debridement paper - hydrofera

#603 Applewhite FINAL

A Reprint from Surgical Technology International XXVIGENTIAN VIOLET AND METHYLENE BLUE POLYVINYL ALCOHOL

FOAM ANTIBACTERIAL DRESSING AS A VIABLE FORM OFAUTOLYTIC DEBRIDEMENT IN THE WOUND BED

ANDREW JOSEPH APPLEWHITE, MDPHYSICIAN

BAYLOR WOUND CENTER, DALLAS, TEXAS

PAUL ATTAR, PHD, MBAPRESIDENT

BRIDGE PTS, SAN ANTONIO, TEXAS

BROCK LIDEN, DPMSTAFF, CIRCLEVILLE FOOT & ANKLE CENTER

REYNOLDSBURG PODIATRY CENTER, REYNOLDSBURG, OHIO

QUYEN STEVENSON, ARNP, CWOCNWOUND AND OSTOMY NURSE PRACTITIONER

VETERANS AFFAIRS PUGET SOUND HEALTHCARE SYSTEMSEATTLE, WASHINGTON

TThe objective of this article is to describe the results of a comparative porcine study that evaluated the

effectiveness of a gentian violet and methylene blue (GV/MB) polyvinyl alcohol (PVA) antibacterial

foam dressing in debriding eschar. The authors performed an in vivo, preclinical study on eschar-cov-

ered porcine wounds. Two clinical case studies are also included. Test products, GV/MB antibacterial foam

dressing, collagenase ointment, collagenase ointment plus GV/MB antibacterial foam dressing, medical-

grade honey, and moist gauze dressing (control), were applied to porcine wounds using a split-back study

design. The percent of eschar removal and wound closure were measured and recorded at time points up to

14 days. Statistically significant reduction in eschar was observed with GV/MB dressing and with GV/MB

dressing with collagenase. By day 14, the wounds with GV/MB dressing alone and GV/MB dressing with col-

lagenase had eschar covering less than 25% of the wound bed area compared with collagenase alone, medical

grade honey, or moist gauze control, which showed eschar still covering over 75% of the wound bed area.

Autolytic debridement activity of GV/MB foam dressings was evident in the porcine eschar study, as well as

in the cases described.

Gentian Violet and Methylene BluePolyvinyl Alcohol Foam Antibacterial

Dressing as a Viable Form of AutolyticDebridement in the Wound Bed

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ABSTRACT

Wound HealingSURGICAL TECHNOLOGY INTERNATIONAL XXV

ANDREW JOSEPH APPLEWHITE, MDPHYSICIAN

BAYLOR WOUND CENTERDALLAS, TEXAS

PAUL ATTAR, PHD, MBAPRESIDENT

BRIDGE PTSSAN ANTONIO, TEXAS

BROCK LIDEN, DPMSTAFF, CIRCLEVILLE FOOT & ANKLE CENTER

REYNOLDSBURG PODIATRY CENTERREYNOLDSBURG, OHIO

QUYEN STEVENSON, ARNP, CWOCNWOUND AND OSTOMY NURSE PRACTITIONER

VETERANS AFFAIRS PUGET SOUND HEALTHCARE SYSTEMSEATTLE, WASHINGTON

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The wound healing process is com-plex and can be prolonged with thepresence of nonviable tissue in thewound bed. Debridement is an essentialcomponent of the wound healingprocess with multiple goals, includingthe removal of necrotic devitalized tis-sue, slough, senescent cells, andmechanical barr iers.1 In addition,debridement stimulates growth factoractivity, reduces matrix metalloproteas-es, and reinitiates the wound healingcascade.2,3 There are five main methodsof debridement: surgical or sharp,autolytic, enzymatic, mechanical, andbiosurgery/maggots.4 A detailed reviewof the advantages and disadvantages ofeach debridement method is beyond thescope of this paper; however, it isimportant for clinicians to have a work-ing knowledge of the methods availableto serve the well-being of each patient.5

The clinical decision regardingdebridement methodology is based onmultiple factors, including evidence ofefficacy, pain tolerance of the patient,clinician skill level required to performthe procedure, products being utilized,and potential risks and side effects ofthe procedure. Sharp debridement isgenerally considered to be the quickestand most effective of the modalities;however, many patients are not candi-dates or do not consent to the proce-dure due to the pain. Chemical andautolytic agents are commonly used tofacilitate debridement with or withoutsharp debridement.

