The Science ofThe Science ofWound Bed PreparationWound Bed Preparation

Becky Adkins, RN, MSN, CWSNurse Practitioner

April 28, 2004

Objectives

• Differentiate normal wound healing from chronic wound healing

• Discuss factors that contribute to impaired healing in the the chronic wound

• Identify the components of Wound Bed Preparation to include debridement, bacterial burden, moisture balance

Components of Normal Wound Healing

Cell types involved

PlateletsPlateletsCoagulation Process

PlateletsPlateletsMacrophagesMacrophagesNeutrophilsNeutrophilsInflammatory

ProcessMacrophagesMacrophagesLymphocytesLymphocytesFibroblastsFibroblastsEpithelial cellsEpithelial cellsEndothelial cellsEndothelial cells

Migratory/ ProliferativeProcess

FibroblastsFibroblastsRemodeling Process

Injury/Hours/Days Weeks23Kane DP, Krasner D. In: Chronic Wound Care. 2nd ed. Health Management Publications Inc; 1997:1-4.

Degrades ECMDegrades ECM•• impaired cell migrationimpaired cell migration•• impaired connective tissue depositionimpaired connective tissue depositionDegrades Growth Factors Degrades Growth Factors

Prolonged Inflammation Prolonged Inflammation Stimulation of macrophage and Stimulation of macrophage and

neutrophils to wound bedneutrophils to wound bed

Release of proRelease of pro--inflammatory inflammatory cytokinescytokines

↑↑ Production MMPs and Production MMPs and ↓↓ TIMPsTIMPs

Chronic WoundChronic WoundDelayed HealingDelayed HealingRepeated Trauma

Local Tissue IschemiaNecrotic Tissue

Heavy Bacterial BurdenTissue Breakdown

TNFTNFαα and ILand IL--11ββ

Biochemical Differences

Healing Wounds• cell mitosis• pro-inflammatory

cytokines• MMPs• Growth factors• Cells capable of

responding to healing signals

Chronic Wounds• mitogenic activity• pro-inflammatory

cytokines• MMPs• Varied # growth

factors• Senescent cells

Clinical Assessment

• Does this patient have the ability to heal?

• Consider overall goals of care• Address wound etiology• Consider factor that contribute to

impaired wound healing

Wound Etiology

MechanicalArterialVenousNeuropathicMalignancyVasculiticOther

Address the Address the etiologyetiology

Assessment

Systemic Factors

Medications

Tissue Oxygenation

Concomitant Disease

Age

Body Build

Stress

Nutrition

Assessment

Local FactorsPerfusion

Mechanical stressors

Edema

Wound temperature

Cytotoxic agents

Necrotic tissue

Bacterial Burden

Desiccation

Excess exudate

Wound Bed Preparation - Defined

Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other

therapeutic measures

1Falanga, 2003

International Advisory Panel on Wound Bed Preparation

Keith Harding, MD

Marco Romanelli, MD

Michael Stacey, DS

Luc Teot, MD, PhD

Wolfgang Vanscheidt, MD

Gregory Schultz, PhD

Vincent Falanga, MD

Gary Sibbald, MD

Elizabeth Ayello, PhD

Caroline Dowsett

Wound Bed Preparation:A Systematic Approach to Wound Management

Wound Repair and Regeneration, 2003; 11:1-28

20Schultz, Sibbald, Falanga, et al, 2003

TIME Principles of Wound Bed PreparationTissue non viable or deficient

Infection or inflammation

Edge of Wound non advancing or undermined

Moisture imbalance

High bacterial counts or prolonged inflammation

Defective matrix and cell debris

Desiccation or excess fluid

Non-migrating keratinocytesNon-responsive wound cells

Biological Agents Adjunct Therapies

Debridement

Restore wound base and ECM proteins

Low bacterial counts and controlled inflammation

Restore cell migration, maceration avoided

Stimulate keratinocytemigration

Dressings Compression

Debridement Antimicrobials

TTTissue:

