3.2.1 Results: pH: clinical studies

An overview of the results for the pH outcomes is presented in Table 2.

TABLE 2. Results for pH—clinical studies Author, year Intervention Comparator Start of Study Outcome Funding Romanelli et al., (2010)4 Polyhexamethylene biguanide (PHMB) and Betaine and for Wound cleanser Saline solution in association with standard wound care

M Median range pH

8. 8.9+/− 0.6

M Median range pH 7.0 7.0 +/− 0.3 in (p (P < .05)

Y Yes

Partially financed by B. Braun Medical AG

Kumar et al., (2015)7 Limited access dressing (LAD) (Negative pressure and moist wound dressing. Dressed daily with 5% povidone-iodine soaked gauze

LAD

Day 0: 8.33 ± 0.35 (mean ± SD)

Conventional dressing

Day 0: 8.31 ± 0.38

LAD

Day 10: 7.5 ± 0.43 (mean ± SD)

Conventional dressing Day 10: 7.9 ± 0.47 (P = .048)

No Agrawa et al. (2017)30 1% Acetic Acid No comparator Start of study pH 9 End of study pH 7 No Rafter et al.,(2017)66 Manuka Honey No comparator Reduction in wound pH at end of study (P < .05)

Yes

Educational grant Advancis Medical.

Strohal et al., (2018),67 Acid oxidising Solution No comparator

Day 0:

pH (9.25 +/− 0.61).

Wound size cm23.06 0.49–32.79 (min/max)

Day 28:

pH (7.68 +/− 0.71) (P = .0001). Wound size cm2.59 0–15.25 (min/max)

(P = .001)

Yes

APR Applied Pharma research

Romanelli et al.,4 conducted a single-blind, single centre, prospective, controlled explorative comparison trial of 40 participants with chronic leg ulcers. This study evaluated the efficacy and tolerability of a wound cleansing solution containing propyl betaine and PHMB to eliminate or reduce bacterial burden. Propyl betaine and PHMB were used to clean wounds and to moisten absorbent wound dressings. The participants were randomised electronically into two groups; In Group A, 20 participants were treated on alternate days with propyl betaine and PHMB cleansing solution, combined with conventional wound care (polyurethane foam and elastic compression); In group B, 20 participants were treated on alternate days with saline solution combined with conventional wound care (polyurethane foam and elastic compression). Thirty-eight participants concluded the study, two participants from the control group were lost to follow-up during treatment. The surface pH was measured using a flat glass electrode connected to a meter (skin pH meter H199181, Hanna Instruments Italy). Wound size was measured with dedicated polarimetry software (Silhouette). Measurements were taken after dressing removal before cleansing. The baseline, median range pH at the wound surface in the group using polyhexamethylene biguanide (PHMB) and betaine was initially 8.9 +/− 0.6. After the 4 weeks, this decreased to 7.0 +/− 0.3. This reduction in pH was statistically significantly lower (P < .05) in the group treated with the active cleanser (PHMB and betaine). The group treated with the PHMB and betaine were reported to have shown significantly better control of the bacterial burden both clinically and by means of instrumental evaluation compared with the control group. However, results for this were not reported in the study.

Kumar and Honnegowda,7 conducted an RCT on the effect of limited access dressing (LAD) on the surface pH of chronic wounds. LAD combines moist wound healing and negative pressure. One hundred and forty patients were randomised into two groups by simple randomization. Limited access dressings combine moist wound healing with negative pressure utilising an intermittent negative pressure regimen of 30 minutes, followed by a 3.5 hours period of rest.7 In the LAD group, 64 participants were treated with intermittent negative pressure. In the control group, 76 participants were treated every day with gauze soaked in 5% povidone-iodine. The wounds were cleaned daily for both groups. The participants were followed up for a period of 10 days. The pH of the wound bed was measured using pH indicator strips MQuant® (Merck). Would size was not measured in this study. Fifty-six participants were lost to follow up or withdrawn from the study; this included 22 participants in the Limited Access Dressing LAD group and 34 participants in the control group. The findings demonstrated that the LAD treated patients exhibited a reduction in the wound pH as compared with those who received a standard dressing (control). On day 0 the wound surface pH was similar for both groups, in the LAD group the mean and standard deviation (mean ± SD) was 8.33 ± 0.35, whereas it was 8.31 ± 0.38 (mean ± SD) for the control group. On day 10, the mean wound surface pH (± SD) in the LAD group was 7.5 ± 0.43 compared with 7.9 ± 0.47 for the control group (standard dressing). At the end of the study, the mean wound surface pH (± SD) in the LAD group was 0.83 ± 0.52 compared with 0.41 ± 0.26 (P = .048) in the control group. The pH was significantly lower (P = .048) in the LAD group.