Successful use of chemical agents andenzymatic ointments has been reported

in the debridement and treatment ofinfected wounds.1,6 However, while theuse of chemical debriding agents hasgrown in recent years, certain factorsincreasingly limit their use in clinicalpractice. For example, cost increasesand reimbursement changes haveseverely reduced the amount of enzy-matic debriding ointment allowed innumerous care settings, given the 2014U.S. Hospital Outpatient ProspectivePayment System.7

Autolytic debridement may be thesafest form of wound debridementbecause it is highly selective in removingonly devitalized tissue. The body’sphagocytic cells and endogenous prote-olytic enzymes are used to break downdead tissue, thus liquefying slough andnecrotic tissue only. Autolytic debride-ment can be enhanced in conjunctionwith the use of occlusive and semi-occlusive dressings to maintain a moistenvironment.8

Preliminary evidence suggests a gen-tian violet and methylene blue(GV/MB) antibacterial foam dressingmay be effective in promoting autolyticdebridement in cer tain wounds.9

GV/MB antibacterial dressings are ster-ile, absorptive foam dressings made bypreferentially binding two antibacterialdyes, methylene blue and gentian violet,to open-celled polyvinyl alcohol (PVA)foam. The binding of the pigments tothe foam helps prevent the pigmentsfrom washing away and becoming dilut-ed. The GV/MB antibacterial dressingis cut to the desired size, then moist-ened with sterile saline or sterile water.Excess moisture is squeezed out, andthe dressing is placed in the wound andsecured with a secondary dressing to

prevent displacement and maintainmoisture content. Dressings may be leftin place for up to three days.

GV/MB antibacterial foam dressingsare highly absorptive without risk ofresidual absorption.10,11 Gentian violetand methylene blue pigments have his-torically shown broad spectrum activityagainst microorganisms commonlyfound in wounds and external surfacesof the skin. GV/MB foam dressingshave been found in vitro not to exhibitany signs of cytotoxicity or systemictoxicity.11 As such, the dressings can beused for extended periods and through-out all phases of wound healing. Thepurpose of this article is to describe theresults of a comparative in vivo, preclini-cal porcine study that evaluated theeffectiveness of a GV/MB PVA antibac-terial foam dressing in debriding eschar,and to present clinical case studies thatillustrate the clinical effects of the dress-ing on autolytic debridement.

ANIMAL STUDY METHODS

An in vivo porcine model was utilizedto evaluate the wound debridementactivity of four test articles and con-trols: (1) a GV/MB antibacterial foamdressing, (2) a collagenase ointment, (3)collagenase ointment plus GV/MBantibacterial foam dressing, (4) medical-grade honey, and (5) moist dressing(control). Debridement performancewas tested using a Yorkshire pig model,which has previously been recognized asan effective animal model for testingnew debriders.12 The animals werehoused and cared for in accordance withthe guidelines published by the NationalResearch Council and approved by theAssociation for Assessment and Accred-itation of Laboratory Animal Care.13

Approval for this study was granted bythe Bridge PTS Institutional AnimalCare and Use Committee in San Anto-nio, Texas.

Three pigs were premedicated andanesthetized. Each pig was prepared forsurgery by scrubbing with chlorohexa-dine and isopropyl alcohol in an alter-nating fashion three times to mimic theskin preparation in humans and thetreatment site. In order to create aneschar suitable for a debridement study,a series of 20 eschar segments were cre-ated with a heated brass rod (10 on eachside, 20 mm in diameter and 2 cm


Gentian Violet and Methylene Blue Polyvinyl Alcohol Foam Antibacterial Dressing as a Viable Form of Autolytic Debridement in the Wound BedAPPLEWHITE/ATTAR/LIDEN/STEVENSON

INTRODUCTION

Figure 1. A series of eschar segments was created with a heated brass rod (10 on each side, 20 mm indiameter, and 2 cm apart).

