WOUND CLEANING AND WOUND HEALING – A CONCISE REVIEW Robert G. Wilkins1, Kevin E. Minnich2, Martin Unverdorben2 „ 1Healthcare Consulting, Basking Ridge, NJ, USA, 2B.Braun Medical Inc., Allentown, PA, USA Desert Foot 9th Annual high Risk Diabetic Foot Conference „ Arizona Grand Resort, Phoenix, AZ, USA „ November 14, 2012

Background Results & Summary Conclusions

Polyhexanide/Betaine „ Three procedures; debridement, irrigation, and Povidone „ There are very few adequate studies on the cleaning form the basis of standard wound care Options for Wound Cleaning „ Solutions or gels containing 0.1% of the wound cleaning properties of most of the agents „ Povidone iodine preparations are effective and are widely held to improve the healing of „ Efficacy in enhancing wound healing is reported antimicrobial agent polyhexanide and 0.1% of the discussed in this review, and thus insufficient antimicrobial agents, but positive effects on chronic wounds. in a number of ways: time to complete healing or surfactant betaine, are used for wound cleaning evidence of their clinical effects on wound wound healing are not well defined, and percent reduction in wound area at a given time and have been recently shown to enhance healing. ¾ Debridement describes the mechanical systemic iodine absorption may produce point; by the use of surrogate markers such as wound healing. Polyhexanide causes expansion „ With more credible evidence of local toxicity, remov al of dead tiss ue ; clinically significant side-effects. Comprehensive infection or colonization rates; or by the use of and fluidization of negatively charged phospho- consensus opinion rejects the routine use of ¾ Irrigation the application of fluid streams reviews describe the conflicting results of subjective markers such as wound appearance lipid bi-layers, making the bacterial cell in chronic wound care. under pressure to the wound; and multiple animal and human studies assessing or degree of encrustation. Many studies are membrane leak and ultimately causing cell the potential toxicity and the effect on healing „ Recent data suggests that polyhexanide / betaine ¾ Cleaning (also termed “cleansing”) the more small, uncontrolled or anecdotal, and are often death6. Polyhexanide / betaine in concentrations rates associated with povidone iodine may be both effective and non-toxic. gentle application of any fluid to the wound. old: of the 116 studies initially identified only 36 of up to 2µg/mL does not inhibit human preparations12,13. One explanation may be that „ Data from in vitro studies may be indicative but „ Published literature shows that cleaning (31%) had been published in the last five years. keratinocytes7, and, thus, the healthy skin. povidone iodine solutions do not inhibit wound are no proof of clinical efficacy. improves the wound environment and Polyhexanide has a biocompatibility index >1 „ There is a wide range of solutions available to healing in vivo, but many commercially available accelerates healing. Although the cleaning of indicating that tissue toxicity is low. clean a wound. Water and saline have been preparations also include detergents, which do wounds with solutions prevents Polyhexanide / betaine remove coagulated widely used, but are ineffective in reducing the delay wound healing, and the wound must be infection1 it is not well established that irrigating plasma protein deposits more effectively than bio-burd en associ at ed with wound s, and th ei r irrigated with water or saline after use if wounds with antiseptic solutions enhances Ringer’s solution and saline. In a randomized KRfKey References use is not associated with improved wound povidone iodine cleansers with detergent are to wound healing. controlled porcine study, cleaning with healing. Tap (potable) water is as (in)effective as be used14. No studies have shown a statistically polyhexanide was associated with the most rapid sterile saline. such as povidone