wound cleansing, topical antiseptics and wound healing

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

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Page 1: Wound cleansing, topical antiseptics and wound healing

ORIGINAL ARTICLE

Wound cleansing, topicalantiseptics and woundhealingBishara 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

ABSTRACTQuality of care is a critical requirement for wound healing and ‘good’ care of wounds has been synonymouswith topical prevention and management of microbial contamination. Topical antiseptics are antimicrobial agentsthat kill, inhibit or reduce the number of microorganisms and are thought to be essential for wounds infectioncontrol. However, they have long and commonly been used on wounds to prevent or treat infection, the meritsof antiseptic fluid irrigation have received little scientific study. Unlike antibiotics that act selectively on a specifictarget, 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 withvarying degrees of antimicrobial activity, concerns have been raised. Wound cleansers may affect normal humancells and may be antimitotic adversely affecting normal tissue repair. Repeated and excessive treatment of woundswith antiseptics without proper indications may have negative outcomes or promote a microenvironment similarto those found in chronic wounds. However, when applied at the proper times and concentrations, some classesof antiseptics may provide a tool for the clinician to drive the wound bed in desired directions. The present reviewsummarises the various antiseptics in use and their negative impact on the wound healing mechanisms. It is clearthat 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

INTRODUCTIONThe practice of wound cleansing or antiseptic

Key Points

• there are no diagnostic tests toallow health care practitionersto identify whether the bacte-rial load in a wound is capableof causing infection

• it is believed that all woundsshould undergo some formof cleansing to decrease thebacterial inoculum to levelsthat can be managed by hostdefenses

• the ideal topical therapy wouldinclude periodic reduction ofbacterial contamination andremoval of soluble debris with-out adversely impacting cellu-lar activities vital to the woundhealing process

management has a dichotomous historyanchored in tradition and science (1). It is anintegral part of the management of acute trau-matic wounds (2) as well a chronic wounds.Although there is a consensus that woundcleansing reduces infection rates (2) there is,however, evidence to suggest that it is notalways necessary (3). There are no diagnostictests to allow health care practitioners toidentify whether the bacterial load in a wound

Authors: BS Atiyeh, MD, FACS, Division Plastic andReconstructive Surgery, American University of Beirut MedicalCenter, Beirut, Lebanon; SA Dibo, MD, Department of Surgery,American University of Beirut Medical Center, Beirut, Lebanon;SN Hayek, MD, Division Plastic and Reconstructive Surgery,American University of Beirut Medical Center, Beirut, LebanonAddress for correspondence: BS Atiyeh, MD, FACS,Clinical Professor, Division Plastic and Reconstructive Surgery,American University of Beirut Medical Center, Beirut, LebanonE-mail: [email protected]

is capable of causing infection. For this reason,it is believed that all wounds should undergosome form of cleansing to decrease the bacterialinoculum to levels that can be managed by hostdefenses (3). The choice of a cleansing agent,however, remains controversial. The use ofantiseptics has been especially questioned (2).

‘Good’ care of wounds has been syn-onymous with topical prevention and man-agement of microbial contamination (4,5). Infact, successful management of the contami-nated wound must remove contaminants whileinflicting minimal injury to tissues (3). On thepremise that bacterial reduction translates to areduced potential for infection (6) and withoutoverlooking the deleterious effects of infectionon wound repair (5), the ideal topical therapywould include periodic reduction of bacterialcontamination and removal of soluble debriswithout adversely impacting cellular activi-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

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With advances in understanding of the woundhealing process strategies that optimise the tis-sue repair process beyond the mere fact of justcontrolling surface bacterial contamination, itis now obvious that quality of care is a criticalrequirement for wound healing and for promo-tion of healing (5) and that the ultimate goalof wound management is to minimise the riskof opportunistic infection while promoting thedevelopment of healthy granulation tissue (9)and initiate and aid the healing process (10,11).

Topical antiseptics are antimicrobial agentsthat kill, inhibit or reduce the number ofmicroorganisms and are thought to be essentialfor wounds infection control (6,12). However,they have long and commonly been usedon wounds to prevent or treat infection (13),the merits of antiseptic fluid irrigation havereceived little scientific study (1). Antisepticsare considered drugs by the Food and DrugAdministration (FDA) and are regulated assuch (12). Topical antiseptics are active againstboth resident and transient flora on the skinand are able to reduce microbial numbersby mechanical removal, chemical action orboth (14). Antiseptic formulations use a vari-ety of mechanisms, act at various rates andpersistence intervals, show various levels oftoxicity and are more or less likely to trig-ger resistance (12). Unlike antibiotics that actselectively on a specific target, antiseptics havemultiple targets and a broader spectrum ofactivity, which include bacteria, fungi, viruses,protozoa and even prions (9,13). Both thelower resistance rates and allergic risks associ-ated with antiseptic compounds lend to theirpresent popularity (9,13).

