WOUND CARE:WOUND CARE:Basics and updates in the Basics and updates in the

management of chronic woundsmanagement of chronic wounds

Rhonda C. Quick, MD, FACSRhonda C. Quick, MD, FACSTucson Vascular SpecialistsTucson Vascular Specialists

Medical Director of Carondelet Wound Medical Director of Carondelet Wound Healing CenterHealing Center

OBJECTIVESOBJECTIVES

Understand the differences between acute and Understand the differences between acute and chronic woundschronic woundsUnderstand the stages of wound healingUnderstand the stages of wound healingUnderstand the topical agents available and their Understand the topical agents available and their usageusage

DISCLOSURESDISCLOSURES

SpeakerSpeaker’’s Bureau Organogenesiss Bureau Organogenesis

WHAT IS A WOUND?WHAT IS A WOUND?

woundwound

n.n.1. 1. An injury, especially one in which the skin or An injury, especially one in which the skin or

another external surface is torn, pierced, cut, or another external surface is torn, pierced, cut, or otherwise broken.otherwise broken.

2. 2. An injury to the feelings.An injury to the feelings.

WOUND HEALINGWOUND HEALING

Patient factorsPatient factorsMacroscopic and microscopic environmentMacroscopic and microscopic environmentHighly orchestrated processHighly orchestrated processInvolves different cell types which have Involves different cell types which have different functionsdifferent functionsResults in restoration of anatomic continuity, Results in restoration of anatomic continuity, function and cosmesisfunction and cosmesis

TYPES OF WOUND HEALINGTYPES OF WOUND HEALING

PrimaryPrimarySurgical incisionSurgical incisionMinimal scar tissueMinimal scar tissue

Delayed primaryDelayed primaryWounds left open for 3Wounds left open for 3--5 days due to edema or infection and 5 days due to edema or infection and then closedthen closed

Secondary healingSecondary healingNot approximated. Not approximated. More granulation tissueMore granulation tissueScar tissueScar tissue

NORMAL RESPONSENORMAL RESPONSE

Extracellular matrix forms Extracellular matrix forms (collagen,fibrin,fibronectin)(collagen,fibrin,fibronectin)Formation of collagen by fibroblastsFormation of collagen by fibroblastsAngiogenesis beginsAngiogenesis beginsWound fills in with granulation tissueWound fills in with granulation tissueEpithelial cells migrate in from the marginEpithelial cells migrate in from the marginSkin coverage achievedSkin coverage achieved

STAGES OF WOUND STAGES OF WOUND HEALINGHEALING

CoagulationCoagulationPlatelets are primary cell linePlatelets are primary cell linePDGFPDGF--attracts fibroblastsattracts fibroblastsTGFTGFßß--attracts fibroblasts and smooth muscle cellsattracts fibroblasts and smooth muscle cells--stimulates collagen stimulates collagen productionproduction

InflammatoryInflammatory44--6 days6 daysNeutrophils and macrophagesNeutrophils and macrophages

ProliferativeProliferativeBegins day 6 and lasts several weeksBegins day 6 and lasts several weeksFibroblast Fibroblast

RemodelingRemodeling

Normal Wound Healing Requires Normal Wound Healing Requires Cells, Signals, and a MatrixCells, Signals, and a Matrix

1. Hunt TK, et al. 1. Hunt TK, et al. Adv Skin Wound CareAdv Skin Wound Care. 2000;13(suppl 2):6. 2000;13(suppl 2):6--11; 2. Barrientos S, et al. 11; 2. Barrientos S, et al. Wound Repair RegenWound Repair Regen. 2008;16:585. 2008;16:585--601; 3. Falanga 601; 3. Falanga V V LancetLancet 2005;366:1736 2005;366:1736-1743 1743

Keratinocytes and fibroblasts: 2 of the essential cell types1

Growth factors and cytokines; provide

cell-to-cell communication2

Extracellular matrix (ECM) formation and

maintenance3

PROCESSPROCESS KeratinocyteKeratinocyte FibroblastsFibroblasts BothBoth

MIGRATIONMIGRATION XX XX XX

PROLIFERATIONPROLIFERATION XX XX XX

BASEMENT BASEMENT MEMBRANEMEMBRANE

XX

Epidermal Epidermal DifferentiationDifferentiation

XX

ECM ECM ProductionProduction

XX XX

Essential Cellular Processes in the Essential Cellular Processes in the WoundWound

