Volume 43 Number 1

Clinical question

What is the best available evidence for use of traditional hypochlorite solutions for reducing wound infection and/or improving wound healing?

Summary

Traditional hypochlorites have been used to manage local wound infection since their introduction in the early 1900s¹. Traditional hypochlorite solutions are those that have a high pH varying from 7.5 to 11.8^2-5. In contrast, recently developed hypochlorite solutions are pH-neutral, making them more appropriate for application to healing wound tissue. Level 5 bench research has demonstrated that traditional hypochlorite solutions have anti-bacterial properties;^6-8 however, the effect may be short-lived⁹. Although Level 5 bench research has suggested that traditional hypochlorite solutions are toxic to cells and may delay wound healing,^{6, 8, 10, 11} Level 1 and 2 evidence^{2, 12-16} showed that acceptable healing outcomes can be achieved using traditional hypochlorite solutions, with one study demonstrating superior outcomes compared to an inert solution.¹⁷ Level 1 and 4 evidence^{12, 13, 16-20} indicated that traditional hypochlorite solutions are associated with reduction in signs and symptoms of local wound infection. Level 1 and 2 evidence^{13, 14, 16} showed that topical phenytoin^{13, 16}, honey¹⁴ and nanocrystalline silver gel¹⁶ achieved better outcomes than a traditional hypochlorite solution, and these options could be considered in settings with access. The risk of delaying healing of the wound should be considered in the context of managing local wound infection and reducing the risk of spreading and systemic infection, when alternative less cytotoxic antiseptics are not available in the setting.

Clinical practice recommendations

All recommendations should be applied with consideration to the wound, the person, the health professional and the clinical context.

Sources of evidence: search and appraisal

This summary was conducted using methods published by the Joanna Briggs Institute.^21-23 The summary is based on a literature search combining search terms related to hypochlorites/EUSOL/Dakin’s® solution/Milton® solution and wound infection. Searches were conducted in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed®, Google Scholar and Health Internetwork Access to Research Initiative (Hinari) databases and in the Cochrane Library for evidence conducted in human wounds reporting the use of traditional hypochlorite preparations published to October 2022 in English. Levels of evidence for intervention studies are reported in Table 1.

Table 1. Levels of evidence for clinical studies

Background

Traditional hypochlorites are preparations that occur as a reaction between chlorine and an alkaline salt, most commonly sodium or calcium ^{28, 29}. They typically have a pH from 7.5 up to 11.8.^2-5 Commonly used traditional hypochlorites include household bleach, Dakin’s® solution, Edinburgh University Solution of Lime (EUSOL) and Milton® solution. (N.b., no evidence on the use of Milton® solution for wound healing was identified).

Dakin’s^® solution is a preparation of bleach diluted in distilled water to 0.5% concentration for clinical use. In some reports of its use, traditional Dakin’s^® solution is diluted to half or quarter strength by mixing with additional water¹⁹. The preparation was developed by Henry Dakin on the war fields in France in 1915 to manage wound infection and to improve clinical outcomes for bullet and shrapnel wounds^{28, 30, 31}. Bench research has demonstrated Dakin’s^® solution has action against a range of microorganisms and biofilms, including (but not limited to) S. aureus, C. albicans, E. coli, K. pneumoniae, and P. aeruginosa^{6, 8, 9, 17, 25, 27} (Level 5).

EUSOL solution is made from chlorinated lime (calcium oxide) and boric acid (sodium salts) at a 0.25% concentration^{2, 24, 32, 33}.The solution, which was also developed in the early 1900s, is traditionally used as a debriding agent and to manage infection.^{32, 34}

Traditional hypochlorites are unstable and have a short shelf life.^{29, 34} They have a high pH^2-5, which is associated with impaired wound healing. Both full strength (0.5%) Dakin’s® solution⁸ and half strength (0.25%) Dakin’s® solution⁶ have been reported to be cytotoxic to fibroblasts in laboratory studies, raising concerns that traditional hypochlorites at their full concentration may delay wound healing^{11, 16, 29-31, 34-36}. To address these limitations, hypochlorites are now prepared electro-chemically to produce contemporary hypochlorites referred to as super-oxidised solutions^{29, 37}. Although super-oxidised solutions have a longer shelf-life and a neutral pH, and they appear to have a good safety profile,^{29, 38} they are not universally available. In low resource settings, traditional hypochlorites are still used for managing wound infection^{39, 40}.

Clinical evidence on dakin’s^® solution

Studies reporting clinical outcomes of interest for treatment with traditional Dakin’s® solution are summarised in Table 2.