ANIMAL STUDY METHODS

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apart) (Fig. 1). No surgical debridementoccurred after the rods were applied, topermit eschar to develop from the devi-talized tissue.

Test products were applied to theporcine eschar wounds using a split-back study design. For each of the threepigs, half of the wounds (n = 10) weretreated with one dressing, and the otherhalf were treated with a different dress-ing according to Table I. All productswere applied and changed in accordancewith their instructions for use.

The GV/MB foam dressing wasmoistened, excess moisture was wrungout, and the dressing was covered with4-layer gauze, taped, and wrapped withan absorbent underpad. To ensure therewas no mechanical debridement due toproduct dryness, the dressing wasremoistened prior to removal. Collage-

nase was covered with gauze. In thecase of collagenase combined withGV/MB foam, collagenase was coveredwith moistened and wrung-outGV/MB foam, then covered with drygauze and wrapped with an absorbentunderpad.

All the treated and control wounds(including those treated with GV/MBfoam dressings) were covered with atransparent film dressing as the primarydressing and underpad as the secondarydressing. The occlusive layer of the blueunderpad was placed against the skin.The pigs were wrapped with a layer ofelastic bandage over the blue pad to pre-vent movement of the dressings under-neath. If gauze became adherent to thewound bed during dressing changes,sterile saline was applied to help loosenit from the underlying tissue.

Visual assessment of the eschar wasperformed at each dressing change. Foreach wound, calipers were used to mea-sure the distance across the widest partof the wound as well as the narrowestpar t of the wound. The estimatedwound and eschar areas were calculatedby using the equation for an ellipse (nar-rowest X widest X 3.14 / 4).

Presence of eschar was documentedin the following manner:

1 = No evidence of eschar formation 2 = Eschar covering ≤25% of wound

area 3 = Eschar covering 26% to 50% of

wound area4 = Eschar covering 51% to 75% of

wound area5 = Eschar covering 76% to ≤100%

of wound area.



Table ISplit-back study design protocol during porcine eschar wound study

Porcinesubject Left side treatment Right side treatment Dressing change

frequency

1 GV/MB moistened and covered with4-layer gauze and taped

Moist dressing control q 72 hours

2 Collagenase covered with dry gauze Collagenase covered with moistGV/MB dressing

q 24 hours

3 Medical-grade honey covered with drygauze

Moist dressing control q 24 hours

Table IIPresence of eschar

Day 0 1 4 7 10 13 14 p-values .

GV/MB foam dressing 5 5 5 4 4 3 2 <.01

Collagenase 5 5 5 5 4 4.5 5 0.49

Collagenase-GV/MB foam dressing 5 5 5 5 3 2 2 <.01

Medical grade honey 5 5 5 5 4 4 5 0.16

Moist gauze (control) 5 5 5 5 5 5 5

1 = No evidence of eschar formation 2 = Eschar covering ≤25% of wound area 3 = Eschar covering 26% to 50% of wound area4 = Eschar covering 51% to 75% of wound area5 = Eschar covering 76% to ≤100% of wound area

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RESULTS

Statistically significant reduction ineschar was seen with GV/MB dressingand with GV/MB dressing with collage-nase (Table II). By day 14, the woundswith GV/MB dressing alone andGV/MB dressing with collagenase hadeschar covering less than 25% of thewound bed area compared with allother products, which had eschar stillcovering over 75% of the wound bedarea. Figures 2a and 2b show signifi-cantly reduced eschar with GV/MBantibacterial dressing versus honey onday 14. No statistically significant differ-ences in wound size were seen at day14. All of the products tested were sim-ilarly nonirritating and resulted in littleor no swelling.

