October 2021

A Case for Hypochlorous Acid Solution as a Replacement for NSS in Wound Hygiene: A Review

By James McGuire DPM, LPT, LPed, FAPWHc; Madeline Hobbs, BA, and Yunkyung Jessica Ho, BA

Given its lack of efficaciousness in decreasing bioburden, normal sterile saline may not be the best solution for this important task.

Chronic hard-to-heal wounds pose a significant burden on both patients and the health care system. Chronic wounds, whether pressure, arterial, venous, or wounds from multiple causes, share certain characteristics, including the presence of biofilms, prolonged inflammation, secondary infection, and delayed healing.1 Patients with chronic wounds have been shown to have a decreased quality of life due to pain, decreased mobility, and withdrawal from social settings due to the presence of odor or exudate.2 The economic burden of these wounds accounted for 1% – 3% of total health care expenditure in 2017, with these costs including, but not limited to, increased wound care materials used, increased consumption of analgesics and antibiotics, outpatient therapy costs, and subsequent amputations.3 Any approach to lessen the psychological and financial burdens of chronic wounds, and decrease wound healing time through the utilization of optimal wound care therapies is welcome.

Normal sterile saline (NSS) cleansing and irrigation have been a staple of wound management for many years. However, a case can be made that NSS is not very efficacious in decreasing wound bioburden or improving healing time, as compared to other wound hygiene solutions.4 This raises the question of whether it would be advantageous to stop using NSS for chronic wounds all together, and whether to replace it with a more effective solution. While there are a multitude of commonly used products on the market currently, hypochlorous acid (HOCl) stands out not only for its antimicrobial properties, but for its success in biofilm reduction and its lack of cytotoxicity to healthy tissue.5-7 This article will review literature discussing the efficacy of NSS versus HOCl in treating wounds, as well as the properties of HOCl that make it an ideal wound hygiene product compared to its competitors, and the differences between various preparations of the solutions.

Wound Hygiene Today

“Wound hygiene” is a term commonly used by health professionals, but there are various interpretations of what this practice embodies. In its commonly used form, “hygiene” is a standard of maintaining daily routines to keep the body free of unwanted germs. For instance, we practice oral hygiene by regularly brushing our teeth to prevent gum disease and cavities, and hand hygiene by washing our hands with an antibacterial soap or hand sanitizer to stop the spread of communicable diseases. These repetitive activities are considered necessary to maintain an enhanced healthy life. The standard practice of our personal hygiene is analogous to “wound hygiene” in a clinical setting. To recognize the need for preventative hygiene for wounds before they progress to the chronic stage is essential. Early hygienic intervention prevents progression along the wound infection continuum, preventing species accumulation and biofilm formation, reducing the chance of local or systemic infection, and inhibiting the generation of resistant species.

Wound cleansing, along with thorough debridement, is essential for bacterial clearance and is a prerequisite for proper wound healing.8,9 The use of wound irrigation rapidly decontaminates the wound, removes necrotic tissues, enhances effectiveness of other advanced healing modalities, and prevents the accumulation of competing biofilms.10 The standard for wound hygiene, what is now referred to as biofilm-based wound care, consists of appropriate wound debridement of nonviable or necrotic tissue, foreign debris, bacterial biofilms, and excess exudate to remove barriers to healing and convert the wound from a chronic to an acute wound surface.11

Bacteria, whether single or multiple species, produce biofilms to increase their chances of survival. Chronic wound biofilms consist of a polymicrobial community of microorganisms that produce a protective polysaccharide extracellular matrix (ECM) to facilitate inter-organism communication and protect the community from environmental stresses and the host’s immune system. Wound debridement and regular hygiene should be performed to remove biofilms that quickly reform within 24 hours after removal.4,11 Leaving biofilms alone allows them to develop pathogenic characteristics due to horizontal gene transfer within the biofilm.12 Frequent debridement allows for the natural healing process to continue uninterrupted and hastens wound closure.8

It is common practice to cleanse the area to be debrided, rinse the area frequently during debridement, and apply a moist wound dressing upon completion. The solution of choice for most clinics is NSS. In wounds with observable secondary signs of biofilm accumulation, an antimicrobial topical or dressing may be applied to prevent reformation of the biofilm. With the advent of biofilm-based wound care and the renewed concept of wound hygiene, clinicians are using more antimicrobial solutions in their protocols. Choices for these solutions and cleansers are based on microbial effectiveness and lack of tissue toxicity. Solution choices include Dakin’s Solution (sodium hypochlorite – NaOCl), polyhexadine/betaine (PHMB), povidone-iodine (PVI), hydrogen peroxide (H2O2), chlorhexidine, surfactants, and hypochlorous acid (HOCl).

