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  • WOUND CLEANSING

    Antiseptics, iodine, povidoneiodine and traumatic woundcleansingMuhammad N KhanGeneral Surgery, North Hampshire Hospital NHS Trust, Basingstoke.Abul H NaqviGeneral Surgery, St Luke's Hospital Kilkenny, County Kilkenny, Ireland

    Key words: antiseptic, iodine, povidone, traumatic wound cleansing

    Received 19 July 2005, accepted for publication 1 November 2005

    AbstractWound cleansing is an integral part of the management ofacute traumatic wounds. There is consensus that itreduces infection rates. However, the choice of cleansingagent remains controversial, especially the use ofantiseptics has been questioned. This article reviews thecurrent literature on the use of antiseptics particularlypovidine iodine in traumatic wound cleansing anddiscusses the beneficial and harmful effects of suchpractice.

    IntroductionNumerous studies have shown the conflicting results ofbactericidal properties, cytotoxicity and suppression ofwound healing with the use of antiseptics. Due to the lackof powerful clinical studies, a standardised regimen hasyet to be established.

    The existing evidence regarding the use of povidoneiodine is complicated by the mixture of laboratory,human and animal studies. In vitro studies have shownthe toxic effects at a cellular level but clinical studies havefailed to show statistically significant difference comparedwith control interventions. With the emergence ofantibiotic resistance, there has been a reappraisal of theuse of povidone iodine especially in the management ofcontaminated and infected wounds.

    Acute wounds are defined as wounds that heal withinan expected time frame without complications'.Traumatic wounds are one category of acute wounds that

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    account for about 20-25% of the accident and emergencydepartment workload2. Depending upon the mechanismof injury they can vary from abrasions and contusions tolacerations and avulsions or degloving injuries] Traumaticlacerations occur when the body is subjected to a forcethat exceeds the strength of skin or the underlyingtissues" Due to the presence of devitalised tissue, foreignbodies and bacteria, traumatic wounds often predisposeto the development of invasive infection, which mayrange from cellulites to deep myositis.

    Wound cleansingWound cleansing forms a critical part of the managementof these wounds. It applies to the application of fluid toaid removal of exudate, debris, slough and contaminants'.Any traumatic wound should be consideredcontaminated at presentation6. Thorough cleansing ofthese wounds has shown to reduce the infection rate78

    The objective of wound cleansing is to remove theorganic and inorganic debris and to create optimum localconditions for wound healing". However, unnecessaryremoval of the exudate may deprive the wound of thenecessary repair agents and enzymes responsible for thecoordinated sequence of wound healing and will result indrying of the wound, which goes against the principles ofmoist wound healing'o,,,.

    Different terms including wound cleansing, woundcleaning and wound irrigation have been used in theliterature. Unfortunately these terms have not beenstandardised in studies and are used interchangeably.Swabbing and irrigation are the usual cleansingtechniques but bathing or showering are other options

    VOL 16 NO.4 NOVEMBER 2006

  • described in the hterature.Apart from different techniques used for cleaning and

    irrigating wounds, there is disparity among the solutionsused for cleansing. Different solutions ranging from tapwater to normal sahne to antiseptics have been used, allhaving their own disadvantages and advantages. Theassessment and protocol of management, however, seemsrituahstic rather than evidence based1213

    Although there is evidence to suggest that woundcleansing is not always necessari4, there is no diagnostictest that would allow healthcare professionals to identifythe bacterial load in the wound capable of causing woundinfection". The situation is further complicated by studiesshowing that bacterial colonisation of the wound does notnecessarily indicate infection and there is no need toremove the bacteria in the absence of clinical signs ofinfection'6.".

    AntisepticsThe use of antiseptics, particularly povidone iodine, in themanagement of acute traumatic wounds has remained acontroversial issue over the last two decades. It is alsoimportant to realise that the term iodine has sometimesbeen used to describe all formulations including povidoneiodine, cadexomer iodine and others. These preparationshave different iodine concentrations and differentcharacteristics of their component parts. This raises thequestion of whether they should be grouped and studiedseparately.