HUMAN CASE STUDIES

The following clinical case studies inhumans are examples of effectivewound debridement demonstrated withuse of the GV/MB antibacterial dress-

ing in chronic wounds. In all cases, theoriginal goals for the dressing were tominimize potential recurrent bioburdenand biofilm buildup, provide a lesspainful and easier removal of the dress-ing, and assist with absorption of exu-date. In each of these cases, cliniciansreported autolytic debridement ofslough and necrotic tissue with use ofthe GV/MB antibacterial dressing.

Clinical Case Study 1: NecrobiosisLipoidica in a Nondiabetic Patient

A 34-year-old male presented withwounds that had spontaneously openedsix years prior on his left lower extrem-ity. The patient had no prior injuries orsurgeries, but reported a history ofchronic untreated edema and mild pso-riasis in the lower extremities. Thepatient had received unknown treat-ment previously at an outpatient hospi-tal-based clinic.

At the initial clinic visit, the woundswere washed with an antimicrobial soap(Fig. 3a). Skin biopsies and tests werenegative for malignancy and underlyingvascular or ar ter ial disease. Apseudomonas infection was treated suc-cessfully, with some improvement in

wound healing. Throughout the courseof the first week, the patient had apainful allergic reaction to all silver-based products, including silver algi-nates, foams, and creams.

The patient received 3 weeks ofGV/MB antibacterial dressing treat-ments used in conjunction with com-pression bandages changed weekly in anoutpatient wound clinic (Fig. 3b), perphysician utilization and preference.The patient was treated as if he hadchronic venous insufficiency and lowerextremity edema, as all other possibleetiologies were ruled out by originalbiopsy. The wound bed improved,appearing clean and beefy red. Withweekly GV/MB antibacterial dressingchanges and compression, the woundcontinued to improve, and at sixmonths, the wound was closed. Follow-ing multiple additional tests and biop-sies, the patient was being treated withoral steroids for necrobiosis lipoidica.

Clinical Case Study 2: NonhealingVenous Ulceration

A 66-year-old male presented to thewound clinic after failed treatment ofmultiple bilateral lower extremity



Figure 2a. Day 14 eschar that has been treated with honey. Eschar is stillintact.

Figure 2b. Day 14 eschar that has been treated with GV/MB antibacterialdressing and collagenase. Eschar is almost completely debrided.

Figure 3a. At initial clinic visit after lower extremity chronic wounds werewashed with an antimicrobial soap.

Figure 3b. Wounds after three weeks of GV/MB antibacterial dressing treat-ments used in conjunction with aggressive class II compression bandagesystems.

RESULTS

HUMAN CASE STUDIES

a b

a b

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ulcerations that had been present for 4months following hospitalization foracute exacerbation of congestive heartfailure (Figs. 4a & 4b). The patient’smedical history included atrial fibrilla-tion, Hodgkin’s lymphoma, testicularcancer, stage III-IV chronic renal failure,hypothyroidism, new onset of uncon-trolled type II diabetes mellitus,obstructive sleep apnea, and chronicobstructive pulmonary disease. Previoustreatments included collagen with andwithout silver, silver and standard calci-um alginate dressing, silver and standardfoam dressings, collagenase debride-ment ointment, and silver gels andcreams in combination with class IIcompression bandage systems.

The GV/MB antibacterial dressingwas dampened with normal saline andapplied bilaterally to all wounds, fol-lowed by abdominal pads, and class IIcompression bandage systems. Dress-ings were changed two times per weekat an outpatient wound clinic. At twoweeks, the wounds were smaller andbeefy red, and did not require repeatdebridement (Fig. 4c). After the patienthad multiple recurrent hospitalizationsfor congestive heart failure exacerbationand kidney failure, the wounds contin-ued to improve and eventually healedafter 8 months of treatment withGV/MB dressings.