FIBROBLASTSFIBROBLASTS

Critical role in collagen synthesisCritical role in collagen synthesisSynthesize glycosaminoglycans (maintains Synthesize glycosaminoglycans (maintains hydration of the ECMhydration of the ECMMyofibroblastsMyofibroblasts--wound contractionwound contraction

CrossCross--talk Between Keratinocytes talk Between Keratinocytes and Fibroblasts in Wound Healingand Fibroblasts in Wound Healing

Barrientos S, et al. Barrientos S, et al. Wound Repair RegenWound Repair Regen. 2008;16:585. 2008;16:585--601; 601; Parentau NL, et al. Parentau NL, et al. J Cell Biochem.J Cell Biochem. 1991;45:2451991;45:245--251; Werner S, et al. 251; Werner S, et al. J J Invest Dermatol.Invest Dermatol. 2007;127:9982007;127:998--1008; 1008; Martin P. Martin P. ScienceScience. 1997;276:75. 1997;276:75--8181; Singer AJ, Clark RA. ; Singer AJ, Clark RA. N Engl J MedN Engl J Med. 1999;341:738. 1999;341:738--746; Witte MB, Barbul A. 746; Witte MB, Barbul A. Surg Clin North Am.Surg Clin North Am.1997;77:5091997;77:509--528.528.

IL-6TGF-βEGF

IGF-1FGF-10

Keratinocytes

Fibroblasts

12

IL-1, 6, 8, 18IFN-α, β, γ

TNF-αPDGFVEGF

Activin

The ECM consists of noncellular proteins produced by The ECM consists of noncellular proteins produced by cells cells

Structural proteins Structural proteins (e.g., collagen, elastin)(e.g., collagen, elastin)Adhesion proteins Adhesion proteins (eg, fibronectin, laminin)(eg, fibronectin, laminin)Proteoglycans Proteoglycans (eg, core protein + GAGs) (eg, core protein + GAGs)

Synthesis and deposition of Synthesis and deposition of the ECM are criticalthe ECM are critical

Provides structural/functional integrityProvides structural/functional integrityPlays a major role in determining tissue functionPlays a major role in determining tissue functionServes as a reservoir for growth factors and other proteinsServes as a reservoir for growth factors and other proteins

The Extracellular Matrix Plays an Essential Role The Extracellular Matrix Plays an Essential Role in Wound Healingin Wound Healing

chultz GS, Wysocki A. chultz GS, Wysocki A. Wound Repair RegenWound Repair Regen. 2009;17:153. 2009;17:153--162.162. 13

Disruption of Cellular FunctionDisruption of Cellular Function

Noncycling (senescent) cells

Impairedmigration and proliferation

Decreased response to

signaling molecules

Barrientos S, et al. Barrientos S, et al. Wound Repair RegenWound Repair Regen. 2008;16:585. 2008;16:585--601; Data on file. Organogenesis Inc.; 2010; Herrick SE, et al. 601; Data on file. Organogenesis Inc.; 2010; Herrick SE, et al. J Invest J Invest DermatolDermatol. 1996;106:187. 1996;106:187--193; Cook H, et al. 193; Cook H, et al. J Invest DermatolJ Invest Dermatol. 2000;115:225. 2000;115:225--233; Kim BC, et al. 233; Kim BC, et al. J Cell PhysiolJ Cell Physiol. 2003;195:331. 2003;195:331--336; 336; Vande Berg JS, Robson MC. Vande Berg JS, Robson MC. Surg Clin North AmSurg Clin North Am. 2003;83:509. 2003;83:509--520. 520. 14

Imbalance of Signaling MoleculesImbalance of Signaling Molecules

Barrientos S, et al. Barrientos S, et al. Wound Repair RegenWound Repair Regen. 2008;16:585. 2008;16:585--601601

Abnormal levels of cytokines and growth factors

15

Imbalance of Cytokines and Growth FactorsImbalance of Cytokines and Growth Factors

Adapted from: Barrientos S, et al. Adapted from: Barrientos S, et al. Wound Repair RegenWound Repair Regen. 2008;16:585. 2008;16:585--601.601.

Levels in Growth Factors/Chronic Wounds Cytokines Function

16

Matrix Impairment in Chronic Matrix Impairment in Chronic WoundsWounds

Cook H, et al. Cook H, et al. J Invest DermatolJ Invest Dermatol. 2000;115:225. 2000;115:225--233. 233.

