Use of Transcutaneous Application of CO2 in Diabetic Foot Pathology

Abstract

In neuropathic foot ulcers, the most prominent finding is the loss of peripheral sensation and is typically seen in diabetic patients. In addition, vasculopathy may lead to foot ulcerations in diabetic patients. CO2 therapy was found to improve chronic wound healing in patients with vascular impairment. It refers to the transcutaneous and subcutaneous application of CO2 as well as CO2 water baths for therapeutic purpose. In the method used, gaseous CO2 is applied transcutaneously using the PVR system®. CO2 is applied by means of a single-use, low-density polyethylene bag which is wrapped around the leg being treated and secured with an elastic strap. The advantages of this method, compared to injecting CO2 into subcutaneous tissue, are non-invasiveness, the absence of pain and protection against infection. Compared to CO2 balneotherapy this approach enables the use of higher CO2 concentrations, application to chronic wound patients and, with appropriate precautionary measures, prevents the increase of CO2 in the surrounding air. Finzgar et al. observed that the transcutaneous application of gaseous CO2 caused a significant increase in the Laser Doppler (LD) flux in cutaneous microcirculation in vivo in humans. The favourable clinical and microcirculatory effects of gaseous CO2 have further been observed in studies of patients with intermittent claudication as well as patients with primary and secondary Raynaud's phenomenon. The reviewed studies suggest that the increased delivery of CO2 to the ulcerated area will cause vasodilation and an increase in blood flow. The improved angiogenesis and oxygenation will result in healing of the chronic wound. This principle may be applied in the treatment of diabetic foot ulceration. Moreover, the effect on blood flow may also be important in preventive and curative treatment of patients with impaired mobility due to organic or functional causes. Further work is needed for the development of therapeutic strategies to optimize CO2 use in diabetic foot patients.

Full text

Use of Transcutaneous Application of CO2 in Diabetic Foot Pathology
Igor Frangez1*, Jure Colnaric1, Danijela Truden2
1Department of Traumatology, University Medical Centre Ljubljana, Zaloška Cesta, Ljubljana, Slovenia
2Center for Peripheral Vascular Rehabilitation, Koprska Ulica, Slovenia
*Corresponding Author: Igor Frangez, Department of Traumatology, University Medical Centre Ljubljana, Zaloška Cesta, Ljubljana, Slovenia, Tel: +386 1 522 3255; E-
mail: ifrangez@gmail.com
Rec Date: Mar 27, 2017; Acc Date: Apr 12, 2017; Pub Date: April 19, 2017
Copyright: © 2016 Frangez I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
In neuropathic foot ulcers, the most prominent finding is the loss of peripheral sensation and is typically seen in
diabetic patients. In addition, vasculopathy may lead to foot ulcerations in diabetic patients. CO2 therapy was found
to improve chronic wound healing in patients with vascular impairment. It refers to the transcutaneous and
subcutaneous application of CO2 as well as CO2 water baths for therapeutic purpose. In the method used, gaseous
CO2 is applied transcutaneously using the PVR system®. CO2 is applied by means of a single-use, low-density
polyethylene bag which is wrapped around the leg being treated and secured with an elastic strap. The advantages
of this method, compared to injecting CO2 into subcutaneous tissue, are non-invasiveness, the absence of pain and
protection against infection. Compared to CO2 balneotherapy this approach enables the use of higher CO2
concentrations, application to chronic wound patients and, with appropriate precautionary measures, prevents the
increase of CO2 in the surrounding air. Finzgar et al. observed that the transcutaneous application of gaseous CO2
caused a significant increase in the Laser Doppler (LD) flux in cutaneous microcirculation in vivo in humans. The
favourable clinical and microcirculatory effects of gaseous CO2 have further been observed in studies of patients
with intermittent claudication as well as patients with primary and secondary Raynaud's phenomenon. The reviewed
studies suggest that the increased delivery of CO2 to the ulcerated area will cause vasodilation and an increase in
blood flow. The improved angiogenesis and oxygenation will result in healing of the chronic wound. This principle
may be applied in the treatment of diabetic foot ulceration. Moreover, the effect on blood flow may also be important
in preventive and curative treatment of patients with impaired mobility due to organic or functional causes. Further
work is needed for the development of therapeutic strategies to optimize CO2 use in diabetic foot patients.
