Extending the TIME concept: what have we learned … antiseptics (silver, honey and iodine-based...

ORIGINAL ARTICLE

Extending the TIME concept:what have we learnedin the past 10 years?*David J Leaper, Gregory Schultz, Keryln Carville, Jacqueline Fletcher,Theresa Swanson, Rebecca Drake

Leaper DJ, Schultz G, Carville K, Fletcher J, Swanson T, Drake R. Extending the TIME concept: what have we learnedin the past 10 years? Int Wound J 2012; 9 (Suppl. 2):1–19

ABSTRACTThe TIME acronym (tissue, infection/inflammation, moisture balance and edge of wound) was first developed morethan 10 years ago, by an international group of wound healing experts, to provide a framework for a structuredapproach to wound bed preparation; a basis for optimising the management of open chronic wounds healing bysecondary intention. However, it should be recognised that the TIME principles are only a part of the systematic andholistic evaluation of each patient at every wound assessment. This review, prepared by the International WoundInfection Institute, examines how new data and evidence generated in the intervening decade affects the originalconcepts of TIME, and how it is translated into current best practice. Four developments stand out: recognition ofthe importance of biofilms (and the need for a simple diagnostic), use of negative pressure wound therapy (NPWT),evolution of topical antiseptic therapy as dressings and for wound lavage (notably, silver and polyhexamethylenebiguanide) and expanded insight of the role of molecular biological processes in chronic wounds (with emergingdiagnostics and theranostics). Tissue: a major advance has been the recognition of the value of repetitive andmaintenance debridement and wound cleansing, both in time-honoured and novel methods (notably using NPWTand hydrosurgery). Infection/inflammation: clinical recognition of infection (and non infective causes of persistinginflammation) is critical. The concept of a bacterial continuum through contamination, colonisation and infectionis now widely accepted, together with the understanding of biofilm presence. There has been a return to topicalantiseptics to control bioburden in wounds, emphasised by the awareness of increasing antibiotic resistance.Moisture: the relevance of excessive or insufficient wound exudate and its molecular components has led to thedevelopment and use of a wide range of dressings to regulate moisture balance, and to protect peri-wound skin, andoptimise healing. Edge of wound: several treatment modalities are being investigated and introduced to improveepithelial advancement, which can be regarded as the clearest sign of wound healing. The TIME principle remainsrelevant 10 years on, with continuing important developments that incorporate new evidence for wound care.Key words: Chronic wounds • Debridement • Infection • Inflammation • Moisture balance • TIME • Wound bed preparation

INTRODUCTIONThe TIME acronym was first developed morethan 10 years ago, by an international groupof wound healing experts, to provide a

Authors: DJ Leaper, MD, ChM, FRCS, FACS, FLS, Section of Wound Healing, Institute for Translation, Innovation, Methodology andEngagement, Cardiff University, Cardiff, UK; G Schultz, PhD, Department of Obstetrics and Gynecology, Institute for Wound Research,University of Florida, Gainesville, FL, USA; K Carville, RN, STN(Cred), PhD, Silver Chain Nursing Association & Curtin University, OsbornePark, Western Australia; J Fletcher, MSc, BSc, PGCE, RN, FHEA, Institute for Translation, Innovation, Methodology, and Engagement,Cardiff University, Cardiff, UK; T Swanson, RN, NPWM, AA/Dip Nursing (USA), CC(WNDM), PGC(Periop), PGDip HSc (Nursing), Masters HSc(Nursing), International Wound Infection Institute, South West Healthcare, Warrnambool, Victoria, Australia; R Drake, BSc, London, UKAddress for correspondence: Prof. David J Leaper, Section of Wound Healing, Institute for Translation, Innovation, Methodology,and Engagement, Cardiff University, Cardiff CF14 4XN, UKE-mail: [email protected]*Sponsored by Smith & Nephew Wound Management.

framework for a structured approach to woundbed preparation (1). This concept was adoptedfrom a principle used in plastic surgery toensure optimal preparation of a recipient

© 2012 The AuthorsInternational Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc 1

Extending the TIME concept

wound bed before split thickness skin grafting,and which was deemed to be a relevant frame-work for optimising the management of openchronic wounds healing by secondary inten-tion. The framework was therefore termed‘wound bed preparation’ and was subse-quently published in 2003 by Schultz et al. (1).Since then the TIME acronym has been widelyused as a practical guide for the assessmentand management of chronic wounds. The clin-ical observations and interventions relating towound bed preparation are grouped into fourareas, all of which need to be addressed at eachwound assessment:

• Tissue: assessment and debridement ofnon viable or foreign material (includ-ing host necrotic tissue, adherent dress-ing material, multiple organism-relatedbiofilm or slough, exudate and debris) onthe surface of the wound.

• Infection/inflammation: assessment of theaetiology of each wound, need for topicalantiseptic and/or systemic antibiotic useto control infection and management ofinappropriate inflammation unrelated toinfection.

• Moisture imbalance: assessment of theaetiology and management of woundexudate.

• Edge of wound: assessment of non advanc-ing or undermined wound edges (andstate of the surrounding skin).

The TIME acronym was first presented atthe 2003 annual meeting of the EuropeanWound Management Association and has sincebeen cited frequently in wound managementpapers, guidelines, protocols and consensusdocuments, in addition to being included inseveral other formats such as practical teach-ing aids and product formulary tools. Althoughcertain aspects of the TIME acronym have beenconsidered by some to be problematic (whichare discussed later), it has generally been foundto be a useful tool. Nevertheless, the TIME prin-ciples should always be considered as part of asystematic and holistic evaluation of the patientand their healing environment (Figure 1).

Since the TIME acronym was developed,there have been several developments inwound healing science, notably in the fieldsof molecular and biological research, andin the development, introduction and use

of new wound management therapies. Fourdevelopments stand out:

• Recognition of the presence of biofilmsin chronic wounds has increased expo-nentially. Although still the source ofmuch debate and discussion, biofilms arenow known to have a significant negativeinfluence in chronic wounds, and the man-agement and eradication of biofilms is anintegral part of wound healing.

• Increasing use of negative pressure woundtherapy (NPWT), which has had anexpanding influence in the treatment ofseveral wound types, including acute sur-gical wounds as well as chronic wounds.

• Evolution of a number of topical antimi-crobial treatments (particularly silver andother antiseptic dressings).

• Expanded insight into the molecular biol-ogy of wounds and the role of proteasesand pro-inflammatory markers in chronicwounds, which has led to the continuingemergence of a range of diagnostic andtheranostic devices.

In response to these developments and adecade of new evidence found in the literature,the International Wound Infection Institute hasre-examined the TIME acronym and the prin-ciples of wound bed preparation to determineits validity for current best practice. The origi-nal table from the 2003 publication (1) has beenevaluated in the context of these new develop-ments, and a new version has been produced,detailing important developments that affectthe principles of TIME.

