Wound Healing: A Practical Approach

Kevin Sexton Bonus Conference 5/2/12

Goals
1) To list the phases of wound healing and have a basic understanding of each. 1) List the types of wound closure and components of the reconstructive triangle. 2) Be exposed to current wound dressings/therapies.

Why bother?
6.5 million chronic wounds in the US 4 Main Types
Pressure sores Diabetic ulcers ($38 billion dollars in 2007) Venous stasis ulcers Arterial insufficiency

Americans are getting older

MUSTOE T. Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy. The American Journal of Surgery 2004;187(5):S65S70. Driver VR, Fabbi M, Lavery LA, Gibbons G. The costs of diabetic foot: the economic case for the limb salvage team. J Vasc Surg 2010;52(3 Suppl):17S22S.

Wound Classification
Acute
< 3 months old

Chronic
> 3 months old Problem with inflammation

All may occur simultaneously

Individual Processes May Overlap

Sabiston Textbook of Surgery; ISBN-13: 978-0721604091

What are the primary cells responsible for each wound healing phase?

Myofibroblast

Sabiston Textbook of Surgery; ISBN-13: 978-0721604091

Sabiston Textbook of Surgery; ISBN-13: 978-0721604091

How strong is the wound?

1 Week 3% 3 Weeks 30% 12 Weeks 80% 16 Weeks 80%

What are you going to tell your patients about activity?

Sabiston Textbook of Surgery; ISBN-13: 978-0721604091

Wound Closure
Primary
First intention Immediate Closure Suturing, skin graft placement, flap closure, etc Wound is allowed to close spontaneously Highly contaminated wounds Delayed primary closure Control infection Wound Closure

Secondary Tertiary

Sabiston Textbook of Surgery; ISBN-13: 978-0721604091

The Reconstructive Triangle

Flaps / Grafts

Tissue Expansion

Microsurgery

Wound Care
3 Healing Gestures Washing the wound Making Plasters Topicals to aid in wound healing Bandaging the wound

Carved into a stone tablet dated 2200 BC

A brief history of wound healing. Yardley, PA: Oxford Clinical Communications; 1998.

Modern Wound Therapy

Prepare the wound bed
Minimize hypoxia Minimize bacterial content

Create a warm, damp occluded environment

Maximizes epithelialization Minimizes pain

Disrupt the environment as little as possible Minimize the impact of comorbidities

Oxygen Delivery
Wound ischemia is detrimental to all processes
Initial factor for chronic wounds

Relative hypoxia more common

Initially stimulates fibroblast proliferation and angiogenesis Higher oxygen tension is required thereafter
IMPEDIMENTS TO WOUND HEALING/STADELMANN ET AL. THE AMERICAN JOURNAL OF SURGERY VOLUME 176 (Suppl 2A) AUGUST 1998

Relative Hypoxia
PaO2 of 30-40 mm Hg of O2
No fibroblast replication Collagen production severely limited

Hunt TK, Hussain Z. Wound microenvironment. In: Cohen IK, Diegelmann, RF, Lindblad WJ, (eds) Wound Healing Biochemical & Clinical Aspects. Philadelphia: W.B. Saunders Company; 1992:27481.

Treatment Options
Angioplasty Bypass Minimize comorbidities
Stop Smoking Therapy for heart failure

Blood Transfusions
If relative hypoxemia is bad, then a low hemoglobin concentration must impair wound healing. Actually, if compensatory mechanisms maintained (cardiac output, adequate pulmonary gas exchange, and normalizing lactate) then the data is equivocal.
Peacock EE Jr. Wound Repair, 3rd ed. Philadelphia: W.B. Saunders Co., 1984. Bains JW, Crawford DT, Ketchum AS. Effect of chronic anemia on wound tensile strength: correlation with blood volume, total red cell volume, and proteins. Ann Surg. 1966;164:243. Heughan C, Grislis G, Hunt TK. The effects of anemia on wound healing. Ann Surg. 1974;179:163. Jonsson K, Jensen JA, Goodson WH 3rd, et al. Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients. Ann Surg. 1991;214:605 613.

Infection
Health is not sterility. Number of organisms present per gram of tissue 10 5 organisms/gram tissue
> chances of wound closure 20% < 94 % chance of closure
Robson MC. Infection in the surgical patient: an imbalance in the normal equilibrium. Clin Plast Surg. 1979;6:493503. Robson MC, Krizek TK, Heggers JP. Biology of surgical infection. In: Ravitch MM (ed.). Current Problems in Surgery. Chicago: Yearbook Medical Publishers, 1973:1 62. Krizek TK, Robson MC, Kho E. Bacterial growth and skin graft survival. Surg Forum. 1967;18:518 519.