DISCUSSION

Analysis of the visual clinical assess-ments in the porcine eschar modelshowed a significantly lower medianscore of eschar remaining in woundstreated with GV/MB foam as well asthe combination of GV/MB foam and

collagenase, versus collagenase alone,medical-grade honey, or the moist gauzecontrol. Autolytic debridement activitywas evident in the porcine eschar study,as well as in the cases described. Similarrates of wound size reduction werereported with GV/MB foam versus thecontrol on day 14. Meanwhile, signifi-cantly greater eschar reduction wasobserved with the GV/MB foam andcollagenase-GV/MB foam combinationversus the control on day 14. Woundsize reduction occurred in controlwounds despite the lack of debridedeschar. This difference suggests thatreduction in eschar in the acute porcinewounds may not have been associatedwith wound size reduction.

The exact mechanisms of action lead-ing to the observed faster rate of autolyt-ic debridement and reduction of escharare not fully understood, but severalmechanisms have been proposed. Oneproposal is that because the hydrophilic,three-dimensional, open-cell structureof PVA foam is known to be highlyabsorptive with substantial retention andwicking,14 the efficient management ofexcess exudate can enhance the naturalprocess of autolytic debridement.15 Con-tact of the moist dressing with thewound bed appeared to maintain a bal-anced, moist wound environment need-ed for autolytic debridement to occur.Shi and colleagues have previously con-firmed compatibility of the GV/MBfoam with enzymatic debriding oint-ments.16 However, the similar rates ofeschar and wound size reductionachieved with or without collagenase inthe porcine study suggest that the addi-tion of collagenase with GV/MB foammay not aid in overall debridement ofacute wounds with eschar.

The antibacter ial nature of the

GV/MB dressing may also contribute toautolytic debridement effects. Heavybacterial burden in a wound leads to tis-sue degradation and slough formation.The two antibacterial organic pigments,methylene blue and gentian violet, arepreferentially bonded to the PVA foamdressing, These pigments have beenshown in previous studies to alter theredox environment to a state that is notconducive to bacterial growth or attach-ment.17,18 Additionally, the pigments inthe GV/MB dressing do not appear toinhibit fibroblast growth factor activi-ty.19 The GV/MB antibacterial foamdressing is indicated for pressure ulcers,diabetic ulcers, venous stasis ulcers,arterial ulcers, superficial burns, donorsites, postsurgical incisions, traumawounds, abrasions, and lacerations.

Published research regarding theeffects of GV/MB foam dressing inwound healing is limited. Because thedressing is classified as antibacterial,usage has naturally been concentratedon bioburden control in colonizedwounds.9,20 In a small ser ies of 15patients with lower extremity chronicwounds treated with GV/MB foamdressing, improvements in surface criti-cal colonization and pain score at theend of the study period were noted insome patients, particularly in patientswith diabetic foot ulcers. Decreasedwound size was observed in 8 of 14patients (57%) at week 4. The authorsalso observed autolytic debridement insome wounds, with the presence ofslough on the surface of the removeddressing.9

The porcine eschar model studydescribed herein is the first to show thecomparative autolytic debridementeffects of GV/MB antibacterial foamdressing. This debridement effect may



Figure 4a. Right venous leg ulcer at initial presen-tation.

Figure 4b. Left venous leg ulcer at initial presenta-tion.

Figure 4c. Bilateral venous ulcers after two weeksof treatment with GV/MB antibacterial dressingsand compression. Repeat debridement no longerrequired.

DISCUSSION

a b c

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be of particular benefit in wounds thatcontain slough or eschar. However, larg-er-scale trials are needed to detect sta-tistically significant differences indebridement effects of the GV/MBdressing in humans, and these resultsshould be interpreted with caution.

Although thermal rods were used tocreate 3rd-degree burns in the porcinemodel, the primary purpose of the ani-mal study was to test the effect ofdressings in debriding eschar, ratherthan in treating thermal burn wounds.GV/MB foam dressings are not indi-cated for 3rd-degree burns in humans.The thermal burn method of escharcreation was chosen for this animalstudy based on the benefit of a consis-tent and readily controlled degree oftissue damage and eschar through acombination of weight, time, and tem-perature. Due to known differences ineschar reduction following thermalinjury, these eschar reduction resultsmay not be generalizable to greaterwound populations.