TIME – TISSUEOver the past decade, there have been con-siderable developments in wound care tech-nology; in particular, the devices or therapiesused for wound debridement, such as low-frequency ultrasound, hydrosurgery devices,larvae and enzymatic agents. Furthermore,there is increased understanding of the role thatdebridement plays in the treatment of woundbioburden and infection, biofilm manage-ment, and subsequent maintenance of moisturebalance.

DebridementNecrotic, non viable tissue and excessivelycolonised, multiple organism-related biofilm

© 2012 The Authors2 International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc


Tissue debridement

Moisture balance

Inflammation Infection

Epithelial edge

Therapeutic services environment

Holistic & systemic

evaluationCost benefit &

QoL issues

Surrounding skin

Wound bed preparation

Patient environment

Healing environment

Figure 1. The TIME concept as part of the overall patient evaluation (created by David Leaper & Dianne Smith, with thanks toCaroline Dowsett for the original concept of the Care Cycle).

or slough, exudate and debris are common inchronic non healing wounds and are knownto delay healing, provide a focus for infec-tion, exacerbate the inflammatory response andimpede optimal progression of wound gran-ulation, contraction and epithelialisation. Theremoval of this material is therefore consideredto be beneficial in stimulating healthy tissue toheal (2–4). The methods of debridement aresummarised in Table 1 (5–11).

A number of guidelines and recommenda-tions on wound bed preparation have beenpublished following publication of the firstconcept of TIME. The Debridement Perfor-mance Index was published in 2002 and wasshown to be an independent predictor ofsuccessful wound closure. It assesses callusremoval, undermining of the wound edges andwound bed necrotic tissue (12). A wound bedscore (WBS) system has been developed (13),which provides a more general assessmentof the wound and wound bed preparation.It scores the following clinical parameters(from 0 to 2): healing edges (wound edgeeffect), presence of eschar, greatest wounddepth/granulation tissue, amount of exudate,oedema, peri-wound skin inflammation, peri-wound callus and/or fibrosis, and presence ofa pink/red wound bed. A total score of 16 canbe achieved, and a significantly higher WBS canbe expected in wounds that go on to achievefull closure, than in those that fail to heal.

Recommendations by another expertpanel (14) propose the use of maintenance-debridement for removal of tissue in the woundbed when it is colonised with an excessivebacterial burden. The aim is to help main-tain the wound in a healing mode, and it isrecommended that maintenance-debridementshould be performed if the wound is not show-ing evidence of closure – even if the woundbed appears clinically ‘healthy’.

A list of top tips for wound debridement (5)recommends that specified procedures andprinciples be adhered to when undertak-ing commonly used methods of debridement(Box 1). Before beginning any debridementprocedure, the clinical practitioner is encour-aged to ensure that the patient understands theprocedure, and the patient’s consent should beobtained.

Wound CleansingTwo recent Cochrane reviews have sum-marised methods that are used for woundcleansing. The first reviewed wound cleansingfor pressure ulcers, and concluded that there islimited evidence to support the use of a salinespray containing aloe vera, silver chloride anddecyl glucoside in these wounds, but could findno strong evidence to support the use of anyparticular solution or technique for cleansingpressure ulcers (15). The second review con-cluded that there is no evidence that using tap



Table 1 Methods of debridement

Type of debridement Methods used

Autolytic debridement• Moistens necrotic tissue, allowing

degradation by host enzymes (2,5)

Occlusive or semi-occlusive dressings (i.e. hydrocolloids) or hydrogels (2,5,6)

Hypertonic saline and honey, dressings promote autolytic debridement byosmosis (7)

Polyacrylate, activated by Ringer’s solution (8)

Some antiseptics (silver, honey and iodine-based products) can also be used asautolytic debriding agents

Enzymatic debridement• Frequent dressing changes needed• Slow but specific• May be used with other debridementstrategies

Collagenase/papain: not available worldwide (papain has been discontinued,as have streptokinase/streptodornase & fibrinolysindesoxyribonuclease) (9,10)

Mechanical debridement (5)• Non specific but gives fast results• Can be painful & harm viable tissue

Hydrosurgery or wound cleansing debridement – wound cleansing 4–14 psiHydrosurgical 15 000 psi (11)

Whirlpool debridement

Recently developed debriding pads with monofilaments which allegedly retaindead tissue and bacteria

Ultrasound debridement (5): Two types: contact and non contactUltrasound probe – agitates the wound bed directly; works by cavitation and

acoustic streamingAtomised saline – gas-filled bubbles explode at the wound bed lifting necrotic

tissue and bacterial cells

Larval (maggot) therapy (5)• Selective microdebridement

Lucilia sericata, Phaenicia sericata and Lucilia cuprina used

Sharp debridement (5)• Not selective• Risks of bleeding & tissue damage

For removal of necrotic/septic tissue using scalpel & scissors

Surgical debridement (5)• Surgeon or advanced practitioner• Not selective• Risks of bleeding & tissue damage

For large-scale removal of necrotic/septic tissue using scalpel & scissors – by askilled practitioner only

Chemical debridement Antiseptics (octenidine, silver, povidone iodine and chlorhexidine, PHMB)

Older debridement agents can be painful & have toxic effects onhealthy tissue, but can also be effective when used for limitedperiods of time

water to clean a wound increases the risk ofwound infection, and that there is no strongevidence to suggest that wound cleansingdecreases infection or promotes healing (16).This review was updated in 2012 (17), butno new studies were identified as eligible forinclusion. However, in this update, the authorsconcluded that there is some evidence thatusing potable tap water to clean a wound mayreduce infection, and that it is likely to be assafe as sterile water or saline. Nonetheless, cau-tion should be exercised in the use of tap waterin immune-compromised patients, particularlyif the water might be non potable (18). The use

of non cytotoxic antiseptic irrigants for woundcleansing is widely practiced but the evidencebase for their use is weak and requires furtherresearch.

Negative pressure wound therapyThe use of NPWT, or vacuum-assisted woundtherapy, has become increasingly prominent inwound management. Negative pressure, whenapplied to the wound via a sealed foam orgauze dressing, facilitates wound drainage,and reduces oedema and the bioburdenof microorganisms, while increasing woundperfusion. Recent developments have revealed



Box 1

TOP TIPS FOR DEBRIDEMENT (5)

• Environment

• Ensure that the room chosen fortreatment is suitable, with adequatedisposal facilities

• The room should include privacy,adequate lighting and positioningcapacity

• Close doors and windows to preventcross-contamination

• Basic equipment should be provided,for example, scalpel, forceps, curette,sharp scissors

• Wound inspection

• Carry out a thorough inspection ofthe wound bed

• Focus on the material in the woundbed that is to be removed

• Ensure that no structures such as lig-aments or blood vessels are involvedwith the tissue to be removed

• Consider patient and wound condi-tion plus goal of treatment

• Ensure that the appropriate debride-ment method is selected for the vol-ume of tissue to be removed

• Competency

• Ensure that the debridement methodselected falls within the clinician’straining and competency

that NPWT may loosen slough and necrosis,and facilitate sharp debridement (19), althoughcaution is recommended when tissue ismore than 20% devitalised. The combinationof NPWT with several other debridementmethods has been demonstrated to supportTIME principles, as it expedites removal ofexudate and infective material and promotesgranulation tissue formation, contraction andepithelialisation (20).

