Successful Cold Atmospheric Plasma as Adjunctive Chronic Wound Therapy: A Case Report and Literature Review

Summary:

Cold atmospheric plasma, a novel therapeutic modality, has demonstrated promising effects in promoting wound healing through its antimicrobial, inflammation-modulating, and pro-angiogenic properties. However, its clinical application in wound management remains limited. We present the case of a 52-year-old woman with extensive third- to fourth-degree burns, complicated by a chronic postoperative wound secondary to flap necrosis following reconstructive surgery, and persistent infection despite standard wound care and antibiotic therapy. She underwent 2 courses of cold atmospheric plasma treatment, totaling 19 sessions, in conjunction with standard management. The treatment resulted in successful wound healing and eradication of the bacterial infection without adverse effects. This case highlighted the potential of cold atmospheric plasma as a safe and effective adjunctive therapy for chronic, difficult-to-heal wounds with infection, warranting further investigation to establish its role in clinical practice.

Burn injuries are a prevalent trauma requiring prolonged intensive care, including extended hospitalizations, reconstructive procedures, and frequent follow-up. Flap necrosis remains a challenging complication in reconstructive procedures.¹ Additionally, wound infection can markedly impair healing; therefore, bactericidal agents that eliminate bacteria without cytotoxicity would benefit wound recovery. Wound healing involves 3 overlapping phases: inflammation, re-epithelialization, and remodeling.² It requires coordinated cellular migration, angiogenesis, and a balance between inflammation and repair.³ Oxidative stress and cytokine dysregulation can disrupt this balance and delay healing.⁴ Therefore, proper wound care is essential to promote tissue repair and prevent infection.

Cold atmospheric plasma (CAP), the fourth state of matter, is a low-temperature, partially ionized gas. In recent decades, CAP has gained attention for its medical applications, including wound healing. The therapeutic mechanism of CAP is primarily driven by the interaction between its active components and the wound microenvironment.² The charged particles in CAP interacting with ambient air generate reactive nitrogen and oxygen species.² These reactive species modulate protein signaling pathways and cellular responses, thereby influencing processes such as cell proliferation, migration, and angiogenesis. In addition, CAP possesses antibacterial properties, promoting wound healing.⁵

Despite its potential, the clinical application of CAP in wound management remains limited, and few studies have investigated CAP in chronic, hard-to-heal wounds with infection. We present a case demonstrating the successful integration of CAP into standard wound care for a chronic wound resulting from flap necrosis, complicated by persistent infection. This study was approved by the institutional review board, and written informed consent was obtained for publication.

CASE PRESENTATION

A 52-year-old woman with absence seizures and catamenial epilepsy sustained a severe burn when her right hand was immersed in a hotpot during a seizure. Examination revealed third- to fourth-degree scald burns involving the entire right hand and second-degree burns above the wrist, totaling about 3% of total body surface area.

The patient underwent a series of interventions during the 3 months following the accident, including debridements, skin and fat grafting, free anterolateral thigh flap transfer, tendon reconstruction, and abdominal flap reconstruction with staged flap division. During hospitalization, partial flap necrosis was observed after reconstruction, accompanied by a wound infection. Wound cultures yielded Klebsiella pneumoniae, for which 1000 mg of intravenous ertapenem was administered once daily for 1 month. After her wound condition stabilized, she was discharged with instructions to perform daily wound dressings using Green Guard and neomycin ointment, along with 500 mg of oral ciprofloxacin 500 mg every 12 hours for 2 weeks. However, at the 2-week outpatient follow-up, no significant improvement was noted. The wound still exhibited necrotic tissue with extensive eschar formation over the thumb and palm region (Fig. 1A, B). Consequently, CAP therapy was initiated to facilitate wound healing and reduce microbial burden. CAP was administered twice weekly using a plasma jet device, with each session lasting 5 minutes at a maintained application distance of 1 cm from the wound site, while standard wound care was continued concurrently. Notably, exudate from the palm and distal thumb was markedly reduced, along with a slight regression in wound size. After 10 sessions of CAP therapy, the patient underwent a scheduled scar release and full-thickness skin graft surgery for further wound closure improvement.