    The term antiseptic was first used by Pringle in 1750'"'An antiseptic is a substance that inhibits the growth anddevelopment of micro-organisms causing sepsis inwounds'9. They may be either bactericidal orbacteriostatic. Commonly used antiseptics for woundcleansing include chlorhexidine, iodine compounds,alcohol, benzalkonium chloride and hydrogen peroxide.

    The use of antiseptics in wound care is controversial.The debate started after Fleming's lecture in 1919 abouthis work on antiseptics in septic wounds. The use ofantiseptics began to decrease in 1929 after the discoveryof penicillin. Stringer et al showed that antiseptics conferno benefit as compared to sahne in cleansing wounds'o Invitro experiments by Brennan and Leaper2' demonstratedantiseptics were detrimental to the production ofcollagen, impairing epithehal migration and inhibitingmicrocirculation. Furthermore antiseptics are inactivatedby contact with body fluids, blood, and proteins'However, they need to be in contact long enough toreduce bacterial numbers23

    This evidence led to a decrease in the popularity ofantiseptics for wound cleansing and there was a decline intheir use with more emphasis on antibiotics in thetreatment of contaminated/infected wounds. However,with the emergence of bacterial resistance to antibiotics,there has been a reappraisal in the use of antiseptics, andespecially iodine compounds.

    VOL 16 NO.4 NOVEMBER 2006

    Iodine is one of the long established antiseptics. Earlypreparations caused local pain and tissue reaction.Povidine iodine was introduced 40 years ago. It containspolyvinylpyrrolidone iodine, which is a water solublecomplex of elemental iodine with a synthetic polymer.10% solution in water is the most commonlymanufactured form.

    It has a bactericidal action and is effective against awide range of bacteria, fungi and even spores24 .The killingaction occurs in seconds and is thought to be frominactivation of vital cytoplasmic substrates, which arenecessary for bacterial viability25. Plasm~ proteins can bindup to 80% of free iodine'6

    The presence of organic matter has a markeddepressant effect on the minimum lethal concentrationsof iodine. In the absence of inhibitors the disinfection israpid, probably less than 10 seconds27

    Antiseptics were the main stay of wound managementuntil the mid-1980s, when research by Brennan andLeaper showed the effects of antiseptic solutions onwound healing physiology. They evaluated the effects ofvarious antiseptics on wound micro-circulation in therabbit ear chamber model of healing. The action ofantiseptics on micro-circulation within the granulationtissue was examined with a laser Doppler flow meter. Inwounds exposed to Eusol and chloramines T, the tissueperfusion ceased immediately and even after several daysof observation these vessels did not re-open. Sahne andhydrogen peroxide did not result in any change in thepattern of blood flow. Chlorhexidine caused a fewcapillaries to close down. The effect of povidine iodinewas concentration dependent. At a concentration of 5%,blood flow ceased in small blood vessels but a 1% solutionwas innocuous. This study is quoted as the strongestevidence against the use of antiseptics.

    However, the sample size was small, with only twowounds for each cell type. In order to be statisticallysignificant this study needs to be rephcated. There shouldalso be some concern in transferring the data from anexperimental model to a clinical situation. Furthermorethere is no strong evidence on human models of woundhealing. The authors have shown that the apphcation ofantiseptics irreversibly destroys angiogenesis, however itshould be remembered that angiogenesis is just one stepin the complex healing cascade. The Doppler flow meterused by the authors to monitor the micro-circulationcould not be calibrated in order to provide a reading offlow per unit time. This may have affected the rehabihtyof measurements. They also used the term 'flooding theear chambers with antiseptic', which needs cleardefinition.

    Further in vitro studies have shown that the weakersolutions of hypochlorites, compatible with thepreservation of fibroblast function, can still inhibit thegrowth of bacteria including Staphylococcus aureus,Pseudomonas, Bacteriodes, and Eschericia colf8

    7

  • WOUND CLEANSING

    But it must be remembered that in vivo the presenceof pus, blood and exudate can further dilute theconcentrations of these antiseptics and decrease theirefficacy. Hypochlorites also result in skin irritation andare harmful to granulation tissue29. Research by Tatnall eta130 has shown that at concentrations recommended forwound cleansing, hypochlorite, hydrogen peroxide andchlorhexidine, all result in 100% killing of culturedkeratinocytes and fibroblasts, with the hypochloritesbeing the most toxic. Hence the routine use ofhypochlorites in wound cleansing is not advisable.

