Wound Cleansing, Topical Antiseptics and Wound Healing Bishara S Atiyeh, Saad a Dibo, Shady N Hayek

ORIGINAL ARTICLE Wound cleansing, topical antiseptics and wound healing Bishara S Atiyeh, Saad A Dibo, Shady N Hayek

Atiyeh BS, Dibo SA, Hayek SN. Wound cleansing, topical antiseptics and wound healing. Int Wound J 2009; 6:420–430

ABSTRACT Quality of care is a critical requirement for wound healing and ‘good’ care of wounds has been synonymous with topical prevention and management of microbial contamination. Topical antiseptics are antimicrobial agents that kill, inhibit or reduce the number of microorganisms and are thought to be essential for wounds infection control. However, they have long and commonly been used on wounds to prevent or treat infection, the merits of antiseptic fluid irrigation have received little scientific study. Unlike antibiotics that act selectively on a specific target, antiseptics have multiple targets and a broader spectrum of activity, which include bacteria, fungi, viruses, protozoa and even prions. Although certain skin and wound cleansers are designed as topical solutions with varying degrees of antimicrobial activity, concerns have been raised. Wound cleansers may affect normal human cells and may be antimitotic adversely affecting normal tissue repair. Repeated and excessive treatment of wounds with antiseptics without proper indications may have negative outcomes or promote a microenvironment similar to those found in chronic wounds. However, when applied at the proper times and concentrations, some classes of antiseptics may provide a tool for the clinician to drive the wound bed in desired directions. The present review summarises the various antiseptics in use and their negative impact on the wound healing mechanisms. It is clear that the role of antiseptics on wounds and their role in wound care management need to be reconsidered. Key words: Wounds • Wound healing • Wound cleansing • Antiseptics • Topical wound management

Key Points INTRODUCTION is capable of causing infection. For this reason, The practice of wound cleansing or antiseptic it is believed that all wounds should undergo • there are no diagnostic tests to management has a dichotomous history some form of cleansing to decrease the bacterial allow health care practitioners anchored in tradition and science (1). It is an inoculum to levels that can be managed by host to identify whether the bacte- integral part of the management of acute trau- defenses (3). The choice of a cleansing agent, rial load in a wound is capable of causing infection matic wounds (2) as well a chronic wounds. however, remains controversial. The use of • it is believed that all wounds Although there is a consensus that wound antiseptics has been especially questioned (2). should undergo some form cleansing reduces infection rates (2) there is, ‘Good’ care of wounds has been syn- of cleansing to decrease the however, evidence to suggest that it is not onymous with topical prevention and man- bacterial inoculum to levels that can be managed by host always necessary (3). There are no diagnostic agement of microbial contamination (4,5). In defenses tests to allow health care practitioners to fact, successful management of the contami- • the ideal topical therapy would identify whether the bacterial load in a wound nated wound must remove contaminants while include periodic reduction of inﬂicting minimal injury to tissues (3). On the bacterial contamination and premise that bacterial reduction translates to a removal of soluble debris with- Authors: BS Atiyeh, MD, FACS, Division Plastic and out adversely impacting cellu- Reconstructive Surgery, American University of Beirut Medical reduced potential for infection (6) and without Center, Beirut, Lebanon; SA Dibo, MD, Department of Surgery, lar activities vital to the wound overlooking the deleterious effects of infection American University of Beirut Medical Center, Beirut, Lebanon; healing process SN Hayek, MD, Division Plastic and Reconstructive Surgery, on wound repair (5), the ideal topical therapy American University of Beirut Medical Center, Beirut, Lebanon would include periodic reduction of bacterial Address for correspondence: BS Atiyeh, MD, FACS, contamination and removal of soluble debris Clinical Professor, Division Plastic and Reconstructive Surgery, American University of Beirut Medical Center, Beirut, Lebanon without adversely impacting cellular activi- E-mail: [email protected] ties vital to the wound healing process (5,7,8).