significant benefit from the use of povidone closure of superficial wounds, significantly iodine, ionized (alone or in an activated iodine in wounds other than burns although 1. Scimeca CL, Bharara M, Fisher TK, Kimbriel H, Mills JL, (p<0.05) reducing the time to closure to 22.9 days Armstrong DG. An update on pharmacological charcoal dressing), , alcohol, acetic pooled data from two studies in the healing of Objective to 24.1 days compared to placebo (Ringer’s interventions for diabetic foot ulcers. Foot Ankle Spec. acid, , and chlorine-based lacerations suggest that povidone iodine might solution)8. 2010 Oct;3(5):285-302. agents such as and N- be superior to saline. chlorotaurine, have also been used in spite of „ Polyhexanide is well tolerated with sensitization 2. Murandu M, Webber MA, Simms MH, Dealey C. Use of „ The objective of this review is to evaluate the granulated sugar therapy in the management of sloughy or their in vitro toxicity to human fibroblasts. rates of about 0.5%. In an open study of ten safety and efficacy of currently available wound necrotic wounds: a ppyilot study. J Wound Care. 2011 patients with chronic wounds who had cleaning agents and their ability to enhance Chlor hex idine, povid one i odi ne and h yd rogen Implications for Clinical Practice May;20(5):206, 208, 210 passim. peroxide have been shown to delay wound previously been treated with saline cleansing, wound healing. „ The efficacy of the various agents for wound 3. Ovington LG. Battling bacteria in wound care. Home healing. There are no adequate studies polyhexanide / betaine cleansing produced cleansing is summarized in Table 1 together with Health Nurse. 2001 Oct;19(10):622-30. improvement in patient quality of life, reduction documenting the efficacy of alcohol, acetic acid the strength of evidence classification. While all in wound odor, exudate, pain and wound size9. 4. Main RC. Should chlorhexidine gluconate be used in or hydrogen peroxide in enhancing wound active agents are effective antimicrobially In a retrospective case-controlled study of 112 wound cleansing? J Wound Care. 2008 Mar;17(3):112-4. healing. effective in vitro, efficacy in enhancing wound Methods patients with chronic leg ulcers, polyhexanide / 5. Atiyeh BS, Dibo SA, Hayek SN. Wound cleansing, topical „ Alternative agents such as tea tree oil have been healing is uncertain. The one exception seems to betaine was compared with cleansing with saline antiseptics and wound healing. Int Wound J. 2009 evaluated in pilot studies, with no success in be polyhexanide / betaine, with several studies Dec;6(6):420-30. or Ringer’s solution10. In a single blind, eliminating resistant Staphylococcus indicating efficacy in enhancing wound healing. „ This review is based on a literature search for randomized, controlled study of 40 patients with 6. Gilliver S: PHMB: a well-tolerated antiseptic with no aureus (MRSA). As well as liquid cleansing Water and electrolyte solutions are ineffective. studies add ress ing c lea nin g of chr oni c w oun ds. chronic leg ulcers polyhexanide / betaine was reported toxic effects. J Wound Care/ ACTIVA Healthcare agents, solids applied to the wound may be 2009;(suppl 2):14. The search was performed in February 2012 at compared with saline cleaning. Follow-up was „ To summarize, some level of effectiveness PubMed using the following terms: Chronic[All effective. In a pilot study application of sugar to regarding wound healing in vivo has only been 7. Wiegand C, Abel M, Kramer A, Müller G, Ruth P, Hipler U- the wound subjectively improved wound healing, restricted to four weeks, after which time no Fields] AND ("wounds and injuries"[MeSH Terms] difference in wound size was observed; however documented for polyhexanide / betaine (1B) and C: Stimulation of proliferation and biocompatibility of in vitro evaluation showed reduced bacterial polihexanide. GMS Krankenhaushyg Interdiszip 2007; OR ("wounds"[All Fields] AND "injuries"[All polyhexanide / betaine patients reported to a lesser degree (2C) for povidone iodine and growth2. Honey is similarly effective. 