Keywords Carbon dioxide therapy; Microcirculation; Contralateral
limb; Vasculopathy; Polyneuropathy
Introduction
Carbon dioxide therapy refers to the transcutaneous and
subcutaneous application of CO2 as well as CO2 water baths for
therapeutic purposes. CO2 rich water bathing has been used since 1930
and was found to improve chronic wound healing in patients with
vascular impairment. With neuropathic foot ulcers, the most
prominent nding is the loss of peripheral sensation and is typically
seen in diabetic patients. Repeated stress and lack of sensation lead to
trauma, breakdown of overlying tissue and eventual ulceration. At
pressure points, vascular impairment may additionally lead to
ulceration.
One major goal of treatment is to improve microcirculation and
thereby oxygen supply and the transport of metabolic pathway end-
products. e eects of CO2 therapies on skin microcirculation have
been studied in animal models. Duling BR [1] observed increased
microvascular diameter and increased perivascular pO2 at sites of
exposure to a CO2 aqueous solution. e increased diameter was due
to the vasodilatory eect of topical CO2, the phenomenon also known
as active hyperaemia. e increased perivascular pO2 was due to the
eect of CO2 on the oxyhemoglobin dissociation curve. Irie et al. [2]
demonstrated that CO2 immersion induced the production of plasma
vascular endothelial growth factor (VEGF), resulting in no-dependent
angiogenesis associated with the mobilization of endothelial progenitor
cells. Hayashi et al. [3] showed that CO2 immersion increased blood
ow in feet to a much higher extent than plain water and it improved
the limb salvage rate in critical limb ischemia patients without the
option of revascularization. ese results showed the potential role of
topical CO2 in eective adjunctive treatment to prevent diabetic ulcer
exacerbation.
Materials and methods
Gaseous CO2 with 99.995% purity (medical grade) was applied
transcutaneously using the PVR system® (produced by DermaArt Ltd.,
Brezice, Slovenia). e PVR system consists of a compressor, a CO2
level monitoring sensor and a conduit tube for CO2. CO2 was applied
by means of a single-use, low-density, polyethylene bag which was
wrapped around the leg being treated and tightened with an elastic
strap. e 35-minute therapies are performed twice a week over a
period of 5 weeks. e PVR system enables the safe and controlled
application of a high concentration of CO2 to the body. e method of
application is completely safe and prevents any inhalation of CO2. e
device also has an electronic sensor system which constantly monitors
the air quality in the room.
Discussion
Brandi et al. [4] studied the eect of the subcutaneous application of
gaseous CO2 in the treatment of chronic lower limb lesions. Laser
Doppler ux and transcutaneous pO2 were measured in two groups. In
one group, CO2 therapy was used in addition to the standard methods
of treatment for such lesions. e patients in the control group were
Clinical Research on Foot & Ankle Frangez et al., Clin Res Foot Ankle 2017, 5:2
DOI: 10.4172/2329-910X.1000232
Mini Review OMICS International
Clin Res Foot Ankle, an open access journal
ISSN:2329-910X
Volume 5 • Issue 2 • 1000232
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treated using only standard methods. In the group that underwent
subcutaneous treatment with CO2, a signicant increase in tissue
oxygenation values were observed. ey showed progress in healing
and a decrease in size of the injured area.
Finzgar et al. [5] conducted a study of the eect of the
transcutaneous application of gaseous CO2 on cutaneous blood ow in
vivo in humans. e Laser Doppler (LD) ux in cutaneous
microcirculation was measured simultaneously in a group of 33
healthy men during rest and a 35-minute CO2 therapy. One lower limb
of each subject was exposed to gaseous CO2. e contralateral limb
was the control, being exposed to air. e CO2 therapy caused a
statistically signicant increase in the LD ux of the studied extremity,
whereas in the LD ux of the control extremity was not statistically
signicant. Aside from a minor decrease in heart rate, no systemic
eects were found. e LD ux change is most likely an indirect sign of
the successful diusion of CO2 molecules through the skin into
microcirculation and a direct indicator of the vasodilatory eect of
CO2.