Treatment Options
Debridement
Presence of foreign debris reduces number of bacteria to cause a wound infection by a factor of 10,000 Elek SD. Experimental staphylococcal infections in the skin of
man. Ann NY Acad Sci. 1956;65:85.

Antibiotics

Systemic antibiotic are ineffective unless there are systemic symptoms Topical antibiotics deliver high concentrations of drug where they are most effective.
Robson MC, Edstrom LE, Krizek TJ, et al. The efficacy of systemic antibiotics in the treatment of granulating wounds. J Surg Res. 1974;16:299 306.

Dressings Qualities
Protect wound from bacteria and foreign material Absorb exudate Prevent heat and fluid loss Provide compression
Minimize edema and dead space

Be nonadherent to limit wound disruption Be aesthetically attractive

Occlusive Dressings
Winter Experiment Rate of epithelialization doubled in wounds that were covered in occlusive dressing

Winter GD. Formation of the scab and the rate of epithelialization of superficial wounds of the skin in the young domestic pig. Nature 1962;193:2934.

 Damp, mildly acidic environment

Epidermal migration, angiogenesis, connective tissue synthesis

Occlusion

Relatively lower oxygen tension

Stimulates angiogenesis Good initially, bad if persists

Granulation stimulated by cytokines

Preserved if wound environment occluded
Bolton L, Pirone L, Chen J, et al. Dressings effects on wound healing. Wounds 1990;2:12634. Varghese MC, Balin AK, Carter M, et al. Local environment of chronic wounds under synthetic dressings. Arch Dermatol 1986;122:527. Hunt TK, Zederfdeld B, Goldstick TK. Oxygen and healing. Am J Surg 1969;118:5215. Knighton DR, Silver IA, Hunt TK. Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. Surgery 1981;90:26270. Alvarez OM, Mertz PM, Eaglstein WH. The effect of occlusive dressings on collagen synthesis and reepithelialization in superficial wounds. J Surg Res 1983;35:1428. Alvarez O, Rozint J, Wiseman D. Moist environment: matching the dressing to the wound. Wounds 1989;1:3551.

Occlusion is Better than Sliced Bread.

Barnett A, Berkowitz RL, Mills R, et al. Comparison of synthetic adhesive moisture vapor permeable and fine mesh gauze dressings for split-thickness skin graft donor sites. Am J Surg 1983;145:3 7981.

There are no perfect dressings.

Infected wounds
Need non-occlusive dressing

Heavily Exudative wounds

Need absorbent dressing

Necrotic Wounds
Need debriding dressings

But there are a lot of choices

Lionelli GT, Lawrence WT. Wound Dressings. Surg Clin N Am. 2003 Volume 83. pages 617-38.

Nonadherent Fabrics
Hydrophobic More Occlusive Xeroform
3% Bismuth tribromophenate in petroleum Limited antimicrobial activity
Staphylococcus aureus Escherichia Coli

Hydrophilic Facilitate drainage of fluid into overlying layers Adaptic Fine mesh gauze

Vaseline Gauze Telfa

Absorptive Dressings
Gauze Wide-Mesh
Kerlix

Foam Dressings Hydrophobic, polyurethane foam sheets

Allevyn Mepilex Biopatch

Sticks to wounds
Debridement

Overwrap
Wick moisture

Absorbent Nonadherent

Occlusive Dressings
Non-Biologic Films Hydrocolloids Alginates Hydrogels Biologic Allograft
Alloderm

Xenograft
Strattice

Benefits of Both: insulation moisture retention mechanical barrier

Amnion Skin Substitutes

Integra

Films
Tegaderm Op-Site Waterproof Allow Gas Transmission
Oxygen Carbon Dioxide Water Vapor

Nonabsorptive Leak Need to have intact skin surrounding wound

Hydrocolloids
Hydrocolloid matrix
Gelatin, pectin, carboxymethylcellulose

Wafers, Pastes, Powders Duoderm Water contact leads to swelling and gel formation

Alginates
Based on alginic acid (seaweed) derivatives Exudative wounds Forms gel with water contact Must change when begins to bleed Sorbsan

 Acetic Acid

Antibacterial Solutions

gram - coverage, Pseudomonas 0.5% concentration for effect 0.25% killed 100% of fibroblasts in vitro Slows wound epithelialization Decreased PMN function

Dakins (bleach)
Non-descriminant killer
Wounds slower to epithelialize and neovascularize
Lineaweaver W, Howard R, Soucy D, et al. Topical antimicrobial toxicity. Arch Surg 1985;120:26770. Lineaweaver W, McMorris S, Soucy D, et al. Cellular and bacterial toxicities of topical antimicrobials. Plast Reconstr Surg 1985;75:3946. Dakins HD. The antiseptic action of hypochlorites: the ancient history of the new antiseptic. BMJ 1915;2:80910. Kozol RA, Gillies C, Elgebaly SA. Effects of sodium hypochlorite (Dakins Solution) oncells of the wound module. Arch Surg 1988;123:4203.

