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A retrospective review of burn dressings on a porcine burn model

A retrospective review of burn dressings on a porcine burn model
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  A retrospective review of burn dressings on a porcine burn model Xue-Qing Wang a, * , Olena Kravchuk b , Roy M. Kimble a a Department of Paediatrics and Child Health, University of Queensland, Royal Children’s Hospital, Brisbane 4029, Australia b Biometrics Unit of School of Land, Crop and Food Sciences, University of Queensland, Brisbane 4072, Australia 1. Introduction The non-surgical treatment of small partial-thickness burnswith is usually covering burns with dressings with or withouttopical agents after initial cleansing of the wounds [1–3]. The dressings can contain either antiseptic/biological property ornot, and can be grouped into silver release (e.g. Acticoat TM ),biosynthetic (e.g. Biobrane TM ), occlusive (e.g. polyurethanefilm, Tegaderm), paraffin gauze dressings (e.g. Jelonet) andothers. Currently, for small partial-thickness burns the choiceof dressings and the application of a topical antimicrobialagent vary among burn centers around the world, withoutuniform and standard practice patterns [4–7]. In the UK, while Biobrane was favored by the majority of burns units (69%) forthe treatment of partial-thickness burns [4], paraffin gauze(38.8%) and Mepitel (35.5%) were also used for small partial-thickness burns ( < 10%) in children [7]. In addition, topicalantimicrobials were not applied in small partial-thicknessburns in thesechildren in 45%of burn centers[7]. Globally,forpartial-thickness burns  < 15–20% total body surface area(TBSA), silver sulfadizine, antibiotic cream, impregnatedgauze and Acticoat are preferred [5]. Nonetheless, it is burns 36 (2010) 680–687 a r t i c l e i n f o  Article history: Accepted 4 June 2009 Keywords: Burn injuryBurn wound healing Porcine burn modelBurn dressing  a b s t r a c t Thisisastudytocomparewoundhealingamongthreetypesofdressingsonaporcinemodelwith deep-dermal-partial-thickness burns. The burns in this study were from eight animaltrials conducted in the past for other purposes and only burns with a uniform pale appear-ancethathadservedascontrolsinoriginalexperimentswereselected.Intotal,therewere57burns in 33 pigs, using one of following three dressings: Acticoat ( Silver ) (3 trials), Jelonet( Gauze )(3trials),andSolositeGel/Jelonet( Gel/Gauze )(2trials).Thewoundhealingassessmentsincluded wound re-epithelialisation during a 6-week period, clinical and histologicalscar assessments at week 6 after burn. Of all wound healing/scar assessments, onlyre-epithelialisation showed statistical difference between dressings. Earlier re-epithelialisa-tionwasobservedin Gel/Gauze dressingscomparedto Silver and/or Gauze dressings.However,this study revealed huge variation in wound healing outcome between 3 trials within both Silver  and/or  Gauze  dressings, supported by significant differences on re-epithelialisation,clinical and histological scar measurements. In addition, it was found that larger animalshealedbetterthansmallerones,basedonweightsfrom21pigs.Ofalldressings, Silver deliversthe best protection for wound colonization/infection. Wound colonization/infection wasfound to confine wound healing and lead to thinner RND in scars. From this study, wecannotfindenoughevidencetosuggestthebeneficialeffectofonedressing(s)overothersonburn wound healing outcome on a porcine model with small deep-dermal-partial-thicknessburns with a relative small sample size. # 2009 Elsevier Ltd and ISBI. All rights reserved.*  Corresponding author . Tel.: +61 7 3365 5019; fax: +61 7 3365 5455.E-mail address: (X.-Q. Wang). available at www.sciencedirect.comjournal homepage: 0305-4179/$36.00 # 2009 Elsevier Ltd and ISBI. All rights reserved.doi:10.1016/j.burns.2009.06.200  generally agreed that topical antimicrobial agents/dressingsshould to small be applied deep-partial-thickness burns,but not necessary for small-superficial-partial-thicknessburns [1–3]. The application of some of these dressings is supported byclinical studies (either prospective or retrospective), mostlywhen compared to silver sulfadiazine. Acticoat consists of layers of polyethylene mesh coated with nanocrystallinesilver, and releases silver ions once dressing is moisturised. Ithas been reported to promote wound healing by reducing inflammation and facilitating the early phase of woundhealing  [8,9]. The beneficial effects of Acticoat include the shortening of hospital stays [10], reduced pain at dressing changes [11,12], less frequent dressing changes [13] and enhanced healing on burn wounds and on meshed skin graftareas [14–16]. Biobrane is a biosynthetic wound dressing  constructed of a silicone film with a nylon mesh bound withporcine collagen. It has been shown to be