Advances In Wound CareAdvances In Wound Care20072007

Rex Moulton-Barrett,MDRex Moulton-Barrett,MD

Wound aspectsWound aspects

o Etiologyo Types: Acute/Chronico Patho-physiologyo Treatment:Pain

UlcerationEdemaExudate

Components of Normal Wound Components of Normal Wound HealingHealing•Coagulation Coagulation processprocess

•Inflammatory Inflammatory processprocess

•Migratory/ Migratory/ ProliferativeProliferativeprocessprocess

•Remodeling Remodeling processprocess

Injury: hours / days weeks

A) Immediate to 2-5 days B) Hemostasis : Vasoconstriction , Platelet

aggregation , Thromboplastin clot C) Inflammation: Vasodilation , Phagocytosis

A) 2 days to 3 weeks B) Granulation: Fibroblasts lay collagen, Fills & new capillaries C) Contraction: Wound edges pull together to reduce defect D) Epithelialization: Crosses moist surface up to 3 cm

A) 3 weeks to 2 years B) New collagen forms which increases tensile strength C) Scar tissue is only 80 percent as strong as original tissue

Biochemical DifferencesBiochemical Differences

Healing woundsHealing wounds• cell mitosiscell mitosis• pro-inflammatorypro-inflammatory cytokinescytokines• Matrix Matrix

metalloproteinasesmetalloproteinases• Growth factorsGrowth factors• Cells capable of Cells capable of responding to responding to

healing signals healing signals

Chronic Chronic woundswounds

• mitogenic mitogenic activityactivity

• pro-inflammatorypro-inflammatory cytokinescytokines• MMPsMMPs• Varied # growth Varied # growth factorsfactors• Senescent cellsSenescent cells

Wound EtiologyWound Etiology

MechanicalMechanicalArterialArterialVenousVenousNeuropathicNeuropathicMalignancyMalignancyVasculiticVasculiticMetabolicMetabolic

Address the etiologyAddress the etiology

Types of Types of UlcersUlcers & & PathophysiologyPathophysiology

• DiabeticDiabetic: : pressure(joint/bone)>neuropathic>ischemic>infectivepressure(joint/bone)>neuropathic>ischemic>infective

• VenousVenous Stasis: intercellular pressure>ischemia ( post- Stasis: intercellular pressure>ischemia ( post-capillary )capillary )

• ArterialArterial: ischemia ( pre-capillary ): ischemia ( pre-capillary )• Pressure/Decubitus SorePressure/Decubitus Sore: neuropathic>boney/joint pressure: neuropathic>boney/joint pressure

soft tissue infection is a secondary acute or chronic event soft tissue infection is a secondary acute or chronic event joint infection and or osteomyelitis chronic joint infection and or osteomyelitis chronic secondary amyloidosis chronic secondary amyloidosis chronic Marjolin Ulcer: squamous cell carcinoma or sarcoma >3 yrs Marjolin Ulcer: squamous cell carcinoma or sarcoma >3 yrs

Pressure Sore Staging National Pressure Ulcer Advisory Panel (NPUAP)

• Stage 1 Nonblanchable erythema intact skin, discoloration of the skin, warmth, edema, induration, or hardnes

ulcer defined area of persistent redness in lightly pigmented skin,

in darker skin tones, persistent red, blue, or purple hues.

• Stage 2 Partial thickness skin loss involving epidermis, dermis, or both. ulcer is superficial with abrasion, blister, or shallow crater.

• Stage 3 Full thickness skin loss subcutaneous tissue that may extend to, but not through, underlying fascia. ulcer may have deep crater or undermining adjacent tissue.

• Stage 4 Full thickness skin loss with, tissue necrosis, muscle, bone, or supporting structures (e.g., tendon, joint capsule)

Undermining and sinus tracts

Diabetic Foot UlcerDiabetic Foot Ulcer

• DM: 10 Million USA todayDM: 10 Million USA today

• Immunopathy, vasculopathy, neuropathy,erythrocyte hemopathyImmunopathy, vasculopathy, neuropathy,erythrocyte hemopathy

• Misconception: small vessel diseaseMisconception: small vessel disease

• Multidisciplinary approach: podiatry, vascular, plastics, physical therapyMultidisciplinary approach: podiatry, vascular, plastics, physical therapy