Agrawal et al.,30 conducted a prospective analysis study, evaluating the topical use of 1% of acetic acid for the treatment of infected wounds. The pH of 1% of acetic acid was 2.5. One hundred participants with infected wounds of mixed aetiologies, including diabetic, trauma, burns venous ulcers, and graft donor sites were treated with topical application of 1% acetic acid. There was no comparator in this study. Normal saline was used to dilute acetic acid to a concentration of 1%. Following the removal of the old dressing, an immersion bath with 0.1% acetic acid was given for 15 minutes to create an acidic environment. Normal saline was then used to cleanse the wounds. A non-adhesive sterile Vaseline gauze was placed on the wound, then a gauze soaked in 1% acetic acid solution was placed over this covered with a sterile dressing. Wounds were dressed daily, or on alternate days, for a period of seven to 21 days. During the study period, the patients received no systemic antibiotics. The pH of the wound bed was measured using paper strips. For each wound, a wound swab was collected before commencing acetic acid (1%) and subsequently on day 3, 7, 10, and 14. Wounds were assessed clinically for the amount of discharge, odour, wound size, and quality of granulation tissue. The average pH of infected wounds at the start of the study was alkaline at pH 9.0, the pH decreased with improved granulation tissue to pH 7.0. Whereas, infected wounds were alkaline (pH 9). There was a reported decrease in wound size, inflammation, and induration after treatment with acetic acid, suggestive of wound healing; however, these results were not shown. It is unclear in the study if the pH remained consistently low between dressing changes as measurements are not shown.

Rafter et al.,66 conducted a clinical evaluation study of 100% medical grade Manuka honey for chronic wounds. Twenty-two participants with a total of 40 chronic wounds were recruited for this study. The type of wounds varied and included pressure ulcers, diabetic foot ulcers, leg ulcers, wounds caused by trauma, and surgical wounds. The Manuka honey dressing was used as a primary dressing with a superabsorbent secondary dressing. The patients were followed over a period of 8 weeks. The participants had their dressing changed on alternate days, the tissue viability nurse consultant performed an assessment of the wound and dressing change once weekly on days 1, 7, 14, 28, 35, 42, 49, and 56. Inpatients had their wound assessed twice a week to ensure concordance with the regimen. When the patients were discharged home, they had their dressings changed every other day by the district nursing teams. A detailed wound assessment was conducted weekly by the tissue viability nurse consultant. A wound swab (n-108) was taken on days 1, 14, 35, and 49. The pH of the wound bed was measured at every dressing change with a pH indicator strip. The authors were unable to analyse the effectiveness of medical grade Manuka honey on infections as patients were on antibiotics. Results from T-tests indicated that Manuka honey reduced wound pH significantly (P < .05). pH values for different time points were not shown and wound size was not measured.

Strohal et al.,67 conducted a prospective single arm open-label clinical case series. This was a pilot study including 30 participants, investigating the use of acid-oxidising solution (AOS) for chronic leg ulcers. The AOS dressing was applied on each leg ulcer at every dressing change for a period of 35 days. Wounds were dressed daily if critically colonised, and wounds that were not infected were dressed on alternate days. The procedure was as follows; after removal of the old dressing, the ulcers were cleaned with a dry gauze after which, the AOS was sprayed over the entire wound, then after 2 minutes, the ulcers were cleaned again with sterile gauze. The AOS was sprayed again over the entire wound, then a non-adherent dressing that was soaked in the AOS was placed on the wound and a sterile highly absorbent dressing was then applied on top. In addition, all patients with venous leg ulcers were treated with compression therapy. Patients with non-venous ulcers did not receive any additional treatment. There was no comparator in this study. Wound size was measured using digital planimetry software and wound pH was measured using a probe and pH meter.

The ulcers showed a highly alkaline pH (9.25 +/− 0.61) at the start of the study. The mean pH decreased significantly (P < .0001), and over time ulcers demonstrated an almost neutral pH value (7.68 +/− 0.71) by visit 5 (day 28 +/−2). At the onset of the study, the median wound size was 3.06cm2 (0.49–32.79 cm2), the size decreased to a median of 0.59cm2 (0–15.25 cm2) at the end of the study. Notably, the researchers reported that the decreased wound size correlated significantly with the reduced pH value of the wound (r = 0.1957, P = .0108). However, this value (r = 0.1957, P = .0108) is substantially below 0.3 or 0.4 and therefore does not indicate a significant correlation between wound size and pH. The researchers reported that there was a statistically significant correlation between the pH change and the successful control of infection was also detected (r = 0.6960; P < .0001).