superior to 1% silversulfadiazine, by reducing pain medication and hospital stay,and enhancing wound healing for partial-thickness burns,particularly in children [4,17–19]. Paraffin gauze dressings are considered to be satisfactory wound covers for superficial-/mid-dermal-partial thickness burns [2,3] and have been used considerablyinsomeburncentresaroundtheworldandinUK[4,5,7]. In a prospective clinical trial, paraffin gauze dressing  was found to be better than polyurethane film in treating outpatient burns [20]. In a porcine burn model, dry gauzeshowed no difference from silver sulfadiazine, octylcyanoa-crylate, polyurethane film in treating partial-thickness burns[21]. In the current study, a review of wound healing wasconductedonburnscoveredwithoneoffollowingdressings:asilver releasing dressing, paraffin gauze, and paraffin gauzewith hydrate gel, on a porcine burn model with 1–2% TBSAdeep-dermal-partial-thickness burns. 2. Materials and methods 2.1. Study design This was a review of wound healing from several animaltrials conducted for other purposes in our laboratorybetween 2004 and 2007, and the results from some of thesetrials were never published previously due to non-signifi-cant findings. The purpose of this study was to compare theoutcome of burn wound healing between different typesof burn dressings on our porcine burn model [22,23]. The dressings in these animal trials were selected for thepurpose of srcinal experiments and included: (1) silverdressings (Acticoat TM ) (Smith and Nephew), abbreviated as Silver , (2) paraffin gauze (Jelonet TM ), abbreviated as  Gauze ,and (3) paraffin gauze and hydrate gel (Solosite Gel TM ),abbreviated as  Gel/Gauze . Only the control burns with auniform pale appearance were selected. In total, 57 thermalburns (33 pigs) from trials involving 284 burns (120 pigs)were selected for this study, including 21 burns –  Silver  (3trials), 21 burns –  Gauze  (3 trials), and 15 burns –  Gel/Gauze dressings (2 trials). The trials in  Silver  and  Gauze  groups wereconducted during 2004–2006, and the trials in  Gel/Gauze dressing group were conducted during 2006–2007. 2.2. Histology of burn depth assessment In previous studies, histological analysis was conducted onbiopsies collected on burns with either a pale or pinkappearance. For pale burns, histological analysis of samplestaken immediately after the burn injury showed necroticepidermis with hair follicles in mid-dermis being completelynecrotic, and even in the deep dermis in some areas. Thecapillaries are congested.On the following 2 days,neutrophilsare seen between the collagen bundles in the dermis andwithin the walls of small dermal vessels. For pink burns,histologicalanalysisshowedthermaldamagetotheepidermisand at least partial thermal injury to the hair follicle onsamples taken immediately after the burn injury. However,some of the hair follicles in the middle dermis maintain theirstructure and are not damaged. The capillaries in these burnsare more dilated and congested in the superficial and middermis, with extravasation of red blood cells. During thefollowing 2 days, there is less inflammatory responseindicated by less neutrophils in the dermis, compared to theburns with pale appearance. We then conclude that the burnswith a uniform pale appearance represent middle/deep-dermal-partial-thickness burn. Therefore, in this study, onlyuniform pale appearance burns were selected. 2.3. Animal experiment The animal trials were approved by the University of Queensland Animal Ethics Committee. All animals weretreated humanely and in compliance with the QueenslandAnimal Care and Protection Act 2001 and the Australian Codeof Practice for the Care and Use of Animals for ScientificPurposes. Large White pigs (female, juvenile aged 6–8 weeks)were selected. The animals were weighed at the days of burncreation and dressing changes. However, this data was notrecorded from the earliest experiments (most were  < 20 kg from memory), and 21 of 33 pigs had weights recorded andwere around 20–30 kg at the start of experiments. Adequateanesthetization was given on the day and following day of burncreation,andat everydressingchange.Closemonitoring ofanimalsforanyalteredbehavioursforafewdayspost-burnwasprovidedandnoobviouspainordiscomfortwasobserved.The circular burns sized 40–50 cm 2 were created by directcontact with a hot water bottle preheated to 92  8 C for 15 s[22,23]. The burns included in this study were created in two patterns,onewith2burns/pig(1/eachside)andanotherwith4burns/pig (2/each side). In the later pattern, two burns/pig included in this study were created on the same side, locatedon the thoracic rib region near either the head or tail [24], andwere the ones in 2 trials in  Gel/Gauze , and in 1 trial in  Silver dressing group. All burns included in this study served ascontrols (not applied with topical agents or not debrided) andwerecoveredwithoneofthedressingsdescribedabove.Whilemost of dressings were left untouched between dressing changes,  Silver  dressings were moistened regularly (3 times/day) by the application of 5 mL of sterile water to ensureantimicrobials of the  Silver  dressing. All wounds were thenprotected with non-stick cotton and acrylic fibre pad, fixedwithadhesivedressing,andcoveredwithaspecialgarmenttoprevent tearing of dressings. The dressings were changed burns 36 (2010) 680–687  681  eitheronceortwiceaweekfor6weeksafterburncreationandthe wound healing was assessed at every dressing change. 