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Kronična rana ne cijeli u očekivanom razdoblju jer je zaostala u upalnoj fazi cijeljenja. Razlog tome je prisutnost nekrotičnog tkiva, velikog broja mikroorganizama - dominantno bakterija koje izlučuju biofi lm - uz ishemiju, hipoksiju i edem. Biofilm je prisutan u 90 % kroničnih i 6 % akutnih rana. Biofilm je korporativna zajednica mikroba adheriranih na površine (rana) kojom upravljaju quorum sensing molekule. Zajednica je okružena s hidratantnim matriksom od ekstracelularnih polimernih sastojaka (slime) koji štite mikrobe od djelovanja antibiotika, antiseptika, obrane makroorganizma i stresa. Primarni uzrok kroniciteta rane je biofi lm, jer uzrokuje permanentnu upalu, odgođeno formiranje granulacijskog tkiva, migraciju epitelnih stanica i rezervoar je mikroba koji uzrokuju infekciju kronične rane. Cilj dobre kliničke prakse jest da omogući cijeljenje kronične rane u očekivanom razdoblju. Za postizanje cilja nužno je reducirati i cjelovito ukloniti biofi lm iz rane i prevenirati njegovu rekonstrukciju. To se postiže primjenom antibiofi lm aktivnih spojeva i postupcima koji će razgraditi quorum sensing molekule, degradirati ekstracelularne polimerne sastojke (EPS) i blokirati prihvaćanje za površine. Suvremena istraživanja ukazala su da primjena antiseptika ima učinak u prevenciji infekcije i potpora je ciljanom liječenju. Činjenica je da su samo neki antiseptici primjenjivi za kronične rane i aktivni na biofi lmove primarnih uzročnika infekcije Staphylococcus spp, Streptococcus spp, Pseudomonas aeruginosa. Učinkoviti antiseptici su oktenidin dihidroklorid, poliheksanidi, povidon jodin i kadeksomer, nanokristalno srebro i manuka-tip meda. Nepokoreni biofi lm je perzistentan problem kroničnih i kroničnih inficiranih rana. Činjenica je da ni jedan pojedinačni terapijski postupak, kao ni pojedini antiseptik, ne mogu cjelovito uništiti biofilm. To je razlog da suvremeni postupci liječenja i skrbi o kroničnoj rani primjenjuju multimodalnu strategiju u obliku kombinacije mehaničko-kemijskih postupaka: debridement, antiseptici, antimikrobne potporne obloge. Debridmanom se otvara terapijski „prozor“ za djelovanje antiseptika i antibiotika tijekom 72 sata što omogućuje uklanjanje biofi lma i aktivno uništavanje sesilnih i planktonskih bakterija. Tim se postupkom onemogućuje i reformacija biofi lma. Postupci se moraju intenzivno ponavljati, antiseptici i potporne obloge izmjenjivati ovisno o stadiju ležišta rane i komorbiditetnim čimbenicima bolesnika. Rezultati kliničkih studija ukazuju da samo takav proaktivan pristup kroničnoj rani omogućuje cijeljenje u očekivanom razdoblju., Chronic wound does not heal within the expected time frame because it remains in the infl ammation phase of healing. The reason for this is the presence of necrotic tissue and a large number of microorganisms, primarily bacteria that secrete the biofi lm, along with ischemia, hypoxia and edema. Biofilm is present in 90% of chronic wounds and 6% of the acute ones. Biofi lm is a corporative association of microbes which adhere to the surface of the wound, guided by quorum sensing molecules. The association is surrounded by a moisturizing matrix of extracellular polymeric substances (slime) which protect the microbes from the impact of antibiotics, antiseptics, macro-organism defense and stress. Biofilm is the primary cause of the wound chronicity because it causes permanent inflammation, delayed granulation tissue formation and migration of epithelium cells, thus providing a reservoir of microbes that lead to infection of the chronic wound. The aim of good clinical practice is to enable healing of a chronic wound within the expected time frame. In order to achieve this aim, it is necessary to reduce and thoroughly remove the biofi lm from the wound and prevent its reappearance. This is achieved by the application of active anti-biofilm compounds and procedures that disintegrate the quorum sensing molecules, degrade the extracellular polymeric substances and block adherence