Pearls for Practice: The Influence of pH on Chronic Wound Healing and the Antimicrobial Activity of Chlorine

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Lawton A. Seal, PhD; and Martin C. Robson, MD Robson Research Consultants, Inc, Stuart, Florida

An ever-increasing number of wound cleansers has been developed to remove devitalized tissue, debris, and other noxious materials to effect wound bed preparation.1 Once it was understood that wounds must be cleansed of bacteria as well as debris, wound cleansers often had additional antimicrobial properties. This was especially important in treating traumatic wounds during times of armed conflict. Overwhelming fatal wound sepsis was a major problem following combat wounds during World War I. To attempt to control the problem, a research team was organized that included Henry Dakin, an English chemist, and Alexis Carrel, a French Army surgeon. Dakin wanted a chemical that was as effective as carbolic acid at killing bacteria but less cytotoxic to the wound tissue; he found that sodium hypochlorite at a concentration of 0.5% fulfilled his requirement.2 This became known as Dakin’s solution. The problem was that it had a high pH (~10) and became ineffective when neutralized. It was also extremely unstable, requiring repeated irrigations. 

A decreasing pH from 9 to ~5 is observed in chronic wound and burn healing. For chlorine-based antimicrobials, a pH of 5.0 or less results in enhanced antimicrobial activity that helps control bioburden and further supports the healing processes. The decreasing pH associated with healing and the chlorine-induced reduction in bioburden have a positive impact on wound healing. The contributions and benefits of these properties warrant discussion.

Several studies3-5 confirmed that as chronic wounds and burns heal, wound pH decreases significantly (see Figure 1). In addition to the effects of decreased protease activity and increased oxygen release, reduced toxicity of bacterial end products such as ammonia and enhanced destruction of abnormal collagen in the wound bed have been noted. In addition, an increase in angiogenesis, enhanced macrophage and fibroblast activity (cells that release growth factors), and the control of proteolytic enzymes were observed. Therefore, researchers reported an association between wound pH and healing processes, resulting in the suggestion by Schreml et al3 and Sharpe et al4 that the correlation between pH and wound outcomes could be used as an additional diagnostic tool in support of improved burn or chronic wound therapy (see Figure 2).

In their review of burn wound progression, Sharpe et al4 included 30 burn patients between the ages of 17 and 75 years with burn depths ranging from superficial to full-thickness and a total burn surface area ranging from 0.4% to 4.0%. On admission and at each dressing change, the pH of the wound surface was assessed; both healing and nonhealing wounds were found to decrease in pH with each dressing change. However, the authors noted at the second dressing change that wounds that went on to heal had a significantly lower pH (7.32) in comparison with wounds that failed to heal and required grafting (pH = 7.73; P = .004). The authors concluded that the correlation between pH and burn wound progression could be used as an additional diagnostic tool to predict burn healing. 

Sharpe et al5 and Gethin6 reviewed the effect of pH on the attachment, proliferation, and migration of keratinocytes and fibroblasts in in vivo and ex vivo skin growth models and determined the optimal pH for growth of both keratinocytes and fibroblasts is between 7.2 and 8.3, as noted in granulating wounds. Yet, as these wounds continued the healing process and progressed toward closure, the wound pH decreased to values between 4 and 6.

Nagoba et al7 reviewed 45 published articles using search terms that included acidic environment, surface pH, and wound healing. The studies showed that an acidic environment created by the use of acid helps in wound healing by controlling wound infection, increasing antimicrobial activity, altering protease activity, releasing oxygen, reducing toxicity of bacterial end products, and enhancing epithelialization and angiogenesis. The authors concluded that monitoring wound pH and creating an acidic environment may have additional benefits that positively influence the wound healing process.

Block8 reported pH has the greatest influence on the antimicrobial activity of chlorine in solution. He noted that an increase in pH substantially decreases the biocidal activity of chlorine in solution; it took twice as long for hypochlorite solutions to kill microorganisms when pH increased from 6 to 8. He also documented that decreasing the pH from 9 to 4.4 produced a molecule (hypochlorous acid) that was effective on vegetative cells, bacterial endospores, and yeast. However, as the pH of the chlorinated solution is further lowered, the hypochlorous acid becomes unstable, resulting in a change of the chloride from solution into chlorine gas.9 Therefore, the most expedient and effective way for chlorine solutions to kill microorganism is to maintain a pH in the range of 5.0, as observed for intact skin.

