Chapter 60 The Wound Care Center and Limb Salvage
Knowledge about the management of wounds has evolved into a distinct subspecialty requiring knowledge of normal and nonhealing wound physiology, products to accelerate wound healing, and new therapies for the treatment of recalcitrant wounds. Many subspecialties, such as vascular surgery, plastic surgery, podiatry, and primary care, share a role in managing wounds in the community. Current literature and research regarding wound healing often is published outside of traditional surgical or medical journals, so that many vascular surgeons are not familiar with up-to-date best practices
In many institutions, vascular surgeons are the primary consultant for the management of wounds. This new role in managing wounds has occurred because few other physicians are trained in the evaluation and treatment of wounds.
One of the most common clinical presentations for patients with peripheral arterial disease (PAD) is a nonhealing ischemic wound. Although revascularization may be required for limb salvage, the meticulous management of the primary wound after the surgery determines the success of limb salvage, as well as the time that it will take for a patient to return to function. Wound care after revascularization may be required for months or even years and a nonhealing wound can lead to limb loss, even if revascularization has been successful.
Patients with PAD who have limb-threatening ischemia often have diabetes. Not only are lower extremity ulcers common in diabetics, but they may also develop during the course of treatment. Diabetic wounds require specific management and often are managed by the vascular surgeon.
In the process of limb salvage, vascular surgeons create surgical wounds in ischemic limbs by harvesting vein conduit and exposing distal vessels. These newly created wounds occasionally result in graft exposure, infection, or delay the return to normal activity. Knowledge about the methods of minimizing the risk of creating wounds in ischemic limbs and the management of them is the province of vascular surgery.
Other surgical specialties, whose physicians used to be trained in wound healing, no longer receive training in contemporary wound management and wound healing. The training they receive in wound care is often based on outmoded concepts of wound care. Consequently, the specialist with the most exposure to nonhealing wounds, the vascular surgeon, has become the local expert in wound healing.
Normal Wound Healing
Wound healing is a complex process, the details of which we are only beginning to understand. Ideally, wound healing involves a well-organized, multifaceted series of events beginning after the actual event of wounding and ends with the formation of mature scar tissue (Figure 60-1). The acute wound is caused by external trauma, and acute wounds heal within a predictable time frame by progressing through orderly phases. Chronic wounds, however, do not follow this predictable course of events and may be the result of or impeded by internal events. However, correction of the internal problem does not always guarantee that the wound will heal in a timely fashion. Health care providers are just now beginning to comprehend the complex cellular and biological abnormalities that are inherent in the wound that has failed to heal.
FIGURE 60-1 The normal process of wound healing is complex and involves a series of phases that overlap.
Much of the latest research on wound healing involves investigation of the effects of various cytokines, growth factors, proteinases and their regulators and how they control the process of wound healing (Figure 60-2). To understand the effect of these substances on the chronic wound, the normal healing process of the acute wound must be understood. In acute wounds, the healing process begins with tissue injury and progresses predictably through the four phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. These stages of healing, while occurring in a predictable manner, can overlap and can last for months.
FIGURE 60-2 Balance of healing and nonhealing factors in wounds.
(Adapted from Schulz GS, Sibbald G, et al: Wound bed preparation: a systemic approach to wound management, Wound Rep Reg 11:1-28, 2003.)
Acute Wounds
Hemostasis
At the time of the initial injury, platelet activation and vasoconstriction occur after injury to the endothelium. Platelet aggregation, vasoconstriction, and clot formation begin the process of hemostasis. A number of soluble mediators are released by the platelets, including platelet-derived growth factor (PDGF), insulin-derived growth factor 1 (IGF-1), epidermal growth factor (EGF), fibroblast growth factor (FGF), and transforming growth factor-β (TGF-β). These mediators are responsible for initiating the healing process. Growth factors stimulate proliferation of wound cells, act as chemotactant agents, and regulate the differentiated functions of wound cells.1 Neutrophils and macrophages are recruited to the injured site, attracted by the chemotactant release by the platelets.