CONCLUSION

GV/MB antibacterial foam dressingsappeared to be a safe, noncytotoxicmethod for managing porcine escharwounds as well as chronic wound casespresented in this study. Use of GV/MBfoam dressings as well as the combina-tion of GV/MB foam and collagenaseled to significantly greater eschar reduc-tion in porcine wounds versus collage-nase alone, medical-grade honey, or themoist gauze control. Although theGV/MB antibacterial foam dressing isnot specifically indicated for debride-ment, the porcine and clinical resultsreferenced in this manuscript suggestthe dressing does aid in autolyticdebridement. Additional research iswarranted to further evaluate the stand-alone or adjunctive autolytic effects ofGV/MB antibacterial foam dressings inclinical practice.

AUTHORS’ DISCLOSURES

Dr. Applewhite, a consultant forHollister Wound Care, received pay-ment for manuscript preparation. Dr.Attar, a consultant for Hollister WoundCare, received a corporate grant fromHollister to conduct the animal studyreviewed in this manuscript. Dr. Liden,a consultant for Hollister Wound Care,received payment for manuscript prepa-ration. Quyen Stevenson, a member ofthe Hollister Wound Care SpeakersBureau, received payment for manu-script preparation.

REFERENCES

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bound with gentian violet and methyleneblue. Adv Skin Wound Care 2014;27(3 Suppl1):9–13.10.Woo KY, Alam T, Marin J. Topicalantimicrobial toolkit for wound infection.Surg Technol Int 2014;25:45–52.11.United States Food and Drug Administra-tion. “Premarked Notification 510(K) Hydro-fera LLC.” January 4, 2014. Available at:http://www.accessdata.fda.gov/cdrh_docs/pdf13/K130670.pdf. Accessed January 12,2015.12.Shi L, Ermis R, Lam K, et al. Study on thedebridement efficacy of formulated enzymaticwound debriding agents by in vitro assessmentusing artificial wound eschar and by an in vivopig model. Wound Repair Regen2009;17(6):853–62.13.National Research Council. Guide for thecare and use of laboratory animals, 8th Edi-tion. The National Academies Press. 2013.Available at: http://grants.nih.gov/grants/olaw/Guide-for-the-care-and-use-of-labora-tory-animals.pdf. Accessed on November 3,2014.14.Ovington LG. Dressings and skin substi-tutes. In: McCulloch JM, Kloth LC (eds).Wound healing: evidence-based management.4th ed. Philadelphia: F.A. Davis Company: pp231–47, 2010.15.Romanelli M, Vowden K, Weir D. Exu-date management made easy. Wounds Inter-national 2010;1(2):1–6.16.Shi l, Ermis R, Kiedaisch B, et al. Theeffect of various wound dressings on the activ-ity of debriding enzymes. Adv Skin WoundCare 2010;23(10);456–63.17.Ingraham MA. The bacteriostatic action ofgentian violet and its dependence on the oxi-dation-reduction potential. J Bact 1933;26:573–98.18.Dubos R. The relation of the bacteriostaticaction of certain dyes to oxidation-reductionprocesses. J Exptl Med 1929;49:575–92.19.Ramsay S, Jelf C, Aust D, et al. Compari-son of the effects of antimicrobial wounddressings on cell viability, proliferation, andgrowth factor activity. Poster presented at:World Union of Wound Healing SocietiesCongress, June 4–8, 2008, Toronto, Canada.20.Sibbald RG, Ovington LG, Ayello EA, etal. Wound bed preparation 2014 update:management of critical colonization with agentian violet and methylene blue absorbentantibacterial dressing and elevated levels ofmatrix metalloproteases with an ovine colla-gen extracellular matrix dressing. Adv SkinWound Care 2014;27(3 Suppl 1):1–6.



REFERENCES

STI

CONCLUSION

AUTHORS’ DISCLOSURES

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