At a pH of approximately 5, the dominate species is hypochlorous acid, which is bactericidal, fungicidal, virucidal, and sporicidal without any reported skin irritation, sensitization, cytotoxicity, oral toxicity, or ocular toxicity.10 The molecule is produced naturally in human neutrophils during the oxidative burst pathway. The function of the neutrophil is to find and phagocytize (ie, destroy) invading microorganisms. Post phagocytosis, hypochlorous acid is transformed into N-chlorotaurine, a molecule that can provide a measure of antimicrobial persistence in situ11 and that serves as a unique and natural antiseptic produced and managed in vivo in the human body.12

It is important to recognize that hypochlorous acid, used by health care professionals for more than 100 years, is being reintroduced and requires education regarding its unique nature and utility. Marketed as Vashe Wound Solution (SteadMed Medical, LLC, Fort Worth, TX), the human-friendly, tissue-friendly pH and enhanced antimicrobial activity of this product lacks the cytotoxicity and related issues associated with the very high pH Dakin’s solution. Vashe Wound Solution, with a pH of 5.1 to 5.5, is a wound cleanser that aids wound bed preparation without damaging wound tissue. 

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References

1. Robson MC. Advancing the science of wound bed preparation for chronic wounds. Ostomy Wound Manage. 2012;58(11):10,12.

2. Dakin HD. The antiseptic action of hypochlorites: the ancient history of the “New Antiseptic.”. Br Med J. 1915;2(7):809–810.

3. Schreml S, Szeimies RM, Karrer S, Heinlin J, Landthaler M, Babilas P. The impact of the pH value on skin integrity and cutaneous wound healing. J Eur Acad Dermatol Venereol. 2010;24(4):373–378.

4. Sharpe JR, Booth S, Jubin K, Jordan N, Lawrence-Watt D, Dheansa B. Progression of wound pH during the course of healing in burns. J Burn Care Res. 2013;3(3):e202–e208.

5. Sharpe JR, Harris KL, Jubin K, Bainbridge NJ, Jordan NR. The effect of pH in modulating skin cell behaviour. Br J Dermatol. 2009;161(3):671–673.

6. Gethin G. The significance of surface pH in chronic wounds. Wounds UK. 2007;3(3):52–56.

7. Nagoba BS, Suryawanshi NM, Wadher B, Selkar S. Acidic environment and wound healing: a review. Wounds. 2015;27(1):5–11.

8. Block SS. Chlorine and chlorine compounds. In: Block SS. Disinfection, Sterilization, and Preservation. 4th ed. Philadelphia, PA: Lea & Febiger; 1991.

9. Wang L, Bassiri M, Najafi R, et al. Hypochlorous acid as a potential wound care agent: Part I. Stabilized hypochlorous acid: a component of the inorganic armamentarium of innate immunity. J Burns Wounds. 2007;6(4):65–79.

10. Puricore Data Set on File: USP 51 Antimicrobial Effectiveness Test, Biocompatibility Data, and Toxicity Data. Data available at: www.realmtx.com.

11. Gottardi W, Nagl M. N-chlorotaurine, a natural antiseptic with outstanding tolerability. J Antimicrob Chemother. 2010;6(3):399–409.

12. Corca-Huber D, Ammann CG, Fille M, Hausdorfer J, Nogler, Nagl M. Biocidal activity of N-chlorotaurine against biofilm-forming bacteria grown on metal disks. Antimicrob Agents Chemother. 2014;58(4):2235–2239.

Pearls for Practice is made possible through the support of SteadMed Medical., LLC, Fort Worth, TX (www.steadmed.com). The opinions and statements of the clinicians providing Pearls for Practice are specific to the respective authors and not necessarily those of SteadMed Medical, OWM, or HMP. This article was not subject to the Ostomy Wound Management peer-review process.