420 © 2009 The Authors. Journal Compilation © 2009 Blackwell Publishing Ltd and Medicalhelplines.com Inc • International Wound Journal • Vol 6 No 6 Wound cleansing, topical antiseptics and wound healing

With advances in understanding of the wound scrubbing in the operating room and hand healing process strategies that optimise the tis- washing by medical personnel. In clinical Key Points sue repair process beyond the mere fact of just practice, antiseptics are broadly used for both • the ultimate goal of wound controlling surface bacterial contamination, it intact skin and wounds (13). The usefulness of management is to minimise the is now obvious that quality of care is a critical antiseptics on intact skin is well established and risk of opportunistic infection requirement for wound healing and for promo- broadly accepted. However, the use of anti- while promoting the development of healthy granulation tion of healing (5) and that the ultimate goal septics as prophylactic anti-infective agents for tissue and initiate and aid the of wound management is to minimise the risk open wounds, such as lacerations, abrasions, healing process of opportunistic infection while promoting the burns and chronic ulcers, has been an area of • unlike antibiotics that act selec- development of healthy granulation tissue (9) intense controversy for several years. Citing tively on a specific target, anti- and initiate and aid the healing process (10,11). cytotoxicity data, many authors have advised septics have multiple targets and a broader spectrum of Topical antiseptics are antimicrobial agents against their use on open wounds (13). Some activity, which include bacte- that kill, inhibit or reduce the number of mayevencontaindetergents,whichrender ria, fungi, viruses, protozoa and microorganisms and are thought to be essential them too harsh for use on non intact skin (13). even prions for wounds infection control (6,12). However, Although certain skin and wound cleansers • both the lower resistance they have long and commonly been used are designed as topical solutions with vary- rates and allergic risks associated with antiseptic com- on wounds to prevent or treat infection (13), ing degrees of antimicrobial activity, con- pounds lend to their present the merits of antiseptic fluid irrigation have cerns have been raised. Wound cleansers popularity received little scientific study (1). Antiseptics may affect normal human cells and may be • the use of antiseptics as pro- are considered drugs by the Food and Drug antimitotic, adversely affecting normal tissue phylactic anti-infective agents Administration (FDA) and are regulated as repair (4,5,13). Some authors strongly disap- for open wounds, such as lacerations, abrasions, burns and such (12). Topical antiseptics are active against prove the use of antiseptics in open wounds. chronic ulcers, has been an both resident and transient flora on the skin On the other hand, others believe antiseptics area of intense controversy for and are able to reduce microbial numbers have a role in wound care, and their use may several years by mechanical removal, chemical action or favour wound healing clinically (13). Two offi- • there is still much to learn both (14). Antiseptic formulations use a vari- cial guidelines have been released recently con- about the effectiveness of different methods currently used ety of mechanisms, act at various rates and cerning antiseptic use on wounds. Povidone- for the irrigation of open persistence intervals, show various levels of iodine has been FDA approved for short-term wounds be it acute or chronic toxicity and are more or less likely to trig- treatment of superficial and acute wounds. The ger resistance (12). Unlike antibiotics that act statement includes that povidone-iodine has selectively on a specific target, antiseptics have not been found to either promote or inhibit multiple targets and a broader spectrum of wound healing. On the other hand, guidelines activity, which include bacteria, fungi, viruses, for the treatment of pressure ulcers by the protozoa and even prions (9,13). Both the US Department of Health and Human Ser- lower resistance rates and allergic risks associ- vices strongly discourage the use of antiseptics ated with antiseptic compounds lend to their and promote the use of normal saline only present popularity (9,13). for cleansing pressure ulcers (13). There is still Antiseptic uses and indications vary; how- much to learn about the effectiveness of differ- ever, their use as prophylactic anti-infective ent methods currently used for the irrigation agents for open wounds, such as lacerations, of open wounds (15) be it acute or chronic. abrasions, burns and chronic ulcers, has been Several antiseptic categories exist, includ- an area of intense controversy for several ing alcohols (ethanol), anilides (triclocarban), years (13). Currently available antiseptic prod- biguanides (chlorhexidine), bisphenols (tri- ucts are diverse, targeted for different popula- closan), chlorine compounds, iodine com- tions, use settings and specific indications (6). pounds, silver compounds, peroxygens and There are many types of topical antiseptics quaternary ammonium compounds. The most designed for various purposes; each may be commonly used products in clinical practice used for health care, veterinary workers, food today include povidone-iodine, chlorhexidine, handlers or public consumers (14). Several alcohol, acetate, hydrogen peroxide (H2O2), antiseptic agents intended for health care per- boric acid, silver nitrate, silver sulfadiazine sonnel mainly focus on cleansing intact skin and sodium hypochlorite (13). Although acte- and are used for prepping patients preoper- tate (a radical) and silver sulphadiazine (an atively and prior to intramuscular injections antibiotic) as well as other products are not or venous punctures, pre- and postoperative really antiseptics, they are however listed