2.4. Wound healing assessments The detailed assessment of the wound healing, clinical scarscale and clinical wound colonization scale has been pub-lished previously [23,25,26]. This mainly includes clinical wound assessment on site twice/week or weekly for 6 weeks(re-epithelialisation, wound appearance and wound coloniza-tion), histological scar assessment at week 6 after burn, andclinical scar assessment on site/scar photographs taken atweek6post-burn.Theassessmentsdetailedinthisstudywerere-epithelialisation, the clinical scar appearance (cosmeticoutcome),woundsize,histologicalscarassessment(thicknessof epidermis, total dermis, scar tissue [OGT] and remaining normaldermis[RND]),andwoundcolonizationscores.Fortheearlier experiments, due to insufficient information on thenotes, the re-epithelialisation was judged on the woundphotographs took weekly from week 2 to 6 at this review. Thereference porcine scar photographs were used to standardisescar assessment for all scars and each scar was assessedindependently by 3 assessors (experienced clinicians andscientists). The inter-rater reliability analysis showed goodagreements of    80% on cosmetic outcomes of 57 burn scarsassessed by 3 assessors. 2.5. Statistical analysis Univariatestatisticalanalysisofwoundhealingoutcomeswasperformed with the general linear model option of Minitab forWindows v.15 (Minitab Inc., Chicago, 2008). Dressing was themain factor, trials were a factor nested in dressings, and pigswere treated as random experimental units and wounds assub-samples. The means were calculated for each dressing group; bars in the figures represent one standard error fromthe estimated parameters; and most  p -values are listed inFigures and some  p -values are reported in the text. In thediscussion, the 5% level of significance was chosen. 3. Results 3.1. Re-epithelialisation The statistical analysis showed that the mean time to reach50% re-epithelialisation was around 18–22 days in thesethree dressing groups (Fig. 1a).  Gel/Gauze  dressing wassignificantly quicker than  Gauze  dressing. The mean timetaken to reach 80% re-epithelialisation was more than 3weeks for all three dressing groups (Fig. 1b). However, burnscovered with  Silver  and  Gauze  dressings took significantlylonger to heal than burns covered with  Gel/Gauze  dressings.Further analysis also revealed significant differences at both50% and 80% of re-epithelialisation between trials within Silver  and  Gauze  dressings. 3.2. Clinical scar assessments Previously we showed that the scar cosmetic outcome is thebest indicatorfor ourporcineclinicalscarassessments [25]. In this study, all burns healed with significant scarring withmeanscoresof   2.9forcosmeticoutcomeatweek6post-burnfor all three dressing groups (Fig. 2a). The statistical analysis Fig. 1 – Re-epithelialisation post-burn injury. The days to reach 50% (a) and 80% (b) of re-epithelialisation in three types of dressing groups. There were 3 trials (  n  = 5/8/8) in  Silver  dressing (  n  = 21), 3 trials (  n  = 6/8/7) in  Gauze  dressing (  n  = 21), and 2trials (  n  = 6/9) in  Gel/Gauze  dressing (  n  = 15) groups. The means from each dressing group are indicated by solid circles (  *  ),and the means for each trial within dressings are indicated by open circles (  * , trial 1), open triangles (  ~ , trial 2) and opensquares (  & , trial 3). All  p -values are listed and the  p -values  = 0.05 are in bold. burns 36 (2010) 680–687 682  revealed no significant difference between dressings. How-ever, the difference was statistically significant between trialswithin  Silver  dressings. At week 6 after burn, all woundsfailedto heal with a normal rate of skin expansion, and most wereseverelycontractedwithmeans of72–84%of theoriginalburnsize for all dressing groups (Fig. 2b). The statistical analysisalso revealed no significant difference between these dres-sings, but significant difference between trials within  Silver and  Gauze  dressings. 3.3. Histological scar assessments Allburnshealedwithsignificantlythickerscars,withmeansof   0.16–0.19 mm for epidermis,  3.98–4.39 mm for total dermis,  3–3.4 mm for scar tissue (OGT) and   0.8–1.24 mm forremaining normal dermis (RND) for three dressing groups(Fig.3).Thestatisticalanalysisshowednosignificantdifferencebetween dressings on most histological scar assessments.Statistically significant differences in thickness of scar tissueand RND were found between trials within  Silver  dressing. 