    IodineThere have been conflicting studies regarding theusefulness of iodine in managing traumatic wounds",nClinical trials have shown mixed success33,34,35.

    Roberts et a136 published a series of 418 patients withhand lacerations who were randomly allocated to a groupwhere the injury was treated with povidone iodine beforesuturing and to a control group. They found no adverseeffects of iodine on healing and the overall infection ratewas significantly lower in the group treated withpovidone iodine.

    Similar results were seen by Gravett et al (1987) whenthey compared 1% povidone iodine to normal saline inthe management of traumatic lacerations and found astatistically significant difference between the two groupswith an infection rate of 5.4% and 15.4% respectively''.Gordon (1993) found iodine very effective againstMRSA and its value in helping control MRSA outbreaksis well recognised38,39.

    Similarly Goldenheim (1993) demonstrated thatpovidine iodine .preparations do not have a deleteriouseffect on healing, It is useful in the treatment of burnsbecause of its broad-spectrum activity and highpenetration power'o. However, he recommended that itshould not be used in pregnant women, newborns andthose with thyroid disorders.

    Research by Cooper and Lawrence" found thatwound cleansing with povidone iodine or cetrimide didnot significantly reduce the number of bacteria present incontaminated lacerations.

    The mere presence of bacteria in a wound does notnecessarily mean infection as wounds are usuallycolonised by bacteria. However, if the bacterial countreaches a certain level where the host defences cannotmaintain the balance of organisms in the wound, it isreferred to as critical colonisation42 and it can be apredecessor of invasive infection,

    Timely and appropriate use of topical antiseptics mayreturn a wound from critical colonisation back to thestate conducive to wound healing. Bacteria in the woundnot only delay healing but also produce malodour; their

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    toxins can be destructive to the wound bed and they canresult in an increase in the amount of exudate.

    Medicated wound dressings impregnated with iodinehave also been evaluated in the management of acutewounds and have met with m.i..,'Xed success. Cadexomeriodine ointment has been found to be highly efficaciousand has been reported to accelerate epithelisation ascompared to air exposed wounds, with out any deleteriouseffects". It has also proven effective against proliferation ofMRSA in wounds. Davison and Keenan" have reported arandomised trial of three different wound dressings afternail matrix ablation with phenol. Povidone-iodine dressing,'amorphous hydrogel dressing and a paraffin gauze dressingwere compared, The main outcome measure was clinicalinfection rate and there was no statistically significantdifference between the three groups.

    Iodine released from cadexomer iodine has beenshown to have a pro-oxidant effect, which couldstimulate fibroblast proliferation in vitro". It also inducestumour necrosis factor alpha and inhibits the productionof Interleukin-6 (IL-6) from macrophages, growth factorsthat are important for inflammation induction'6.

    Development of resistance to antiseptics is thought tobe rare. However, certain species such as bacterial spores,mycobacteria and gram-negative bacteria possess intrinsicresistance and several bacteria can acquire plasmidmediated resistance".

    Development of resistance to povidone iodine is veryunlikely because it requires alteration in the bacterial cellproteins'8. Povidone iodine also has an effect on thebacterial exotoxins and enzymes, which can cause furthertissue damage'9. Yasuda et al's study' looked at theantiseptic resistance of 20 bacterial strains and found thatpovidone iodine killed all bacteria within 20 seconds,

    This study showed that iodine is effective againstintrinsically resistant and non-resistant gram negativebacteria. Studies have shown that the acquisition ofresistance to the long-term use of povidone iodine is notobserved".

    Iodine solutions are deactivated in the presence oforganic material, pus, slough and necrotic tissue in thewound52,53,5'. In vitro experiments by Lawrence5s haveshown that although the presence of exudate deactivatespovidone iodine dressings, they can reduce the bacterialcounts of the wounds to a very low level as compared tocontrols.