Fig. 1.

Photographs of wound condition before initiating CAP and wound condition after 1-year follow-up. A,C, Palmar site. B,D, Dorsal site.

However, the ulcers failed to improve, and surgical-site cultures consistently yielded K. pneumoniae following the surgical intervention, indicating inadequate wound bed perfusion and persistent infection. A second course of CAP therapy with the same protocol was initiated, in conjunction with ongoing wound care, including 200 mg of oral cefixime every 12 hours administered for 1 month during CAP treatment. Silicone-faced dressings with neomycin ointment were applied starting at the sixth CAP session. After the second course of 9 CAP applications, the ulcerated areas on the distal palm and thumb had contracted markedly, and cultures confirmed eradication of K. pneumoniae. No adverse events occurred, and the wounds remained fully epithelialized at the 1‑year follow-up (Fig. 1C, D).

DISCUSSION

In our case, CAP shows promise as an adjunctive therapy for chronic wounds complicated by flap necrosis following reconstructive surgery and persistent infection. CAP has antioxidant properties that modulate the redox state, mitigating oxidative stress and promoting healing.^2,5 It modulates inflammation by increasing interleukin-17 levels, promoting cell differentiation and the secretion of various cytokines.^4,6 The expression of cytokines including interleukin-1β and tumor necrosis factor-alpha increased, leading to the recruitment of neutrophils and macrophages to the injury site.⁴ These reactive species signals stimulated nitric oxide synthesis from fibroblast cells and macrophages in the nitrate-nitrite pathway, correlating with angiogenesis and epithelialization processes,¹ and finally enhanced wound healing. We reviewed previously reported mechanisms of CAP,^2–4,6–9 which may have been key factors contributing to successful healing, especially given the initially poor wound bed perfusion. (See table, Supplemental Digital Content 1, which displays a review of the CAP mechanism, https://links.lww.com/PRSGO/E657.)

CAP reduced bacterial load without damaging healthy tissue, and K. pneumoniae could be effectively inactivated with a 3-minute treatment using dielectric barrier discharge plasma, a different type of technique for generating CAP.¹⁰ The antibacterial effects involved reactive species generation, charging, and membrane permeabilization.¹⁰ CAP was unlikely to induce microbial resistance due to the direct effect on the bacteria’s natural environment and the complex chemical and physical diversity of plasmas. In our case, combining CAP with antibiotics successfully eradicated the K. pneumonia infection. No adverse effects were observed, consistent with previous clinical findings.⁵

CAP devices are relatively accessible through medical equipment suppliers in Taiwan. Their availability may vary internationally and across institutions. In our center, CAP treatment can be delivered in the outpatient setting, thereby avoiding prolonged hospitalization and potentially offsetting treatment expenses associated with repeated debridements or extended antibiotic use.

The limitation of this study is the single-case design without a control group, making it difficult to draw definitive conclusions. Further comparative studies are needed to validate CAP’s efficacy.

CONCLUSIONS

This case highlighted CAP as a promising adjunctive therapy for chronic wounds following flap necrosis and persistent infection after burn reconstruction. Its integration into standard care accelerated healing and reduced bacterial burden without adverse effects. Future large-scale studies are needed to confirm CAP’s efficacy and optimize treatment protocols for chronic wound management.

DISCLOSURES

The authors have no financial interest to declare in relation to the content of this article. This study was supported by a grant (No. V114B-004) from Taipei Veterans General Hospital, Taiwan (NSTC 114-2314-B-075-049); a grant from the National Science and Technology Council, Taiwan; and the Medical Scholarship Foundation in memory of Professor Albert Ly-Young Shen, Taiwan.

Supplementary Material

gox-14-e7483-s001.pdf ^{(97.6KB, pdf)}