to the surfaces. Recent researches have shown that the application of antiseptics is effective in the prevention of infection and is a support to targeted treatment. However, the fact is that only some antiseptics are applicable to chronic wounds and can have an impact on biofilms of the primary infective agents such as Staphylococcus spp., Streptococcus spp., and Pseudomonas aeruginosa. Effective antiseptics are octenidine dihydrochloride, polyhexanides, povidone and cadexomer iodine, nanocrystal silver and Manukatype honey. Immobile biofi lm is a persistent problem of chronic and chronic infected wounds. In fact, there is no isolated therapeutic procedure or an individual antiseptic that can fully destroy the biofilm. For this reason, modern strategy in the management of chronic wound applies a multimodal approach which combines mechanical-chemical procedures such as debridement, antiseptics, and antimicrobial supportive compresses. Debridement creates a therapeutic ‘window’ for the action of antiseptics and antibiotics in a 72-hour period, which enables removal of the biofi lm and active destruction of the sessile and planktonic bacteria. This approach also prevents de novo formation of the biofilm. The above procedures must be intensively repeated, and antiseptics and supportive compresses changed, depending on the phase of the wound bed and comorbidity factors in the patient. The results of clinical studies show that only such a proactive approach to chronic wound enables achievement of healing within the expected period of time.

Kronične rane posljedica su brojnih komorbiditetnih čimbenika, a dominantni patoiziološki procesi su ishemija, edem i infekcija uz dob, neuropatiju i traumu. Raspadom integriteta kože nastala rana biva kontaminirana, a zatim i kolonizirana primarno iziološkom lorom domaćina, a zatim mikrobima iz okoline. Sve kronične rane su kolonizirane, a infekcija se razvija u 5 %-40 % slučajeva ovisno o vrsti, lokalizaciji, komorbiditetnim čimbenicima, trajanju, skrbi i liječenju. Posljedica patoizioloških procesa u kroničnoj rani je perzistetna kronična upalna faza s odgođenim cijeljenjem, koje može progredirati u lokalnu infekciju, sepsu, multiorgansko zatajenje i smrt. Različite tvari primjenjuju se u liječenju kroničnih rana milenijima, nažalost bez razumijevanja njihovog djelovanja, koje je često puta posve nejasno. Suvremena istraživanja ukazala su na primjenu antiseptika za kronične rane s efektivnim djelovanjem u prevenciji razvoja infekcije, širenja lokalne infekcije i kao potpora ciljanom liječenju. Prosudba o primjeni antiseptika ovisi o klinički deiniranoj infekciji i kvatitativnoj mikrobiološkoj obradi uzorka kronične rane, uz precizno deiniranu i samu kroničnu ranu. Cilj antisepse je da ubije ili inaktivira mikrobe - primarno bakterije u rani, redukcijom broja ili sprječavanjem multiplikacije u što dužem razdoblju. Antiseptici se primjenjuju u proilaktičke svrhe jednokratno, nekoliko puta tijekom jednog dana ili jednokratno u trajanju od 5 do 7 dana (obloge). Antiseptici primijenjeni u terapijske svrhe primjenjuju se višekratno, kroz duže vrijeme, 7 - 10 - 14 dana ili do početka stvaranja granulacija. Primjena antiseptika je ciljani i ograničeni postupak, osobito pri infekciji kronične rane. Infekcija kronične rane karakterizirana je prisustvom velikog broja mikroba >105CfU/g, miješanom mikrobnom lorom, te brojnim virulentnim čimbenicima od kojih je najznačajniji bioilm. Antiseptici su aktivne tvari, različite kemijske strukture koji se razlikuju po sastavu, spektru djelovanja, učinkovitosti, citotoksičnosti, teratogenosti, indukciji rezistencije i aktivnosti na bioilm. Idealan antiseptik ne postoji pa izbor treba biti praktičan i sa što manje nuspojava. Praktičan izbor antiseptika za kroničnu ranu ovisi o indikaciji, očekivanom patogenu ili patogenima, lokalnoj ili sistemskoj toleranciji, izvedivom vremenju ekspozicije, kumulativnom ili remanentnom djelovanju, lokalnoj i sistemskoj sigurnosti. Apsolutna indikacija za primjenu antiseptika je inicirana