by several reports discussing topical prepa- antiseptic to reduce infectious complications Key Points rations for wound care as such creating some and topical iodine forms have been used • the purpose of this review confusion in the classification of topical dis- for wound treatment. The simplest form of is to critically examine value infectants, antiseptics and antibiotics. Disin- iodine is Lugol’s solution, which has irritating as well as potential harm to fectants have a broad spectrum effect on all and caustic properties (18). Tincture of iodine, patient outcome by the use of vegetative forms of microorganisms, includ- topical antiseptic preparations containing approximately 2% iodine, has been on open wounds ing spores, but usually have a toxic effect on long used as a preoperative skin prepara- tissues and probably are not suitable for use tion (12). Iodophors are the most common in open wounds. Antiseptics have as well a form of topical iodine and depend on the broad spectrum antimicrobial effect. They are release of free iodine as the active agent. toxic to multiple components of bacterial cell The complexing molecule acts only as a metabolism rather than to the more specific carrier. Iodophors increase the solubility of sites of antibiotic action such as enzyme inhi- iodine and allow for sustained-release (12). bition and are believed to be relatively non The iodophor, povidone-iodine, a complex toxic to tissues. They may even have the effect using 1-vinyl-2-pyrrolidinone polymer and a of promoting healing (16). The purpose of this halogen-releasing agent is a time-release for- review is to critically examine value as well mulation of iodine that attacks key proteins, as potential harm to patient outcome by the use of topical antiseptic preparations on open nucleotides, and fatty acids in the bacterium wounds. eventually causing cell death (9,12,17). The iodine released when the complex is in con- COMMONLY USED ANTISEPTIC tact with the skin is not only available to COMPOUNDS kill microorganisms, but is also adsorbed by Alcohol dead skin cells or other organic material. The Although several alcohols have been shown killing spectrum of iodines and iodophors is to be effective antimicrobials, ethyl alco- broad and includes gram-positive and gram- hol (ethanol, alcohol), isopropyl alcohol (iso- negative bacteria, fungi, viruses and proto- propanol, propan-2-ol) (used in the United zoa (12). Povidone-iodine absorption has been States) and n-propanol (in particular in Europe) a concern in the treatment of pregnant and are the most widely used for both hard- lactating mothers because of the possibility of surface disinfection and skin antisepsis (12,17). induced transient hypothyroidism (12). Classified as Category I, they are safe and Cadexomer-iodine is a hydrophilic modi- effective for health care personnel handwash, fied-starch polymer bead where molecules surgical hand scrub and patient preopera- of iodine are immobilised. Upon application tive skin preparation (12). These alcohols have the polymer beads are swollen by wound excellent in vitro bactericidal activity against exudates and gradually release incorporated most gram-positive and gram-negative bacte- iodine (18). Its most general indication is for ria. They also kill Mycobacterium tuberculosis, the treatment of sloughy, exudating or infected various fungi and certain enveloped viruses; ulcers (19). Preparations that could prolong however, they are not sporicidal and have the topical antibacterial effect would offer an poor activity against certain non enveloped obvious advantage (16), however, the iodine viruses (12,17). Generally, the antimicrobial contained in these products has different chem- activity of alcohols is significantly lower at ical structures, their effects are assumed to concentrations below 50% and is optimal in the 60–90% range (17). The alcohol killing be equivalent (18). Through bactericidal and mechanism appears to stem from membrane bacteriostatic mechanisms, iodine products damage and rapid denaturation of proteins, effectively reduce bacterial load and are active with subsequent interference with metabolism against most species, certainly those encoun- and cell lysis protein coagulation and tered in chronic wound care (16). Despite the denaturation (12,17). antimicrobial advantages obtained through the use of iodine products, several potential dis- Iodine advantages were observed in their clinical For more than a century, iodine has been application for wound treatment with different regarded as one of the most efficacious and controversial results (18).

Biguanides: chlorhexidine gluconate osteoblasts and endothelial cells to polyhex- and polyhexanide/polyhexamethylene anide at concentrations with questionable biguanide antibacterial activity resulted in severe cell Chlorhexidine, a biguanide antiseptic, is prob- damage raising some questions about the feasi- ably the most widely used biocide in antiseptic bility of using antiseptics in bone cement for the products, in particular, in hand washing and treatment of total arthroplasty infections (23) oral products but also as a disinfectant and and probably about the effect of PHMB on preservative (9,17). It is produced in two forms: wound healing (23). a 0.05% dilution for wound cleansing and a 4% solution for use as a surgical skin preparation Halophenols (chloroxylenol) and hand scrub. Recently 2% solutions have Chloroxylenol (4-chloro-3,5-dimethylphenol; been made available for surgical skin prepa- p-chloro-m-xylenol) is the key halophenol ration (10,12). Chlorhexidine gluconate (CHG) used in antiseptic or disinfectant formula- has been used for more than 30 years in the tions (17). Chloroxylenol is bactericidal (17). clinical setting. It has a high level of antimi- Surprisingly, its mechanism of action has been crobial activity, low toxicity and strong affinity little studied despite its widespread use over for binding to the skin and mucous mem- many years. Because of its phenolic nature, branes (12). It seems to impart its antimicrobial it would be expected to have an effect on activity at the membrane level, damaging both microbial membranes (17). At