The optimization of post-surgical wound healing is an area of utmost importance and interest. In an attempt to mitigate this risk and improve surgical outcomes, multiple topical products continue to be used. Traditionally, this includes both topical antibiotics and antiseptics. Topical antiseptics, including chlorhexidine and povidone-iodine, can have a cytotoxic effect on keratinocytes and may actually impede wound healing as a result. In addition, chlorhexidine in particular can produce both otologic and ocular toxic effects when used on the face. Emerging products, such as hypochlorous in acid, may be a potential alternative to the more commonly used agents, as it has effective antimicrobial actions and minimal adverse effects
Venous Leg Ulcers
1. Bongiovanni (2014). "Effects of Hypochlorous Acid Solutions on Venous Leg Ulcers (VLU):
Experience With 1249 VLUs in 897 Patients." J Am Coll Clin Wound Spec 6(3): 32-37.
“897 patients with 1249 venous leg ulcers were treated with aqueous solutions of hypochlorous acid (HCA) rather than the standard normal saline. This protocol caused all ulcers to close completely. Venous leg ulcer care protocols that clean, debride, pack and dress with hypochlorous acid solutions can reduce the effects of some comorbidities while accelerating healing times”
2. Selkon, Cherry et al. (2006). "Evaluation of hypochlorous acid washes in the treatment of chronic venous leg ulcers." J Wound Care 15(1): 33-37.
“Patients who failed to achieve a 44% reduction in wound size with standard treatment (compression bandaging) received HOCl washes. Of the 20 ulcers, nine (45%) healed and five (25%) reduced in size by over 60%, when treated with HOCL. All patients became free of pain. These findings confirm the clinical efficacy of treating venous leg ulcers with hypochlorous washes. Use of HOCl washes as an adjunctive therapy for recalcitrant venous leg ulcers appreciably increases healing and rapidly relieves pain”
3. Strohal, Mittlbock et al. (2018). "The Management of Critically Colonized and Locally Infected Leg Ulcers with an Acid-Oxidizing Solution: A Pilot Study." Adv Skin Wound Care 31(4): 163-171. “The study authors tested a new acid-oxidizing solution (AOS [Nexodyn]; APR Applied Pharma Research S.A., Balerna, Switzerland) to determine its ancillary antimicrobial properties and potential support for wound healing. In the study, 30 patients with critically colonized or locally infected chronic leg ulcers of any origin were included. Application of the solution was well tolerated, and no adverse events were recorded. In all patients, local infection was overcome, and wound bed pH and wound area decreased significantly. In addition, patient pain levels decreased to a level where interventions were not required after study day 7. In 37% of all patients, a complete resolution of chronic ulcers was achieved by the end of the study period.
“Exit-site infection (ESI), tunnel infection and associated peritonitis are major causes of morbidity and catheter loss in chronic peritoneal dialysis patients. Meticulous exit-site care is vital in preventing ESI. Avoiding trauma to the exit-site and daily cleaning of the exit-site with a dedicated antimicrobial soap is essential for the longevity of the peritoneal dialysis catheter. ESI rates in peritoneal dialysis patients treated with HOCL for the exit-site care are similar or lower”
Managing cavity wounds that cannot be cleaned using standard irrigating solution is challenging. An immunocompromised patient with a horseshoe perianal abscess was selected to represent a heavy infection in cavity wounds. Diluted povidone-iodine was initially used to lavage the wounds, but the fever persisted and the irrigation was painful. Hypochlorous acid was then used to irrigate the wound. One day after administration of the hypochlorous acid, the fever began to subside, suggesting that this solution was able to adequately destroy the infecting microorganisms. The patient rated his pain during this procedure as 2/10. The infection had cleared within 2 weeks, and a swab culture found no microbial growth. The wound volume was reduced by more than 90% after 5 weeks, and final wound closure was achieved after 6 weeks. By comparison, another patient with a horseshoe perianal abscess who underwent traditional irrigation with diluted povidone-iodine and wet-to-dry dressing faced similar problems, but the fever in this case did not subside, and