Diabetic Wound Management With Ozone

7/30/2019 Diabetic Wound Management With Ozone

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Diabetic Wound Management WithOzone

A Key Ingredient is Missing

by Grard V. Sunnen, M.D. March 2007

Continued...

Factors contributing to skin lesions in diabetes:

Circulatory impairment

Arteries and arterioles in chronic diabetes are prone to plaquebuildup (Tesfaye 2005). The precise reason for this phenomenon isstill elusive, yet it is well documented that Type II non-insulindependent diabetes is linked to abnormal blood lipid profiles knownas diabetic dyslipidemia (Goldberg 2004). Low-density lipoproteinsparticles are smaller in size and thus more apt to adhere to vesselwalls, resulting in progressive vascular occlusion (Beckman 2002;Renard 2004). Lowered oxygen and nutrient supplies stress tissueresilience and impair recovery from injury (Chapnick 1996).

Neuropathy

Poorly controlled diabetes is correlated with peripheral nervedysfunction. The mechanisms of diabetic injury to neurons arepoorly understood. Higher blood glucose level seem to promoteoxidative stress in neurons, but much more complex mechanismsare implicated (Tomlinson 2002).

Diabetic neuropathy can involve motor, sensory, and autonomicsystem neurons. Sensory neuron malfunction is translated as lossof feeling, reflex loss, problems with limb position sense, tingling(paresthesias) and pain. Motor impairment shows as muscleweakness. Autonomic neuropathy alters local circulation (Boulton

2004, Bensal 2006).Mechanical stress

Chronic and repeating pressure on the skin compresses dermalarterioles, inhibiting tissue perfusion. Tissue weakness leads toulceration. Ulcers are fertile ground for pathogenicmicroorganisms, and surrounding tissues become prone to


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cellulitis. At times, the ulcer crater reaches the underlying bone,initiating osteomyelitis (Boulton 2000).

Ozone

The oxygen atom exists in nature in several forms: (1) As a free

atomic particle, singlet oxygen (0), it is highly reactive andunstable. (2) Oxygen (02), its most common and stable form, iscolorless as a gas and pale blue as a liquid. (3) Ozone (03), has amolecular weight of 48, a density one and a half times that ofoxygen, and contains a large excess of energy (03 g 3/2 02 + 143KJ/mole). It has a bond angle of 127 3, resonates amongseveral hybrid forms, is distinctly blue as a gas, and dark blue as asolid. (4) 04, a very unstable, rare, nonmagnetic pale blue gasreadily breaks down into two molecules of oxygen.

Ozone, as a triatomic configuration of oxygen, possesses supremeoxidizing power derived from its marked tropism for extractingelectrons from other molecules, simultaneously releasing one of itsown oxygen atoms in the process.

Ozone as a drug

Ozones capacity for inactivating microorganisms has beenincreasingly appreciated since the turn of the last century (Viebahn1999). In the past few decades, ozones action against bacteria,viruses and fungi has sparked keen interest for its use, not only for

purifying water supplies, but also for medical objectives.Ozone/oxygen mixtures exert significant antimicrobial activity. Aswith many medications, however, ozone has a range of action that,in the terminology of pharmacokinetics, is referred to as atherapeutic window (Bocci 2005). Indeed, ozone applied inconcentrations that are too low, has little therapeutic effect.Applied externally in high concentrations, ozone may becomeirritating and tissue-toxic.

Due to ozone's demarcated therapeutic range, ozone

concentrations administered to the patient need to be carefullycalibrated and controlled. Optimally therapeutic ozone/oxygenmixtures require state of the art quantitative (dosage,concentration), as well as qualitative (purity) controls currentlyavailable in contemporary ozone generation technologies, allpredicated upon the evaluation of the lesions under treatment.

Ozone generation and administration


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Ozone is a gas with a half-life of approximately one hour at roomtemperature. Medical ozone generation and delivery systemstherefore require that ozone be created at the moment it is to beadministered. Ozone, in this sense is not a drug that has a shelf

life enabling it to be kept for long periods of time.Ozone is created by applying energy to oxygen. The oxygen sourceshould be pure and devoid of nitrogen or other impurities. Thepresence of too much nitrogen favors the production of tissue-toxicnitrogen oxides.