TIME – Tissue. What has changed? Theoriginal TIME table indicated that non viabletissue, multiple organism-related biofilmor slough, exudate and debris signifies adefective wound bed that needs debridementto restore successful wound healing. This

principle has not changed, although someof the practices used to facilitate thishave changed over the intervening years.Advances in debridement technology such aslow-frequency ultrasound, hydrosurgery andadd-on use of NPWT devices with existingtechnology have led to more efficaciousoutcomes, as have advances in traditional nonsurgical debridement methods such as larvaland enzymatic debridement. The practice ofrepetitive or maintenance-debridement forthe management of static chronic woundshas also improved outcomes.

TIME – INFECTION/INFLAMMATIONInflammation is a physiological response towounding and is required for wound healingto progress. However, excessive or inappro-priate inflammation, often in the presence ofinfection, may have serious consequences forthe patient. Chronicity or the stalling of healingin wounds may be due to persistent inflam-mation (2,18). Wounds that do not progressbeyond an inflammatory phase often demon-strate an increased activity of proteases suchas matrix metalloproteinases (MMPs) and elas-tase, as well as the persistence of inflammatorycells. Prolonged degradation of the extracellu-lar matrix and suppression of growth factorsmay also hinder wound healing. The presenceof wound biofilm may further inhibit downreg-ulation of the immune response, causing sys-temic debilitation, unless adequately disruptedand treated (21). Elimination or reduction ofprolonged inflammation revitalises tissue heal-ing, reduces exudate and is usually associatedwith a reduction in bioburden. It is impor-tant that the clinician can confidently distin-guish signs and symptoms of inflammationrelated to normal physiological healing fromthose related to excessive inflammation causedby underlying adverse aetiologies and infec-tion. The clinician should, however, be awarethat inflammation may also be the result ofa number of non infective, autoimmune dis-eases, such as systemic lupus erythematosus,rheumatoid arthritis, vasculitis or scleroderma,or due to an inflammatory condition such asinflammatory bowel disease where pyodermagangrenosum may result. Their recognitionand management is beyond the scope of thisarticle.



The signs and symptoms of infection maybe subtle or non specific (Box 2) – so careshould be taken to ensure that they are recog-nised (22). All wounds are potentially sub-ject to exogenous and endogenous microbialcontamination. The microbial bioburden in awound can range from contamination, coloni-sation or critical colonisation and ultimatelyto local and systemic infection if not appropri-ately controlled (Table 2). It has been suggestedthat this progression is also influenced by thepresence of maturing bacterial biofilm in thewound (23).

The clinician needs to be aware of the signsand symptoms of localised, spreading (suchas cellulitis and lymphangitis) and systemicinfection. The classic signs of infection areusually obvious in acute or surgical woundsin otherwise healthy patients. When patientsare immunosuppressed or malnourished, how-ever, or have comorbidities such as diabetesmellitus, anaemia, renal or hepatic impairment,malignancy, rheumatoid arthritis, morbid obe-sity or arterial, cardiac and respiratory disease,these signs of infection may be more subtle.An increase in pain and wound size in chronicwounds are probably the two most useful pre-dictors (24). The decision to use systemic or top-ical antibiotics should be carefully consideredin light of the risk of antimicrobial resistance,but topical antiseptic dressings might prove tobe valuable prophylactic measures in patientswhere infection is suspected – particularly asmore recent evidence suggests that they mayprevent attachment, as well as maturation, ofbiofilm (25).

BiofilmsA biofilm is a complex microbial commu-nity, consisting of bacteria embedded in aprotective matrix of sugars and proteins (gly-cocalyx). Biofilms are known to form on thesurface of medical devices and are also foundin wounds (21,23,26). Biofilms provide a pro-tective effect for the microorganisms embed-ded within them, improving their toleranceto the host’s immune system, antimicrobialsand environmental stresses. Biofilm commu-nities interact with host tissue resulting instable attachment, sustainable nutrition anda parasitic relationship (21,23,26,27). The bac-teria in biofilms have considerable phenotypicand genotypic diversity (21).

Box 2

MADE-EASY GUIDELINE FORSIGNS OF INFECTION INCHRONIC WOUNDS (22)

General signs

• Malaise• Appetite loss

Local wound signs

• Increased discharge• Delayed healing• Wound breakdown• Pocketing at the base of the wound• Epithelial bridging• Unexpected pain or tenderness• Friable granulation tissue• Discolouration of the wound bed• Abscess formation• Malodour

Biofilms first form a reversible attachment tothe wound surface, which may then becomepermanent with bacterial differentiation andfurther accumulation of the protective glyco-calyx. Biofilm structures have been recognisedin biopsies, using scanning electron and con-focal microscopy, in 60% of chronic woundsand 6% of acute wounds (28). Biofilms are amajor contributing factor to persistent, chronicinflammatory changes in the wound bed, andit is likely that almost all chronic wounds con-tain biofilm communities on at least part of thewound bed (21,23,26). They are a problem inwounds because of the chronic inflammatoryresponse that they stimulate, which benefitsthe organisms in the biofilm. Mature biofilmsalso shed biofilm fragments, planktonic bac-teria and microcolonies, which can disperse toform new biofilm colonies, with the risk of localor distant invasive infection.

The recommended treatment for managingbiofilms is a combination strategy to reducethe biofilm burden and prevent it reconstitut-ing itself. Once the biofilm has been disrupted,it reconstitutes itself via a metabolically active,growth phase of the microorganisms presentand is more vulnerable to treatment agentsduring this stage. It is important to understandthe genetics of the biofilm using moleculardiagnostic methods, thereby allowing ther-apy to be more specifically targeted. The



Table 2 Overview of the wound infection continuum

Contamination Bacteria do not multiply or cause clinical problemsColonisation Bacteria multiply but wound tissues are not damagedCritical colonisation/localised infection Bacteria multiply to the extent that healing is impaired & wound tissues damaged

May also mean that biofilm communities are present in the wound bedSpreading infection Bacteria spread from wound, causing problems in nearby healthy tissue (cellulitis and

erythema)Systemic infection Bacteria spread from wound, causing infection throughout the body (systemic

inflammatory response, sepsis and organ dysfunction)

use of frequent aggressive debridement, long-duration high-dose systemic antibiotics, selec-tive biocides and combinations of antibacterialbiofilm agents are major strategies in biofilm-based wound care (Box 3) (21,23,26). There isevidence that silver-containing dressings canbe useful in preventing biofilm reformation.However, their efficacy has been found to bevariable, with silver-impregnated charcoal andalginate-carboxymethylcellulose-nylon dress-ings not being able to prevent biofilm forma-tion (29).

