Therapeutic Options For Transdermal CO2

Therapeutic Options For Transdermal CO2

Richard Rivers, M.D., Ph.D
Microvascular Physiologist
Johns Hopkins University
Associate Professor
Baltimore, Maryland

The paper discusses the use of transdermal carbon dioxide and offers a list of resources documenting positive therapeutic outcomes including enhanced endurance, cancer therapy, fractures, and blood flow disorders related to peripheral vascular disease, skin flaps, and Raynaud’s

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Medical therapy through the skin is a well-described practice. Specifically, transdermal applications of patches containing medicine for treating pain, nausea, heart failure, and dementia are commonplace. All these regimens permit the prolonged transfer of drugs into the body, so there is a continuous amount of the drug in the bloodstream. An alternative option for transdermal therapy is to use a gas, instead of a patch. The use of gas is less common due to the difficulty in transporting the gas and administering it in a controlled fashion. A new device is now on the market that will allow providers to offer this new therapeutic option. 

Carbon dioxide gas is the most recent entry into the gas therapy market. Hyperbaric oxygen is probably the best recognized. Carbon dioxide therapy has been around for over one hundred years. It has been identified as one of the most significant therapeutic components of popular natural bath springs. This natural therapeutic option has been the focus of many studies. Studies include those performed in the natural baths, as well as those performed in laboratories using baths with controlled concentrations of carbon dioxide. 

Laboratory studies in animals and humans clearly demonstrate that carbon dioxide will increase tissue blood flow, increase tissue oxygenation, and increase the number of small blood vessels. It should also be noted that carbon dioxide gas is bacteriostatic, which means that bacteria will not grow or multiply in a CO2 environment. This leads to many therapeutic possibilities to treat diseases burdened by poor blood circulation. 

Studies of patients or animals partially immersed in water containing carbon dioxide have shown positive therapeutic effects including: 

  • Reduced fluctuations in blood pressure (calming effect) 16

  • Increased swimming endurance 1

  • Increased oxygenation, blood flow, and blood vessels in ischemic limbs 5,15

Treatment using baths is of limited practical utility because it is so cumbersome. Investigators have therefore looked at other methods for transcutaneous carbon dioxide therapy, namely the use of carbon dioxide gas itself (CO2 GAS). To investigate the therapeutic effect of CO2 GAS, it has been applied in chambers and in plastic reservoirs that enclose limb(s), the lower body, or the entire body of a human or animal. Some of the studies are a case series while others are more controlled studies using placebo controls. I will only discuss studies with appropriate experimental controls. These studies have shown many positive therapeutic responses including: 

  • Reduction of symptoms from peripheral vascular disease including claudication 2,4,10

  • Increased oxygenation, blood flow, and blood vessels in ischemic limbs 5

  • Enhanced endurance 14

  • More rapid healing of fractures 8

  • Suppressed metastasis of oral squamous cell carcinoma 13

  • Induced tumor cell apoptosis and suppressed metastasis 3

  • Improved Raynaud’s disease 11

  • Repaired skeletal muscle 9

  • Increased blood vessel formation in skin flaps for plastic surgery 12

  • Stimulation of immune responses and raised endorphins 7

  • Increased skin blood flow 6

Thus, there are many possibilities for therapeutic use of carbon dioxide gas. Many of these studies have only been performed in small animals, so there is a lot of opportunity for more prospective studies in large animals and humans using the new device from Respiderm. 

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 © 2018 Respiderm Corporation

 References:

 

  1. Akamine T and Taguchi N. Effects of an Artificially Carbonated Bath on Athletic Warm-up. Journal of Human Ergology 27: 22-29, 1998.

  2. Fabry, Monnet, Schmidt, Lusson, Carpentier, Baguet and Dubray. Clinical and microcirculatory effects of transcutaneous CO2 therapy in intermittent claudication. Randomized double-blind clinical trial with a parallel design. Vasa 38: 213-224, 2009.