Importantly, the humidity level of the ozone/oxygen mixtureenters into the treatment protocol. Indeed, in certain wounds,humidity added to the ozone/oxygen mixture, markedly enhancestherapeutic results.

Ozones actions on wound pathogensBacteria fare poorly when exposed to ozone, a fact appreciatedsince the 19th century (Viebahn 1999). Ozone is a stronggermicide needing only micrograms per liter for measurable action.At a concentration of 1 mg per liter of water at 1C, ozone rapidlyinactivates coliform bacteria, staphylococcus aureus, andAeromonas hydrophilia (Lohr 1984). The inactivation rate for E.coli, takes place in relatively small concentrations of ozone, and isinfluenced by pH and temperature (Ivanova 1983).

At dosage concentrations used in external therapy, ozoneessentially inactivates all bacterial species. This holds true foroxygen-dependent aerobic organisms, for oxygen-independentanaerobic bacteria associated with gangrene, and for facultativespecies that can function with or without oxygen. Spores and cystsare neutralized as well (Ishizaki 1986, Langlais 1986). Spores ofBacillus cereus and Bacillus megaterium are susceptible to ozoneexposure (Broadwater 1973). Ozones universal antibacterial actionmakes it an agent of choice in the management of woundinfections colonized by bacterial species belonging to diverse

groups.

An incomplete list of bacterial families susceptible to ozoneinactivation includes the Enterobacteriaceae, a large group whosenatural habitat is the intestinal tract of mammals. These Gram-negative organisms include Escherichia coli, Salmonella,Enterobacter, Shigella, Klebsiella, Serratia, and Proteus. Other


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ozone-sensitive bacterial species include Streptococci,Staphylococci, Legionella, Pseudomonas, Yersinia, Campylobacteri,and Mycobacteria (Dyas 1983, Broadwater 1973).

The cell envelopes of bacteria are composed of intricate

multilayers. Covering the bacterial cytoplasm to form theinnermost layer of the envelope is the cytoplasmic membrane,made of phospholipids and proteins. Next, a polymeric layer builtwith giant peptidoglycan molecules provides bacteria with a stablearchitecture. In Gram-positive organisms, the pepticoglycan shellis thick and rigid. By contrast, Gram-negative bacteria possess athin pepticoglycan lamella on which is superimposed an outermembrane made of lipoproteins and lipopolysaccharides. In acid-fast bacteria, such as Mycobacterium, up to one half of the capsuleis formed of complex lipids (Parish 2005, Hogg 2005).

The most cited explanation for ozone's bactericidal effects centerson disruption of cell membrane integrity through oxidation of itsphospholipids and lipoproteins. There is evidence for interactionwith proteins as well (Mudd 1969). In one study exploring theeffect of ozone on E. coli, evidence was found for ozone'spenetration through the cell membrane, breaking the closedcircular plasmid DNA, which would presumably diminish theefficiency of bacterial procreation (Ishizaki 1987).

Fungi

Fungi are frequent inhabitants of chronically infected wounds. Onestudy (Moussa 1999) found colonization by Candida andAspergillus. Fungal organisms neutralized by ozone exposureinclude Candida, Aspergillus, Histoplasma, Actinomycoses, andCryptococcus. The multilayered cell walls of fungi, composed ofcarbohydrates, proteins and glycoproteins, contain many disulfidebonds sensitive to ozone oxidation.

Protozoa

Protozoan organisms are often found in chronically infectedwounds. Species disrupted by ozone include Giardia,Cryptosporidium, and free-living amoebas, includingAcanthamoeba, Hartmonella, and Negleria. Several authors havedemonstrated ozones capacity to penetrate through the walls ofGiardia cysts causing fatal structural damage (Widmer 2002,Wickramanayake 1984).


