• 1

    Jupiter DC, Thorud JC, Buckley CJ, et al.: The impact of foot ulceration and amputation on mortality in diabetic patients. I: from ulceration to death, a systematic review. Int Wound J 13: 892, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Thorud JC, Plemmons B, Buckley CJ, et al.: Mortality after nontraumatic major amputation among patients with diabetes and peripheral vascular disease: a systematic review. J Foot Ankle Surg 55: 591, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    American Diabetes Association: Standards of medical care in diabetes—2015 abridged for primary care providers. Clin Diabetes 33: 97, 2015.

  • 4

    Lipsky BA, Aragón-Sánchez J, Diggle M, et al.: IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev 32: 45, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Lipsky BA, Hoey C: Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis 49: 1541, 2009.

  • 6

    Lavery LA, Davis KE, Berriman SJ, et al.: WHS guidelines update: diabetic foot ulcer treatment guidelines. Wound Repair Regen 24: 112, 2016.

  • 7

    Dakin HD: The antiseptic action of hypochlorites: the ancient history of the “new antiseptic”. BMJ 2: 809, 1915.

  • 8

    Coetzee E, Whitelaw A, Kahn D, et al.: The use of topical, un-buffered sodium hypochlorite in the management of burn wound infection. Burns 38: 529, 2012.

  • 9

    Cornwell P, Arnold-Long M, Barss SB, et al.: The use of Dakin’s solution in chronic wounds: a clinical perspective case series. J Wound Ostomy Continence Nurs 37: 94, 2010.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Lindfors J: A comparison of an antimicrobial wound cleanser to normal saline in reduction of bioburden and its effect on wound healing. Ostomy Wound Manage 50: 28, 2004.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Younes NA, Albsoul AM: The DEPA scoring system and its correlation with the healing rate of diabetic foot ulcers. J Foot Ankle Surg 43: 209, 2004.

  • 12

    Jeon BJ, Choi HJ, Kang JS, et al.: Comparison of five systems of classification of diabetic foot ulcers and predictive factors for amputation. Int Wound J 14: 537, 2017.

  • 13

    Monteiro Soares M, Martins Mendes D, Vaz Carneiro A, et al.: Classification systems for lower extremity amputation prediction in subjects with active diabetic foot ulcer: a systematic review and meta analysis. Diabetes Metab Res Rev 30: 610, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Monteiro Soares M, Martins Mendes D, Vaz Carneiro A, et al.: Lower limb amputation following foot ulcers in patients with diabetes: classification systems, external validation and comparative analysis. Diabetes Metab Res Rev 31: 515, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    López-Callejas R, Peña-Eguiluz R, Valencia-Alvarado R, et al.: Alternative method for healing the diabetic foot by means of a plasma needle. Clin Plasma Med 9: 19, 2018.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Daburkar M, Lohar V, Rathore AS, et al.: An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer. J Pharm Bioallied Sci 6: 205, 2014.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Allison GM, Flanagin E: How ESKD complicates the management of diabetic foot ulcers: the vital role of the dialysis team in prevention, early detection, and support of multidisciplinary treatment to reduce lower extremity amputations. Semin Dial 33: 245, 2020.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Lavery LA, Fulmer J, Shebetka KA, et al.: The efficacy and safety of Grafix for the treatment of chronic diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J 11: 554, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Lipsky BA, Holroyd KJ, Zasloff M: Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream. Clin Infect Dis 47: 1537, 2008.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Gardner SE, Frantz RA, Saltzman CL, et al.: Diagnostic validity of three swab techniques for identifying chronic wound infection. Wound Repair Regen 14: 548, 2006.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Clinical and Laboratory Standards Institute: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Approved Standard, 9th Ed, CLSI document M07-A9, Clinical and Laboratory Standards Institute, Wayne, PA, 2012.

    • Search Google Scholar
    • Export Citation
  • 22

    Clinical and Laboratory Standards Institute: Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria. Approved Standard, CLSI Publication Number M11-A8, Clinical and Laboratory Standards Institute, Wayne, PA, 2012.

    • Search Google Scholar
    • Export Citation
  • 23

    Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing, 23rd Informational Supplement M100-S23, Clinical and Laboratory Standards Institute, Wayne, PA, 2013.

    • Search Google Scholar
    • Export Citation
  • 24

    Ceri H, Olson M, Stremick C, et al.: The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol 37: 1771, 1999.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Nen E: Chemical disinfectants and antiseptics—quantitative suspension test for the evaluation of bactericidal activity of chemical disinfectants and antiseptics used in food, industrial, domestic, and institutional areas test method and requirements (phase 2, step1). European Committee for Standardization, Brussels, Belgium, 1997. Available at: https://www.intertek.com/microbiology/en-1276-chemical-disinfectants-bactericidal-activity-testing/. Accessed.September1,2015.

    • Search Google Scholar
    • Export Citation
  • 26

    Rutala WA, Weber DJ; the Healthcare Infection Control Practices Advisory Committee (HICPAC): Guideline for disinfection and sterilization in healthcare facilities. Available at: https://www.cdc.gov/infectioncontrol/pdf/guidelines/disinfection-guidelines-H.pdf. Accessed. September 1, 2015.