Antiseptic uses and indications vary; how-ever, their use as prophylactic anti-infectiveagents for open wounds, such as lacerations,abrasions, burns and chronic ulcers, has beenan area of intense controversy for severalyears (13). Currently available antiseptic prod-ucts are diverse, targeted for different popula-tions, use settings and specific indications (6).There are many types of topical antisepticsdesigned for various purposes; each may beused for health care, veterinary workers, foodhandlers or public consumers (14). Severalantiseptic agents intended for health care per-sonnel mainly focus on cleansing intact skinand are used for prepping patients preoper-atively and prior to intramuscular injectionsor venous punctures, pre- and postoperative

scrubbing in the operating room and handKey Points

• the ultimate goal of woundmanagement is to minimise therisk of opportunistic infectionwhile promoting the develop-ment of healthy granulationtissue and initiate and aid thehealing process

• unlike antibiotics that act selec-tively on a specific target, anti-septics have multiple targetsand a broader spectrum ofactivity, which include bacte-ria, fungi, viruses, protozoa andeven prions

• both the lower resistancerates and allergic risks asso-ciated with antiseptic com-pounds lend to their presentpopularity

• the use of antiseptics as pro-phylactic anti-infective agentsfor open wounds, such as lac-erations, abrasions, burns andchronic ulcers, has been anarea of intense controversy forseveral years

• there is still much to learnabout the effectiveness of dif-ferent methods currently usedfor the irrigation of openwounds be it acute or chronic

washing by medical personnel. In clinicalpractice, antiseptics are broadly used for bothintact skin and wounds (13). The usefulness ofantiseptics on intact skin is well established andbroadly accepted. However, the use of anti-septics as prophylactic anti-infective agents foropen wounds, such as lacerations, abrasions,burns and chronic ulcers, has been an area ofintense controversy for several years. Citingcytotoxicity data, many authors have advisedagainst their use on open wounds (13). Somemay even contain detergents, which renderthem too harsh for use on non intact skin (13).

Although certain skin and wound cleansersare designed as topical solutions with vary-ing degrees of antimicrobial activity, con-cerns have been raised. Wound cleansersmay affect normal human cells and may beantimitotic, adversely affecting normal tissuerepair (4,5,13). Some authors strongly disap-prove the use of antiseptics in open wounds.On the other hand, others believe antisepticshave a role in wound care, and their use mayfavour wound healing clinically (13). Two offi-cial guidelines have been released recently con-cerning antiseptic use on wounds. Povidone-iodine has been FDA approved for short-termtreatment of superficial and acute wounds. Thestatement includes that povidone-iodine hasnot been found to either promote or inhibitwound healing. On the other hand, guidelinesfor the treatment of pressure ulcers by theUS Department of Health and Human Ser-vices strongly discourage the use of antisepticsand promote the use of normal saline onlyfor cleansing pressure ulcers (13). There is stillmuch to learn about the effectiveness of differ-ent methods currently used for the irrigationof open wounds (15) be it acute or chronic.

Several antiseptic categories exist, includ-ing alcohols (ethanol), anilides (triclocarban),biguanides (chlorhexidine), bisphenols (tri-closan), chlorine compounds, iodine com-pounds, silver compounds, peroxygens andquaternary ammonium compounds. The mostcommonly used products in clinical practicetoday include povidone-iodine, chlorhexidine,alcohol, acetate, hydrogen peroxide (H2O2),boric acid, silver nitrate, silver sulfadiazineand sodium hypochlorite (13). Although acte-tate (a radical) and silver sulphadiazine (anantibiotic) as well as other products are notreally antiseptics, they are however listed

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by several reports discussing topical prepa-rations for wound care as such creating someKey Points

• the purpose of this reviewis to critically examine valueas well as potential harm topatient outcome by the use oftopical antiseptic preparationson open wounds

confusion in the classification of topical dis-infectants, antiseptics and antibiotics. Disin-fectants have a broad spectrum effect on allvegetative forms of microorganisms, includ-ing spores, but usually have a toxic effect ontissues and probably are not suitable for usein open wounds. Antiseptics have as well abroad spectrum antimicrobial effect. They aretoxic to multiple components of bacterial cellmetabolism rather than to the more specificsites of antibiotic action such as enzyme inhi-bition and are believed to be relatively nontoxic to tissues. They may even have the effectof promoting healing (16). The purpose of thisreview is to critically examine value as wellas potential harm to patient outcome by theuse of topical antiseptic preparations on openwounds.

COMMONLY USED ANTISEPTICCOMPOUNDSAlcoholAlthough several alcohols have been shownto be effective antimicrobials, ethyl alco-hol (ethanol, alcohol), isopropyl alcohol (iso-propanol, propan-2-ol) (used in the UnitedStates) and n-propanol (in particular in Europe)are the most widely used for both hard-surface disinfection and skin antisepsis (12,17).Classified as Category I, they are safe andeffective for health care personnel handwash,surgical hand scrub and patient preopera-tive skin preparation (12). These alcohols haveexcellent in vitro bactericidal activity againstmost gram-positive and gram-negative bacte-ria. They also kill Mycobacterium tuberculosis,various fungi and certain enveloped viruses;however, they are not sporicidal and havepoor activity against certain non envelopedviruses (12,17). Generally, the antimicrobialactivity of alcohols is significantly lower atconcentrations below 50% and is optimal inthe 60–90% range (17). The alcohol killingmechanism appears to stem from membranedamage and rapid denaturation of proteins,with subsequent interference with metabolismand cell lysis protein coagulation anddenaturation (12,17).