Table 2. Summary of the evidence for Dakin’s solution

Dakin’s^® solution for promoting wound healing

An RCT¹⁷ at high risk of bias explored the use of Dakin’s® solution for treating infected diabetic foot ulcers (DFUs). Ulcers were surgically debrided on admission and received evidence based DFU care in conjunction with daily 10-minute irrigation with either Dakin’s® solution diluted to 0.1% concentration or normal saline, followed by application of a silver sheet dressing. Treatment was delivered in hospital for at least five days. On discharge, patients cleansed their own wounds every second day by soaking the DFU for 30 minutes in the assigned solution. Treatment continued for at least three months. Approximately 35% of DFUs treated with Dakin’s® solution were totally healed compared to 4% in the control group (odds ratio 11.9, 95% confidence interval 2.53 – 55.5, p < 0.001)¹⁷ (Level 1).

Dakin’s^® solution for treating signs and symptoms of wound infection

In the RCT¹⁷ comparing Dakin’s® solution to normal saline for DFUs, quantitative wound swab analysis showed DFUs treated with Dakin’s solution had a reduction from baseline in microbial load of 1 log cycle or more after five days (statistically significant versus control, p < 0.001). Local wound infection resolved in more DFUs treated with Dakin’s® solution compared to normal saline (35.6% versus 4.4%, p = not reported)¹⁷ (Level 1).

There are numerous case reports^18-20 of infected wounds of various aetiologies that have been successfully treated with regimens that include regular irrigation with Dakin’s® solution. Many of the wounds were reported to be extensive and deep, with exposed ligament and bone and/or necrotising tissue. Wounds were either confirmed or suspected to be colonised with anaerobic bacteria²⁰ or fungal organisms¹⁸. To treat wound odour¹⁹, wound exudate¹⁹ and extensive slough^18-20 (all recognised signs and symptoms of local wound infection⁴¹) wounds were surgically debrided and regularly irrigated with full, half or quarter strength Dakin’s® solution. Many of the regimens also included systemic antibiotics, serial surgical debridement, negative pressure wound therapy and split skin grafting. The cases were reported to achieve resolution of signs and symptoms of local wound infection and development of healthy granulation tissue or complete epithelialisation^18-20 (Level 4).

Clinical evidence on eusol solution

Studies reporting clinical outcomes of interest for treatment with traditional Edinburgh Solution of Lime (EUSOL) solution are summarised in Table 3.

Table 3. Summary of the evidence for EUSOL solution

EUSOL solution for improving wound healing

Five Level 1 studies and one Level 2 study provided evidence on EUSOL for improving healing of wounds of various aetiologies. In the first RCT¹⁴ (32 children with 43 wounds), which was at moderate risk of bias, open wounds (surgically excised pyomyositis abscesses) were packed twice daily with either EUSOL-soaked gauze or honey-soaked gauze. At 3-week follow-up, 55% of the EUSOL-treated abscesses achieved complete healing; compared to the 87% healing rate in the honey group (p < 0.047)¹⁴ (Level 1).

The second RCT,² also at high risk of bias, reported use of EUSOL dressings to treat infected traumatic wounds. In this study, EUSOL was compared with an antibiotic-impregnated collagen granule dressing. At 4-week follow-up, 53.8% of the EUSOL-treated wounds were completely healed, and the remaining wounds had healthy granulation tissue. This was not statistically significantly different from the group treated with collagen granules, of which 69% completely healed, with the remainder achieving healthy granulation (p = 0.416)² (Level 1).

A comparison of EUSOL-soaked gauze to sugar dressings is reported in a third RCT¹² at high risk of bias that was conducted in traumatic, contaminated wounds (n = 50).  After four weeks of daily wound dressings, wounds treated with the EUSOL dressing achieved superior results to the wounds treated with sugar dressings, including wound size reduction (p = 0.0042), achievement of granulation (p = 0.0048) and wound closure rate (p = 0.008)¹² (Level 1).

In a fourth RCT¹³ at high risk of bias, chronic leg ulcers (n = 102) were treated daily with debridement followed by application of either EUSOL or topical phenytoin. Ulcers that achieved uniform granulation were treated with skin grafts. Wound surface area and presence of granulation tissue were evaluated weekly during the 28-day treatment period. The ulcers treated with EUSOL showed a mean reduction in surface area of about 60% over 28 days; this improvement appeared to be inferior to the topical phenytoin group (p = not reported). Although 86% of the ulcers receiving EUSOL achieved healthy granulation by 28 days, this was statistically significantly poorer outcome than the phenytoin group¹³ (Level 1).

The final RCT¹⁵, which was also at high risk of bias, reported a comparison of EUSOL-soaked gauze with a topical silver nitrate (0.01% w/v) liquid for treating pressure injuries (PIs) in people with spinal cord injury (n = 22). The groups were matched for severity of PIs at baseline. All Stage 1 PIs healed within two weeks of treatment. For Stage 2 PIs, those treated with EUSOL decreased in wound size by a mean of 47% after four weeks. For Stage 3 PIs treated with EUSOL, the average reduction in wound area at 4 weeks was 17%, compared with a mean size reduction of 26% for the silver-based treatment (p values = not reported). No Stage 4 PIs healed in the 4-week study duration¹⁵ (Level 1).