Non-viable or Deficient

Debridement

Why debride?• Enhance wound assessment• Decrease potential for

infection• Necrotic tissue delays

formation of granulation and epithelial tissue

Debridement

What to debride?• Slough - moist yellow, tan or

gray non-viable tissue.• Eschar - dry, leathery

Debridement Methods

SurgicalMechanicalAutolytic

EnzymaticBiological

Select the most appropriate method for the patient’s condition and goals of care

Surgical Debridement

• Scalpel• Scissors• Curet• Laser

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

Surgical DebridementConsiderations• The most aggressive debridement• Requires adequate perfusion• Tissue or bone cultures• Not recommended for severely compromised

patients• Analgesia/anesthesia required• Licensure/Skill• Associated with increased healing rates

among patients with diabetic foot ulcers5

5Steed et al, 1996

Surgical Debridement

Courtesy David Armstrong, MD

Mechanical Debridement

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

Methods– Irrigation– Wet-to-dry dressings– Hydrotherapy

Mechanical Debridement

Considerations• Aggressive debridement• Wet-to-dry dressing may be painful• Trauma to capillaries can cause bleeding• Skin maceration may occur• Dressing changes may be time-consuming

Mechanical Debridement

A B

Autolytic Debridement

Definition - The process by which the wound bed utilizes phagocytic cells and proteolytic enzymes to remove debris.

This process can be promoted and enhanced bymaintaining a moist woundenvironment.

Autolytic Debridement

Considerations• Less aggressive debridement• Slower than other methods• Easy to perform• Little or no discomfort• Performed in any setting• Contraindicated in the presence of infection

Autolytic Debridement

Enzymatic Debridement

Definition - The use of topically applied chemical agents to stimulate the breakdown of necrotic tissue.

Common Topical Agents– Papain-Urea– Papain-Urea - Chlorophyllin– Collagenase

Enzymatic 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 Debridement

Papain-Urea• Proteolytic enzyme derived papaya6

• Urea is added as a denaturant6

• Site of action – cysteine residues on protein8

• Inactive against collagen6

• Aggressive debridement

6Falabella (1998) 8 Sherry and Fletcher (1962

Papain-Urea Mode of Action

Enzymatic Debridement

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

Chlorophyllin • Sodium copper chlorophyllin is a chlorophyll

derivative– Anti-agglutinin

• Results in anti-Inflammatory action– Reduces odor

7Morrison J, Casali J (1957)

Enzymatic DebridementConsiderations• Should be painless• Less traumatic than surgical or mechanical

debridement• Easy dressing change• Observe caution with infected wounds• Consider the use of enzymatic debridement

for individuals who:– Cannot tolerate surgery– Reside in a long-term-care facility– Receive care at home*

*Agency for Healthcare Research and Quality (1994)

Enzymatic Debridement

Eschar Preparation• Cross Hatching• Hydrating agents

Debridement Methods

More Aggressive• Surgical• Mechanical• Papain-Urea

Less Aggressive• Autolytic• Collagenase• Papain-Urea

Chlorophyllin

Debridement Decisions:Clinical Indications

Aggressive Methods• Majority of wound

covered with necrotic tissue

• Goal of therapy is quick removal of necrotic tissue

• Wound continues to improve with current therapy

Debridement Decisions:Clinical Indications

• Majority of wound is clean and granulating

• No threat to patient’s health

Less Aggressive Methods

Debridement Decisions

Selecting the Appropriate Method• Wound characteristics• Degree of desired aggressiveness• Time available for debridement• Skill/licensure of clinician• Care setting

Clinicians may choose more than one method of debridement – e.g., surgical, followed by enzymatic

Most Aggressive - Surgical

Aggressive

Less Aggressive

The right method is a clinical decision that requires judgment

IIInfection or

Inflammation

Risk Factors that Increase the Risk for Infection

Systemic• Vascular disease• Edema• Malnutrition• Diabetes mellitus• Alcoholism• Prior surgery or radiation• Drugs e.g.

corticosteroids• Inherited immune

defects

Local• Large wound area• Increased wound depth• Degree of chronicity• Anatomic location (distal

extremity, perineal)• Presence of foreign bodies• Necrotic tissue• Mechanism of injury

Degree of post-wounding contamination

• Reduced perfusion

Bacterial Burden

Contamination - Infection Continuum

INFE

CTION

CRITICALL

Y

COLONIZE

D

CONTAMIN

ATION

COLONIZE

DLocal Systemic

Bacterial Burden

Why is an increased Bacterial Burden Problematic?