Saline Efficacy

The use of NSS as the primary cleansing agent in wound care is one of convention and economics, but new information demonstrates not only the clinical advantages, but the cost-effectiveness, of other solutions. Several sources highlight the efficacy of other various products in comparison to NSS for wound hygiene. Lindfors13 compared the efficacy of NaOCl versus NSS in decreasing bioburden and wound size over 2 months of treatment. After 2 months, wounds treated with NaOCl showed 100% reduction in aerobic bioburden, 86% reduction in anaerobic bioburden, and 33% of the wounds decreased in size. Those treated with NSS showed 33% reduction in aerobic bioburden, 0% reduction in anaerobic bioburden, and 11% of the wounds decreased in size. It is worth noting that 56% of NSS-treated wounds actually increased in size.

Wilkens and Unverdorben5 reviewed several wound care agents in relation to NSS. They highlighted multiple cases showing the inefficacy of NSS in reducing bioburden compared to agents such as PHMB and PVI. PHMB proved to be more effective in removing coagulated plasma protein deposits, reducing wound odor, pain, exudate, size, and healing times in comparison to NSS. When healing open wounds, NSS proved inferior to PVI. Assadian et al14 showed similar results in that hypochlorite/hypochlorous acid, polyhexanide, and PVI solutions showed greater reduction in biofilm burden when compared to 0.9% NSS.

Landmans et al15 discusses the clinical outcome of wound healing with HOCl alone, HOCl plus levofloxacin, and NSS plus levofloxacin. The outcome showed HOCl alone had the highest percentages of success and improvement with wound healing but was not statistically significant compared to HOCl plus levofloxacin. HOCl plus levofloxcain showed a greater reduction in microbial species compared to HOCl alone. Both treatment modalities with HOCl overall showed higher success, cure rate, and lower microbial species than NSS plus levofloxacin. Overall, the authors state that HOCl is an effective adjunct in treatment of diabetic foot ulcers.

NSS has not even shown superiority over regular tap water.16 Data collected on 634 infected wounds that were irrigated with either NSS or tap water showed no significant difference in reduction between the 2 irrigants. Considering these findings, it appears that we would be advised to reevaluate the commonplace use of NSS and that it be replaced with a more efficacious product that is safe and provides greater benefit to the patient.

The efficacy of HOCl has been shown in various settings beyond just diabetic foot ulcers. A literature review by Joachim that compared the use of HOCl versus NSS in various wound care scenarios showed HOCl to be superior in decreasing bacterial burden, odor, pain, local erythema or cellulitis, and reducing hospital stay.17 In another study, patients treated with HOCl-irrigated wounds had a 25% post-operative closure failure and 102 bacterial counts, compared to those with NSS-irrigated wounds, who showed 80% post-operative closure failure and 105 bacterial counts.18

Overall, the ideal wound irrigant should not harm local tissue, should not impede the wound healing process and should effectively reduce microbial infection.4 While HOCl exhibits all of these qualities, NSS exhibits none. Given these characteristics, it is suggested that NSS is not appropriate for wounds that are diagnosed with infection or biofilm formation, or even for wounds at risk of infection.

Tissue Toxicity

HOCl is an ideal wound hygiene agent due to its minimal tissue toxicity. Based on in vitro studies, HOCl exhibits low risk for collateral damage on healthy tissue as compared to alternative agents.19 Wang6 discussed that 0.1% NaOCl has been shown to increase epidermal hyperplasia and inflammatory influx, thus indicating “thermal injury.” Even at doses as low as 0.0025%, NaOCl has been shown to have direct cytotoxicity on wound healing cells such as keratinocytes, fibroblasts, and macrophages, whereas HOCl has not.7 HOCl also proves to have the strongest antimicrobial activity at safe, low doses in comparison to NaOCl and H2O2.6 There have also been no proven signs of HOCl systemic toxicity.6