Favorable clinical and microcirculatory eects of gaseous CO2 were
further observed in studies of patients with intermittent claudication
[6] and patients with primary and secondary Raynaud's phenomenon
[7]. e same principle is applied in the treatment of diabetic foot
ulceration. e reviewed studies suggest that CO2 therapy can be a safe
outpatient treatment option for patients with chronic wounds [8].
ere are a number of other possible application for CO2 therapy as
well. Indications include intermittent claudication, peripheral artery
disease and arteriolar blood ow occlusion/disorders, diabetic feet,
diabetic vasculopathy and polyneuropathy, and bedsores.
Contraindications include acute pyretic diseases, consumptive diseases
and ulcers, severe hypertension, new cardiac infarctions, aortic and
mitral valve stenosis, severe congenital heart failure, cor pulmonale,
broncho pulmonary diseases accompanied by hypercapnia and acute
inammatory vascular diseases [9].
Conclusion
e reviewed studies suggest that the increased delivery of CO2 to
the ulcerated area results in vasodilation and an increase in blood ow.
e improved angiogenesis and oxygenation enhances the healing of
chronic wounds. is principle may be applied in the treatment of
diabetic foot ulcerations. e eect on blood ow may be important in
the preventive and curative treatment of patients with impaired
mobility due to organic or functional causes. Further work is needed
for the development of therapeutic strategies to optimize CO2 use in
diabetic foot patients.
Refrences
1. Duling BR (1973) Changes in microvascular diameter and
oxygen tension induced by carbon dioxide. Circulation Research
32: 370-376.
2. Irie H, Tatsumi T, Takamiya M, Zen K, Takahashi T, et al. (2005) Carbon
dioxide-rich water bathing enhances collateral blood ow in ischemic
hindlimb via mobilization of endothelial progenitor cells and activation
of NO-cGMP system. Circulation 111: 1534-1539.
3. Hayashi H, Yamada S, Kumada Y, Matsuo H, Toriyama T, et al. (2008)
Immersing feet in carbon dioxide-enriched water prevents expansion and
formation of ischemic ulcers aer surgical revascularization in diabetic
patients with critical limb ischemia. Ann Vasc Dis 1: 111-117.
4. Brandi C, Grimaldi L, isi G, Brafa A, Campa A, et al. (2010) The
role of carbon dioxide therapy in the treatment of chronic
wounds. In Vivo 24: 223-226.
5. Finzgar M, Melik Z, Cankar K (2015) Eect of transcutaneous application
of gaseous carbon dioxide on cutaneous microcirculation. Clin Hemor
Microcir 60: 423-435.
6. Fabry R, Monnet P, Schmidt J, Lusson JR, Carpentier PH, et al. (2009)
Clinical and microcirculatory eects of transcutaneous CO2 therapy in
intermittent claudication. Randomized double-blind clinical trial with a
parallel design. Vasa 38: 213-224.
7. Schmidt J, Monnet P, Normand B, Fabry R (2005) Microcirculatory and
clinical eects of serial percutaneous application of carbon dioxide in
primary and secondary Raynaud's phenomenon. Vasa 34: 93-100.
8. Cankar K, Finzgar M, Melik Z (2014) The effect of
transcutaneous carbon dioxide application on cutaneous
microcirculation. Cardiovasc Res 103: 453-460.
9. http://www.mesotherapyworldwide.com/images/pdf/
Carbon_Dioxide_Bath.pdf.
Citation: Frangez I, Colnaric J, Truden D (2017) Use of Transcutaneous Application of CO2 in Diabetic Foot Pathology. Clin Res Foot Ankle 5:
232. doi:10.4172/2329-910X.1000232
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Clin Res Foot Ankle, an open access journal
ISSN:2329-910X
Volume 5 • Issue 2 • 1000232