IodineFor more than a century, iodine has beenregarded as one of the most efficacious

antiseptic to reduce infectious complicationsand topical iodine forms have been usedfor wound treatment. The simplest form ofiodine is Lugol’s solution, which has irritatingand caustic properties (18). Tincture of iodine,containing approximately 2% iodine, has beenlong used as a preoperative skin prepara-tion (12). Iodophors are the most commonform of topical iodine and depend on therelease of free iodine as the active agent.The complexing molecule acts only as acarrier. Iodophors increase the solubility ofiodine and allow for sustained-release (12).The iodophor, povidone-iodine, a complexusing 1-vinyl-2-pyrrolidinone polymer and ahalogen-releasing agent is a time-release for-mulation of iodine that attacks key proteins,nucleotides, and fatty acids in the bacteriumeventually causing cell death (9,12,17). Theiodine released when the complex is in con-tact with the skin is not only available tokill microorganisms, but is also adsorbed bydead skin cells or other organic material. Thekilling spectrum of iodines and iodophors isbroad and includes gram-positive and gram-negative bacteria, fungi, viruses and proto-zoa (12). Povidone-iodine absorption has beena concern in the treatment of pregnant andlactating mothers because of the possibility ofinduced transient hypothyroidism (12).

Cadexomer-iodine is a hydrophilic modi-fied-starch polymer bead where moleculesof iodine are immobilised. Upon applicationthe polymer beads are swollen by woundexudates and gradually release incorporatediodine (18). Its most general indication is forthe treatment of sloughy, exudating or infectedulcers (19). Preparations that could prolongthe topical antibacterial effect would offer anobvious advantage (16), however, the iodinecontained in these products has different chem-ical structures, their effects are assumed tobe equivalent (18). Through bactericidal andbacteriostatic mechanisms, iodine productseffectively reduce bacterial load and are activeagainst most species, certainly those encoun-tered in chronic wound care (16). Despite theantimicrobial advantages obtained through theuse of iodine products, several potential dis-advantages were observed in their clinicalapplication for wound treatment with differentand controversial results (18).

422 © 2009 The Authors. Journal Compilation © 2009 Blackwell Publishing Ltd and Medicalhelplines.com Inc

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Biguanides: chlorhexidine gluconateand polyhexanide/polyhexamethylenebiguanideChlorhexidine, a biguanide antiseptic, is prob-ably the most widely used biocide in antisepticproducts, in particular, in hand washing andoral products but also as a disinfectant andpreservative (9,17). It is produced in two forms:a 0.05% dilution for wound cleansing and a 4%solution for use as a surgical skin preparationand hand scrub. Recently 2% solutions havebeen made available for surgical skin prepa-ration (10,12). Chlorhexidine gluconate (CHG)has been used for more than 30 years in theclinical setting. It has a high level of antimi-crobial activity, low toxicity and strong affinityfor binding to the skin and mucous mem-branes (12). It seems to impart its antimicrobialactivity at the membrane level, damaging bothouter and inner bacterial membranes, causingleakage and possibly disrupting membranepotentials critical for ATP generation (9,17).It disrupts the microbial cell membrane andprecipitates the cell contents. CHG (0.5–4%)is more effective against gram-positive thangram-negative bacteria and has less activityagainst fungi and tubercle bacilli. It is inac-tive against bacteria spores, except at elevatedtemperatures. Numerous studies indicate thatCHG is not absorbed through the skin and hasa low skin-irritancy potential. However, CHGshould not come into contact with eyes, themiddle ear or meninges. The immediate bac-tericidal action of CHG surpasses antisepticpreparations containing povidone-iodine, tri-closan, hexachlorophene or chloroxylenol (12).

Polyhexanide/polyhexamethylene big-uanide (PHMB) is considered to be highlyhistocompatible non cytotoxic and is one ofthe most frequently used wound antisepticsnowadays (20). Polyhexanide in a hydrogelpreparation has gained much attention afterit was shown that methicillin-resistant Staphy-lococcus aureus detected on skin or woundsjust as a contamination or as colonisationwithout clinical and/or serological signs ofinfection could be successfully eradicated (21).Polihexanide proved also clinically and histo-logically superior to povidone-iodine and sil-ver nitrate for the treatment of second-degreeburns. Its antiseptic efficacy does not inhibitthe re-epithelialisation process (22). However,it was also shown that the exposure of human

osteoblasts and endothelial cells to polyhex-anide at concentrations with questionableantibacterial activity resulted in severe celldamage raising some questions about the feasi-bility of using antiseptics in bone cement for thetreatment of total arthroplasty infections (23)and probably about the effect of PHMB onwound healing (23).