the wound became more complicated. He complained of pain during the irrigation with diluted povidone-iodine, giving the procedure a pain score of 10/10. Wound care was also difficult due to fecal contamination. As a result, the patient had to undergo colostomy to divert feces to the abdomen, thus preventing it from contaminating the wound. Time to final wound closure was 10 weeks. These cases illustrate the effectiveness of hypochlorous acid in dealing with infection in wound cavities. Managing tiny cavity wounds that cannot be reached using conventional equipment is challenging. Although there has been significant development in silver-impregnated dressings, these advanced pads cannot be inserted into 1–2 mm cavities. Irrigating solution, such as normal saline or diluted povidone-iodine, is often used to overcome this hurdle,1 but these common solutions are sometimes not sufficient, and may cause pain or delay healing.2,3
To represent heavy infection in tiny cavity wounds, an immunocompromised patient with a horseshoe perianal abscess was selected. A 42-year-old man came to the hospital with horseshoe perianal abscess (Fig. 1). He had underlying lymphoma and was receiving chemotherapy. After incision and drainage, the wound consisted of a large outer cavity (marked in red) and a tiny inner cavity (marked in yellow), as illustrated in Video 1. (See Video 1 [online], which displays how hypochlorous acid is used to irrigate cavity wounds and its efficacy.) The outer cavity wounds were covered with a hydrofiber with silver (Aquacel Ag+ Extra; Convatec, UK). The secondary dressing was an adhesive sodium carboxymethylcellulose foam dressing (Adhesive Aquacel Foam; Convatec, USA), which has been found to be effective for dressing infected wounds in the perianal area.4Debridement and curettage of the slough and biofilm were performed weekly. A polyacrylate pad with silver matrix (UrgoClean Ag; Urgo Healthcare Product, France) was applied to the wound for 1 day before curettage to ease the process.5 The problem was the tiny cavity wound, which was first irrigated with normal saline and then with diluted povidone-iodine. A swab culture of the wound revealed Escherichia coli. Ceftazidime and metronidazole were administered intravenously. However, at 7 days after the operation, the fever had not yet subsided. In addition, large amounts of exudates were found during irrigation, which implied that the infection had not been adequately managed and that a different approach would be necessary. Hypochlorous acid (Granudacyn, SastoMed GmbH, Germany) was used to irrigate the tiny cavity wound beginning on day 7 after the operation, as shown in Figure 2 and Video 1. It was in a ready-to-use form and thus did not require mixing or dilution. Dry gauze was then used to wipe the excess fluid out of the wound to prevent skin maceration. The hypochlorous acid was left inside the cavity, which was not washed with normal saline. One day after the application of hypochlorous acid (Granudacyn, SastoMed GmbH, Germany), the patient’s fever began to subside, suggesting that this solution was able to adequately destroy the infecting microorganisms, even in this difficult-to-access cavity. The patient rated his pain as 2/10 using a visual analogue scale. The infection had cleared within 2 weeks, and a swab culture found no microbial growth. Wound progression was measured weekly using a three-dimensional wound measurement device (inSight, eKare, Inc., USA), which has been reported to yield high accuracy and provide both inter-rater and intra-rater reliability of >0.99.6,7 The wound volume was reduced by more than 90% after 5 weeks, and final wound closure was achieved after 6 weeks. A comparison is shown in a 60-year-old immunocompetent male patient with a horseshoe perianal abscess, who underwent traditional irrigation with diluted povidone-iodine and was treated using a wet-to-dry dressing. This patient faced similar problems, but his fever did not subside, and the wound became more complicated. His wound was significantly inflamed and extremely sensitive to pain. He complained of the pain caused by irrigation with diluted povidone-iodine, rating it as 10/10 using visual analogue scale. Wound care was also difficult due to feces contamination. As a result, the patient had to undergo colostomy to divert feces to the abdomen, thus preventing it from contaminating the wound. Time to final wound closure was 10 weeks.