ImpairedECM production and

maintenance

17

Imbalance of ECM in Chronic WoundsImbalance of ECM in Chronic Wounds

1. Hodde JP, Johnson CE. 1. Hodde JP, Johnson CE. Am J Clin DermatolAm J Clin Dermatol. 2007;8:61. 2007;8:61--66; 2. Xue M, et al. 66; 2. Xue M, et al. Expert Opin Ther TargetsExpert Opin Ther Targets. 2006;10:143. 2006;10:143--155; 3. Wysocki 155; 3. Wysocki AB, Grinnell F. AB, Grinnell F. Lab InvestLab Invest. 1990;63:825. 1990;63:825--831; 831; 4. Wysocki AB, et al. 4. Wysocki AB, et al. J Invest DermatolJ Invest Dermatol. 1993;101:64. 1993;101:64--68; 5. Vaalamo M, et al. 68; 5. Vaalamo M, et al. Hum PatholHum Pathol. 1999;30:795. 1999;30:795--802.802.

Deficiency of TIMPs creates MMP imbalance1-5

MMPsMatrix

metalloproteinases

TIMPsTissue inhibitors of

metalloproteinases

18

Maintenance

Degradation

CHRONIC WOUNDSCHRONIC WOUNDS

Remain in the inflammatory phaseRemain in the inflammatory phaseHigh concentration of matrix metalloprotenasesHigh concentration of matrix metalloprotenasesAbnormal fibroblast morphology and activityAbnormal fibroblast morphology and activity

Abnormal growth ratesAbnormal growth ratesImpaired response to growth factorsImpaired response to growth factors

ACUTE VS CHRONICACUTE VS CHRONIC

Orderly & timelyOrderly & timelyClosed woundClosed woundViable tissueViable tissueSingle injurySingle injuryControlled inflammationControlled inflammationControlled bacteriaControlled bacteria

Complex & delayedComplex & delayedOpen ulcerOpen ulcerCompromised tissueCompromised tissueRepeated injuryRepeated injuryUncontrolled Uncontrolled inflammationinflammationUncontrolled bacteriaUncontrolled bacteria

TREATMENTSTREATMENTS

TREATMENT OF WOUNDSTREATMENT OF WOUNDS

Address underlying etiologyAddress underlying etiologyAddress underlying patient related factors that Address underlying patient related factors that led to the wound and that negatively effect led to the wound and that negatively effect wound healingwound healingDebride devitalized tissue if wound is not Debride devitalized tissue if wound is not ischemicischemicCreate a wound environment which facilitates Create a wound environment which facilitates cellular proliferation and healingcellular proliferation and healing

ISCHEMIC ULCERSISCHEMIC ULCERS

Physical ExaminationPhysical ExaminationMeasurement of foot Measurement of foot perfusionperfusion

ABIsABIsSPPSPP

Revascularization if Revascularization if necessarynecessary

VENOUS ULCERSVENOUS ULCERS

Physical examinationPhysical examinationCompressionCompression

Multilayer wrapsMultilayer wrapsHoseHose

Venous duplexVenous duplexVenous intervention if Venous intervention if necessarynecessaryAdvanced productsAdvanced products

DIABETIC FOOT ULCERDIABETIC FOOT ULCER

Glucose controlGlucose control

OffloadingOffloadingAssure adequate Assure adequate vascularityvascularityEvaluate for Evaluate for osteomyelitisosteomyelitisHyperbaric oxygen if Hyperbaric oxygen if appropriateappropriate

DRESSINGSDRESSINGS

IDEAL DRESSINGIDEAL DRESSING

Wound moist and the periWound moist and the peri--wound skin drywound skin dryRemove the exudate but does not dessicateRemove the exudate but does not dessicateProvide a bacterial barrier yet allow gaseous Provide a bacterial barrier yet allow gaseous exchangeexchangeOne your patient can afford and get changed at One your patient can afford and get changed at the appropriate frequencythe appropriate frequency

WET TO DRY DRESSINGSWET TO DRY DRESSINGS

Cotton fibers left in wound with the dressings Cotton fibers left in wound with the dressings result in foreign body reaction and chronic result in foreign body reaction and chronic inflammatory stateinflammatory stateTissue dries and becomes a perfect medium to Tissue dries and becomes a perfect medium to grow bacteriagrow bacteriaEpithelial cells grow into gauzeEpithelial cells grow into gauzeAppropriate for some freshly debrided wounds Appropriate for some freshly debrided wounds

TOPICALSTOPICALS

HydrogelsHydrogelsSafegel,hydrogel,amerigelSafegel,hydrogel,amerigel

Enzymatic debridersEnzymatic debridersSantylSantylHoneyHoney

Silver productsSilver productsAquaAqua--cel AG, acticoat, silvergelcel AG, acticoat, silvergel

