The Effect of Transcutaneous Application Of Gaseous CO2 on Diabetic Chronic Wound Healing—A Double-Blind Randomized Clinical Trial

SLR - February 2022 - Jacob N. Rizkalla

Reference: Macura, M, Ban Frangez, H, Cankar, K, Finžgar, M, Frangez, I. The Effect of Transcutaneous Application Of Gaseous Co2 on Diabetic Chronic Wound Healing—A Double-Blind Randomized Clinical Trial. Int Wound J. 2020; 17: 1607– 1614.

Level of Evidence: Level II

Scientific Literature Review

Reviewed By: Jacob N. Rizkalla, DPM
Residency Program: East Liverpool City Hospital – East Liverpool, OH

Podiatric Relevance: Adequate peripheral blood flow is a well known component for the healing of all lower extremity wounds and diabetes is systemic condition with downstream effects that alter this peripheral flow. While carbon dioxide-rich water bathing is known to be effective in the treatment of peripheral vascular disorder due to its vasodilatory and angiogenic properties it also can negatively alter wound bed moisture levels. In an attempt to gain the benefits of a C02-rich-environment without the drawbacks of excessive moisture, the application of transcutaneous gaseous CO2 has been posited as an alternative treatment modality. The reviewed study below aimed to evaluate its effect on the healing of chronic diabetic wounds.

Methods: A prospective, randomized, double-blind clinical research study was performed for patients to receive either transcutaneous gaseous C02 or placebo in addition to standard of care treatment - debridement of necrotic tissue, infection control, and maintenance of wound bed moisture. A total of 47 patients with 61 chronic wounds were enrolled. The study’s measurements included wound area and wound volume (measured by 3D scanner), as well as, evaluation of the Falanga wound bed score by a blinded third party. For treatment, the participant’s lower extremities were sealed in a wrap and filled with C02 gas for a 45 minute session. Treatments continued Monday through Friday for a maximum of four weeks (20 therapies) or until the wound was healed, whichever came first.

Results: Initial statistical evaluation showed the study (C02) and placebo (air) groups contained comparable wound areas, volumes and Falanga scores. After treatment concluded, the wound area of the C02 group changed 486 mm² to 35 mm² while the placebo group only changed from 407 mm² to 305 mm². Wound volume followed a similar trend; the C02 group initially measured 1,746 mm³ and finished at 35 mm³ while the placebo group started at 613 mm³ and finished at 438 mm³. Additionally, 20 of the 30 (67 percent) wounds in the study group were completely healed. At final comparison, there was a statistically significant difference in wound area, wound volume and Falanga score between the study and control groups (P =.001). 

Conclusions: Diabetic lower extremity wounds place a large burden on the patient, physician, as well as the healthcare system, so all promising therapies warrant further investigation. The results of this one study show transcutaneous application of gaseous C02 significantly improved the healing of chronic wounds in diabetic patients. Limitations of the study include a lack of information regarding the patient’s overall health habits, problem list, and etiology of their wounds. Additionally, the small sample size and geographical constraints of a single center study lend to the possibility of sampling bias. All of these factors suggest more rigorous, high-powered studies are needed to further evaluate the role transcutaneous gaseous C02 has to play in the treatment of diabetic lower extremity wounds, if any.