    • Search Google Scholar
    • Export Citation
  • 27

    Zhang P, Lu J, Jing Y, et al.: Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Ann Med 49: 106, 2017.

  • 28

    Brownrigg JRW, Hinchliffe RJ, Apelqvist J, et al.: Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review. Diabetes Metab Res Rev 32: 128, 2016.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    AlAyed MY, Younes N, Al-Smady M, et al.: Prevalence of foot ulcers, foot at risk and associated risk factors among Jordanian diabetics. Curr Diabetes Rev 13: 182, 2017.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Wilcox JR, Carter MJ, Covington S: Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA Dermatol 149: 1050, 2013.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Heggers JP, Sazy JA, Stenberg BD, et al.: Bactericidal and wound-healing properties of sodium hypochlorite solutions: the 1991 Lindberg Award. J Burn Care Rehabil 12: 420, 1991.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Hidalgo E, Bartolome R, Dominguez C: Cytotoxicity mechanisms of sodium hypochlorite in cultured human dermal fibroblasts and its bactericidal effectiveness. Chem Biol Interact 139: 265, 2002.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Heling I, Rotstein I, Dinur T, et al.: Bactericidal and cytotoxic effects of sodium hypochlorite and sodium dichloroisocyanurate solutions in vitro. J Endod 27: 278, 2001.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Bowler PG: The 10(5) bacterial growth guideline: reassessing its clinical relevance in wound healing. Ostomy Wound Manage 49: 44, 2003.

    • Search Google Scholar
    • Export Citation
  • 35

    Gardner SE, Frantz RA: Wound bioburden and infection-related complications in diabetic foot ulcers. Biol Res Nurs 10: 44, 2008.

  • 36

    Abbas M, Uçkay I, Lipsky BA: In diabetic foot infections antibiotics are to treat infection, not to heal wounds. Expert Opin Pharmacother 16: 821, 2015.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Leaper DJ, Schultz G, Carville K, et al.: Extending the TIME concept: what have we learned in the past 10 years? Int Wound J 9: 1, 2012.

  • 38

    Duarte B, Formiga A, Neves J: Dakin’s solution in the treatment of severe diabetic foot infections. Int Wound J 17: 277, 2020.

Effect of Diluted Dakin’s Solution Versus Standard Care on Diabetic Foot Ulcer Management: A Randomized Controlled Trial

View More View Less
  • 1 Department of Clinical Pharmacy, School of Pharmacy, Zarqa University, Zarqa, Jordan.
  • | 2 School of Pharmacy, The University of Jordan, Amman, Jordan.
  • | 3 School of Medicine, The University of Jordan, Amman, Jordan.
Restricted access

Background: Diabetic foot ulcers (DFUs) are the main cause of hospitalizations and amputations in diabetic patients. Failure of standard foot care is the most important cause of impaired DFU healing. Dakin’s solution (DS) is a promising broad-spectrum bactericidal antiseptic for management of DFUs. Studies investigating the efficacy of using DS on the healing process of DFUs are scarce. Accordingly, this is the first evidence-based, randomized, controlled trial conducted to evaluate the effect of using diluted DS compared with the standard care in the management of infected DFUs.

Methods: A randomized controlled trial was conducted to assess the efficacy of DS in the management of infected DFUs. Patients were distributed randomly to the control group (DFUs irrigated with normal saline) or the intervention group (DFUs irrigated with 0.1% DS). Patients were followed for at least 24 weeks for healing, reinfection, or amputations. In vitro antimicrobial testing on DS was performed, including determination of its minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, minimum biofilm eradication concentration, and suspension test.

Results: Replacing normal saline irrigation in DFU standard care with 0.1% DS followed by soaking the ulcer with commercial sodium hypochlorite (0.08%) after patient discharge significantly improved ulcer healing (P < .001) and decreased the number of amputations and hospitalizations (P < .001). The endpoint of death from any cause (risk ratio, 0.13; P = .029) and the amputation rate (risk ratio, 0.27; P < .001) were also significantly reduced. The effect on ulcer closure (OR, 11.9; P < .001) was significantly enhanced in comparison with the control group. Moreover, DS irrigation for inpatients significantly decreased bacterial load (P < .001). The highest values for the in-vitro analysis of DS were as follows: minimum inhibitory concentration (MIC), 1.44%; minimum bactericidal concentration (MBC), 1.44%; minimum biofilm inhibitory concentration (MBIC), 2.16%; and minimum biofilm eradication concentration (MBEC), 2.87%.

Conclusions: Compared with standard care, diluted DS (0.1%) was more effective in the management of infected DFUs. Dakin’s solution (0.1%) irrigation with debridement followed by standard care is a promising method in the management of infected DFUs.

Corresponding author: Amal G. Al-Bakri, PhD, Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, The University of Jordan, Amman 11942, Jordan. (E-mail: agbakri@ju.edu.jo)