Methodological aspects of dose calculations in transdermal carbon dioxide therapy: estimation of absorbed dose and confirmation of systemic distribution

Abstract

Carbon dioxide (CO2) gas is well characterized for medical applications. It is a chemically stable, biocompatible agent that has a long history of traditional use (in natural “mofettes”) particularly in Hungary, as a natural infallible remedy. Medical CO2 gas has been widely used in various area of medicine, mostly in surgical laparoscopy and endoscopic procedures in gastroenterology as an insufflation gas, since it is considered as an inert gas without side effects and the residuals easily absorbed in vascular tissues. On the other hand, the scope of intended use in case of transdermal or intradermal application is substantially different. Based on its primary mechanism of action carbon dioxide along with some other metabolites can cause prompt vasodilation of precapillary sphincters of blood vessels, and consequently a reduction of peripheral resistance and an increase the flow of microcirculation in tissues. Additionally, an increase in perivascular partial oxygen pressure in tissues (tcPO2) has been detected, because of a shift on the oxyhemoglobin dissociation curve, which resulted in an overall enhancement of oxygenation for cells. Scientific literature revealed some other aspects of physiology during transdermal CO2 gas administration, mainly in the field of microcirculation and tissue oxygenation. In this report we confirm the rate of absorption and the systemic elimination and highlight the principles of calculation for distribution and dosing utilizing the methodology of stable isotope ratio analysis. All these data may provide at least one further step supporting the use of carbon dioxide as an effective, non-invasive, convenient therapy. For the future this low-cost treatment option can be considered either (i) as a therapy with a reasonable cost-effectiveness ratio; or (ii) as an adjuvant therapy in rehabilitation with significant increase in quality of life for patients, alternatively (iii) as a prevention transdermal CO2 may provide a safe method for public access with a potential health benefit and reducing the symptoms of arterial and venous disease development.