• Neuropathy primary problemNeuropathy primary problem: small muscle contractures ( intrinsic minus ): small muscle contractures ( intrinsic minus )

• Secondary ligament and tendon glycosation leads to shorteningSecondary ligament and tendon glycosation leads to shortening

• Secondary joint contracture: asensate pressure soreSecondary joint contracture: asensate pressure sore

• Treatment: restore balance and distribute load and protect surfacesTreatment: restore balance and distribute load and protect surfaces

• Examples: midfoot ulcer: remove underlying metaphysis (118,000 lb/sq”)Examples: midfoot ulcer: remove underlying metaphysis (118,000 lb/sq”)

heel ulcer: Tendo achilles Z lengthening to 90 degreesheel ulcer: Tendo achilles Z lengthening to 90 degrees

Cuboid dislocation and Charcot Foot: requires internal fixationCuboid dislocation and Charcot Foot: requires internal fixation

Venous Stasis UlcerVenous Stasis Ulcer

• Cause: intercellular & post-capillary stasis and edemaCause: intercellular & post-capillary stasis and edema

• Secondary causes: infection, dry wound, shearing forcesSecondary causes: infection, dry wound, shearing forces

• Classic management: Zinc and compression Una BootClassic management: Zinc and compression Una Boot

• Rule out concomitant arterial ischemiaRule out concomitant arterial ischemia

• Modern Work-up and treatment: Modern Work-up and treatment: – Duplex u/s and culturesDuplex u/s and cultures– If significant venous reflux disease: end-venous ablation and If significant venous reflux disease: end-venous ablation and

venectomyvenectomy– Local treatment is a 4 component weekly:Local treatment is a 4 component weekly:

silver dressingsilver dressing

3 layer compression3 layer compression

With or without absorbent dressingWith or without absorbent dressing

Venous Stasis Ulcers & Venous Stasis Ulcers & CompressionCompression

• Circ-aid ( R:Allegra Medical ): Circ-aid ( R:Allegra Medical ): Nonelastic, latex-free,

40 mmHg compression therapy system Uses interlocking Velcro® bands Washable and reusable

• Circ-aid vrs Una Boot: 45% faster , 38% cheaper than Una BootCirc-aid vrs Una Boot: 45% faster , 38% cheaper than Una Boot

• Cir-aid: less surface shear and focal compression than 30mmHg Cir-aid: less surface shear and focal compression than 30mmHg stockingsstockings

at 2 months 1/2 the edema remains a.c.t. similar at 2 months 1/2 the edema remains a.c.t. similar stockingsstockings

67% of pts. With failed Una and stockings healed at 12 67% of pts. With failed Una and stockings healed at 12 monthsmonths

Ischemic and Post - Radiation Ischemic and Post - Radiation UlcersUlcers

• Multidisciplinary approachMultidisciplinary approach• Work-up arteriograms and duplex u/s Work-up arteriograms and duplex u/s

digital toe pressuresdigital toe pressures• Primary treatment: revascularize Primary treatment: revascularize

arterialarterial• Secondary infections, osteomyelitis Secondary infections, osteomyelitis

benefit from hyperbaric oxygen benefit from hyperbaric oxygen providing arterial supply adequate, ie providing arterial supply adequate, ie toe pressures helpfultoe pressures helpful

Assessment – Systemic Assessment – Systemic FactorsFactors

• AgeAge

• Body buildBody build• • StressStress

• NutritionNutrition

• MedicationsMedications

• Tissue Tissue oxygenationoxygenation

• Concomitant Concomitant diseasedisease

Assessment – Local FactorsAssessment – Local Factors

• PerfusionPerfusion

• Mechanical Mechanical stressorsstressors

• EdemaEdema

• Wound Wound temperaturetemperature

• Cytotoxic Cytotoxic agentsagents

• Necrotic tissueNecrotic tissue

• Bacterial burdenBacterial burden

• Desiccation Desiccation

• Excess exudateExcess exudate

TIMETIME Principles of Wound Bed Principles of Wound Bed PreparationPreparation Wound bed preparation accelerates healingWound bed preparation accelerates healing

Tissue non viable or deficient

Infection or inflammation

Moisture imbalance

Edge of wound non advancing or undermined

Defective matrix and cell debris

High bacterial counts or prolonged inflammation

Desiccation or excess fluid

Non-migrating keratinocytesNon-responsive wound cells

Debridement

Antimicrobials

Dressings compression

Biological agents Adjunct Therapies Debridement

Restore wound base and ECM proteins

Low bacterial counts and controlled inflammation

Restore cell migration, maceration avoided

Stimulate keratinocyte migration

Suction VacSuction Vac

• 0.15 mm pore, 125 mmHg suction:0.15 mm pore, 125 mmHg suction:

• Increased angiogenesis, VEGF, nitric Increased angiogenesis, VEGF, nitric oxide?oxide?