concentrations outer and inner bacterial membranes, causing of 0.5–4.0% it acts by microbial cell wall leakage and possibly disrupting membrane disruption and enzyme inactivation. It has potentials critical for ATP generation (9,17). good activity against gram-positive bacteria, but it is less active against gram-negative It disrupts the microbial cell membrane and bacteria, Mycobacterium tuberculosis,fungiand precipitates the cell contents. CHG (0.5–4%) viruses (12). is more effective against gram-positive than gram-negative bacteria and has less activity Bisphenols (triclosan) against fungi and tubercle bacilli. It is inac- Triclosan and hexachlorophane are the most tive against bacteria spores, except at elevated widely used biocides in this group, especially temperatures. Numerous studies indicate that in antiseptic soaps and hand rinses. Both com- CHG is not absorbed through the skin and has pounds have been shown to have cumulative a low skin-irritancy potential. However, CHG and persistent effects on the skin (17). should not come into contact with eyes, the Hexachlorophene is primarily effective middle ear or meninges. The immediate bac- against gram-positive bacteria. It is a chlo- tericidal action of CHG surpasses antiseptic rinated bisphenol that interrupts bacterial preparations containing povidone-iodine, tri- electron transport, inhibits membrane bound closan, hexachlorophene or chloroxylenol (12). enzymes at low concentrations and rup- Polyhexanide/polyhexamethylene big- tures bacterial membranes at high concentra- uanide (PHMB) is considered to be highly tions. (17,24) Three percent hexachlorophene histocompatible non cytotoxic and is one of kills gram-positive bacteria within 15–30 sec- the most frequently used wound antiseptics onds, but a longer time is needed for gram- nowadays (20). Polyhexanide in a hydrogel negative bacteria (12). Hexachlorophene has preparation has gained much attention after been associated with severe toxic effects, it was shown that methicillin-resistant Staphy- including deaths. It can be absorbed through lococcus aureus detected on skin or wounds damaged skin of adults and the skin of pre- just as a contamination or as colonisation mature infants (23). Baby powder accidentally without clinical and/or serological signs of contaminated with 6% hexachlorophene has infection could be successfully eradicated (21). caused infant deaths (12). Polihexanide proved also clinically and histo- Triclosan is a diphenyl ether (12). It exhibits logically superior to povidone-iodine and sil- particular activity against gram-positive bacte- ver nitrate for the treatment of second-degree ria. Its efficacy against gram-negative bacteria burns. Its antiseptic efficacy does not inhibit and yeasts can be significantly enhanced by for- the re-epithelialisation process (22). However, mulation effects. The specific mode of action of it was also shown that the exposure of human triclosan is unknown, but it has been suggested

that the primary effects are on the cytoplasmic of the number of pathogens in the wound Key Points membrane (12,17). and the likelihood of developing wound • in any wounding process, the infection same as the presence of foreign divided edges of the wound are Silver compounds bodies (14). more susceptible to infection In one form or another, silver and its Although it has been widely recognised for than the unwounded tissue compounds have long been used as antimicro- centuries that severe bacterial infection often • soft-tissue injuries because of develops in wounds containing dirt and soil, shear forces of cuts by either bial agents (17). Currently, the antibiotic silver a piece of glass or the metal sulfadiazine is the most clinically relevant there has been little knowledge until recently of edge of a knife resulting silver compound. It is thought to mainly the role of components of soil in this infection in a linear laceration that act at the DNA level as silver ions bind to process (14). Specific infection-potentiating require very little energy to the helix thereby blocking transcription (9,17). factors have been identified in the soil, which produce tissue failure exhibit include its organic components as well as its considerable resistance to the Irrespective of the source of silver, whether development of infection released from solutions, creams and oint- inorganic clay fractions. For wounds contam- • wounds in which the mech- ments or nanocrystalline silver, silver is inated by these fractions, only 100 bacteria anism of injury is compres- highly toxic to both keratinocytes and fibr- are necessary to elicit infection (14). Their sion or tension rather than oblasts (24). ability to enhance the incidence of infection shear forces requiring consid- seemstoberelatedtotheirdamagetohost erably greater energy and with Hydrogen peroxide characteristic stellate lacera- defenses. In the presence of these fractions, tion with abrasions of adja- H2O2 is a widely used biocide for disinfec- leukocytes are not able to ingest and kill bac- cent skin to the wound and tion, sterilisation and antisepsis. It is a clear, teria. This deleterious effect on white blood reduction in blood flow have colourless liquid that is commercially avail- cell function is a result of a direct interaction an increased susceptibility to able in a variety of concentrations ranging between the highly charged soil particles and infection from 3% to 90% (17). This readily available • the environs in which the injury white blood cells. Soil infection-potentiating occurred are also predictive of oxidant is rapidly converted to the highly reac- fractions also have considerable influence on the number of pathogens in tive hydroxyl radical that damages an array of non specific humoral factors. Exposure of the wound and the likelihood cellular components. Although widely consid- fresh serum to these fractions eliminates its of developing wound infection ered innocuous and environment friendly, rel- bactericidal activity. As expected, these parti- same as the presence of