  3. Harada R, Kawamoto T, Ueha T, Minoda M, Toda M, Onishi Y, Fukase N, Hara H, Sakai Y, Miwa M, Kuroda R, Kurosaka M and Akisue T. Reoxygenation using a novel CO2 therapy decreases the metastatic potential of osteosarcoma cells. Experimental cell research 319: 1988-1997, 2013.

  4. Hartmann BR, Bassenge E, Hartmann M and Hartmann BR. Effects of Serial Percutaneous Application of Carbon Dioxide in Intermittent Claudication: Results of a Controlled Trial. Angiology 48: 957-963, 1997.

  5. Irie H, Tatsumi T, Takamiya M, Zen K, Takahashi T, Azuma A, Tateishi K, Nomura T, Hayashi H, Nakajima N, Okigaki M and Matsubara H. Carbon Dioxide-Rich Water Bathing Enhances Collateral Blood Flow in Ischemic Hindlimb via Mobilization of Endothelial Progenitor Cells and Activation of NO-cGMP System. Circulation 111: 1523-1529, 2005.

  6. Ito T, Moore JI and Koss MC. Topical application of CO2 increases skin blood flow. The Journal of investigative dermatology 93: 259-262, 1989.

  7. Kallistratos E, Toliopoulos I, Fragkoraptis D, Gerou S and Fragkoraptis E. The impact of CO2 dry baths on subpopulations of NK and NK-T lymphocytes, cytotoxic activity, level of inflammation and pain management in elderly with musculoskeletal syndromes - a pilot study. Experimental Medicine 1: 19, 2009.

  8. Koga T, Niikura T, Lee SY, Okumachi E, Ueha T, Iwakura T, Sakai Y, Miwa M, Kuroda R and Kurosaka M. Topical cutaneous CO2 application by means of a novel hydrogel accelerates fracture repair in rats. The Journal of bone and joint surgery. American volume 96: 2077-2084, 2014.

  9. Oe K, Ueha T, Sakai Y, Niikura T, Lee SY, Koh A, Hasegawa T, Tanaka M, Miwa M and Kurosaka M. The effect of transcutaneous application of carbon dioxide (CO 2) on skeletal muscle. Biochemical and Biophysical Research Communications 407: 148-152, 2011.

  10. Savin E, Bailliart O, Bonnin P, Bedu M, Cheynel J, Coudert J and Martineaud J. Vasomotor Effects of Transcutaneous CO2 in Stage II Peripheral Occlusive Arterial Disease. Angiology 46: 785-791, 1995.

  11. Schmidt, Monnet, Normand and Fabry. Microcirculatory and clinical effects of serial percutaneousapplication of carbon dioxide in primary and secondary Raynaud’s phenomenon. Vasa 34: 93-100, 2005.

  12. Sönmez A, Yaman M, Yalçın Ö, Ersoy B, Serin M and Sav A. Carbon dioxide therapy increases capillary formation on random pedicled skin flaps in the rat. Journal of Plastic, Reconstructive & Aesthetic Surgery 62: e237, 2009.

  13. Takeda D, Hasegawa T, Ueha T, Imai Y, Sakakibara A, Minoda M, Kawamoto T, Minamikawa T, Shibuya Y, Akisue T, Sakai Y, Kurosaka M and Komori T. Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo. PloS one 9:e100530, 2014.

  14. Ueha T, Oe K, Miwa M, Hasegawa T, Koh A, Nishimoto H, Lee S, Niikura T, Kurosaka1 M, Kuroda1 R and Sakai1 Y. Increase in carbon dioxide accelerates the performance of endurance exercise in rats. J Physiol Sci DOI: 10.1007/s12576-017-0548-6: 2017.

  15. Xu Y, Elimban V and Dhalla NS. Carbon Dioxide Water-bath Treatment Augments Peripheral Blood Flow through the Development of Angiogenesis. Can J Physiol Pharmacol 2017.

  16. Yamamoto N and Hashimoto M. Immersion in CO2-rich water containing NaCl diminishes bloodpressure fluctuation in anesthetized rats. Int J Biometeorol 52: 109-116, 2007.

Veterinary Transdermal