It is not possible to categorically state whena wound is biofilm-free, because there is a lackof definitive clinical signs and available labora-tory tests. The most likely clinical indicator isprogression of healing, with reduction in exu-date and slough. Standard clinical microbiol-ogy tests are not optimised to adequately mea-sure biofilm bacteria; the most reliable methodof detecting microbial biofilm is by using spe-cialised microscopy. A simple diagnostic iseagerly awaited. The clinician’s judgement isvital when deciding how to manage woundsthat contain a suspected biofilm. It is impor-tant to frequently reassess the wound and alsoto practice a holistic approach to the patient’shealth to promote healing. Antibiofilm agents(such as silver, PHMB, iodine and honeydressings) are recommended for treatmentof wounds containing biofilm or suspectedbiofilm, but wounds must be regularly assessedon a patient-by-patient basis (26).

Are biofilms visible?

Although the existence of wound biofilms isaccepted, there is still much discussion abouttheir visibility to the naked eye (30). It has beensuggested that the opaque material seen onchronic wounds may be biofilm that reformsafter removal, and may indicate the pres-ence of critical colonisation that precedes overt

Box 3

SUGGESTED STRATEGIES FORREMOVAL AND PREVENTION OFBIOFILM

1. Biofilm removal

• Physical disruption (aggressive/sharp debridement is generallyagreed to be the best method ofremoving biofilm)

• Regular debridement to reduce thebiofilm potential for regrowth

• Accompanied by vigorous physi-cal cleansing (such as irrigation orultrasound)

Some products are thought to aid physicalcleansing by facilitating removal of biofilm anddebris, and disturbing biofilm (for example,PHMB is thought to be effective in disruptingbiofilm due to its surfactant component).

2. Prevention of biofilm reconstitution

• Rational dressing use to preventfurther wound contamination

• Use of a topical broad-spectrumantimicrobial (silver, iodine, honey,PHMB) to kill planktonic microor-ganisms

• Change to a different antimicro-bial if there is a lack of progress

infection. Wound biofilm, if it is visi-ble to the naked eye, may therefore alsorepresent an assessment tool in managingchronic wounds (31). However, this evidence isentirely conjectural and biofilm will continue toneed confocal or scanning electron microscopyor molecular technologies for definition. Theappeal for a diagnostic is clear.



Managing wound colonisation withmicroorganismsPrudent use of modern antiseptic-impregnateddressings or irrigants may reduce microorgan-isms on the wound surface and in biofilms.The concerns relating to traditional antisep-tics and their toxicity to host tissue have beenwidely discussed (32), but the prevailing clin-ical view is that it is appropriate to use mostcontemporary antiseptic solutions and dress-ings, in accordance with the manufacturer’sinstructions or local protocols.

Antimicrobials

The term ‘antimicrobial’ is used broadlyto describe disinfectants, antiseptics andantibiotics. The main reason for using antimi-crobials in wound care is to prevent or treatinfection, and thereby facilitate the woundhealing process. Unlike antibiotics, disinfec-tants and antiseptics have broad-spectrumantimicrobial activity, and microbial resistanceis rare, particularly in human pathogens. How-ever, antibiotics have a selective antimicrobialactivity, and microbial resistance to antibioticsis a serious concern (33–35). Colonisation andinfection in chronic wounds are usually due to amixed population of microorganisms. To selectthe most appropriate antimicrobial therapy,accurate diagnosis of the infecting organismsis vital, especially when antibiotics are beingused, as microbial sensitivities can also be usedto guide the best therapy choice. Diagnosis canbe performed by tissue biopsy or by swab cul-ture; in particular, high accuracy has been seenwhen using the Levine technique (36,37).

Microbial resistance

Microbial resistance to antibiotics is of increas-ing concern (34). The major difference betweenantibiotics and antiseptics is that antibioticswork more specifically, allowing bacteria anopportunity to mutate and form resistance,whereas antiseptics work at all levels of cellbiology, so bacterial resistance is less likelyto occur. The activity of topical antimicro-bial agents has been tested against multi-drugresistant (MDR) bacteria isolated from burnwounds. No susceptibility of topical antimi-crobial agents was found to be associated withMDR isolates; mafenide acetate was the mosteffective agent against Gram-negative bacteria,and silver also had moderate efficacy (38). No

silver resistance has been found in a collectionof bacterial strains tested from 349 clinical and170 non clinical isolates from humans, meatand production animals (39). The use of topi-cal antibiotics is not generally recommended asthey further increase the induction of resistanceand allergy.

Topical antiseptic dressings are recom-mended for the following (22):

• Prevention of infection in patients who areconsidered to be at an increased risk.

• Treatment of localised wound infection.• Local treatment of wound infection in

cases of local spreading or systemicwound infection, in conjunction withsystemic antibiotics.

Use of antiseptic dressings should be con-tinued for 14 days (the ‘2-week rule’) and theneed for further topical antimicrobial therapyshould then be reassessed (40). Use of antisep-tic dressings should be considered for thosepatients at high risk of infection, or for theearly treatment of locally infected wounds(cellulitis, lymphangitis or erythema), and dis-continued if these signs of spreading or localinfection resolve. However, if signs of infectionpersist, use of a systemic antibiotic is war-ranted and should be prescribed in accordancewith microbiological wound swab culture orblood culture results and sensitivities. Empiri-cal treatment with broad-spectrum antibioticsmay be commenced following clinical diagno-sis, but specific antibiotic regimens should beprescribed once the infecting organisms andtheir antibiotic sensitivities have been iden-tified. Concurrent use of topical antisepticdressings and debridement may reduce thelocal wound bioburden.

Silver dressings

Silver has a long history of use as a topicalantimicrobial in wound care – from historicalapplication directly to wounds in its solidform to the modern day application of sil-ver salt solutions such as silver nitrate forwound cleansing and creams or ointmentssuch as silver sulfadiazine (SSD) (40). Metal-lic silver (Ag0) is relatively inert, but whenexposed to moisture, highly reactive silver ions(Ag+) are released, which avidly bind to tissueproteins and cause structural changes in bac-terial cell walls and intracellular and nuclear



membranes. This antimicrobial action, enactedthrough the ionised Ag+ ion, forms strongcomplexes with essential bacterial metabolicpathways, rendering them unworkable andleading to microbial death.

Several silver-containing dressings are avail-able to manage wound bioburden and areavailable in a number of different forms:

• Elemental: silver metal, nanocrystallinesilver.

• Inorganic: silver oxide, silver phosphate,silver chloride, silver sulphate, silver-calcium-sodium phosphate, silver zirco-nium compound, SSD.

• Organic: silver-zinc allantoinate, silveralginate, silver carboxymethylcellulose.

Silver is incorporated into dressings eitheras a coating, within the dressing itself, aspart of the dressing, or as a combina-tion of these agents. Dressings incorporatingnanocrystalline technology donate a high sus-tained release of Ag+ ions at the wound surface.Silver salts are associated with minimal toxi-city when applied topically, and there havebeen no substantiated clinical reports of silvertoxicity. Nanocrystalline silver dressings havebeen associated with improved wound heal-ing (41,42). In a clinical study, nanocrystallinesilver dressings, under four-layer compres-sion bandages, promoted healing in patientswith recalcitrant chronic venous leg ulcers(VLUs). The VLUs were not clinically infectedbut treatment was found to reduce biobur-den and neutrophil-related inflammation (43).Nanocrystalline silver dressings have also beenfound to promote healing with reduced lev-els of MMPs, in a porcine model of woundinfection (44).