foreign atively high concentrations need to be applied bodies cles, which are highly charged species, react • it is argued that all wounds because of the significant catalase activity of chemically with amphoteric and basic antibi- are contaminated with bacteria several key pathogenic bacteria (9,17). otics, limiting their activity in contaminated and that this alone will not wounds (14,25). disrupt the wound healing WOUND CONTAMINATION The major inorganic infection-potentiating process • it is when this contamination AND WOUND INFECTION particles are the clay fractions, which reside changes to a state of critical In any wounding process, the divided edges in heaviest concentration in the subsoil rather colonisation or infection that of the wound are more susceptible to infection than in topsoil (14). Consequently, traumatic the bioburden in the wound is than the unwounded tissue. The magnitude soft-tissue injuries occurring in swamps or the most important contribut- of this enfeebled resistance, however, varies excavations run a high risk of being con- ing factor that impedes healing with the mechanism of injury (14). Soft-tissue taminated by these fractions, which predis- injuries because of shear forces of cuts by pose the wound to serious infection (14). either a piece of glass or the metal edge A corollary to these observations is that some of a knife resulting in a linear laceration soil contaminants, such as sand grains, are that require very little energy to produce relatively innocuous. This fraction, which tissue failure exhibit considerable resistance hasalargeparticlesizeandalowlevel to the development of infection, with the of chemical reactivity, exerts considerably infective dose being 106 bacteria per gram less damage on tissue defenses than do the of tissue or greater. Wounds in which the other infection-potentiating fractions. Surpris- mechanism of injury is compression or tension ingly, the black dirt on the surface of high- rather than shear forces requiring considerably ways also seems to have minimal chemical greater energy and with characteristic stellate reactivity (14). laceration with abrasions of adjacent skin to the wound and reduction in blood flow have CHRONIC WOUNDS an increased susceptibility to infection (104 It is argued that all wounds are contaminated bacteria per gram of tissue) (14). The environs with bacteria and that this alone will not in which the injury occurred are also predictive disrupt the wound healing process (9,26,27).

Interestingly, studies have suggested that Even though there is no strong evidence colonisation of the wound with microflora of that cleansing wounds per se increases heal- Key Points the skin can actually enhance healing (9,13). ing or reduces infection (31) it is almost uni- • prevention of wound infection It is when this contamination changes to a versally recommended and applied. The two is considered the most impor- state of critical colonisation or infection that the cleansing techniques generally used are irriga- tant contributing factor if an acute wound is to be prevented bioburdeninthewoundisthemostimportant tion and scrubbing. Although irrigation with from becoming chronic contributing factor that impedes healing (26). a large amount of saline and brushing are • three factors contribute to Unfortunately the progression of colonisation recommended, excessive brushing to remove the development of a chronic into infection is a multifactorial process involv- sand, debris or fragments will damage soft tis- wound. These are firstly, cel- ing many host and microbial components (9), sues and impairs the wound’s ability to resist lular and systemic factors that occur because of ageing; nevertheless, prevention of wound infection infection and allows residual bacteria to elicit secondly, repeated ischaemia is considered the most important contributing an inflammatory response (14,32). and reperfusion injury often factor if an acute wound is to be prevented Irrigation has long been considered one of with underlying ischaemia; and from becoming chronic (26). the most appropriate methods of cleansing a thirdly, bacterial colonisation, Many chronic wounds seem to be con- wound. Substantial evidence exists that this also known as bioburden • recent developments in wound fined to the inflammatory phase of the heal- should involve irrigation with a fluid that has care have identified that many ing process (9) and present a challenge that a similar osmotic pressure to that found in liv- of these bacteria live in com- is costly in terms of quality of life to the ing cells (26). Wound cleansing solutions must munities known as biofilms. patient and in financial terms for the National benontoxictohumantissues,remaineffective Biofilms are highly resistant to Health Service (26). Three factors contribute to in the presence of organic material, reduce the cleansing by irrigation and by treatment with antibiotics the development of a chronic wound. These number of microorganisms, not cause sensi- • irrigation has long been con- are firstly, cellular and systemic factors that tivity reactions and be widely available and sidered one of the most appro- occur because of ageing; secondly, repeated cost effective (10). Suggested cleansing agents priate methods of cleansing a ischaemia and reperfusion injury often with are normal saline, sterile water and even sim- wound • underlying ischaemia; and thirdly, bacterial ple tap water (10). In austere environments substantial evidence exists that this should involve irrigation colonisation, also known as bioburden (26,28). such as mobile military hospitals, supply lines with a fluid that has a similar It is also claimed that in addition to the may not be able to meet these requirements, osmotic pressure to that found wound’sbioburdenotherfactors,suchasfor- especially in a mass casualty situation. Alter- in living cells eign matter or necrotic tissue, if present in native irrigation solutions may be necessary in • suggested cleansing agents are a wound, can delay or prevent normal heal- the