It has been argued that the literature regarding cytotoxicity of PVI has been deemed low quality, conflicting, and rendered as weak recommendations.5,7 This may lead one to believe that PVI may be a safe alternative as a wound hygiene product. Recent literature though has highlighted PVI toxicity to human cells and most clinicians now avoid prolonged application of the solution. In vitro, PVI has been shown to disrupt migration of skin fibroblasts and keratinocytes in a wound healing assay, whereas HOCl encouraged migration.20 In addition to fibroblasts, PVI has decreased cell survival and migration in human myoblasts and osteoblasts.21 It also has been noted in several studies that wounds treated with HOCl showed greater reduction in periwound erythema, wound size, healing time, and pain compared to those treated with PVI.16,22

PHMB has recently gained acceptance as a wound cleanser. However, in higher concentrations it has been shown to be cytotoxic to human cells.23-25 PHMB was also deemed carcinogenic in 2015 by the Scientific Committee on Consumer Safety (SCCS).26 It is worth noting though that the SCCS stated lower concentrations of the agent are likely safe, and that additional data was needed regarding PHMB’s use outside of cosmetic preservatives.

Microbiocidal Characteristics

Diabetic foot ulcers (DFUs), pressure ulcers (PU), venous leg ulcers (VLU), and surgical site infections (SSIs) are all general classes of chronic wounds.12 Utilization of HOCl in wound therapy as a cleansing agent can decrease the rate of bacterial accumulation and hence biofilm formation by killing off microorganisms that are frequently seen in in these polymicrobial wounds. After being cultured, studies have shown that pathogens identified from these chronic wounds include gram-positive cocci, Staphylococcus aureus being the most common (25.5%), 8% of which were methicillin-resistant Staphylococcus aureus (MRSA) strains. Gram-negative bacteria included 16.3% Enterococcus spp., 17.7% Proteus mirabilis, 14.3% Pseudomonas aeruginosa, and Escherichia coli 9.5%.13 It is estimated that about 60% of DFUs are already infected upon presentation, and that the prevalence of colonization with MRSA is high within diabetic patients due to the incidence of repetitive use of antibiotics.27,28

Regular use of antimicrobial cleansers decreases the risk of biofilm formation due to their ability to kill particularly difficult pathogens such as MRSA, as well as vancomycin-resistant E. faecium and Bacillus anthracis spores.6 HOCl has shown superior kill time compared to other agents by effectively killing E. coli, P. aeruginosa, and S. aureus in under 1 minute, whereas NaOCl and H2O2 were 5 – 15 and 10 minutes, respectively.6 In patients with VLUs, debridement with HOCl-soaked cotton gauze at a maximum of every 36 hours showed decreased bioburden and biofilm formation throughout the healing process.29 In patients with infected DFUs, HOCl application had wounds infection-free after 15 days of treatment when compared to H2O2 and PVI solution. It was noted that HOCl had the ability to kill Candida, Proteus species, and Klebsiella in this 15-day period as well.21 HOCl overall has been recommended as a primary agent for treatment of DFUs due to its strong capability of controlling and decreasing infection.18

HOCl has been highly effective in killing fungal and viral human pathologies, in addition to bacterial challenges.29 Block et al30 highlighted HOCl as a strongly recommended choice of disinfectant against the COVID-19 virus, in addition to a wide range of other microorganisms. Studies have shown HOCl inactivating coronaviruses within 1 – 10 minutes depending on the concentration used.31 HOCl has also been recommended as a fungal prophylaxis agent due its 1 minute, in vitro, 99% kill rate for an array of mold and yeast species.32

Wound Debridement and Healing

HOCl’s characteristics allow it to have a direct increase in wound bed healing. Bongiovanni28 showed that after 15 – 30 seconds of exposure to HOCl, a VLU wound bed would show increased transcutaneous oxygen pressure (TcpO2), signifying capillary dilation and increased perfusion. A review of several trials utilizing HOCl in ulcers showed overall reduction in size, periwound erythema, pain, and an increase in healthy granulation when compared to various other agents, such as PVI.10