2:Doc43(2007.12.28). Fields]) OR "wounds and injuries"[All Fields] OR significantly less wound pain, and had silver, which is in line with their anti-microbial 8. Kramer A, Roth B, Müller G, Rudolph P, Klöcker N. "wound"[All Fields]) AND (cleaning[All Fields] significantly lower wound pH values, a factor activity in vitro, while for the remaining OR cleansing[All Fields] OR washing[All Fields]) compounds no positive clinical effects on wound Influence of the antiseptic agents polyhexanide and associated with improved wound healing. octenidine on FL cells and on healing of experimental AND "humans"[MeSH Terms]. Silver, chlorhexidine and 6,11 healing have been demonstrated. Laboratory data showed anti-bacterial effects . superficial aseptic wounds in piglets. A double-blind, One hundred and sixteen papers were found and „ Silver, when ionized, is an effective antimicrobial. randomised, stratified, controlled, parallel-group study. 31 were analyzed in detail following a preliminary HitdtiftibhtdHowever, its duration of action may be shortened Table 1: Summary of Cleaning Agents Skin Pharmaco l Phys io l. 2004 May-Jun; 17(3): 141-6. review. Further relevant papers were cited in by binding to proteins or chloride ions, and there 9. Horrocks A. Prontosan wound irrigation and gel: these 31 publications, and have been included. is no evidence that it accelerates healing3. Cleansing Product Improves Wound Healing Effective Anti-microbial Toxicity in management of chronic wounds. Br J Nurs. 2006 Dec 14- Classification of the evidence of the effect of the Chlorhexidine is available both as a dilute Against Common Wound vitro 2007 Jan 10;15(22):1222, 1224-8. cleaning agents was that proposed by the (0.05%) solution for wound irrigation, and as a 2 Contaminants in vitro 10.Andriessen, AE., Eberlin, T. Assessment of a wound American Association of Chest Physicians Task or 4% skin scrub. The latter is sometimes Acetic Acid Ineffective: 2C1 Effective: 1B1 Toxic: 1B1,15 cleansing solution in the treatment of problem wounds. Force (AACP). Wounds 20(6) 2008: 171-175. inappropriately used for wound care. There is Alcohol Ineffective: 2C1 Effective: 1B5 Toxic: 1B15 some evidence of toxicity and little evidence of 11.Kaehn K. Polihexanide: a safe and highly effective biocide. Chlorhexidine Ineffective: 2C1,4,16 Effective: 1B5 Toxic: 1B1,4,15 efficacy at either concentration4. , Skin Pharmacol Physiol. 2010;23 Suppl:7-16. Hydrogen peroxide Ineffective: 2C1,16 Effective: 1B1 Toxic: 1B1,15,17 Acknowledgements isopropanol and n-propanol are widely used for 12. Kramer SA. Effect of povidone-iodine on wound healing: a surfdiiftidkitiiface disinfection and skin antisepsis; Polyhexanide / betaine Effective: 1B1810181,8,10,18 Effective: 1B56115,6,11 Low Toxicity: review. J Vasc Nurs. 1999 Mar;17(1):17-23. 5,6,19 antimicrobial activity requires a concentration of 1B 13.Khan MN, Naqvi AH. Antiseptics, iodine, povidone iodine „ The authors acknowledge the contributions of Ms. 5 > 50% and ideally in the range 60-90% . Povidone Iodine Effective: 2C1,5,12,13,16,20 Effective: 1B5 Toxic: 2C15 and traumatic wound cleansing. J Tissue Viability. 2006 J.Brown (Nazareth, PA) to this presentation. Saline Ineffective: 1A21,22 Nov;16(4):6-10. „ Dr. Wilkins, Mr. Minnich and Dr. Unverdorben Silver (ionized) Effective: 2C3,23,24 Effective: 1B1,24 Toxic: 2C5,15 14.Goldenheim PD. An appraisal of povidone-iodine and disclose they are employees, received a consulting wound healing. Postgrad Med J. 1993;69 Suppl 3:S97- Sodium hypochlorite Ineffective: 2C1,21,26 Effective: 1B1,21 Toxic: 1B1,15,17 fee or honorarium, and/or received payment for 105. writing or reviewing the analysis presented herein Water Ineffective: 1A22 „ Additional references are available upon request. from B. Braun Medical Inc.