Discussion
These two difficult cases illustrate the contrast between standard treatment using diluted povidone-iodine and wet-to-dry dressing and treatment with hypochlorous acid. The standard treatment resulted in colostomy, a prolonged treatment period (10 weeks), and painful irrigation. The patient treated with hypochlorous acid, however, did not require colostomy, had a shorter treatment period (6 weeks), and experienced less pain during irrigation. This clearly illustrates the efficacy of hypochlorous acid. Hypochlorous acid, an antimicrobial substance found in the human body, has the unique ability to kill microorganisms within 1 minute while exhibiting low cytotoxicity to healthy cells.8,9 Once neutrophils are activated, respiratory bursts generate hydrogen peroxide (H2O2), which is then converted to hypochlorous acid (HOCl) in the presence of Cl− and H+.10 It causes cell death through disruption of the cell wall, loss of intracellular contents, oxidation of respiratory components, inhibition of protein synthesis, decreased oxygen uptake, breaks in DNA, and depressed DNA synthesis.8 Although hypochlorous acid is comparable to sodium hypochlorite, which is used as a bleaching agent,9 they differ in that hypochlorous acid is a weak acid and can be dissolved into hydrogen and hypochlorite ions. It remains present in environments where pH ranges from 6.5 to 8.5, but is completely converted to hypochlorite when pH is greater than 8.5.9 This is important because the antibacterial property of hypochlorous acid (HOCl) is much higher than that of hypochlorite ions (OCl−).8,9 Thus, the pH of the wound area should be considered when using hypochlorous acid.
In contrast to other common solutions, saline removes bacteria through the mechanical effect of rinsing and does not have any antibacterial properties. Although povidone-iodine is able to kill bacteria,1 this ability can be hindered by biofilm formation. Moreover, povidone-iodine also inhibits fibroblast growth.2 One study that compared the effectiveness of povidone-iodine to that of hypochlorous acid in terms of wound healing found that povidone-iodine significantly delayed wound healing, while hypochlorous acid did not.8Betaine and 0.1% polyhexanide (Prontosan, B. Braun Medical AG, Switzerland) is another effective solution for diminishing biofilm.11 However, it requires application with gauze for 10–15 min, which might be too long in pain-sensitive areas, and removing the gauze from the wound to disrupt the biofilm can cause the patient further pain.11These disadvantages of the common irrigating solutions make hypochlorous acid’s unique properties of fast action within 1 min and low cytotoxicity serves the difficult cases well.12
Conclusion
Hypochlorous acid is effective in managing infection in wound cavities.
The wound progression was measured weekly using a three-dimensional wound measurement device (inSight, eKare, Inc., USA). The wound volume was reduced by more than 90% after 5 weeks, and final wound closure was achieved after 6 weeks.
The Children's Hospital of The King's Daughters, Norfolk, VA
Problem: Premature infants (<37 wks) have fragile, translucent skin and are sensitive to cleansing agents such as hydrogen peroxide, povidone iodine, Dakins Solution, chlorhexidine, etc.(1). Antibacterials such as silver sulfadiazine cannot be used in infants because of the risk of toxicity. Fungal infections are common related to the high humidity necessary for neonates. Pure hypochlorous acid can remove microorganisms and fungi, is non-cytotoxic, is safe for use around the eyes, ears, mouth, and genitalia, and has been demonstrated to be safe in young children (2). It has not been studied in premature infants.
Methods: Pure hypochlorous acid* was used to treat the skin and wounds on 5 premature infants (<37 weeks gestation). Two of these infants required phototherapy (Bili lights) to control jaundice. Wounds on the patients included rashes, crusting, and open wounds. The hypochlorous acid was used for bathing and temporary wound soaks prior to wound care. No vigorous wiping was used because of diminished cohesion between the epidermis and dermis in the preterm babies (1).
Results: The hypochlorous acid was well-tolerated in all patients and no safety issues arose. The bacterial colonization was controlled and fungal infections did not occur. High humidity was able to be maintained with a decrease of trans-epidermal water loss (TEWL). Skin irritation due to the cleansing did not occur. Bili lights could be used as indicated. Conclusions: Pure hypochlorous acid with no hypochlorite has a pH of 5.1-5.6. This is compatible with the premature infants skin whose pH is 5.6. The reported safety around the eyes, ears, nose, mouth, and genitalia coupled with its lack of cytotoxicity (3) make the agent ideal for use in preterm babies. This series of premature infants demonstrates the safety of pure hypochlorous acid and extends the usage age younger than that previously reported for children
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