• Increased vessels,granulation: up to Increased vessels,granulation: up to 5x’s5x’s

• Decreased exudate, hypoxiaDecreased exudate, hypoxia

• Dressing changes/2 days, but Dressing changes/2 days, but costlycostly rentalrental

76 in Jan 200576 in Jan 2005

KCI: EducationKCI: Education

• http://www.kci1.com/education/indexhttp://www.kci1.com/education/index.asp.asp

• See whp1.swfSee whp1.swf

DebridementDebridement

Why debride ?Why debride ?•Enhanced wound assessmentEnhanced wound assessment•Decrease infection potential/extentDecrease infection potential/extent•Increase granulation Increase granulation

epithelializationepithelialization

TT

What to debride What to debride ??

• Slough-moist yellow, Slough-moist yellow, tantan or gray non-viable or gray non-viable tissuetissue• Eschar-dry, leathery Eschar-dry, leathery

Tissue

Debridement MethodsDebridement Methods

• Surgical: exciseSurgical: excise• Mechanical: adherance,sheer, irrigateMechanical: adherance,sheer, irrigate• Autolytic: topicalAutolytic: topical• Enzymatic: topicalEnzymatic: topical• Biological: topicalBiological: topical

Surgical DebridementSurgical Debridement

• ScalpelScalpel• ScissorsScissors• CuretCuret• LaserLaser• Hydro-ScapelHydro-Scapel• U/S HydroU/S Hydro

Recommended for removal of thick, adherent eschar and devitalized tissue in large

wounds

Mechanical DebridementMechanical Debridement

DefinitionDefinition - - The removal of foreignThe removal of foreign material and dead or damaged material and dead or damaged tissue tissue by the use of physical forces.by the use of physical forces.

MethodsMethods• IrrigationIrrigation• Wet-to-dry dressingsWet-to-dry dressings• Hydrotherapy: WhirlpoolHydrotherapy: Whirlpool• Suction VacSuction Vac

Mechanical Debridement ConsiderationsMechanical Debridement Considerations

• Aggressive debridementAggressive debridement• Wet-to-dry dressing may be painfulWet-to-dry dressing may be painful• Trauma to capillaries can cause bleedingTrauma to capillaries can cause bleeding• Skin maceration may occurSkin maceration may occur• Dressing changes may be time-consumingDressing changes may be time-consuming

Autolytic DebridementAutolytic Debridement

•The process by which the The process by which the wound bed utilizes phagocytic wound bed utilizes phagocytic cells and proteolytic enzymes cells and proteolytic enzymes

to remove debristo remove debris

•This process can be This process can be promoted and enhanced by promoted and enhanced by maintaining a moist wound maintaining a moist wound

environmentenvironment

Autolytic Debridement Autolytic Debridement ConsiderationsConsiderations

•Less aggressive debridementLess aggressive debridement•Slower than other methodsSlower than other methods•Easy to performEasy to perform•Little or no discomfortLittle or no discomfort•Performed in any settingPerformed in any setting•Contraindication: infectionContraindication: infection

Autolytic DebridementAutolytic Debridement

Enzymatic DebridementEnzymatic Debridement

•The use of topically applied The use of topically applied chemical agents to stimulate chemical agents to stimulate the breakdown of necrotic the breakdown of necrotic tissuetissue

•Common Topical AgentsCommon Topical Agents– Papain-UreaPapain-Urea– Papain-Urea-ChlorophyllinPapain-Urea-Chlorophyllin– CollagenaseCollagenase

Enzymatic DebridementEnzymatic Debridement

Collagenase• Derived from Clostridium Hystoliticum

• Highly specific for peptide sequence found in collagen

• Less aggressive debridement

• Site of action – collagen fibers anchoring necrotic tissue to the wound bed

10Harper (1972) 11Boxer (1969) 12Varma (1973)