TOPICALSTOPICALS

FoamsFoamsPolyPoly--memmemMepilexMepilexAMDAMD

Growth factorsGrowth factorsRegranexRegranex

Recombinant PDGFRecombinant PDGFFDA approved for diabetic foot ulcers with healthy tissue FDA approved for diabetic foot ulcers with healthy tissue and adequate perfusionand adequate perfusionEXPENSIVEEXPENSIVE

CYTOTOXIC MATERIALSCYTOTOXIC MATERIALS

DakinDakin’’s solution*s solution*IodineIodinePeroxidePeroxideAcetic acidAcetic acid

*-May be indicated for wounds colonized with pseudomonas

TOXIC TO FIBROBLASTS

COLLAGENSCOLLAGENS

Oxidized regenerated cellulose and collagenOxidized regenerated cellulose and collagenReduces proteolytic enzyme activity in wound Reduces proteolytic enzyme activity in wound by binding to the MMPsby binding to the MMPsProtects biological activity of growth factorsProtects biological activity of growth factorsMay also have a component of silverMay also have a component of silverPromogran, Biostep, prismaPromogran, Biostep, prisma

What about honey?

HONEYHONEY

Natural hydrogen peroxide property which is Natural hydrogen peroxide property which is released after activation of glucose oxidase after released after activation of glucose oxidase after the honey contacts body moisturethe honey contacts body moistureThis peroxide is bactericidal but does not injure This peroxide is bactericidal but does not injure tissuestissuesUsed in diabetic ulcers, venous ulcers, burns, Used in diabetic ulcers, venous ulcers, burns, decubitus ulcers, MRSA infections decubitus ulcers, MRSA infections

UMF (unique manuka factor)UMF (unique manuka factor)

NonNon--peroxide antibacterial activity which is a peroxide antibacterial activity which is a phytochemical property and strain specificphytochemical property and strain specificFlowers of the manuka bush (Flowers of the manuka bush (Leptospermum Leptospermum scopariumscoparium))This particular antibacterial activity diffuses This particular antibacterial activity diffuses deeply into skin tissuesdeeply into skin tissuesUMF of 10 or greaterUMF of 10 or greater

MANUKA HONEYMANUKA HONEY

Filtered and sterilized by gamma radiationFiltered and sterilized by gamma radiationAcidicAcidic--changes wound pHchanges wound pHDebriding effect by osmotic effect of the honeyDebriding effect by osmotic effect of the honeyStimulates angiogenesis, stimulates fibroblast Stimulates angiogenesis, stimulates fibroblast growth (H2O2), stimulates epithelial cell growthgrowth (H2O2), stimulates epithelial cell growth

HONEYHONEY

No large randomized controlled trialsNo large randomized controlled trialsCase seriesCase seriesSmall trialsSmall trials

NEGATIVE PRESSURE THERAPY

KCI WOUND VACKCI WOUND VAC

Introduced in 1996 as negative pressure wound Introduced in 1996 as negative pressure wound therapy (NWPT)therapy (NWPT)GranufoamGranufoamSensitrac (controls suction)Sensitrac (controls suction)PumpPump

GRANUFOAMGRANUFOAM

Open pore polyurethane Open pore polyurethane ether foamether foam400400--600 microns600 micronsIncreases metabolic Increases metabolic activity and stimulates activity and stimulates granulationgranulationEvenly distributes the Evenly distributes the vacuum pressure at the vacuum pressure at the wound surface wound surface

KCI WOUND VACKCI WOUND VAC

Vacuum induces mechanical stress at the wound surfaceVacuum induces mechanical stress at the wound surfaceBlack spongeBlack sponge

Reticulated, porousReticulated, porousMost effective at stimulating granulationMost effective at stimulating granulation

White spongeWhite spongePolyvinyl alcoholPolyvinyl alcoholDense, hydrophilicDense, hydrophilicNonNon--adherentadherentCan control granulationCan control granulation

Decreases maceration, decreases bacterial load, increases tissueDecreases maceration, decreases bacterial load, increases tissueperfusion by decreasing interstitial fluidperfusion by decreasing interstitial fluid

NEGATIVE PRESSURE NEGATIVE PRESSURE THERAPYTHERAPY

Other companies with negative pressure devicesOther companies with negative pressure devicesGauze under suctionGauze under suctionSimilar foams under suctionSimilar foams under suctionVariable costs Variable costs