akutna i kronična rana, kronična kolonizirana rana u imunonekompetentnog i imunokompromitiranog bolesnika, te svi oblici ozljeda, tj. kontaminirane rane. Antiseptici se rabe do časa pojave granulacija. Antiseptici primijenjeni na kronične rane koji su ujedno učinkoviti na bioilm su klorheksidin diglukonat, poliheksanidi, oktenidin dihidroklorid, povidon jodid i nanokristalno srebro. Zdravstveni djelatnici se susreću s manjkom ili nedostatkom jasnih uputa, kako, kada, koliko dugo i koji od antiseptika primijeniti u svakodnevnoj kliničkoj praksi. Pri primjeni antiseptika nužno je jasno deinirati razloge uporabe, ciljeve i trajanje primjene., Chronic wounds are a consequence of numerous comorbidity factors, and the predominant pathophysiological processes are ischemia, edema and infection, in addition to age, neuropathy and trauma. With breakdown of the skin integrity, the wound becomes contaminated, followed by colonization irst with the physiological lora of the host and, then with microbes from the environment. All chronic wounds are colonized and infection develops in 5%-40% of cases, depending on the type and localization of the wound, comorbidity factors, duration, medical care and treatment. The consequence of the pathophysiological processes in chronic wound is the persistent chronic inlammatory phase with delayed healing, which may progress to local infection, sepsis, multiorgan failure and death. Various substances have been applied in the treatment of chronic wounds for millennia, unfortunately, without due understanding of their effect, which often remains completely un- clear. Modern researches have pointed to the application of antiseptics in chronic wounds to prevent development of infection and spread of local infection, and as support to targeted treatment. The judgment on the application of antiseptics depends on the clinically deined infection, microbiological analysis of the chronic wound sample, and the chronic wound itself. The aim of antisepsis is to kill or inactivate the microbes, primarily bacteria, in the wound by reducing their number, to prevent their multiplication for as long as possible. Antiseptics are applied for prophylactic purposes once-only, several times a day, or once-only for 5-7 days (dressing). Antiseptics are applied for therapeutic purposes repeatedly for a longer period, i.e. 7-10-14 days or until granulations start appearing. The application of antiseptics is a targeted and limited procedure, especially in the infection of a chronic wound. The infection of a chronic wound is characterized by a large number of microbes (>105 CfU/g), mixed microbial lora and numerous virulence factors, the most important of which is the bioilm. Antiseptics are active substances of different chemical structure, which come in a range of composition, spectrum of activity, eficiency, cytotoxicity, teratogenicity, induction of resistance, and activity on the bioilm. As there is no ideal antiseptic, the choice must be practical with minimum side effects. Practical choice of antiseptics for a chronic wound depends on the indication, expected pathogen or pathogens, local or systemic tolerance, available time of exposure, cumulative or residual activity, and local and systemic safety. An absolute indication for the application of antiseptic is infected acute or chronic wound, chronic colonized wound in an immunologically incompetent and immunocompromised patient, and all forms of injuries, i.e. contaminated wounds. Antiseptics are applied until the appearance of granulations. The following antiseptics are applied for chronic wounds, at the same time being effective on the bioilm: chlorhexidine digluconate, polyhexanides, octenidine dihydrochloride, povidone iodine, and nanocrystal silver. Medical personnel are faced with a lack or inadequately clear instructions on how, when, for how long and which antiseptic to apply in daily clinical practice. In the application of antiseptics, it is necessary to clearly deine the reasons for their use, aims and duration of application.