absence of saline, or in a situation where normal saline, sterile water and even simple tap water ing by production of metalloproteases (26). It a limited saline supply is reserved for casu- is known that various types of bacteria are alty intravenous resuscitation (33). The use of sustained in chronic wounds (26,27). Recent potable water as an irrigant has been stud- developments in wound care have identified ied in contaminated skin lacerations using an that many of these bacteria live in communities animal model and showed no difference in known as biofilms. Biofilms are highly resis- bacterial reduction between potable water and tant to cleansing by irrigation and by treatment sterile saline (33–35). It has been even recom- with antibiotics (26,29). mended for the irrigation of complex musculoskeletal wounds and open fractures (33). An experimental study established indeed that EVIDENCE-BASED BEST PRACTICE potable water is as effective as normal saline OF WOUND CLEANSING in removing bacteria from a contaminated Mechanical forces are usually used to rid musculoskeletal wound (33). In the absence of the wound of bacteria and other particulate potable tap water, boiled and cooled water as matter retained on the wound surface by adhe- well as distilled water can be used instead as sive forces (14). Under most circumstances, wound cleansing agents (31). debridement alone will reduce bacterial loads Even though various solutions have been with the added benefit of removing necrotic recommended for cleansing wounds, normal tissue that may otherwise increase inflamma- salineisfavouredasitisanisotonicsolution tion and delay healing (9,30). If cleansing is and does not interfere with the normal heal- required, an appropriate solution should be ing process. Tap water is commonly used in selected to optimise the healing process and the community for cleansing wounds because minimise the risk of damage to viable tis- it is easily accessible, efficient and cost effec- sue (10). tive, however, there is an unresolved debate

about its use (31). To date, there is no evidence (7 psi) can be used instead for dirty or heav- Key Points that using tap water to cleanse acute wounds ily contaminated wounds (14). The cleansing • the benefits of pressurised in adults increases infection on the contrary, effect of the bulb syringe irrigation is negligible irrigation are well recognised some evidence suggests that it reduces it (31). because the wound bacterial concentration is • the bacterial removal efficiency Invariably, if cleansing is required, an appro- not significantly affected by this low-pressure of the irrigating stream is priate solution should be selected to optimise irrigation system. High-pressure syringe irri- proportional to the pressure experienced by the wound the healing process and minimise the risk of gation effectively decreases the level of bac- surface damage to viable tissue (10). Antiseptic solu- terial contamination and markedly reduces • the benefits of high-pressure tions may be used exceptionally and caution is the incidence of wound infection in contam- irrigation must be weighed advised as their toxicity might outweigh any inated wounds (14). High-pressure irrigation against potential side effects benefits (10,36). In fact, it has been suggested removes 80% of the soil infection-potentiating such as the dissemination of bacteria into soft-tissue that, rather than the product used itself, it is factors from the wound (14). Changing the wounds the physical action of cleansing that removes composition of the wound irrigation solution • routine unnecessary cleansing debris, contaminants or unwanted exudate by adding chelating agents, flocculants and can traumatize fragile new from a wound bed (10,37). dispersants or a non ionic surfactant does tissue in and around the wound Although there is no clear consensus of opin- not significantly enhance the efficiency of bed ion as to which is best, cleansing of chronic removal of soil infection-potentiating factors wounds to remove foreign matter, necrotic tis- from wounds (14). sue or bacteria is usually either with normal In the clinical setting, high-pressure irri- saline or tap water (26). For chronic wounds, gation is accomplished with an inexpensive the relative risk of developing an infection disposable irrigation assembly consisting of a when cleansed with tap water compared with 19-gauge plastic needle or catheter attached to normal saline is 0.16 (31). It is claimed, how- a 35-mL syringe. This would exert a pressure ever, that because of the complexity of fac- equivalent to 7 psi on the wound surface. In tors influencing a chronic wound, no single contrast, the pressure encountered by a surface therapeutic intervention will have any signif- irrigated by a bulb syringe is only 0.5 psi (14). icant impact on improving the wound (26,28). To minimise exposure to biologically haz- Recently a consensus paper became available ardous material during wound irrigation, that advocated the use of an active sub- an overturned plastic gallipot from a sterile stance, polyhexanide, as a first choice treatment wound dressing pack may be used as a splash- for chronic, hard-to-heal wounds suitable for guard during the irrigation process (14,40–42). wound bed preparation to remove biofilm The benefits of high-pressure irrigation must prior to further treatment and appears to offer, be weighed against potential side effects such in the majority of patients, a safe and cost as the dissemination of bacteria into soft-tissue effective method of cleansing wounds which is wounds. In fact, the irrigation fluid dissemi- more efficient than normal saline (26). nates into the interstices of the wound, pre- Although most surgeons prefer to treat dominantly in a lateral direction. This lateral contaminated wounds as soon as possible, the spread occurs within the loose areolar tissue, effect of timing on the ability of irrigation to contributing to the development of postop- reduce the amount of bacteria in an acute erative oedema. Paradoxically, high-pressure