SNFs SNFs HospitalsHospitals

MAGGOT THERAPY

MAGGOT THERAPYMAGGOT THERAPY

Used throughout historyUsed throughout history11stst known application in the northern known application in the northern hemisphere 1920hemisphere 1920’’ssUsed in the 1920Used in the 1920’’s and 1930s and 1930’’s then fell out of s then fell out of favor with the development of antibioticsfavor with the development of antibiotics

MAGGOT THERAPYMAGGOT THERAPY

Reintroduced secondary Reintroduced secondary to antibiotic resistanceto antibiotic resistanceDisinfected fly larvae Disinfected fly larvae from the blowflyfrom the blowflySecrete a proteolytic Secrete a proteolytic enzymeenzyme

MAGGOT THERAPYMAGGOT THERAPY

Applied to wound and covered with a dressing Applied to wound and covered with a dressing to prevent migrationto prevent migrationIn place 2In place 2--3 days3 daysDebrides and disinfects woundsDebrides and disinfects wounds

ULTRASOUND THERAPYULTRASOUND THERAPY

MISTMIST

Mist of saline and Mist of saline and ultrasound transducerultrasound transducerLow frequency, non Low frequency, non contact ultrasoundcontact ultrasoundStimulates cell growthStimulates cell growthDebrides Debrides Removes bacteriaRemoves bacteriaNot painfulNot painful

ADVANCED BIOLOGICSADVANCED BIOLOGICS

ApligrafApligrafKeratinocytes and fibroblastsKeratinocytes and fibroblastsFDA approved for diabetic foot ulcers and venous leg ulcersFDA approved for diabetic foot ulcers and venous leg ulcers

DermagraftDermagraftFDA approved for diabetic ulcersFDA approved for diabetic ulcers

OasisOasisPorcine small intestinePorcine small intestineActs as a scaffoldingActs as a scaffolding

IntegraIntegraDermal filler/substituteDermal filler/substitute

HYPERBARIC OXYGENHYPERBARIC OXYGEN

Diabetic foot ulcersDiabetic foot ulcersWagner 3Wagner 3Wagner 4Wagner 4

NonNon--healing wounds in radiated fieldshealing wounds in radiated fieldsChronic refractory osteomyelitisChronic refractory osteomyelitis

WOUND SURVIVAL KITWOUND SURVIVAL KIT

SUPPLIESSUPPLIES

Skin tearsSkin tearsTegadermTegadermMepilex bordersMepilex borders

Foot ulcersFoot ulcersMedihoneyMedihoneyHydrogelHydrogel

Exudative woundsExudative woundsAMD foamAMD foam

SUPPLIESSUPPLIES

Venous ulcersVenous ulcersMedihoneyMedihoneyCompression hoseCompression hoseMultilayer wrapMultilayer wrap

UNNA bootUNNA boot3M product3M product

SUPPLIESSUPPLIES

BurnsBurnssilvadenesilvadene

Necrotic/sloughy woundsNecrotic/sloughy woundsEnzymatic debridersEnzymatic debridersHoneyHoney

SUMMARYSUMMARY

Wound healing is a complex process and often Wound healing is a complex process and often does not proceed in an orderly fashiondoes not proceed in an orderly fashionTreatment plans should be tailored as best as Treatment plans should be tailored as best as possible to manage the underlying etiologypossible to manage the underlying etiologyChronic wounds often require advanced Chronic wounds often require advanced modalitiesmodalitiesrqbypass@comcast.netrqbypass@comcast.net

QUESTIONSQUESTIONS

All of the following are stages of wound healing except:

A: Inflammatory phaseB: Proliferative phaseC: RemodelingD: Fibroblast phase

All of the following are stages of wound healing except:

D: Fibroblast phase

Which of the following cell types is most important for wound healing?

A: FibroblastB: KeratinocyteC: BothD: Neither

Which of the following cell types is most important for wound healing?

C: Both

The picture below is a patient with a history of prior DVT, a history of diabetes, and a history of rheumatoid arthritis. The ulcer has been present for 6 weeks with no previous therapy. The patient’s hemoglobin A-1C is 6. The patient has an ABI that shows no arterial insufficiency and the rheumatoid arthritis is mild and well controlled. The initial management of this patient included all of the following except:

A: Enzymatic debridement B: BiopsyC: Compression therapyD: ApligrafE: Nutritional assessmentF: Evaluate for infection

D: Apligraf

Apligraf is an advanced modality, FDA approved for venous leg ulcers that have failed conservative therapy