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Ozones cutaneous physiological effects

Oxygen has long been established as beneficial in manypathological conditions, forming the basis for the use of hyperbaricoxygen treatment for carbon monoxide poisoning, decompression

sickness, gas gangrene and stroke, among others. Oxygen underpressure, applied to infected tissues, inhibits the proliferation ofanaerobic bacteria and stimulates local circulation (Wunderlich2000).

Ozone, when added to oxygen, however, has properties thatclearly transcend oxygen administration alone. The two propertiesinvoked are:

1.Ozones extremely broad range of antipathogenic action and,2.The vasodilation of arterioles promoting tissue oxygenation

and the delivery of nutrients and immunological factors tocompromised tissues; and the vasodilation of veins, increasingvenous outflow and the removal of toxins.

Diabetic skin conditions benefited by ozone therapy:

Wounds with a potential for infection

This category addresses wounds that are not yet infected but havea high probability for eventual infection. Post-surgical wounds,injuries such as abrasions, contusions and lacerations are salient

examples.The use of topical ozone therapy in these cases may be solelypreventive, aimed at inhibiting the proliferation of potentiallyinfective organisms. Preventative topical ozone therapy may thusstave off the development of potentially disastrous infectiouscomplications.

Poorly healing wounds

Wounds healing in an indolent manner are apt to regress iftreatment continuity is interrupted.

In these wounds, anaerobic bacteria - bacteria that do not needoxygen for their growth (e.g., Bacteroides, Clostridium) - may beactive at deeper levels of the dermis, insulated from the influenceof oxygen. While anaerobic bacteria are responsible for manydevastating infections including gas gangrene, aerobic bacterianormally found on skin surfaces such as Staphylococcus epidermis,


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Corynebacteria, and Propionobacteria, given propitiouscircumstances, are capable of remarkable aggressive infectivity.

Diabetic leg ulcers

Diabetic ulceration is accelerated by poor circulation and

neuropathy. One study (Anandi 2004) reported bacterial cultureresults for 107 patients with diabetic foot lesions. They included E.coli, Klebsiella, Pseudomonas, Proteus, Enterobacter, Clostridiumperfringens, Bacteroides, Prevotella, and Peptostreptococcus.

The treatment of diabetic ulcers requires a multidisciplinaryapproach, including surgical, topical, and systemic interventionswhen indicated (Cavanagh 2005, Kruse 2006). Topical antibioticsoften fail to penetrate far enough into the wound and frequentlycause secondary dermatitis and allergy in their own right (De

Groot 1994). For this reason, they are not generallyrecommended. Systemic antibiotics, prescribed for infectionstransgressing ulcer borders, can only address a portion of thespectrum of microorganisms cultured from such wounds. Bacterialresistance is common (e.g., -lactam antibiotic resistance, as inmethicillin-resistant staphylococcus).

Ozone applications in diabetic ulcers provide essential dualfunctions of topical broad-spectrum coverage and circulatorystimulation. In addition, ozone, via multiple serial applications andhigher dose ranges, is able to further its penetration into deepertissue layers where anaerobic bacteria are apt to reside.

Gangrene

Gas gangrene, also known as necrotizing fascitis, myositis, andmyonecrosis is feared because of its rapid evolution leading to thegalloping breakdown of affected tissues (Chapnick 1996, Falanga2002)).

Several bacterial species are implicated in this process, the mostcommon being Clostridium and toxin-producing Group A

Streptococcus families. Other bacterial species implicated in gasgangrene include E. coli, Proteus, Staphylococcus, Vibrio,Bacteriodes, and Fusiforms (Caballero 1998). Gas gangrene maybecome a fatal complication of diabetic and decubitus ulcers.

Anaerobic and facultative bacteria feed on sugars and glycogen,produce lactic acid, and gases such as methane, carbon dioxide,


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and hydrogen. Their life threatening toxins cause severe tissuebreakdown, hemolysis, renal failure, and shock.

These impressively destructive wounds demand emergency ozoneapplication as an important adjunct to their multidisciplinary

interventions.The practice of external ozone therapy in diabetic skinlesions

In every case, an individual assessment has to be made relative tothe skin lesion under treatment. Noted in this evaluation are thesize (diameter and depth) of the lesion, and in deeper lesions, theinvolvement of dermal tissues, ligaments, muscle and bone. Also,the presence of purulence and necrosis, the relative health ofsurrounding tissues, and adjacent circulatory competence.