wound is not fully known (38), although irrigation may make the wound more sus- recently superior bacterial removal with earlier ceptible to infection, so this technique should irrigation was shown in an experimental be reserved for heavily contaminated wounds contaminated wound model (38). only (14). However, in a recently published The benefits of pressurised irrigation are experimental study about the effectiveness of well recognised (14,39). It takes significantly different methods currently used for the irriga- smaller hydraulic pressures to rid the wound tion of open wounds comparing normal saline of large foreign bodies than it does to remove solution, bacitracin solution, castile soap and small particles and bacteria (14) and the bacte- benzalkonium chloride with use of a pulsatile rial removal efficiency of the irrigating stream lavage device (19 psi) then using the same is proportional to the pressure experienced by animal model to compare bulb syringe and pul- the wound surface (14). Low-pressure irriga- satile lavage irrigation with saline solution it tion (0.5 pounds per square inch – psi) is best was concluded that approaches used to remove for clean wounds, and high-pressure irrigation bacteria from wounds, such as irrigants other

than saline solution or high-pressure devices, achieved at 500 μmol/L and 0.2% final concen- may not have the best clinical outcome (15). trations, respectively. Silver-containing com- Key Points Routine unnecessary cleansing can trauma- pounds and chlorhexidine solutions exhibited • it is well established now tise fragile new tissue in and around the wound a different trend. High doses still elicited a that wound exudate may con- bed (10). Moreover, it is well established now decrease in proliferation, but, at lower doses, tain bactericidal properties and that wound exudate may contain bactericidal an increase in proliferation was observed (9). growth factors that will help promote wound healing and properties and growth factors that will help In all instances, the highest doses tested for should only be removed if promote wound healing and should only be all the biocides approached 100% inhibition, copious amounts are present removed if copious amounts are present or indicating potential cytotoxicity at these con- or there are clinical signs of there are clinical signs of infection (10). centrations (9). All of the antiseptics in a infection Disinfection of the skin around the wound dose-dependent manner reduced also migra- by antiseptic agents should be initiated without tion of the NHDF cells which under nor- contacting the wound itself (14). Two widely mal culture conditions would rapidly invade used groups of antiseptic agents, containing the vacant spaces, filling the void within either an iodophore or chlorhexidine, exhibit 24–48 hours (9). H2O2 was the most effective activity against a broad spectrum of organisms compound tested with complete attenuation and suppress bacterial proliferation. The achieved at a 1000 μmol/L concentration. superiority of one antiseptic agent over another Chlorhexidine and povidone-iodine were also has not been shown. Although these agents effective at reducing migration. On the other can reduce the bacterial concentration on intact hand, silver sulfadiazine was the least effective skin, they seem to damage the wound defenses compound at inhibiting migration, however, and invite the development of infection within a reduction in migration of 36% ± 2% was the wound itself. Consequently, inadvertent observed at a dose of 10 μmol/L (9). Cells spillage of these agents into the wound should exposed to H2O2 and povidone-iodine com- be avoided (14). pletely lacked important foot-like projections characteristic of normal polarised motility and migration of cells (9,45). Silver sulfadiazine ANTISEPTIC CYTOTOXICITY and chlorhexidine-treated cells as well pre- AND THE EFFECT ON WOUND sented with fewer and less developed filopodia HEALING at the leading edge as compared to none treated Anecdotal clinical observations and an increas- normal cell (9). ing body of literature suggest that application The same study also showed that Chlorhex- of antiseptics is not as benign as originally idine is a strong inhibitor of pro-MMP (matrix accepted. The cytotoxic effects of antisep- metalloproteinase)-9 and pro-MMP-2 release tics on many of the key cellular participants in stimulated NHDF cells with 10 ng/mL in the wound healing process, such as ker- tumour necrosis factor-α and 10 ng/mL trans- atinocytes and fibroblasts, have been well doc- forming growth factor-β1. Exposure of the cells umented (5,8,9,43,44). Moreover, exposure of to 250 and 500 μmol/L H2O2 reduced the pro- the wound to either Hibiclens™ (Molnlycke¨ MMP-9 release by 70% and 99%, respectively. Health Care US, LLC, Norcross, GA) or A 66% reduction in pro-MMP-2 release was ® Betadine (Purdue Products L.P., Stamford, also seen in both H2O2 treatment groups (9). CT) surgical scrub solution has been shown A dynamic range of effects was exhibited with to damage tissue defenses, and cause pain or silver-containing compounds and povidone- irritation to tissues (14). iodine. When exposed to low levels of silver, In a recently published important experi- a reduction of pro-MMP-2 and an increase mental study, reductions in proliferation of in pro-MMP-9 was observed. Silver sulfadi- normal human dermal fibroblasts (NHDF), azine had a more pronounced effect than pivotal to the wound healing process, were silver nitrate in up-regulating pro-MMP-9 (18% observed when the cells were cultured in increase versus 5%). High doses, however, the presence of various antiseptic compounds attenuated the pro-MMP-9 release and greatly for 96 hours with a few notable excep- reduced pro-MMP-2 levels below those of rest- tions (9). Both H2O2 and povidone-iodine ing levels. Low-dose iodine exposure of these treatment led to dose-dependent reductions cells resulted in almost a threefold increase in proliferation with complete attenuation in pro-MMP-9 release from stimulated cells.