Halophenols (chloroxylenol)Chloroxylenol (4-chloro-3,5-dimethylphenol;p-chloro-m-xylenol) is the key halophenolused in antiseptic or disinfectant formula-tions (17). Chloroxylenol is bactericidal (17).Surprisingly, its mechanism of action has beenlittle studied despite its widespread use overmany years. Because of its phenolic nature,it would be expected to have an effect onmicrobial membranes (17). At concentrationsof 0.5–4.0% it acts by microbial cell walldisruption and enzyme inactivation. It hasgood activity against gram-positive bacteria,but it is less active against gram-negativebacteria, Mycobacterium tuberculosis, fungi andviruses (12).

Bisphenols (triclosan)Triclosan and hexachlorophane are the mostwidely used biocides in this group, especiallyin antiseptic soaps and hand rinses. Both com-pounds have been shown to have cumulativeand persistent effects on the skin (17).

Hexachlorophene is primarily effectiveagainst gram-positive bacteria. It is a chlo-rinated bisphenol that interrupts bacterialelectron transport, inhibits membrane boundenzymes at low concentrations and rup-tures bacterial membranes at high concentra-tions. (17,24) Three percent hexachlorophenekills gram-positive bacteria within 15–30 sec-onds, but a longer time is needed for gram-negative bacteria (12). Hexachlorophene hasbeen associated with severe toxic effects,including deaths. It can be absorbed throughdamaged skin of adults and the skin of pre-mature infants (23). Baby powder accidentallycontaminated with 6% hexachlorophene hascaused infant deaths (12).

Triclosan is a diphenyl ether (12). It exhibitsparticular activity against gram-positive bacte-ria. Its efficacy against gram-negative bacteriaand yeasts can be significantly enhanced by for-mulation effects. The specific mode of action oftriclosan is unknown, but it has been suggested

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that the primary effects are on the cytoplasmicmembrane (12,17).

Silver compoundsIn one form or another, silver and its

Key Points

• in any wounding process, thedivided edges of the wound aremore susceptible to infectionthan the unwounded tissue

• soft-tissue injuries because ofshear forces of cuts by eithera piece of glass or the metaledge of a knife resultingin a linear laceration thatrequire very little energy toproduce tissue failure exhibitconsiderable resistance to thedevelopment of infection

• wounds in which the mech-anism of injury is compres-sion or tension rather thanshear forces requiring consid-erably greater energy and withcharacteristic stellate lacera-tion with abrasions of adja-cent skin to the wound andreduction in blood flow havean increased susceptibility toinfection

• the environs in which the injuryoccurred are also predictive ofthe number of pathogens inthe wound and the likelihoodof developing wound infectionsame as the presence of foreignbodies

• it is argued that all woundsare contaminated with bacteriaand that this alone will notdisrupt the wound healingprocess

• it is when this contaminationchanges to a state of criticalcolonisation or infection thatthe bioburden in the wound isthe most important contribut-ing factor that impedes healing

compounds have long been used as antimicro-bial agents (17). Currently, the antibiotic silversulfadiazine is the most clinically relevantsilver compound. It is thought to mainlyact at the DNA level as silver ions bind tothe helix thereby blocking transcription (9,17).Irrespective of the source of silver, whetherreleased from solutions, creams and oint-ments or nanocrystalline silver, silver ishighly toxic to both keratinocytes and fibr-oblasts (24).

Hydrogen peroxideH2O2 is a widely used biocide for disinfec-tion, sterilisation and antisepsis. It is a clear,colourless liquid that is commercially avail-able in a variety of concentrations rangingfrom 3% to 90% (17). This readily availableoxidant is rapidly converted to the highly reac-tive hydroxyl radical that damages an array ofcellular components. Although widely consid-ered innocuous and environment friendly, rel-atively high concentrations need to be appliedbecause of the significant catalase activity ofseveral key pathogenic bacteria (9,17).

WOUND CONTAMINATIONAND WOUND INFECTIONIn any wounding process, the divided edgesof the wound are more susceptible to infectionthan the unwounded tissue. The magnitudeof this enfeebled resistance, however, varieswith the mechanism of injury (14). Soft-tissueinjuries because of shear forces of cuts byeither a piece of glass or the metal edgeof a knife resulting in a linear lacerationthat require very little energy to producetissue failure exhibit considerable resistanceto the development of infection, with theinfective dose being 106 bacteria per gramof tissue or greater. Wounds in which themechanism of injury is compression or tensionrather than shear forces requiring considerablygreater energy and with characteristic stellatelaceration with abrasions of adjacent skin tothe wound and reduction in blood flow havean increased susceptibility to infection (104

bacteria per gram of tissue) (14). The environsin which the injury occurred are also predictive

of the number of pathogens in the woundand the likelihood of developing woundinfection same as the presence of foreignbodies (14).