Ozone therapy is always individualized to incorporate these clinicalobservations. Accordingly, ozone concentrations are adjusted, asare lengths and frequencies of treatment, all recalibrated astreatment progresses.

In the practice of external ozone application, a specially designedozone-resistant envelope is used to enclose the area being treated.A precise fitting of the envelope is needed in order to ensure aconstant ozone/oxygen concentration within the envelope milieuand a proper containment of the gas. Ozone will thus be prevented

from escaping into the ambient environment, reducing respiratoryexposure to treating personnel.

The ozone concentrations prescribed during the course oftreatment, the duration and frequency of individual sessions, andthe lengths of the overall course of therapy are all predicated uponthe evolution of the specific medical condition under treatment. Inextensive wet ulcers and burns, for example, initial topical ozoneconcentrations need to be low in order to prevent excessivesystemic ozone absorption. With gradual epitheliazation of theulcer wound, applied ozone concentrations will requirecorresponding adjustments.

Advantages of topical ozone therapy in diabetes

1.The ease of administration of this therapy. Once the principlesof ozone dynamics and the art of adapting ozone dosages andtreatment protocols are mastered by the clinician, topical


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oxygen/ozone therapy can safely be applied to a broad rangeof diabetes-related afflictions.

2.Ozone is an effective antagonist to an enormous range ofpathogenic organisms. In this regard, ozone cannot be

equaled. It inactivates aerobic, facultative, and anaerobicbacterial organisms, a wide spectrum of viruses, and acomprehensive range of fungal and protozoan pathogens. Toreplicate this therapeutic action, ulcerative conditions wouldhave to be treated with an assortment of various systemicantibiotic agents. In the context of accepted contemporarymedical practice, this is not feasible.

3.External ozone therapy, applied in a timely fashion, mayobviate the need for systemic antipathogen therapy, thussaving the patient from all the side effects and organ stresses

this option entails. External ozone is both a preventive, acutecare, and chronic care therapeutic agent.

4.External ozone application to superficial tissues whose bloodsupply is reduced enhances tissue blood and oxygen perfusion.

5.There is evidence that ozone, via its oxidizing properties,inactivates bacterial toxins. Toxins, whose function is todestroy tissues, provide bacteria with colonizing advantage.

6.Ozone exerts its anti pan-pathogenic actions through entirelydifferent mechanisms than conventional antibiotic agents. The

latter must be constantly upgraded to surmount pathogenresistance and mutational change. Ozone, on the other hand,presents a direct and powerful oxidative challenge that anyand all pathogens are incapable of circumventing.

7.Externally applied ozone/oxygen mixtures are entirelycompatible with systemically administered antibiotics, as theyare with debridement and other local wound care procedures.

Disadvantages of topical ozone therapy in diabetes

1. Ozone/oxygen mixtures are not transportable and need to becreated at the site and time of administration.

2. Ozone/oxygen mixtures need to be administered serially in diabetic wounds.This may translate, in many circumstances, to daily applications until the lesion

resolves.


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3. Ozone/oxygen mixtures, applied externally, have limited penetrability. Whilethey possess panpathogenic power on ulcer surfaces, their therapeutic action

has limited range at greater depths of ulcer boundaries.

Conclusions

Topical ozone/oxygen therapy has shown effectiveness and safetyin healing diabetic skin afflictions. In this article, the following arecited: Wounds with potential for infection, infected wounds, poorlyhealing wounds, diabetic leg ulcers, decubitus ulcers andgangrene.

Ozone possesses unique physico-chemical attributes enabling it toexert potent antipathogenic activity. Applied to the adjunctivetreatment and management of diabetic leg lesions, ozone can tipthe balance from chronic failure to resolution. There is one crucial

element missing from contemporary therapeutic regimens fordiabetic skin lesions: Ozone

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Diabetic Wound Management With Ozone