Enzymatic DebridementEnzymatic Debridement

• Papain-UreaPapain-Urea• Proteolytic enzyme derived papayaProteolytic enzyme derived papaya66

• Urea is added as a denaturantUrea is added as a denaturant66

• Site of action – cysteine residues on Site of action – cysteine residues on proteinprotein88

• Inactive against collagenInactive against collagen66

6Falabella (1998) 8 Sherry and Fletcher (1962

Papain-Urea Mode of ActionPapain-Urea Mode of Action

Enzymatic DebridementEnzymatic Debridement

• Papain-Urea ChlorophyllinPapain-Urea Chlorophyllin• Contains Papain, Urea and Sodium Copper Contains Papain, Urea and Sodium Copper Chlorophyllin Chlorophyllin

• Sodium copper chlorophyllin is a Chlorophyll Sodium copper chlorophyllin is a Chlorophyll derivativederivative

–Anti-agglutininAnti-agglutinin

–results in anti-Inflammatory actionresults in anti-Inflammatory action

–Reduces odorReduces odor7Morrison J, Casali J (1957)

Enzymatic Debridement Enzymatic Debridement ConsiderationsConsiderations

• Should be painlessShould be painless• Less traumatic thanLess traumatic than surgical or surgical or

mechanicalmechanical debridementdebridement• Easy dressing changeEasy dressing change• Observe caution withObserve caution with infected woundsinfected wounds

*Agency for Healthcare Research and Quality (1994)

•Consider the use of Consider the use of enzymaticenzymatic

debridement for debridement for individualsindividuals

who:who:

– Cannot tolerate surgeryCannot tolerate surgery

– long-term-care facilitylong-term-care facility

– home care*home care*

The right method is a clinical decision that requires judgment

Autolytic, Collagenase, Papain-Urea-Chlorophyllin

Bacterial BalanceBacterial Balance

• Control mechanismControl mechanism• Intact skin is a physical barrierIntact skin is a physical barrier• pH is not conducive to bacterial pH is not conducive to bacterial growthgrowth

• Skin secretes fatty acids and Skin secretes fatty acids and antibacterialantibacterial

polypeptidespolypeptides• Normal flora prevent pathogenic Normal flora prevent pathogenic floraflora

from establishingfrom establishing

IIInfection or inflammation

Risk Factors for InfectionRisk Factors for Infection

• Vascular diseaseVascular disease• EdemaEdema• MalnutritionMalnutrition• Diabetes mellitusDiabetes mellitus• AlcoholismAlcoholism• Prior surgery or radiationPrior surgery or radiation• Drugs e.g. corticosteroidsDrugs e.g. corticosteroids• Inherited immune defectsInherited immune defects

• Large wound areaLarge wound area• Increased wound depthIncreased wound depth• Degree of chronicityDegree of chronicity• Anatomic location (distal Anatomic location (distal

extremity, perineal)extremity, perineal)• Presence of foreign Presence of foreign

bodiesbodies• Necrotic tissueNecrotic tissue• Mechanism of injury Mechanism of injury • Degree of contaminationDegree of contamination• Reduced perfusionReduced perfusion

Systemic Local

Bacterial BurdenBacterial BurdenCo

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Contamination - Infection continuum

Systemic

13Robson (1997) 14Dow (2001)

Bacterial BurdenBacterial Burden

• Tissue bacterial levels > 10Tissue bacterial levels > 1055 have have consistently resulted in impaired consistently resulted in impaired healing causing:healing causing:

• Metabolic loadMetabolic load• Produces endotoxins and proteasesProduces endotoxins and proteases

Bacterial balance

Host resistance Bacterial quantity and virulence

3Sibbald et al (2000) 12Dow (2001)

Local perfusionimmunosuppressionDiabetesmedications

Adhesinscell capsulesbiofilmsAntibiotic resistance

3 Rules for Topical Antimicrobial 3 Rules for Topical Antimicrobial AgentsAgents•Do not useDo not use antibiotics that are used antibiotics that are used systemicsystemically – ability to ally – ability to breed resistant organisms (topical gentamiycin, tobramycin)breed resistant organisms (topical gentamiycin, tobramycin)