Although it has been widely recognised forcenturies that severe bacterial infection oftendevelops in wounds containing dirt and soil,there has been little knowledge until recently ofthe role of components of soil in this infectionprocess (14). Specific infection-potentiatingfactors have been identified in the soil, whichinclude its organic components as well as itsinorganic clay fractions. For wounds contam-inated by these fractions, only 100 bacteriaare necessary to elicit infection (14). Theirability to enhance the incidence of infectionseems to be related to their damage to hostdefenses. In the presence of these fractions,leukocytes are not able to ingest and kill bac-teria. This deleterious effect on white bloodcell function is a result of a direct interactionbetween the highly charged soil particles andwhite blood cells. Soil infection-potentiatingfractions also have considerable influence onnon specific humoral factors. Exposure offresh serum to these fractions eliminates itsbactericidal activity. As expected, these parti-cles, which are highly charged species, reactchemically with amphoteric and basic antibi-otics, limiting their activity in contaminatedwounds (14,25).

The major inorganic infection-potentiatingparticles are the clay fractions, which residein heaviest concentration in the subsoil ratherthan in topsoil (14). Consequently, traumaticsoft-tissue injuries occurring in swamps orexcavations run a high risk of being con-taminated by these fractions, which predis-pose the wound to serious infection (14).A corollary to these observations is that somesoil contaminants, such as sand grains, arerelatively innocuous. This fraction, whichhas a large particle size and a low levelof chemical reactivity, exerts considerablyless damage on tissue defenses than do theother infection-potentiating fractions. Surpris-ingly, the black dirt on the surface of high-ways also seems to have minimal chemicalreactivity (14).

CHRONIC WOUNDSIt is argued that all wounds are contaminatedwith bacteria and that this alone will notdisrupt the wound healing process (9,26,27).

424 © 2009 The Authors. Journal Compilation © 2009 Blackwell Publishing Ltd and Medicalhelplines.com Inc

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Interestingly, studies have suggested thatcolonisation of the wound with microflora ofthe skin can actually enhance healing (9,13).It is when this contamination changes to astate of critical colonisation or infection that thebioburden in the wound is the most importantcontributing factor that impedes healing (26).Unfortunately the progression of colonisationinto infection is a multifactorial process involv-ing many host and microbial components (9),nevertheless, prevention of wound infectionis considered the most important contributingfactor if an acute wound is to be preventedfrom becoming chronic (26).

Many chronic wounds seem to be con-fined to the inflammatory phase of the heal-ing process (9) and present a challenge thatis costly in terms of quality of life to thepatient and in financial terms for the NationalHealth Service (26). Three factors contribute tothe development of a chronic wound. Theseare firstly, cellular and systemic factors thatoccur because of ageing; secondly, repeatedischaemia and reperfusion injury often withunderlying ischaemia; and thirdly, bacterialcolonisation, also known as bioburden (26,28).It is also claimed that in addition to thewound’s bioburden other factors, such as for-eign matter or necrotic tissue, if present ina wound, can delay or prevent normal heal-ing by production of metalloproteases (26). Itis known that various types of bacteria aresustained in chronic wounds (26,27). Recentdevelopments in wound care have identifiedthat many of these bacteria live in communitiesknown as biofilms. Biofilms are highly resis-tant to cleansing by irrigation and by treatmentwith antibiotics (26,29).

EVIDENCE-BASED BEST PRACTICEOF WOUND CLEANSINGMechanical forces are usually used to ridthe wound of bacteria and other particulatematter retained on the wound surface by adhe-sive forces (14). Under most circumstances,debridement alone will reduce bacterial loadswith the added benefit of removing necrotictissue that may otherwise increase inflamma-tion and delay healing (9,30). If cleansing isrequired, an appropriate solution should beselected to optimise the healing process andminimise the risk of damage to viable tis-sue (10).

Even though there is no strong evidencethat cleansing wounds per se increases heal-ing or reduces infection (31) it is almost uni-versally recommended and applied. The two

Key Points

• prevention of wound infectionis considered the most impor-tant contributing factor if anacute wound is to be preventedfrom becoming chronic

• three factors contribute tothe development of a chronicwound. These are firstly, cel-lular and systemic factorsthat occur because of ageing;secondly, repeated ischaemiaand reperfusion injury oftenwith underlying ischaemia; andthirdly, bacterial colonisation,also known as bioburden

• recent developments in woundcare have identified that manyof these bacteria live in com-munities known as biofilms.Biofilms are highly resistant tocleansing by irrigation and bytreatment with antibiotics

• irrigation has long been con-sidered one of the most appro-priate methods of cleansing awound

• substantial evidence exists thatthis should involve irrigationwith a fluid that has a similarosmotic pressure to that foundin living cells

• suggested cleansing agents arenormal saline, sterile water andeven simple tap water

cleansing techniques generally used are irriga-tion and scrubbing. Although irrigation witha large amount of saline and brushing arerecommended, excessive brushing to removesand, debris or fragments will damage soft tis-sues and impairs the wound’s ability to resistinfection and allows residual bacteria to elicitan inflammatory response (14,32).