Silver alginate dressings have been revealedto have broad antimicrobial activity againstwound isolates grown in both the biofilmand non biofilm states (45), and to rapidlydecrease bacterial viability with >90% of thebacterial and yeast cells, on the silver alginatedressing tested, being no longer viable after16 hours (46).

However, not all research has been sup-portive of silver dressing use. The multicentre,prospective, randomised controlled VUL-CAN study examined the efficacy and cost-effectiveness of antimicrobial silver dressingsin treating VLUs by comparing silver dressingswith non antimicrobial, low-adherent control

dressings. No statistically significant differencein healing was found between the two dress-ing types, and it was concluded that therewas a lack of benefit from silver dressings (47).Following this, a review article expressed theopinion that the evidence base supporting sil-ver dressing use was weak and that it wasdifficult to justify the amount spent by the NHSon silver dressings (48). A negative impacton the perception and use of silver dressingsresulted, leading to restrictions in their avail-ability for clinical use (40). Further reviewshave asserted that the VULCAN study hasa number of flaws, the main one being thatthe silver dressings were not used as recom-mended (49–51). Others have commented thatantimicrobial dressings, including silver, arekey components of the management of patientswith wound infection and that failure to usethese products in appropriate cases may putpatients at risk (22,40).

Iodine dressings

Iodine-based preparations have a long historyof use in surgery and wound care. Elementaliodine is toxic to tissues, but in its povi-done iodine (PVP-I) and cadexomer iodineforms, which are both iodophores, it is not (52).There is evidence, including that from a recentCochrane review, to suggest that wound heal-ing rates are higher with cadexomer iodinethan with standard care (52,53), and while itsantimicrobial properties are well known, sev-eral studies have indicated that cadexomeriodine may potentially be effective againstbiofilms. Staphylococcus aureus and its relatedglycocalyx were not detected in the vicinityof cadexomer iodine beads in a mouse dermiswound model (54), and cadexomer iodine hasbeen found to be effective against Pseudomonasaeruginosa biofilm in a porcine skin model (55).A further study has demonstrated that cadex-omer iodine penetrated biofilms more effec-tively than either silver or polyhexamethylenebiguanide (PHMB) (56).

PHMB dressings

The antiseptic PHMB has been in generaluse for more than 50 years, but has nowbeen introduced for management of bioburdenin wounds as PHMB-impregnated dressingsor gels and solutions for wound irriga-tion. The active compound is effective in



both decreasing bacterial load and prevent-ing bacterial penetration of the dressing, whichreduces infection and prevents further infec-tion. PHMB also appears to have low toxicityto human tissue and does not promote bac-terial resistance (50,57,58). Treatment with apolyhexanide-containing biocellulose dressinghas been revealed to remove bacterial burdensignificantly faster than silver dressings (59).

Honey

Medical-grade honey dressings are non toxic,‘natural’ and easy to use; they are avail-able as hydrocolloid, alginate, synthetic tulleor gel-based dressings and promote autolyticdebridement by osmosis, while maintaining amoist wound environment (8). Patients withVLUs have been revealed to have increasedhealing, lower infection and more effectivedesloughing when treated with honey dress-ings compared with controls (60). Applicationof honey also reduces or removes woundmalodour (8,61). Honey is hygroscopic, candehydrate bacteria, and its high sugar con-tent causes inhibition of bacterial growthwith improvement of wound healing throughanti-inflammatory effects and reduction inoedema and wound exudate (62). There is alsoexperimental evidence that honey may disruptor prevent biofilm formation (8,63,64).

Surfactants

Surfactants lower the surface tension of a liq-uid, allowing it to spread more easily; they alsolower the interfacial tension between two liq-uids. Surfactant action in wounds facilitates theseparation of loose, non viable material on thewound surface and has potential for preventingand managing biofilm. Several combinationsof surfactant and products with antimicro-bial activity have been developed (PHMBand undecylenamidopropyl betaine; octeni-dine dihydrochloride and phenoxyethanol;octenidine and ethylhexylglycerin) and areused clinically for skin disinfection (65,66).

TIME – Infection and inflammation. Whathas changed? The original TIME table recom-mended that the removal of infected foci in thewound bed lowers inflammatory cytokinesand protease activity and helps create bac-terial balance and control of inflammation.This remains the case 10 years on, but it is

now the type and behaviour of microorgan-isms in the wound, and the options for theircontrol that is of particular interest. Whenbiofilm microorganisms behave in a differentway to their planktonic phenotype, the actionof certain topical antimicrobial agents suchas PHMB, iodine, silver and honey needsto be better understood, so that these agentsmay be effectively used in conjunction withdebridement to control wound biofilm.

TIME – MOISTUREExcessive or insufficient exudate productionmay adversely affect healing. Excessive exu-date and odour may significantly affect thepatient’s quality of life. Exudate characteris-tics are important, and any alteration such asincreasing bioburden or autolysis of necrotictissue may indicate a change in wound status.Updated recommendations for exudate man-agement focus on the selection of appropriatedressings or devices (18,67).

There are differences in composition betweenacute and chronic wound fluid. Acute woundfluid is rich in leukocytes and nutrients,whereas chronic wound fluid has high levelsof proteases and pro-inflammatory cytokinesand elevated levels of MMPs, which decreaseas healing progresses (68,69). The increasedproteolytic activity of chronic wound exu-date is thought to inhibit healing by damagingthe wound bed, degrading the extracellu-lar matrix and aggravating the integrity ofthe peri-wound skin (67), while the high lev-els of cytokines promote and prolong thechronic inflammatory response seen in thesewounds (69).

Appropriate wound moisture is requiredfor the action of growth factors, cytokinesand cell migration – too much exudate cancause damage to the surrounding skin, toolittle can inhibit cellular activities and leadto eschar formation, which inhibits woundhealing. Biofilm formation has also been linkedto poor exudate management (31), based on thereasoning that wound exudate is a potentiallyimportant nutrient source for wound biofilm.Rapid removal of wound exudate has beenrevealed to facilitate wound healing, althoughnot all patients showed a reduction in woundbacteria (70).

The volume and viscosity of exudate shouldbe considered when choosing a dressing,



as some dressings are better for managingexcessive exudate, while others are better formanaging viscous exudate. The most widelyused methods for managing excessive exudateare absorbent dressings and topical NPWT.Dressings should maintain an appropriatemoisture balance and avoid maceration ordesiccation of the wound bed. Improvedhealing was found in a pooled analysis of threetrials following the use of hydrogel dressingscompared with gauze as standard care indiabetic foot ulcers (DFUs). It is not clear,however, whether this was achieved as a resultof autolytic debridement or hydration of thewound bed (71). The ideal dressing for patientcomfort and convenience is one that is notbulky, not painful to change and reduces thenumber of dressing changes needed. It shouldalso be effective therapeutically, and in termsof cost, should prevent leakage and macerationand be easy to apply and remove (69). Itis also important to protect the peri-woundskin around chronic wounds; the increasedproteolytic activity of chronic wound exudatecan cause skin damage, and excess moisturemay cause maceration and erosion. Dressingsensitivity or allergy is also an importantconsideration, and the peri-wound skin shouldbe monitored for signs of this (67,69).