Iodine Containing Solutions

Kills bacteria For the most part, studies show betadine does not promote good wound healing and impairs wound strength.
Kjolseth D, Frank JM, Barker JH, et al. Comparison of the effects of commonly used wound agents on epithelialization and neovascularization. J Am Coll Surg 1994;179: 305 12. Stahl-Bayliss CM, Grandy RP, Fitzmartin RD, et al. The comparative efficacy and safety of 5% povidone-iodine for topical antisepsis. Ostomy Wound Manage 1990;31:409. Cooper ML, Laer JA, Hansbrough JF. The cytotoxic effects of commonly used topical antimicrobial agents on human fibroblasts and keratinocytes. J Trauma 1991;31: 77584. Kramer SA. Effect of povidone-iodine on wound healing: a review. J Vasc Nurs 1999;17:1723. Sundberg J, Meller R. A retrospective review of the use of cadexomer iodine in the treatment of chronic wounds. Wounds 1997;9:6886.

Silver Dressings
Broad antibacterial spectrum Silver sulfadiazine (1960s)
Antibacterial, antifungal, antiviral Neutropenia

Sulfamylon (first used during WW II)

Both kill fibroblasts in culture, however they increase epithelialization and neovascularization in partial thickness wounds. Acticoat- only have to change every 3 days

Can penetrate eschar Inhibits carbonic anhydrase (metabolic acidosis)

Silver References
Moyer CA, Brentano L, Gravens DL, et al. Treatment of large human burns with 0.5% silver nitrate solution. Arch Surg 1965;90:81267. Bellinger CG, Conway H. Effects of silver nitrate and sulfamylon on epithelial regeneration. Plast Reconstr Surg 1970;45:5825. Moncrief JA, Lindberg RB, Switzer WE, et al. Use of topical antibacterial therapy in the treatment of the burn wound. Arch Surg 1966;92:55865. Kucan JO, Smoot EC. Five percent mafenide acetate solution in the treatment of thermal injuries. J Burn Care Rehabil 1993;14:15863. Ballin JC. Evaluation of a new topical agent for burn therapy: Silver sulfadiazine (Silvadene). JAMA 1974;230:11845. 50] Fox CL. Topical therapy and the development of silver sulfadiazine. Surg. Gynecol Obstet 1983;157:828. Klasen HJ. A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver. Burns 2000;26:1318. McCauley RL, Li YY, Poole B, et al. Differential inhibition of human basal keratinocyte growth to silver sulfadiazine and mafenide acetate. J Surg Res 1992;52:27685. Geronemus RG, Mertz PM, Eaglstein WH. Wound healing: the effects of topical antimicrobial agents. Arch Dermatol 1979;115:13114. Tredget EE, Shankowsky HA, Groenveld A, et al. A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds. J Burn Care Rehabil 1998;19:5317.

Antibacterial Ointments
Gram Positives
Bacitracin, Mupirocin Gram Negatives Neomycin, Polymyxin B

Antibacterial effect for 12 hours Little benefit to epithelialized wounds

Increased Granulation Tissue Increased Wound Blood Flow Increased Angiogenesis Decreases healing time Increased Bacterial Load in wound
Argenta LC, Morykwas MJ: Vacuum-assisted closure: A new method for wound control and treatment: Clinical experience. Ann Plast Surg 1997; 38:563-576.discussion 577 Joseph E, Hamori CA, Bergman S, et al: A prospective randomized trial of vacuum-assisted closure versus standard therapy of chronic nonhealing wounds. Wounds 2000; 12:60-67. Timmers MS, Le Cessie S, Banwell P, et al: The effects of varying degrees of pressure delivered by negativepressure wound therapy on skin perfusion. Ann Plast Surg 2005; 55:665-671. Chen SZ, Li J, Li XY, et al: Effects of vacuum-assisted closure on wound microcirculation: An experimental study. Asian J Surg 2005; 28:211-217. Weed T, Ratliff C, Drake DB: Quantifying bacterial bioburden during negative pressure wound therapy: Does the wound VAC enhance bacterial clearance?. Ann Plast Surg 2004; 52:276-279.discussion 279-280 Obdeijn MC, de Lange MY, Lichtendahl DH, et al: Vacuum-assisted closure in the treatment of poststernotomy mediastinitis. Ann Thorac Surg 1999; 68:2358-2360. Defranzo AJ, Argenta LC, Marks MW, et al: The use of vacuum-assisted closure therapy for the treatment of lower extremity wounds with exposed bone. Plast Reconstr Surg 2001; 108:1184-1191.

Vacuum Therapy

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