Irrigation has long been considered one ofthe most appropriate methods of cleansing awound. Substantial evidence exists that thisshould involve irrigation with a fluid that hasa similar osmotic pressure to that found in liv-ing cells (26). Wound cleansing solutions mustbe non toxic to human tissues, remain effectivein the presence of organic material, reduce thenumber of microorganisms, not cause sensi-tivity reactions and be widely available andcost effective (10). Suggested cleansing agentsare normal saline, sterile water and even sim-ple tap water (10). In austere environmentssuch as mobile military hospitals, supply linesmay not be able to meet these requirements,especially in a mass casualty situation. Alter-native irrigation solutions may be necessary inthe absence of saline, or in a situation wherea limited saline supply is reserved for casu-alty intravenous resuscitation (33). The use ofpotable water as an irrigant has been stud-ied in contaminated skin lacerations using ananimal model and showed no difference inbacterial reduction between potable water andsterile saline (33–35). It has been even recom-mended for the irrigation of complex mus-culoskeletal wounds and open fractures (33).An experimental study established indeed thatpotable water is as effective as normal salinein removing bacteria from a contaminatedmusculoskeletal wound (33). In the absence ofpotable tap water, boiled and cooled water aswell as distilled water can be used instead aswound cleansing agents (31).

Even though various solutions have beenrecommended for cleansing wounds, normalsaline is favoured as it is an isotonic solutionand does not interfere with the normal heal-ing process. Tap water is commonly used inthe community for cleansing wounds becauseit is easily accessible, efficient and cost effec-tive, however, there is an unresolved debate

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about its use (31). To date, there is no evidenceKey Points

• the benefits of pressurisedirrigation are well recognised

• the bacterial removal efficiencyof the irrigating stream isproportional to the pressureexperienced by the woundsurface

• the benefits of high-pressureirrigation must be weighedagainst potential side effectssuch as the disseminationof bacteria into soft-tissuewounds

• routine unnecessary cleansingcan traumatize fragile newtissue in and around the woundbed

that using tap water to cleanse acute woundsin adults increases infection on the contrary,some evidence suggests that it reduces it (31).Invariably, if cleansing is required, an appro-priate solution should be selected to optimisethe healing process and minimise the risk ofdamage to viable tissue (10). Antiseptic solu-tions may be used exceptionally and caution isadvised as their toxicity might outweigh anybenefits (10,36). In fact, it has been suggestedthat, rather than the product used itself, it isthe physical action of cleansing that removesdebris, contaminants or unwanted exudatefrom a wound bed (10,37).

Although there is no clear consensus of opin-ion as to which is best, cleansing of chronicwounds to remove foreign matter, necrotic tis-sue or bacteria is usually either with normalsaline or tap water (26). For chronic wounds,the relative risk of developing an infectionwhen cleansed with tap water compared withnormal saline is 0.16 (31). It is claimed, how-ever, that because of the complexity of fac-tors influencing a chronic wound, no singletherapeutic intervention will have any signif-icant impact on improving the wound (26,28).Recently a consensus paper became availablethat advocated the use of an active sub-stance, polyhexanide, as a first choice treatmentfor chronic, hard-to-heal wounds suitable forwound bed preparation to remove biofilmprior to further treatment and appears to offer,in the majority of patients, a safe and costeffective method of cleansing wounds which ismore efficient than normal saline (26).

Although most surgeons prefer to treatcontaminated wounds as soon as possible, theeffect of timing on the ability of irrigation toreduce the amount of bacteria in an acutewound is not fully known (38), althoughrecently superior bacterial removal with earlierirrigation was shown in an experimentalcontaminated wound model (38).

The benefits of pressurised irrigation arewell recognised (14,39). It takes significantlysmaller hydraulic pressures to rid the woundof large foreign bodies than it does to removesmall particles and bacteria (14) and the bacte-rial removal efficiency of the irrigating streamis proportional to the pressure experienced bythe wound surface (14). Low-pressure irriga-tion (0.5 pounds per square inch – psi) is bestfor clean wounds, and high-pressure irrigation

(7 psi) can be used instead for dirty or heav-ily contaminated wounds (14). The cleansingeffect of the bulb syringe irrigation is negligiblebecause the wound bacterial concentration isnot significantly affected by this low-pressureirrigation system. High-pressure syringe irri-gation effectively decreases the level of bac-terial contamination and markedly reducesthe incidence of wound infection in contam-inated wounds (14). High-pressure irrigationremoves 80% of the soil infection-potentiatingfactors from the wound (14). Changing thecomposition of the wound irrigation solutionby adding chelating agents, flocculants anddispersants or a non ionic surfactant doesnot significantly enhance the efficiency ofremoval of soil infection-potentiating factorsfrom wounds (14).

In the clinical setting, high-pressure irri-gation is accomplished with an inexpensivedisposable irrigation assembly consisting of a19-gauge plastic needle or catheter attached toa 35-mL syringe. This would exert a pressureequivalent to 7 psi on the wound surface. Incontrast, the pressure encountered by a surfaceirrigated by a bulb syringe is only 0.5 psi (14).To minimise exposure to biologically haz-ardous material during wound irrigation,an overturned plastic gallipot from a sterilewound dressing pack may be used as a splash-guard during the irrigation process (14,40–42).