Negative pressure wound therapyUse of NPWT is particularly valuable inoptimising the ‘M’ element of the TIMEconcept, as it provides a closed moist woundhealing environment in patients with highlyexuding wounds. It is particularly effectivein removing viscous exudate, but frequentdressing changes may be painful (67,69).

TIME – Moisture. What has changed?Excessive wound fluid severely affects patientwell-being and wound healing. Exudate reg-ulation has been the cornerstone of chronicwound management since the 1960s, withmoisture balance as the goal. Over the past10 years, the main focus has been in twocore areas – developing ways to understandand improve the moisture management ofdressings and the role of NPWT in removingand containing large amounts of exudate.Research into the components of wound exu-dates, and their relationship to wound healingand infection in particular, continues.

TIME – EDGE OF WOUND (ALSOKNOWN AS EPITHELIAL EDGEADVANCEMENT)The final component of the TIME acronymis probably the one that has led to the mostdebate with regard to what the ‘E’ representsand how it fits in with the other components ofthe TIME concept. If wound bed preparation issatisfactory, the closure of chronic wounds canbe expedited by the use of split thickness skingrafts or biological skin replacements. Assess-ment of wound edges can indicate whetherwound contraction and epithelialisation is pro-gressing, and confirm either the effectiveness ofthe wound treatment being used or the need forre-evaluation. An increasing range of treatmentmodalities are proposed to improve woundhealing and thus influence the ‘edge’ effect.These therapies include electromagnetic ther-apy (EMT), laser therapy, ultrasound therapy,systemic oxygen therapy and NPWT.

The clinician should also consider thecondition of the peri-wound skin in assessingwound contraction, as dry or macerated woundedges may affect the ability of the wound tocontract.

Developments in managing ‘edgeof wound’Electromagnetic therapy

EMT delivers a continuous or pulsed electro-magnetic field, which allegedly induces tissuehealing and cell proliferation, although theexact mechanism is unclear. Pulsed EMT con-sists of short-duration pulses, which has theadvantage of protecting tissues from damageby the heat generated by continuous fields.EMT has been used to treat VLUs, but aCochrane review concluded that there is nohigh-quality evidence to support the hypothe-sis that EMT speeds healing in VLUs. However,the same review suggested that further studiesare needed to explore the effects of EMT as anadjunct to compression therapy or in patientswho cannot undergo compression therapy (72).

Laser therapy

Low-level laser therapy, such as such as heliumneon (HeNe) or gallium arsenide (GaAs) gaslasers, has been used to treat wounds, based onthe hypothesis that this may enhance cellularproliferation or migration. A Cochrane reviewof laser therapy for VLUs concluded that there



is no evidence of either benefit or no benefitfrom using laser therapy on VLUs (73).

Ultrasound therapy

Ultrasound therapy, generated in the mega-Hertz or kiloHertz range, provides mechanicalenergy that is thought to alter cellular activ-ity. Until recently, megaHertz therapy wasused to treat sclerotic peri-wound skin. Therehas been a recent shift towards use of low-frequency ultrasound in the kiloHertz rangefor healing in bone and tissue, which is con-sidered to promote vascular vasodilation anddebridement (74). Several types of commer-cial low-frequency ultrasound therapy devicesare available, with differing mechanismsof action.

Systemic oxygen therapy and wound healing

Oxygen is considered to have a vitally impor-tant role in wound healing, particularly in theinflammatory and proliferative phases. A 2011review on the role of oxygen in wound healingconcludes that supplementing treatment withoxygen (either breathed by mask or hyper-baric therapy) may improve angiogenesis,reduce infection rates and facilitate improvedhealing (75). Further evaluation, however, isrequired before it can be recommended forclinical use in wound healing.

NPWT

The use of NPWT has been revealed to stim-ulate granulation tissue formation and woundclosure (76–78). One study has demonstratedthat tissue changes varied at three layerswithin the wound – each responding differ-ently under NPWT. The most superficial layerdeveloped granulation tissue, while the twodeeper layers demonstrated a decreased pro-liferation rate and clearance of chronic inflam-matory markers and oedema, with tissuestabilisation (76). NPWT has been found tolead to significantly reduced tissue infiltrationof CD68+ macrophages and reduced IL-1β andTNFα expression in skin-grafted free muscleflaps. There was also a reduction in interstitialoedema formation, which improved the micro-circulation and reduced tissue damage (79). Anumber of studies have also demonstratedeffective use of NPWT in wounds that havebacterial colonisation or reveal active signs of

infection (80–84). Increased evidence supportsthe value of NPWT in treating hard-to-healwounds (2); when compared with advancedmoist wound therapy in DFUs, a greaterproportion of wounds achieved closure withNPWT (85). Amputations, secondary to DFUs,also revealed faster postoperative healingwhen treated with NPWT, compared with con-trols (86). However, a systematic review andmeta-analysis of 21 studies found no clear evi-dence that wounds heal either better or worsewith NPWT compared with conventional treat-ment (87), although the authors conceded thatNPWT may have a positive effect on woundhealing. Overall, study evidence supportsimproved wound closure with NPWT (78,85).

TIME – Edge of wound. What has changed?Epithelial edge advancement and an improvedstate of the surrounding skin (which was notdiscussed in the original TIME document) isthe clearest sign of healing, and a 20–40%reduction in wound area after 2 and 4 weeksof treatment is seen as a reliable predictiveindicator of healing (69). Various woundmodalities for stimulating wound healinghave been introduced; further knowledge oftheir role and contraindications is warranted.‘E’ is also a reminder of the importance ofevaluation as there is a sense that, after eachspecific clinical intervention (debridement,infection control or moisture management),a return to the wound should be made withan assessment of wound closure. The originalTIME table supports this by suggesting thatif the wound is not responding, a reassess-ment should be made with consideration ofother adjunctive or corrective therapies.

Psychosocial issuesPatients with chronic wounds have been shownto suffer associated stress and anxiety. As wellas the negative impact on patient well-being,stress and anxiety can also have a negativeimpact on wound healing (88). A questionnairesurvey, investigating the prevalence of mooddisorders among patients with acute andchronic wounds, found that pain (particularlyassociated with dressing changes), lack ofcontrol over treatment, and living with slow-healing chronic wounds caused stress andanxiety (88). Suggested, non pharmacologicaltherapies for relieving pain in patients with



chronic wounds include cognitive behaviouraltherapy, hypnosis, acupuncture, distractionand meditation and prayer (89).