In a comparative study,¹⁶ which was at high risk of bias, EUSOL solution was compared to phenytoin powder and nanocrystalline silver gel for promoting healing in DFUs of Wagner grade 1 (superficial ulcer) and grade 2 (deep ulcer). The DFUs were surgically debrided as required and treated for up to four weeks with the assigned topical treatment. At 4-week follow-up, 73.33% of the DFUs treated with EUSOL solution had granulation tissue in the wound bed (p > 0.05). At baseline the mean ulcer size in the EUSOL-treated group was 16.66 cm² ± 7.52 cm², reducing to a mean of 7.7cm² ± 6.65 cm² by the end of four weeks, which may be clinically significant for patients. However, the EUSOL-treated DFUs achieved statistically significantly inferior results compared with those treated with phenytoin powder or nanocrystalline silver gel¹⁶ (Level 2).

EUSOL solution for reducing signs and symptoms of wound infection

Four of the above studies^{2, 12, 13, 16} reported reduction in signs and symptoms that are associated with local wound infection, including wound-associated pain, wound exudate, and a sloughy wound surface.⁴¹

In the study comparing EUSOL to topical phenytoin, the people with EUSOL-treated ulcers reported reduction in severe wound-associated pain and improvement in wound exudate by the second week of treatment¹³. Although the topical phenytoin group had superior outcomes at week two, there was no statistically significant difference by 28 days In the study comparing EUSOL dressings to sugar dressings, fewer wounds treated with EUSOL had a sloughy wound surface (p = 0.0034) and exudate level (p = 0.011) after four weeks.¹² The infected wounds that were treated with EUSOL in the RCT by Shah et. al. (2017) ² showed improvement in wound exudate characteristics by the fourth week of treatment and this was not statistically significantly different (p = 0.24) to the exudate profile of the antibiotic-impregnated collagen granule group² (Level 1).

In the study conducted in DFUs,¹⁶ EUSOL solution was associated with a small reduction in pain after four weeks of treatment (mean pain score reduction of 1.87 ± 1.57 on a five-point visual analogue scale). This was unlikely to be clinically significant.¹⁶ (Level 2).

Considerations for use

Adverse effects reported with traditional hypochlorites

• Contact sensitivity to traditional hypochlorites has been observed in rare cases²⁴ (Level 4).
• Although skin irritation,³⁴ mild pain on application⁹and chemical burns with using the solution at inappropriate concentrations¹⁶ have been associated with traditional hypochlorites, these adverse events were not observed in the studies reported in this evidence summary.

Preparation of solutions in low resource settings

• A 0.5% Dakin’s® solution can be prepared with 25 mL household bleach mixed with 2 teaspoons of baking soda (bicarbonate of soda/sodium bicarbonate) in 1 L of clean water⁴⁰. The solution has a short shelf-life,^{28, 29} and bench research has suggested the solution may provide inadequate antibacterial effect within 24 hours of preparation⁹. Therefore, the solution should be prepared every 24 hours⁴⁰.
• A EUSOL solution can be prepared with 12.5 g sodium hypochlorite (bleaching powder) and 12.5 g of boric acid combined in 1 L of clean, lukewarm water. The solution has a short shelf life and preparation immediately before use is recommended^{2, 24, 32, 33}.

Conflict of interest

The authors declare no conflicts of interest in accordance with International Committee of Medical Journal Editors (ICMJE) standards.

About wham evidence summaries

WHAM evidence summaries are consistent with methodology published in Munn Z, Lockwood C, Moola S. The development and use of evidence summaries for point of care information systems: A streamlined rapid review approach, Worldviews Evid Based Nurs. 2015;12(3):131-8.

Methods are outlined in resources published by the Joanna Briggs Institute^21-23 and on the WHAM Collaborative website: http://WHAMwounds.com.  WHAM evidence summaries undergo peer-review by an international, multidisciplinary Expert Reference Group. WHAM evidence summaries provide a summary of the best available evidence on specific topics and make suggestions that can be used to inform clinical practice. Evidence contained within this summary should be evaluated by appropriately trained professionals with expertise in wound prevention and management, and the evidence should be considered in the context of the individual, the professional, the clinical setting and other relevant clinical information.

Copyright © 2023 Wound Healing and Management Collaborative, Curtin Health Innovations Research Institute, Curtin University

Author(s)

Emily Haesler
PhD P Grad Dip Adv Nurs (Gerontics), BN, FWA
Adjunct Professor, Curtin University, Curtin Health Innovation Research Institute, Wound Healing and Management (WHAM) Collaborative

Keryln Carville
RN PhD STN(Cred) CF FWA
Professor, Silver Chain Group and Curtin University, Curtin Health Innovation Research Institute, Wound Healing and Management (WHAM) Collaborative

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