The benefits of high-pressure irrigation mustbe weighed against potential side effects suchas the dissemination of bacteria into soft-tissuewounds. In fact, the irrigation fluid dissemi-nates into the interstices of the wound, pre-dominantly in a lateral direction. This lateralspread occurs within the loose areolar tissue,contributing to the development of postop-erative oedema. Paradoxically, high-pressureirrigation may make the wound more sus-ceptible to infection, so this technique shouldbe reserved for heavily contaminated woundsonly (14). However, in a recently publishedexperimental study about the effectiveness ofdifferent methods currently used for the irriga-tion of open wounds comparing normal salinesolution, bacitracin solution, castile soap andbenzalkonium chloride with use of a pulsatilelavage device (19 psi) then using the sameanimal model to compare bulb syringe and pul-satile lavage irrigation with saline solution itwas concluded that approaches used to removebacteria from wounds, such as irrigants other

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than saline solution or high-pressure devices,may not have the best clinical outcome (15).

Routine unnecessary cleansing can trauma-tise fragile new tissue in and around the woundbed (10). Moreover, it is well established nowthat wound exudate may contain bactericidalproperties and growth factors that will helppromote wound healing and should only beremoved if copious amounts are present orthere are clinical signs of infection (10).

Disinfection of the skin around the woundby antiseptic agents should be initiated withoutcontacting the wound itself (14). Two widelyused groups of antiseptic agents, containingeither an iodophore or chlorhexidine, exhibitactivity against a broad spectrum of organismsand suppress bacterial proliferation. Thesuperiority of one antiseptic agent over anotherhas not been shown. Although these agentscan reduce the bacterial concentration on intactskin, they seem to damage the wound defensesand invite the development of infection withinthe wound itself. Consequently, inadvertentspillage of these agents into the wound shouldbe avoided (14).

ANTISEPTIC CYTOTOXICITYAND THE EFFECT ON WOUNDHEALINGAnecdotal clinical observations and an increas-ing body of literature suggest that applicationof antiseptics is not as benign as originallyaccepted. The cytotoxic effects of antisep-tics on many of the key cellular participantsin the wound healing process, such as ker-atinocytes and fibroblasts, have been well doc-umented (5,8,9,43,44). Moreover, exposure ofthe wound to either Hibiclens™ (MolnlyckeHealth Care US, LLC, Norcross, GA) orBetadine® (Purdue Products L.P., Stamford,CT) surgical scrub solution has been shownto damage tissue defenses, and cause pain orirritation to tissues (14).

In a recently published important experi-mental study, reductions in proliferation ofnormal human dermal fibroblasts (NHDF),pivotal to the wound healing process, wereobserved when the cells were cultured inthe presence of various antiseptic compoundsfor 96 hours with a few notable excep-tions (9). Both H2O2 and povidone-iodinetreatment led to dose-dependent reductionsin proliferation with complete attenuation

achieved at 500 μmol/L and 0.2% final concen-trations, respectively. Silver-containing com-pounds and chlorhexidine solutions exhibited

Key Points

• it is well established nowthat wound exudate may con-tain bactericidal properties andgrowth factors that will helppromote wound healing andshould only be removed ifcopious amounts are presentor there are clinical signs ofinfection

a different trend. High doses still elicited adecrease in proliferation, but, at lower doses,an increase in proliferation was observed (9).In all instances, the highest doses tested forall the biocides approached 100% inhibition,indicating potential cytotoxicity at these con-centrations (9). All of the antiseptics in adose-dependent manner reduced also migra-tion of the NHDF cells which under nor-mal culture conditions would rapidly invadethe vacant spaces, filling the void within24–48 hours (9). H2O2 was the most effectivecompound tested with complete attenuationachieved at a 1000 μmol/L concentration.Chlorhexidine and povidone-iodine were alsoeffective at reducing migration. On the otherhand, silver sulfadiazine was the least effectivecompound at inhibiting migration, however,a reduction in migration of 36% ± 2% wasobserved at a dose of 10 μmol/L (9). Cellsexposed to H2O2 and povidone-iodine com-pletely lacked important foot-like projectionscharacteristic of normal polarised motility andmigration of cells (9,45). Silver sulfadiazineand chlorhexidine-treated cells as well pre-sented with fewer and less developed filopodiaat the leading edge as compared to none treatednormal cell (9).

The same study also showed that Chlorhex-idine is a strong inhibitor of pro-MMP (matrixmetalloproteinase)-9 and pro-MMP-2 releasein stimulated NHDF cells with 10 ng/mLtumour necrosis factor-α and 10 ng/mL trans-forming growth factor-β1. Exposure of the cellsto 250 and 500 μmol/L H2O2 reduced the pro-MMP-9 release by 70% and 99%, respectively.A 66% reduction in pro-MMP-2 release wasalso seen in both H2O2 treatment groups (9).A dynamic range of effects was exhibited withsilver-containing compounds and povidone-iodine. When exposed to low levels of silver,a reduction of pro-MMP-2 and an increasein pro-MMP-9 was observed. Silver sulfadi-azine had a more pronounced effect thansilver nitrate in up-regulating pro-MMP-9 (18%increase versus 5%). High doses, however,attenuated the pro-MMP-9 release and greatlyreduced pro-MMP-2 levels below those of rest-ing levels. Low-dose iodine exposure of thesecells resulted in almost a threefold increasein pro-MMP-9 release from stimulated cells.