• ↑ metabolic load• Produces endotoxins and proteases• Stimulates a pro-inflammatory wound

environment• Wounds don’t heal

BacterialBalance

HostResistance

Bacterial quantityand

virulence

AdhesinsCell Capsules

BiofilmsAntibiotic Resistance

Local perfusionImmunosuppression

DiabetesMedications

3Sibbald et al (2000) 14Dow (2001)

Clinical Presentation

“Classic” Signs & Symptoms of Infection

Acute Wound Infectionor

SevereChronic Wound

Infection

Advancing erythemaFeverWarmthEdema / swellingPainPurulence

Clinical Presentation

Critically Colonized-

↑ Bacterial Burden-

Local Wound Infection

Delayed healingChange in color of wound bedFriable granulation tissueAbsent or abnormal granulation tissue↑ or abnormal odor↑ serous drainage↑ pain at wound site

15Cutting & Harding (1994)16Gardner, Frantz & Doebbeling (2001)

Secondary Signs & Symptoms of Infection

Reducing Bacterial Burden

Interventions• Debridement• Wound cleansing• Avoid routine use of antiseptics

– Betadine– Hydrogen Peroxide– Acetic Acid– Dakin’s Solution

Recommendations for Wound Bed PrepCONTA

MINATIO

N

COLONIZ

EDWound progressingWound progressing

•Routine wound cleansing•Exudate management•No indication for cultures

Recommendations for Wound Bed Prep

Delayed healingDelayed healing

Critica

lly

Colonized

Local

Infection

• Thorough cleansing• Exudate management

• Debridement if needed• Consider topical antimicrobials

-Silver dressing-Cadexomer idodine gel

Topical Antimicrobials - Silver

• Centuries of proven antimicrobial activity

• Cytotoxicity concerns associated with carriers not silver - ex. Silver nitrate, Silver sulfadiazine

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

• New silver dressings allow for continued silver release - up to 7 days

17Demling and DeSanti (2001)

Nanocrystalline Silver

• Decreased size of silver particles leads to increased proportion of surface atoms compared with internal atoms15

• It is believed that the nanocrystalline structure is responsible for the rapid and long lasting action15

Magnification of normal silver

Magnification of Nanocrystalline Silver (<1 micron)

17Demling and DeSanti (2001)

Case Study

Day 0

10 year old venous leg ulcers previously treated with compression and SSD

Day 20

After treatment with nanocrystalline silver

18Data on file

Topical Antimicrobials Cadexomer Iodine

• Iodine is a well known antimicrobial agent• 0.9% iodine is carried in polysaccharide

beads• Provides a slow sustained release of

iodine in non-cytotoxic concentrations• High rate of absorption from exudating

ulcers.• No documented cases of bacterial

resistance.

Recommendations for Wound Bed Prep

Impaired healingImpaired healing

Contam

inated

INFE

CTION

Coloniz

ed

Critica

lly

Coloniz

ed

Courtesy AAWC• Thorough cleansing• Debridement if needed • Exudate management• Consider topical antimicrobials

•Silver dressing•Cadexomer iodine gel

• Systemic antibiotics

Moisture Imbalance - Dry

• Desiccation slows epithelial migration• Painful and uncomfortable for the

patient• Delays normal healing process• Acts as a source of infection• Longer treatment time • Increased cost

Moisture Imbalance - Wet

• Maceration of peri-wound skin

• Chronic wound fluid issues

Exudate Management

EdemaBacterialBurden

Breakdown of Necrotic tissue(Debridement)

MicrobialManagement

Compression

Dressing Selection

Chronic Wound Fluid

Chronic Wound Fluid - Edema

Ankle-Brachial Index & Compression< 0.5 --- 0.6 ------------- 0.8 ---------------1.0

NoneNoneReduced Reduced

HighHigh

Dressing Selection Factors

• Amount of exudate • Anatomical location• Presence of dead space (Depth,

undermining, tunneling)• Condition of surrounding skin• Caregiver ability• Healable vs. non-healable wound• Cost

Managing Moisture Imbalance

None Small Moderate LargeNone Small Moderate LargeNone Small Moderate LargeExudate Amount

FilmsHydrogel

HydrocolloidAlginate

Foams

Specialty Absorbent

Small Amount of Exudate

A B

CD

Courtesy AAWC

Moderate Amount of Exudate

A B

C D

Large Amount of Exudate

A B

Edge of Wound Non-advancing or

Undermined

EE

Edge of Wound Non-advancing or UnderminedProblem • Cells not capable of responding to healing

signals• Hyper-proliferation of epidermal cells

occurs at the wound margins• Epidermis fails to migrate across the

wound

Edge of WoundNon-advancing or undermined

Interventions• Debridement• Biological Agents• Skin Grafts• Adjunctive Therapies

20Adapted from Schultz, Sibbald, Falanga, et al, 2003

Continuous Assessment

SystemicFactorsPatientEtiology

Local Factors

Time Principles

References1 Falanga V. (Ed.). New Concepts in Wound Bed Preparation. Springer-Verlag GmbH & Co. KG, Science

Communication Corporate Publishing, Berlin Heidelberg, 2003.