Inflammation
Aggregated platelets begin to degranulate and mediators are released that help form the fibrin clot. Initially in the inflammatory phase, there is significant vasodilation, increased capillary permeability, complement activation, and migration of polymorphonuclear neutrophils (PMN) and macrophages to the site of the wound. The antimicrobial defense and removal of devitalized tissue is initiated by the macrophages and PMNs. As they engulf and destroy bacteria, proteases are released, including elastase and collagenase, which begin the degradation process of the damaged extracellular matrix (ECM) components.
Along with their role in defense and debridement, macrophages and neutrophils induce the formation of granulation tissue by secreting growth factors that stimulate fibroblast proliferation (PDGF), collagen synthesis (TGF-β), and new blood vessel formation (FGF). The cytokine IL-B stimulates the proliferation of fibroblasts, and TNF-α and IL-1β stimulate fibroblasts to synthesize matrix metalloproteinases (MMPs).
Proliferation
The proliferative phase begins as the number of inflammatory cells in the wound bed decreases. The synthesis of growth factors continues in the wound bed but is taken over by the fibroblast, endothelial cells, and keratinocytes. Keratinocytes synthesize TGF-β, TGF-α, and IL-1. Fibroblasts secrete IGF-1, bFGF, TGF-β, PDGF, keratinocyte growth factor and connective tissue factor. Endothelial cells produce b-FGF, PDGF, and vascular endothelial growth factor. The process of cell migration and proliferation continues as the process of new capillary formation and synthesis of ECM components are begun.
Fibrin and fibronectin form a provisional wound bed matrix. New collagen and elastin and proteoglycan molecules that form the initial scar are synthesized by fibroblasts. Proteases have an essential role at this point. No integration of the newly formed matrix with the dermal matrix can occur until the damaged proteins in the existing matrix are removed. Neutrophils, macrophages, fibroblasts, epithelial cells, and endothelial cells secrete proteases. Key proteases include collagenases, gelatinases, and stromelysins, which are all members of the matrix MMP super family, and neutrophil elastase, a serine protease.
In the wound bed, cell proliferation and formation of new extracellular matrix is continuing and is sustained by a dramatic increase in the vascularity of the wound bed. The epidermal layer is reformed by the proliferation and migration of epithelial cells across the highly vascularized ECM.
Remodeling
Once the initial scar is formed, the synthesis of ECM continues for several weeks. The newly healed red, raised scar changes over the course of weeks to months to a scar that is less red and may be barely visible. At the cellular and molecular level, the breakdown of the ECM components reaches a balance with the process of synthesis of ECM, allowing remodeling to occur. The increased concentration of fibroblasts and capillaries present in the early phase of healing declines, primarily through apoptosis. In the final remodeling phase, tensile strength reaches a maximum of 80% of the initial strength, as cross-linking of collagen fibrils plateaus.