DISCUSSIONAlthough the major principles of the TIMEwound bed preparation table remain the same,they are facilitated by many new developments(Table 3):

Tissue: non viable dead tissue andbacterial-related slough and debrisDebridement remains the quickest and mostefficient method of removing these materi-als. Clinicians have a variety of debridementmethods to choose from, depending on theindividual requirements of the patient and theskill set of the practitioner. Autolytic debride-ment is most likely to be used in conjunctionwith other debridement methods, and canalso be used alone if a slower, more conser-vative option is preferred. Newer modalitiessuch as low-frequency ultrasound and hydro-surgical debridement may be selective, butrequire advanced clinician knowledge and fur-ther testing for appropriate and efficacious use.Regardless of which debridement option ischosen, healing potential and outcome goalsmust be determined before commencing withdebridement.

Infection or inflammationInfection and inflammation remain the majorchallenge to healing, particularly in chronicwounds. However, knowledge of the inflam-matory process and its role in chronic woundshas increased since the TIME acronym wasfirst developed. It is now known that reduc-ing excessive inflammation can revitalisetissue with reduction in exudate and inthe risk of infection. The understanding ofbiofilms – what they are and how to detectthem – has improved considerably. Woundbiofilm presents a clinical conundrum, andhow to detect it remains a major issue; a diag-nostic method for biofilm detection is required.Although a number of dressings such as sil-ver, honey, cadexomer iodine and possiblyPHMB have revealed some efficacy in disrupt-ing biofilm, it is generally agreed that the bestway to disrupt biofilm is by debridement. Oncethe biofilm has been disrupted, it is then pos-sible to implement treatment with antiseptic

agents, while the biofilm is more vulnerableto antimicrobials, and prevent its reforma-tion (90). The use of antiseptic dressings andwound irrigants has been more widely rein-troduced and represents another area that hasrevealed a great deal of growth. The increasedrecent use of antiseptics also probably reflectsthe concerns regarding antibiotic resistance,whereas concerns about microbial resistance toantiseptics appear unfounded.

Moisture imbalanceUnderstanding of wound moisture balance hasincreased, and clinicians are more aware of theimportance of maintaining an appropriate levelof wound moisture, as well as the differencesbetween acute and chronic wound fluid. Thereare more dressings available to ‘intelligently’manage exudate, and some of its containedconstituents that can adversely affect woundhealing. NPWT has also proved to be anincreasingly valuable tool, particularly with itsextension for wound management to the homeenvironment.

Edge of woundThere have been considerable developmentsin the means of facilitating wound healing,with greater use of NPWT and new therapies,such as EMT, laser and ultrasound therapy.The original recommendation made by Schultzand colleagues in 2003, of a holistic approachwith treatment of the whole patient, remainsjust as valid today. Causes of poor or delayedhealing, and patient factors that might impedeor facilitate healing, must be reconsideredat every assessment. What is new, however,is the raised awareness of patient concernsand the active effort to promote patientsto act as advocates for their own care andconcerns. One of the treatment modalitieswhich has revealed the most developmentand interest since the TIME acronym was firstdeveloped is NPWT. From its introductionas a simple means of removing exudate andfacilitating wound closure, it now also appearsto have effects on biofilm reduction and to beeffective in infected and hard-to-heal wounds.It may also facilitate wound debridement whenused in combination with other debridementmethods.

Using the TIME concept in practical woundcare raises further questions – for example,



Tabl

e3

Sum

mar

yta

ble

ofne

wde

velo

pmen

tsw

ithin

the

TIM

Eco

ncep

t

Clin

icalo

bser

vatio

nsW

BPDe

velo

pmen

tsFa

ctor

sto

cons

ider

Tiss

ueDe

brid

emen

tN

ewm

etho

ds• L

ow-fr

eque

ncy

ultra

soun

d• H

ydro

surg

ery

• Deb

ridin

gw

ipes

Adva

nces

inus

eof

exist

ing

met

hods

• Lar

vae

• Aut

olyt

ic(h

oney

and

hydr

ogel

s)• U

seof

enzy

mes

(col

lage

nase

)• S

harp

/sur

gica

l(ne

wgu

idel

ines

)• C

hem

ical(

antis

eptic

s,i.e

.silv

eran

dPH

MB)

NPW

T–

asad

d-on

with

exist

ing

debr

idem

entm

etho

ds

Use

ofm

aint

enan

cede

brid

emen

tCo

nsid

erat

ions

arou

ndsa

fepr

actic

e• K

now

ledg

e• S

kills

• Com

pete

nce

• Evi

denc

eof

effic

acy

Wou

ndcle

ansin

gM

icrob

icida

lirri

gatio

nso

lutio

nsIn

fect

ion/

infl

amm

atio

nBa

cter

ialb

alan

ceBi

ofilm • Im

prov

edun

ders

tand

ing

ofbi

ofilm

san

dth

eirr

ole

inno

nhe

alin

gw

ound

s• M

anag

emen

t–co

mbi

natio

nst

rate

gyto

disr

uptb

iofil

man

dpr

even

trec

onst

itutio

n(d

ebrid

emen

tand

antis

eptic

agen

ts)

• Det

ectio

nof

biofi

lmUs

eof

Polym

eras

eCh

ain

Reac

tion

(PCR

)/pyr

oseq

uenc

ing

tech

niqu

esto

iden

tify

bact

eria

/fung

iin

wou

nds

Incr

ease

dba

cter

ialt

oler

ance

toto

pica

l/sys

tem

icag

ents

Mix

edflo

raliv

ing

syne

rgist

ically

Qui

esce

ntst

ate

ofso

me

bact

eria

inbi

ofilm

sre

duce

sef

fect

iven

ess

ofan

tibio

tics

Diag

nost

icfo

rbio

film

dete

ctio

nne

eded

Pers

isten

tinfl

amm

atio

nIm

prov

edun

ders

tand

ing

ofth

ero

leof

pers

isten

tinfl

amm

atio

nin

chro

nic/

stal

led

wou

nds

• Rol

eof

MM

Psan

dot

herp

rote

ases

(dia

gnos

tics

and

inhi

bito

rs)

• Rol

eof

biofi

lms

inpr

omot

ing

wou

ndin

flam

mat

ion

Man

agin

gin

fect

ion/

infla

mm

atio

n• I

ncre

ased

use

ofan

tisep

ticag

ents

• Rol

eof

nano

crys

talli

nesil

vera

san

anti-

infla

mm

ator

y• C

ombi

natio

nof

surfa

ctan

tsw

ithan

timicr

obia

ls–

biofi

lmdi

srup

tion

• NPW

Tco

mbi

ned

with

inst

illat

ion

ofm

icrob

icida

lsol

utio

nsto

redu

cele

vels

ofpl

ankt

onic

and

biofi

lmba

cter

ia• A

ltern

ativ

eus

eof

new

orex

istin

gag

ents

–fo

rexa

mpl

e,us

ing

nano

crys

talli

nesil

vert

oda

mpe

ndo

wn

infla

mm

atio

n• I

mpr

oved

heal

ing

ofw

ound

stre

ated

with

cust

omfo

rmul

atio

nsof

topi

cala

ntib

iotic

s/an

tisep

tics

base

don

bact

eria

lpro

files

Diag

nost

icte

sts

–w

hen

and

how

ofte

n?Po

int-o

f-car

ede

tect

ion

Revi

ewof

appr

opria

tean

timicr

obia

lsRo

tatio

nof

prod

ucts

Micr

obia

lres

istan

ce(p

artic

ular

lyto

antib

iotic

s)