2 Falanga V. Classifications for wound bed preparation and stimulation of chronic wounds. Wound Repair and Regeneration 2000;8:347-352.

3 Sibbald RG, Williamson D, Orsted HL, Campbell K, Keast D, Krasner D, Sibbald D. Preparing the Wound Bed -Debridement, Bacterial Balance and Moisture Balance. O/WM 2000;46(11)14-35.

4 Mast BA, Schultz GS. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair and Regeneration 1996;4:411-420.

5 Steed DL, Donohoe D, Webster MW, Lindsley l, and the Diabetic Ulcer study Group. Effect of Extensive Debridement and Treatment on the Healing Diabetic Foot Ulcer. Journal of the American College of Surgeons 1996;183:61-64.

6 Falabella A. Debridement of Wounds. Wounds 1998:10;1C-9C.7 Morrison J, Casali J. Continuous Proteoplytic Therapy for Decubitus Ulcers. Am Journal of Surgery 1957; 93: 446-448.8 Sherry S. and Fletcher AP. Proteolytic enzymes: a Therapeutic evaluation. Clinical Pharmacology and Therapeutics

196X;1:202-226.

9 Lutterman A, Curtis R, Blache C, Johnston K & Frye K. Accuzyme Papain/Urea Ointment vs. Collagenase Santyl Ointment in the Treatment of Partial Thickness Burn Wounds, presented at SAWC, 2001

10 Harper E. Studies on the Mechanism of Action of Bacterial Collagenase. in Collagenase. Mandl, I., ed., Gordon& Breach, Science Publishers, Inc. New York, 1972.

11 Boxer AM, Gottesman N, Bernstein H, Mandl I. Debridement of Dermal Ulcers and decubiti with collagenase. Geriatrics 1969;24(7):75-86.

12 Varma AO, Bugatch E, German FM. Debridement of Dermal Ulcers with Collagenase. Gynecology & Obstetrics 1973;136:281-281.

13 Robson, MC. Wound Infection: A Failure of Wound Healing Caused by an Imbalance of Bacteria. Surgical Clinics of North America 1997;77(3)637-651.

14 Dow G. Infection in chronic wounds. In: Krasner DL, Rodheaver GT, Sibbald RG (eds). Chronic Wound Care: A Clinical Source Book for Healthcare Professsionals, Third Edition. Wayne, PA: HMP Comunications, 2001:343-356.

15 Cutting KF, Harding KG. Criteria for Identifying wound infection. Journal of Wound Care 1994;3(4):198-201.

16 Gardner SE, Frantz RA, Doebbeling BN. The validity of the clinical signs and symptoms used to identify localized wound infection. Wound Repair and Regeneration 2001;9(3):178-186.

17 Demling R. DeSanti L. Effects of Silver on wound Management. Wounds 2001;13(1) Supplement A:4-15.

18 Data on file

19 Schultz G, Mast B. Molecular Analysis of the Environment of Healing and Chronic Wounds: Cytokines, Proteases and Growth Factors. Wounds 1998;10:1F-9F20 Schultz G. sibbald RG, Falanga V, Ayello A, Dowsett C, Harding K, Romanelli M, Stacey M, Teot L, Vanscheidt W. (2003) Woud bed preparation: a systematic approach to wound management. Wound Repair & Regeneration 11(1): 1-28.21 Enoch S, Harding K. (2003). Wound bed preparation: the science behind the removal of barriers to healing. Wounds, 15(7): 213-229.22 Sibbald RG. Topical Antimicrobials. Ostomy/Wound Management 2003;49(5A-suppl): 3-33.23. Kane DP, Krasner D. In: Chronic Wound Care. 2nd ed. Health Management Publications Inc; 1997:1-4.

References