Chronic Wounds
In contrast to the acute wound, the chronic wound does not heal in a predictable fashion. Lazarus and colleagues2 defines the chronic wound as one in which the normal process of healing has been disrupted at one or more points in the phases of hemostasis, inflammation, proliferation, and remodeling. Chronic ulcers are characterized by defective remodeling of the ECM, a failure to epithelialize, and prolonged inflammation.3–5 In the chronic wound, fibroblasts do not readily respond to growth factors such as PDGF-β and TGF-β; this failure to respond is hypothesized to be due to a form of cellular senescence. Hyperproliferation at the wound margin interferes with normal cellular migration across the wound bed, probably because of inhibition of apoptosis within the fibroblasts and keratinocyte cells.6,7
The phases of wound healing are replete with factors that have played important roles in the progression of wound healing; therefore any alteration in one or more of these components may interfere with the healing progression. Growth factors such as PDGF, EGF, bFGF, and TGF-β are present in the chronic wound, but the levels remain constant, rather than displaying the variation seen in normal acute wound healing. The proinflammatory cytokines such as IL-1, IL-6, and TNF-α remain elevated in chronic wounds, when compared with the normal, acute wound, where a dramatic decrease is seen during healing, because there is a reduction in the inflammatory state.8
Several studies have shown that chronic wounds stall in the inflammatory phase of wound healing process.9–11 The inflammatory phase in wound healing is most often associated with an increased amount of exudate, postulated to be from infection, heavy colonization, or from reaction to increased necrotic tissue in the wound bed. The amount and character of fluid produced by the chronic wound can severely impede and even reverse the healing process.12–15
Studies investigating chronic wounds effluent have provided increasing evidence that the cellular and molecular environments are substantially altered in chronic wounds. Bucalo and colleagues16 collected exudate from venous ulcers and examined the effects of chronic wound fluid on the proliferation of dermal fibroblast, microvascular endothelial cells, and keratinocytes in culture. This study found that not only is wound fluid cytotoxic, it inhibited or failed to stimulate the proliferation of dermal fibroblasts, endothelial cells, and keratinocytes. Fluid from acute wounds, in contrast, has been found to stimulate fibroblast proliferation.17 Proteases in chronic wound fluid have also been shown to degrade growth factors such as PDGF and TGF-1.18,19
MMPs are a necessary component of the wound healing process and have an important role in cell migration and modification of the ECM. If the regulation of these protease molecules is disrupted, excessive MMP production may lead to degradation of the ECM, preventing cellular migration and attachment, and ultimately causing tissue destruction.20 It has been shown that levels of MMP activity are significantly elevated in a high percentage of chronic wounds when compared to acute wounds, suggesting dysregulation in chronic wounds (Figure 60-3). The activity of these proteases decreases consistently in patients whose ulcers progress from a nonhealing to healing phase.21
FIGURE 60-3 Matrix metalloprotein levels in wound fluid remain high in patients with chronic nonhealing wounds, whereas they recede in the normal wound.
The chronic wound can also be heavily colonized or infected by bacteria that can substantially increase the amount of exudate. Thus, a copious amount of exudate produced by the chronic wounds, whatever its cause, can be a barrier to healing.15,16,22,23
Assessment of Wound Healing Capability
With the recognition that there are altered cellular and molecular processes at play in the chronic wound has come the realization that wound management must focus on both the wound and the patient as a whole. The goal of wound management is to attain a healthy, well-vascularized, granulating wound bed. For this to happen, factors that can impede healing must be addressed. The way in which chronic wounds are viewed and managed should be based on a model that is both different from the acute wound paradigm and representative of the complex nature of nonhealing wounds.24
Patient Assessment
Identification of patient factors that would act as an impediment to healing is an essential component of the healing paradigm. The presence of diabetes, renal disease, heart disease, or liver disease can have detrimental effects of wound healing. Autoimmune diseases such as scleroderma, rheumatoid arthritis, vasculitis, or lupus erythematosus will deter wound healing. Systemic steroids, immunosuppressant medications, and nonsteroidal antiinflammatory drugs will also interfere with the healing wound.