Extending the TIME conceptTa

ble

3(C

onti

nued

)

Clin

icalo

bser

vatio

nsW

BPDe

velo

pmen

tsFa

ctor

sto

cons

ider

Moi

stur

eM

oist

ure

bala

nce

Impr

oved

awar

enes

sof

need

tom

aint

ain

appr

opria

tem

oist

ure

leve

lsDr

essin

gse

lect

ion

–w

hatd

ow

ene

edto

cons

ider

?• A

bsor

ptio

n• R

eten

tion

• Pat

ient

com

fort

• Bac

teria

lpoo

l• S

kin

sens

itivi

tyor

alle

rgy

Exud

ate

Impr

oved

unde

rsta

ndin

gof

exud

ate

com

posit

ion

–di

ffere

nces

betw

een

acut

ean

dch

roni

cw

ound

fluid

• Dam

agin

gpr

oteo

lytic

activ

ityof

chro

nic

wou

ndflu

idRe

latio

nshi

pof

exud

ate

with

bact

eria

lbur

den

and

biofi

lmfo

rmat

ion

Sele

ctio

nof

appr

opria

tedr

essin

gsor

devi

ces

fore

xuda

tem

anag

emen

t(i.e

.new

supe

r-abs

orbe

rs)

Gre

ater

emph

asis

onm

oist

ure

man

agem

ent

NPW

T–

forr

emov

alan

dco

ntai

nmen

tofl

arge

exud

ate

volu

mes

Edge

ofw

ound

Epith

elia

ledg

ead

vanc

emen

tIm

prov

edst

ate

ofsu

rroun

ding

skin

Eval

uatio

n–

chec

kw

heth

erw

ound

isclo

sing

Use

ofN

PWT

toen

cour

age

cont

ract

ion

Adju

nctt

hera

pies

(EM

T,la

ser,

ultra

soun

d,sy

stem

icox

ygen

ther

apy)

Revi

sitin

gex

istin

gth

erap

ies

Alte

rnat

ive

use

ofpr

oduc

ts,f

orex

ampl

e,us

ing

NPW

Tto

splin

twou

nds

Role

ofdi

agno

stics

/ther

anos

tics

how moist should a wound be? Knowledge ofexudate management has improved consider-ably but, as discussed above, that question can-not be answered simply but depends on manyfactors, including the type of wound, its loca-tion and the type of exudate associated with it.Wound infection and patient comfort are alsoimportant considerations, as are other issuesrelating to patient needs. Clinicians have devel-oped an increased awareness of psychoso-cial issues relating to wound care – chronicwounds in particular can cause patient stressand anxiety, not just in relation to pain, butin the complexities of caring for a non heal-ing wound, and concerns about social aspectssuch as appearance and malodour. Clinicians,industry, research and health care organisa-tions often focus on complete wound healingas a key outcome measure, while people livingwith a chronic wound may have different pri-orities. This criticism has also occasionally beenlevelled at the TIME acronym itself, focussingas it does on the wound bed, as opposed topatient-centred concerns. More emphasis mayneed to be undertaken within the TIME frame-work to encompass patient-centred concernsand promote a holistic approach to patientwell-being in wound care.

The TIME acronym could be redefined fromits first, assessment stage to become a second,management stage consisting of treatment,implementation, monitoring and evaluation:

i. Treatment: An appropriate treatmentplan is important, based on the objec-tives of care to be achieved, and theobjectives of the original TIME frame-work.

ii. Implementation: Agreed treatment plansshould be implemented consistentlyfor optimal, effective objectives withevaluation of outcomes.

iii. Monitoring: This should include detec-tion of any local or systemic adverseevents and ensure that clinical practiceand products used achieve the best per-formance.

iv. Evaluation: All treatments should beregularly and objectively evaluated toinclude, for example, a wound healingcurve, a validated pain assessment tool,a debridement index or other symptommeasurement, and assessment of impacton quality of life.



CONCLUSIONComplete and timely wound closure is themain objective of all aspects of wound care,although this is not always possible. Chronicwounds, in particular, present a challengeto effective wound care. Since the TIMEacronym was first published a decade ago, theunderstanding of wound bed preparation andthe inflammatory and infective pathways hasincreased considerably, as have available treat-ment options. Of necessity, most clinical guide-lines represent ‘work in progress’ because ofthe continuous changing and understandingof wound pathology, healing and therapeuticagents. Although the basic principles of theTIME concept have not changed greatly sinceits first inception, the application of these prin-ciples has expanded, with developments inknowledge and interventions for wound man-agement. It is important to consider that, whilethe TIME concepts provide a valuable frame-work for wound assessment and management,they are also inextricably linked.

So, 10 years on – is TIME still relevant toclinical practice? Although there are many newdevelopments in the field of wound therapyand our understanding of wounds, the basicconcepts of tissue, infection/inflammation,moisture and edge of wound still remainimportant in guiding clinical practitioners intheir approach to wound management.

ACKNOWLEDGEMENTSThe Wound Infection Institute is an internationalgroup of clinicians, scientists and other stakeholderscommitted to produce original work that contributestowards research, education and evidence inwound infection while remaining an independentmultinational organisation.

The authors are grateful to the commit-tee of the International Wound InfectionInstitute for their comments and enhance-ments to this article. The committee membersare Terry Swanson – Chair (Australia), DavidArmstrong (USA), Joyce Black (USA), KerylnCarville (Australia), Jose Contreras Ruiz (Mex-ico), Marc Despatis (Canada), Val Edwards-Jones (UK), Jacqui Fletcher (UK), GeorginaGethin (Ireland), Jenny Hurlow (USA), DavidKeast (Canada), Patricia Larsen (USA), DavidLeaper (UK), Heather Orsted (Canada), GregSchultz (USA), Dianne Smith (Australia), GeoffSussman (Australia) and Richard White (UK).

The authors would also like to extend theirthanks to the members of the InternationalAdvisory Board on Wound Bed Preparation,who developed the original TIME principles,and to Keith Harding (UK), chair of the Inter-national Wound Infection Institute, 2007–2012.DJL paid speaker or received research grantsfrom BBraun, Convatec, Smith & Nephew,Ethicon, Coloplast, Systagenix; GS receivedresearch grants from KCI, Health Point, Smith& Nephew, and Hollister Wound Care in2011–2012; KC attended education events orpresented for Smith & Nephew during 2012; JFpaid consultancy for KCI, Systagenix, BBraunand Medi in 2011–2012; TS attended edu-cation events or presented for Coloplast,Smith & Nephew, Convatec, IndependenceAustralia, and Molnlycke during 2012; RDundertakes freelance writing and editorialassignments.

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Extending the TIME concept: what have we learned … antiseptics (silver, honey and iodine-based...

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