No significant change in pro-MMP-2 release (0.025%) and povidone (10%) (5). Repeated Key Points was observed at this dose. High-dose expo- and excessive treatment of wounds with anti- • although the type of open- sure to iodine was strikingly different. No septics without proper indications may have wound management must be MMP release was detected in these cells (9). negative outcomes or promote a microenvi- individualized for each wound In addition, low-dose silver, H2O2 and iodine ronment similar to those found in chronic (14), cleansing bacteria, soil all increased the conversion of the pro-MMP-2 wounds (9). However, when applied at the and other debris from traumatic wounds, as well as sur- into the truncated, active form (9). proper times and concentrations, some classes gical debridement cannot be of antiseptics may provide a tool for the overemphasized CONCLUSION clinician to drive the wound bed in desired • although certain skin and Quality of care is a critical requirement for directions (9). Wound management strategies wound cleansers are designed wound healing. Strategies that optimise the tis- address the delicate balance between cytotox- as topical solutions with varying degrees of antimicro- sue repair process have evolved with advances icity and cellular activities. Irritation of intact bial activity, wound cleansers in understanding of the wound healing pro- healthy tissue could seriously impact the rate may also be antimitotic and cess (5). Although the type of open-wound and quality of tissue repair (5). Although the adversely affect normal tissue management must be individualised for each removal of antiseptics from the wound bed repair wound (14), cleansing bacteria, soil and other management arsenal cannot be advocated, care • available experimental data suggest that the effects of anti- debris from traumatic wounds, as well as sur- should be used when administering these septic treatment on fibroblasts gical debridement cannot be overemphasised. products (9). Despite cytotoxicty data, most are more encompassing than Debridement removes tissue heavily contam- antiseptics have not been shown to clearly just toxicity inated by soil infection-potentiating fractions impede healing, especially newer formula- • wound management strategies and bacteria, and excises devitalised tissues tions like cadexomer iodine (which speeds address the delicate balance between cytotoxicity and cellu- that impair the wound’s ability to resist infec- healing) and novel silver delivery systems. lar activities tion (14). These compounds appear to be relatively safe • despite cytotoxicty data, most It is argued that wound cleansing has three and efficient in preventing infection in human antiseptics have not been elements, namely, the technique, the solution wounds (13). shown to clearly impede heal- and the equipment (46,47). Techniques used The continued unjustified use of antibiotics ing, especially newer formulations like cadexomer iodine include high-pressure irrigation, swabbing, will have to be addressed if the rise of resistant (which speeds healing) and low-pressure irrigation, showering, bathing and emergent organisms is to be controlled. novel silver delivery systems. and washing the affected area under a Topical antimicrobials, such as the antisep- These compounds appear to be running solution or total immersion in a tics, could be used more often to avoid the relatively safe and efficient in whirlpool bath. Different cleansing solutions preventing infection in human need for antibiotics particularly in wound wounds are also used, for example, normal saline, care and management protocols (16). Unfor- • the continued unjustified use water and antiseptic solutions. Furthermore, tunately, given this review, it is not possible of antibiotics will have to be wound cleansing requires the use of equipment to formulate rigid guidelines or to propose an addressed if the rise of resistant such as syringes, needles, catheters and pres- algorithm regarding the use of antiseptics for and emergent organisms is to surised canisters (46,47). Some have argued be controlled routine wound cleansing. On the contrary, the • topical antimicrobials, such as that wound cleansing can have a positive role of antiseptics on wounds and their role in the antiseptics,could be used impact on wound healing outcomes, however, wound care management should be critically more often to avoid the need it is conducted mostly without a clear rationale reconsidered (13). for antibiotics particularly in underpinning the practice (46,48). 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