care, and if indicated, systemic antibiotic treatment, noted the researchers. “All wounds received [these] standard wound care procedures [which] may account for the microbial reduction seen in both groups and may dilute the CAP effect on microbial load.”

Taken together, these outcomes signify that CAP exerts its wound healing benefits independently from bacterial load reduction, they said. “These results support the hypothesis that CAP effects do not primarily rely on antimicrobial effects, but directly activate quiescent chronic wounds.”

There was a comparable distribution of expected adverse events (AEs; ie, skin irritation, scar formation, proliferation, and bleeding) between CAP and placebo (n=7 and 6). Despite two severe unexpected AEs (aortic valve stenosis and cardiopulmonary resuscitation), these were unrelated to the procedures and resolved immediately.

Overall, the findings are clinically relevant to both patients and healthcare professionals. “Turning a chronic wound into a healing wound with the application of CAP may be associated with the duration of hospitalization,” they said. Also, CAP does not need to be performed in specialized centres.

It is also imperative to underscore the importance of early assessment and treatment of DFUs, noted the researchers. “The earlier that the chronic status of a wound can be resolved, the more efficiently wound therapy can be applied, and wound closure can be achieved.”

Follow-up is underway for at least 5 years to establish long-term data on the durability and safety of CAP therapy, they added. Future trials evaluating antimicrobial effects should also look into recolonization, as this might have limited the current findings.