•Do not useDo not use agents that are common agents that are common allergensallergens (neomycin, (neomycin, gentamycin, amikacin, tobramycin, bacitracin, lanolin)gentamycin, amikacin, tobramycin, bacitracin, lanolin)

•Do not use agentsDo not use agents that have high that have high cellular toxicitycellular toxicity in healable in healable wounds (povidone iodine, chlorhexidine, wounds (povidone iodine, chlorhexidine, hydrogen peroxidehydrogen peroxide))

22Sibbald 2003

Topical Antimicrobials: Topical Antimicrobials: SilverSilver•Centuries of useCenturies of use•Cytotoxicity associated with carriers not Cytotoxicity associated with carriers not

silver - ex. Silver silver - ex. Silver nitratenitrate, Silver , Silver sulfasulfadiazinediazine

•Traditional delivery required repeated Traditional delivery required repeated applications due to binding with chlorine applications due to binding with chlorine and proteins and proteins

•New silver dressings allow for continued New silver dressings allow for continued silver release in to the dressing - up to 7 silver release in to the dressing - up to 7 daysdays

17Demling and DeSanti (2001)

Why Silver for Wound Bed Why Silver for Wound Bed Preparation?Preparation?• Broad spectrum antimicrobial: yeasts, molds & Broad spectrum antimicrobial: yeasts, molds & bacteria, including MRSA bacteria, including MRSA

• Kills microbes on contact: inhibitiion cellular respirationKills microbes on contact: inhibitiion cellular respiration denatures nucleic acids denatures nucleic acids alters cell membrane permeabilityalters cell membrane permeability

• Does not induce resistance: if used at adequate levelsDoes not induce resistance: if used at adequate levels

• Low mammalian cell toxicityLow mammalian cell toxicity

• Anti-inflammatory activity: delivery system dependent)Anti-inflammatory activity: delivery system dependent)

Nanocrystalline SilverNanocrystalline Silver

•Decreased size of silver particles Decreased size of silver particles leads to increased proportion of leads to increased proportion of surface atoms compared with surface atoms compared with internal atomsinternal atoms1515

\\

•It is believed that the It is believed that the nanocrystalline structure is nanocrystalline structure is responsible for the rapid and long responsible for the rapid and long lasting actionlasting action1515

17Demling and DeSanti (2001)

Magnification of normal Silver

Magnification of Nanocrystalline Silver (< 1 micron)

Evaluating Silver ProductsEvaluating Silver Products

• Minimum bactericidal concentration Minimum bactericidal concentration (MBC) (MBC) - amount of antimicrobial - amount of antimicrobial agentagent

required to kill a given microbe required to kill a given microbe MBC is represented by a log reduction of 3MBC is represented by a log reduction of 3

Stratton et al (1991)Stratton et al (1991) – The silver required varies from 5ppm - 50+ The silver required varies from 5ppm - 50+

ppm for clinically relevant microbes ppm for clinically relevant microbes Yin et al (1999) & Hall (1987) Yin et al (1999) & Hall (1987)

– MBC of silver for MRSA = 60.5 ppmMBC of silver for MRSA = 60.5 ppm Calculated from Maple et al (1992)Calculated from Maple et al (1992)

Case StudyCase Study

• Day 3650 Day 3650 • Day 20• Day 20• 10 year old venous leg ulcers 10 year old venous leg ulcers •• Treated: silver nanocrystal Treated: silver nanocrystal

therapytherapy• previously treated: compression and SSDpreviously treated: compression and SSD

Topical Antimicrobials Cadexomer Topical Antimicrobials Cadexomer IodineIodine

• Iodine is a well known antimicrobial agentIodine is a well known antimicrobial agent• 0.9% iodine is carried in polysaccharide beads0.9% iodine is carried in polysaccharide beads• Provides sustained release iodine:non- cytotoxic Provides sustained release iodine:non- cytotoxic concentrationconcentration

• High rate of absorption from exudating ulcersHigh rate of absorption from exudating ulcers• No documented cases of bacterial resistanceNo documented cases of bacterial resistance

Recommendations for Wound Bed Recommendations for Wound Bed PrepPrep

• Thorough cleansingThorough cleansing• Debridement if needed Debridement if needed • Exudate managementExudate management– Consider topical antimicrobialsConsider topical antimicrobials– Silver Cadexomer iodine gel dressingSilver Cadexomer iodine gel dressing• Systemic antibioticsSystemic antibiotics