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No significant change in pro-MMP-2 releasewas observed at this dose. High-dose expo-sure to iodine was strikingly different. NoMMP release was detected in these cells (9).In addition, low-dose silver, H2O2 and iodineall increased the conversion of the pro-MMP-2into the truncated, active form (9).

Key Points

• although the type of open-wound management must beindividualized for each wound(14), cleansing bacteria, soiland other debris from trau-matic wounds, as well as sur-gical debridement cannot beoveremphasized

• although certain skin andwound cleansers are designedas topical solutions with vary-ing degrees of antimicro-bial activity, wound cleansersmay also be antimitotic andadversely affect normal tissuerepair

• available experimental datasuggest that the effects of anti-septic treatment on fibroblastsare more encompassing thanjust toxicity

• wound management strategiesaddress the delicate balancebetween cytotoxicity and cellu-lar activities

• despite cytotoxicty data, mostantiseptics have not beenshown to clearly impede heal-ing, especially newer formu-lations like cadexomer iodine(which speeds healing) andnovel silver delivery systems.These compounds appear to berelatively safe and efficient inpreventing infection in humanwounds

• the continued unjustified useof antibiotics will have to beaddressed if the rise of resistantand emergent organisms is tobe controlled

• topical antimicrobials, such asthe antiseptics,could be usedmore often to avoid the needfor antibiotics particularly inwound care and managementprotocols

• unfortunately, given thisreview, it is not possible toformulate rigid guidelines or topropose an algorithm regard-ing the use of antiseptics forroutine wound cleansing

• the role of antiseptics onwounds and their role in woundcare management should becritically reconsidered

CONCLUSIONQuality of care is a critical requirement forwound healing. Strategies that optimise the tis-sue repair process have evolved with advancesin understanding of the wound healing pro-cess (5). Although the type of open-woundmanagement must be individualised for eachwound (14), cleansing bacteria, soil and otherdebris from traumatic wounds, as well as sur-gical debridement cannot be overemphasised.Debridement removes tissue heavily contam-inated by soil infection-potentiating fractionsand bacteria, and excises devitalised tissuesthat impair the wound’s ability to resist infec-tion (14).

It is argued that wound cleansing has threeelements, namely, the technique, the solutionand the equipment (46,47). Techniques usedinclude high-pressure irrigation, swabbing,low-pressure irrigation, showering, bathingand washing the affected area under arunning solution or total immersion in awhirlpool bath. Different cleansing solutionsare also used, for example, normal saline,water and antiseptic solutions. Furthermore,wound cleansing requires the use of equipmentsuch as syringes, needles, catheters and pres-surised canisters (46,47). Some have arguedthat wound cleansing can have a positiveimpact on wound healing outcomes, however,it is conducted mostly without a clear rationaleunderpinning the practice (46,48). Althoughcertain skin and wound cleansers are designedas topical solutions with varying degrees ofantimicrobial activity, wound cleansers mayalso be antimitotic and adversely affect normaltissue repair (5).

Skin cleansers are most toxic to fibrob-lasts (5). Available experimental data suggestthat the effects of antiseptic treatment onfibroblasts are more encompassing than justtoxicity (9). Keratinocyte monolayers, repre-senting the in vivo basal layer of the epidermisthat epithelialises the wound surface afterinjury, are more sensitive to wound cleanserssuch as H2O2, modified Dakin’s solution

(0.025%) and povidone (10%) (5). Repeatedand excessive treatment of wounds with anti-septics without proper indications may havenegative outcomes or promote a microenvi-ronment similar to those found in chronicwounds (9). However, when applied at theproper times and concentrations, some classesof antiseptics may provide a tool for theclinician to drive the wound bed in desireddirections (9). Wound management strategiesaddress the delicate balance between cytotox-icity and cellular activities. Irritation of intacthealthy tissue could seriously impact the rateand quality of tissue repair (5). Although theremoval of antiseptics from the wound bedmanagement arsenal cannot be advocated, careshould be used when administering theseproducts (9). Despite cytotoxicty data, mostantiseptics have not been shown to clearlyimpede healing, especially newer formula-tions like cadexomer iodine (which speedshealing) and novel silver delivery systems.These compounds appear to be relatively safeand efficient in preventing infection in humanwounds (13).

The continued unjustified use of antibioticswill have to be addressed if the rise of resistantand emergent organisms is to be controlled.Topical antimicrobials, such as the antisep-tics, could be used more often to avoid theneed for antibiotics particularly in woundcare and management protocols (16). Unfor-tunately, given this review, it is not possibleto formulate rigid guidelines or to propose analgorithm regarding the use of antiseptics forroutine wound cleansing. On the contrary, therole of antiseptics on wounds and their role inwound care management should be criticallyreconsidered (13).

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