The biofilm produced by bacteria impedes wound healing, and thus it is imperative that a successful wound hygiene agent penetrates and eradicates biofilms. It has been shown that prolonged contact time with the wound surface with HOCl increases its effectiveness against biofilms.33,34 Robson33 demonstrated the efficacy of HOCl on dismantling Staphylococcus aureus biofilm with 70% of biofilm polysaccharide and over 90% of biofilm protein removed after 5, 7, and 10 minutes of contact time of HOCl. The Staphylococcus aureus bacteria itself showed a reduction of log6 CFU/cm3 (indicating complete biofilm eradication) after 3, 5, 7, and 10 minutes of exposure to HOCl. Similar results were obtained with an HOCl gel solution in the presence of Psuedomonas aeruginosa biofilm.34

pH of HOCl

Various companies have produced HOCl with different stability and shelf life which appear to be based on proprietary buffering and maintenance of pH. While past literature recommends a more acidic pH for HOCl, recent research leans toward solutions slightly higher on the pH scale. Studies from 2007 have insisted that the ideal pH for maximal HOCl efficacy lies around 3.5 – 5.0.6,35 It was even shown that HOCl, when raised to pH of 4.5, started lacking some of its antimicrobial activity.35 Recent literature, however, states the ideal HOCl pH for bactericidal effects lies between approximately 5.5 – 6.0.7,36,37 It was also noted that a pH of 5.5 for HOCl is more skin-compatible than other chlorinated competitors, such as Dakin’s solution, which is known to irritate the skin with its more alkaline pH (~10.0).7


Hypochlorous acid has also been shown to be a cost-effective wound cleansing alternative. In a study that compared the use of a silver impregnated collagen to the use of hypochlorous on chronic wounds, an 11% reduction in quarterly wound care product cost was seen, along with a 38% reduction in utilization of wound cultures and tests.38 In another study, a wound care regimen that implemented a 5-minute hypochlorous acid soak prior to treatment resulted in a projected annual 85% reduction in cost of wound care products for infection and debridement. Cost savings, based on the findings of the study, were estimated to be $87,696 per year.39 In another study, treating wounds with Santyl™ (Collagenase Santyl, Smith & Nephew, Inc., Fort Worth, TX) alone was compared to wounds cleansed with HOCl and soaked for a short time prior to application before Santyl was applied. A $1,096 decrease in the amount of Santyl purchased per patient, or $420 per wound, was observed.40


Wound hygiene is an essential component in the management of chronic wounds and involves much more than simply cleansing a wound with a non-toxic solution. Hygiene is an entire process of wound bed prep including careful debridement of non-viable materials and biofilm from the wound, as well as proper application of a dressing selected to maintain an optimal wound environment, and facilitate wound healing.41 For many years, NSS has been the solution of choice for this process. After review of the recent literature, it can be said with confidence that utilization of HOCl as a replacement for NSS is of considerable benefit to both the patient and the facilities administering wound care. Stabilized HOCl is a non-toxic, cost-effective wound cleanser with the ability to significantly reduce high tissue bacterial burden on wounds. It has been shown to decrease healing time for chronic wounds such as DFUs, VLUs, and traumatic wounds and be an effective intraoperative irrigant. Aside from its obvious benefits in wound care, the solution has shown several other considerable uses, including, but not limited to, viral disinfectant, antiseptic hand sanitizer, pruritic eye treatment, and skin graft treatment.42 An agent with such a versatile application and clinically proven benefits should be considered for all patients and practices, but specifically for the treatment of hard-to-heal wounds. Future research should include randomized, controlled trials of HOCl use, HOCl effect on bacterial colonization and biofilms, and other chronic wound complications.

James McGuire, DPM, PT, LPed, FAPWHc, is Director of the Leonard S. Abrams Center for Advanced Wound Healing and Professor of Medicine at Temple University School of Podiatric Medicine.

Madeline Hobbs, BA, is a third-year student at Temple University School of Podiatric Medicine.

Yunkyung Jessica Ho, BA, is a fourth year medical student attending Temple University School of Podiatric Medicine in Philadelphia, Pennsylvania. She is part of multiple medical organizations and is currently the president of the student chapter of the American College of Podiatric Medicine (ACPM).


James McGuire reports that he serves as a speaker for Smith & Nephew, Imbed, 3-M, Pure & Clean; receives research support for RedDress, Drexel University; receives product support for Reapplix; and serves as a consultant for NueEsse.

Madeline Hobbs reports no disclosures.

Yunkyung Jessica Ho reports no disclosures.

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