    Studies by others have shown different results.Kunisada et a1'6 tested povidine iodine, chlorhexidine andbenzalkonium chloride solutions against differentnosocomial bacteria. They used solutions of differentconcentrations and exposed them for varying lengths oftime, The bacteria were suspended in differentconcentrations of neutralising plasma serum. The resultsshowed that povidine iodine was highly effective againstall the test organisms at a very low concentration andover a short period of time. However, the in vitro

    VOL 16 NO.4 NOVEMBER 2006

  • evaluation of the antibacterial activity of an antisepticmay not necessarily be a good guide to its activity inclinical use. Its effects on the immune system, toxiceffects on wound healing and inactivation by the bodyfluids should also be taken into accounf5

    Animal studies involving antiseptics have shownchlorhexidine, iodine and hydrogen peroxide to be toxicto fibrobiasts'l. Povidine iodine even at lowconcentrations has been shown to be toxic togranulocytes and monocytes" and results in decreasedchemotaxis5". It is also capable of suppressing lymphocytefunctions59 .

    Mulliken et al60 studied the tensile strength of heahngwounds in winstar rats and found no statistical differencein the rate of gain of tensile strength and histologicalappearance between the control and experimentalgroups. They concluded that apphcation of 1% povidoneiodine solution to clean incised wounds does not affectfibroplasia or collagen cross-linking. In vivo studies haveshown that application of 5% povidone iodine solutioninhibits polymorphonuclear leukocytes and fibroblastmigration and activity61.

    In contrast, research in 2001 by Bennett et a162 onporcine models of wound healing has shown thatapphcation of 10% povidone iodine solution is associatedwith increase in the number of proliferating fibroblasts atday four and enhanced angiogenesis at day seven ascompared to the controls6'. However, different researchmethodologies make the comparison of these studiesdifficult.

    Work in 2002 by Balin and Pratt has shown that evendilute solutions of povidone iodine can be toxic tohuman fibroblasts as at concentrations of 0.1 % and 1%,human fibroblast growth is totally inhibited"3.Concentrations lower than 0.1 % progressively retard thegrowth. However, they have also noted that there waspartial recovery of cell growth after limited exposure.

    The results of the above studies are conflicting,however it must be remembered that the relationshipbetween povidone iodine and free iodine concentrationsis not linear, as it forms a bell shaped curve, which peaksat 0.7% concentration. Higher concentration of povidoneiodine can paradoxically bind more free iodine to thecarrier molecule, thereby lowering the available freeiodine6'.

    Iodine compounds are not hazard free. Toxicsymptoms can result from systemic absorption. Theseinclude nervousness, depression, insomnia, myxoedema,hypersensitivity and skin reactions6s . The absorptiondepends upon the concentration and the particular use ofiodine.

    Absorption is increased in the presence of damagedtissue, hence its use is not recommended in burnsinvolving more than 20% of the body surface area66.Metabolic acidosis and hypernatremia are the otherpossible toxicities6'.

    VOL 16 NO.4 NOVEMBER 2006

    ConclusionWound cleansing remains a corner stone in themanagement of acute traumatic wounds". Due to thelack of powerful clinical studies, a standardised regimenhas yet to be established54

    The existing evidence regarding the use of povidoneiodine is complicated by the mixture of laboratory,human and animal studies. In vitro studies have showntoxic effects at cellular level but clinical studies havefailed to show statistically Significant differences withcontrol groups.

    With the emergence of antibiotic resistance, there hasbeen a re-appraisal of the use of povidone iodineespecially in the management of contaminated andinfected wounds. Well designed in vivo studies arerequired to prove its efficacy, however the debate seemsto be far from resolved.

    AcknowledgementsWe are grateful to Dr. Sadaf Rafique for her generoushelp with the hterature search and proofreading.

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    Antiseptics, iodine, povidone iodine and traumatic wound cleansingAbstractIntroductionWound cleansingAntisepticsIodineConclusionAcknowledgementsReferences