3.4. Wound healing between individual animals Of 33 pigs included in this study, 21 had weights recordedthroughout the experimental period and 12 animals withoutrecorded weights were 1 trial in  Silver  dressing group and 2trials in  Gauze  dressing group. At the day of scalding, animalsweighed19–32.5 kg,withthegreatestrangeinoneof2trialsinthe  Gel/Gauze  dressing group (20–32.5 kg). The means of weightsfortrials were  22–25.6 kg andthegreatestdifferencein mean weights within each dressing was in the  Silver dressing group (Fig. 4a). In general, the analysis showed thatweighthadastatisticalsignificanceonsomeofwoundhealing outcome measurements and larger animals were more likelyto heal burns better than smaller ones by earlier re-epithelialisation, thinner OGT and thicker RND (Fig. 4b–d).But the animal weight had no statistical significance on scarcosmetic outcome and wound contraction (Table 1).Further analysis revealed that the effect of animal weightson wound healing was different between dressings and trialsin this study. The best correlations of animal weights withoutcome of wound healing were the burns covered with  Gel/ Gauze dressing.Itshowedthatlargeranimalsweremorelikelyto heal burns with earlier wound closure, thicker RND andthinner OGT than smaller ones. In 2 trials in  Silver  dressing with recorded weights, the wound healing was significantlybetter in one trial with the mean weight 25.6 kg than that inanother trial with mean 23 kg, supported by earlier re-epithelialisation, better cosmetic outcome, less wound con-traction, and thinner OGT. 3.5. The effect of wound colonization/infection score onwound healing Previously,wedetailedourclinicalcolonization/infectionscaleforourporcinewoundsandreportedthatthisscaleisconsistentwith Gram staining of a total of 228 scar biopsies during a 2-week period after burn [26]. We also reported 19.4% of wounds(59/304) were recorded having    2 colonization scores at leastonce overa 6-weekperiod.The 57burnsselected for thisstudywere derived from 284 burns, and showed 17.5% of woundshaving    2 colonization scores at least once over a 6-weekperiod. Not surprisingly, the wounds covered with  Silver dressing had the smallest scores for wound colonization/ Fig. 2 – The clinical scar outcome at week 6 post-burn injuries. (a) The scar cosmetic outcome in burns covered with  Silver , Gauze , and  Gel/Guaze  dressing groups. All  p -values are listed. No statistical significance is found between dressing groups.However, statistical significance is found between trials within  Silver  dressing. (b) The wound contraction represents thescar size at week 6 post-burns comparing with burn size at scalding. All  p -values are listed. No statistical significance isfound between dressing groups. However, statistical significance is found between trials within  Silver  and  Gauze  dressings. burns 36 (2010) 680–687  683  infection and  Silver  dressing is the best to prevent woundcolonization/infection( Silver 5%, Gauze 33%and Gel/Gauze 13%).Overall, wound colonization/infection scores were onlysignificantly correlated to thickness of RND (negatively)(  p  = 0.048), but not to other wound healing assessments.Further analysis revealed that the effect of wound coloniza-tion/infectionscoresonwoundhealingoutcomewasdifferentbetween dressings and trials. In 3 trials in  Silver  dressing, onehad zero colonization scores for all wounds, in the other 2trials the total colonization scores and the number of woundscored  > 0 were low. Although the results indicated theassociation of colonization with worse wound healing inthese2trials,thiswasnotstatisticallysignificant.Inthe Gauze dressing group, the colonization scores were not significantlycorrelated to wound healing outcomes in all 3 trials, thoughwounds with higher colonization scores healed with slightlythicker OGT and worse cosmetic outcome in one of these 3trials. In both trials in the  Gel/Gauze  dressing group, woundcolonization was associated with deteriorated wound healing andworsehistologicalscaroutcomes (thinnerRND,  p  = 0.024). 4. Discussion The current study compares the wound healing of burnsbetween three types of burn dressings on a porcine burn Fig. 3 – The histological scar outcome at week 6 post-burn injuries. The thickness of epidermis (a), total dermis (b), scartissue (OGT) (c), and remaining normal dermis under scar tissue (RND) (d) in burns covered with  Silver ,  Gauze , and  Gel/Guaze dressing groups. All  p -values are listed. Statistical significance is found in the thickness of OGT and RND between trialswithin  Silver  dressing. burns 36 (2010) 680–687 684
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