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Exudate ManagementExudate Management

1960’s: Moist Wound Environment Dr. George 1960’s: Moist Wound Environment Dr. George WinterWinter

– Improved Collagen synthesis & granulation tissueImproved Collagen synthesis & granulation tissue

– Faster Cell migration and epithelial resurfacing Faster Cell migration and epithelial resurfacing

– Prevention of scabs, crusts, and escharPrevention of scabs, crusts, and eschar

MMmoisture

Moist Wound Moist Wound EnvironmentEnvironment

•Additional benefitsAdditional benefits

•Faster healing Faster healing

•Capacity for autolysisCapacity for autolysis

•Decreased rates of infection Decreased rates of infection

•Reduced wound traumaReduced wound trauma

•Decreased painDecreased pain

•Fewer dressing changesFewer dressing changes

•Cost effectiveCost effective

Moisture Imbalance - Moisture Imbalance - DryDry

•Desiccation slows epithelial Desiccation slows epithelial migrationmigration

•Painful and uncomfortable Painful and uncomfortable for the patientfor the patient

•Delays normal healing Delays normal healing processprocess

•Acts as a source of infectionActs as a source of infection•Longer treatment time Longer treatment time •Increased costIncreased cost

Moisture Imbalance - Moisture Imbalance - WetWet

• Maceration of peri-wound skinMaceration of peri-wound skin

• Chronic wound fluid issuesChronic wound fluid issues

• DifferentDifferent from acute wound from acute wound

• ImbalanceImbalance of growth factors and of growth factors andpro-inflammatory cytokinespro-inflammatory cytokines

• Excessively high levels of Excessively high levels of proteasesproteases

• DegradesDegrades ECM and selectively ECM and selectively inhibitsinhibits proliferating proliferating cells cells

21Enoch and Harding, 2003

Exudate from a Chronic Wound

Exudate ManagementExudate Management

Chronic wound Chronic wound fluidfluid

Breakdown Breakdown of Necrotic of Necrotic

tissuetissue(debridemen(debridemen

t)t)

MicrobialMicrobialmanagememanageme

ntntCompressioCompressio

nn

EdemaEdemaBacterial Bacterial burdenburden

DressingDressingselectionselection

Chronic Wound Fluid - Chronic Wound Fluid - EdemaEdema

•Ankle-Brachial index & compressionAnkle-Brachial index & compression

< 0.5 --- 0.6 ------------- 0.8 ---------------1.0

NoneReduced

High

Dressing Selection Dressing Selection FactorsFactors

• Amount of exudate Amount of exudate • Anatomical locationAnatomical location• Presence of dead spacePresence of dead space

(depth, undermining, tunneling)(depth, undermining, tunneling)• Condition of surrounding skinCondition of surrounding skin• Caregiver abilityCaregiver ability• Healable vs. non-healable woundHealable vs. non-healable wound• CostCost

Small Amount of ExudateSmall Amount of Exudate

A B

C D

Moderate Amount of Moderate Amount of ExudateExudate

Large Amount of Large Amount of ExudateExudate

A B

Managing Moisture Managing Moisture ImbalanceImbalance

• FilmsFilms

• HydrogelHydrogel

• HydrocolloidHydrocolloid

• AlginateAlginate

• FoamsFoams

• Specialty AbsorbentSpecialty Absorbent

• Suction VacSuction Vac

• Exudate amountExudate amountNone Small Moderate Large

EdgeEdge of Wound Non-advancing or of Wound Non-advancing or UnderminedUndermined

• Cells not capable of responding to healingCells not capable of responding to healing signalssignals• Hyper-proliferation of epidermal cellsHyper-proliferation of epidermal cells occurs at the wound marginsoccurs at the wound margins• Epidermis fails to migrate across the Epidermis fails to migrate across the

woundwound

EE

Useful teaching resourcesUseful teaching resources

• Wound Care Information Networkhttp://www.medicaledu.com/default.htmlhttp://www.medicaledu.com/default.html

• KCIhttp://www.kci1.com/products/vac/vac/http://www.kci1.com/products/vac/vac/

index.aspindex.asp

• Smith & Nephewhttp://wound.smith-nephew.com/us/Home.asphttp://wound.smith-nephew.com/us/Home.asp