The nutritional status of the patient is an overlooked factor in wound healing. Protein calorie malnutrition can have devastating effects on the integrity of the body and on any wounds the patient might have. Protein calorie malnutrition is defined as insufficient intake of both protein and calories. In protein calorie malnutrition, morbidity and mortality increases as a result of the proportionate decline in body weight.25 A decrease in lean body mass of greater than 10% is associated with compromised wound healing, despite therapeutic interventions. Once depletion of lean body mass reaches 30%, the wound becomes a secondary issue as the body seeks to restore and replenish lost muscle.26 Correction of any nutritional deficit should begin at the first visit and be maintained throughout the wound healing process. Assessment of dietary intake, including vitamin supplementation, is a necessary part of any wound healing assessment. Appetite stimulants, such as megestrol (Megace), may be helpful. If assessment shows moderate to severe protein calorie malnutrition, supplementation with oxandrolone has been shown to be beneficial to facilitate restoration of lean muscle mass.27
Assessment of Wound Characteristics
Accurate assessment of the wound and classifying the etiology of the wound must be accomplished before instituting a plan of care. Significant harm can occur if an incorrect treatment strategy is implemented; for example, active pyoderma gangrenosum should not be debrided and ischemic wounds should not be compressed. Information from the patient regarding the wound should be obtained if possible. How long has the wound been present, how did it start, what has been the progression, and how much pain exists? What aggravates or relieves the pain? What are the associated diseases, such as peripheral arterial or coronary artery disease, type 1 or 2 diabetes, rheumatoid arthritis?
Assessment of the wound includes the location, size, depth, and color of the wound bed (Table 60-1). A cotton swab has been shown to accurately gauge the depth and involvement of deep structures. The depth of a wound can be used to predict the likelihood of healing without extensive debridement of tendon or bone. The most common classification system of diabetic lower extremity wounds is the Wagner system, which grades the depth from superficial skin involvement to deep, involving tendon and bone.
TABLE 60-1 Documentation of Wound Characteristics
| Category | Observation to be Documented |
|---|---|
| Wound size | Length, width, depth, area, volume |
| Undermining presence, location, measurement | |
| Appearance | Granulation tissue; slough, necrotic, eschar; friability |
| Exudate | Amount, color, type (serous, serosanguineous, sanguinous, purulent), odor |
| Wound edge | Presence of maceration, advancing epithelium, erythema, even, rolled, ragged |
These variables should be photographed, measured, and recorded. The amount and type of exudate should also be assessed. Associated signs such as callous surrounding the ulcer, skin changes in the gaiter (ankle) distribution, peripheral neuropathy, and ischemic (trophic) changes should also be noted and recorded.
Diagnostic Studies for the Nonhealing Wound
There are three questions that need to be answered with diagnostic studies. First, what is the depth of the wound? Depth determines treatment, because involvement of deep structures such as tendon or bone reduces the likelihood of healing without removal of the deep tissue and increases the risk of the ascending infection along tendon sheaths. Subfascial infection is particularly worrisome in diabetic patients who have reduced sensation of the foot and reduced ability to fight infection. The simplest test of depth is to probe the wound to determine whether tendon or bone is involved. This inexpensive and simple method has been shown to be as reliable as more expensive tests in determining the presence of osteomyelitis. Other tests such as plain radiograph and bone scan have less sensitivity and specificity than a magnetic resonance imaging (MRI) scan (Figure 60-4). All these tests have false negatives and positives, so that surgical exploration is often necessary to determine the presence of deep infection and osteomyelitis, as well as to debride and culture the wound.
FIGURE 60-4 A, A foot with a superficial ulcer needs further diagnostic studies to determine the depth. B, Magnetic resonance imaging scan of the foot can show the depth of the wound and evidence of osteomyelitis when it is not clinically apparent.
Second, is the wound infected? The differentiation between colonization, cellulitis, abscess, and osteomyelitis is critical for optimal wound management. Wound culture identifies the organisms and need for topical, oral, and intravenous antibiotics. Colonization often is reflected by a wound culture that has multiple skin organisms. In colonization, there are no clinical signs of infection, such as erythema, swelling, and pain. Tissue biopsy and culture quantitates the number of organisms and determines whether the organisms are merely on the surface of the wound or whether they are present in the deep tissue, which implies an invasive infection and the need for more vigorous treatment. Plain film of the bone in a patient with osteomyelitis becomes positive in the late stages, long after osteomyelitis is established, whereas MRI scan has been shown to be reliable for determining osteomyelitis and detects early signs, such as changes in marrow intensity, periosteal reaction, and cortical erosion.
Third, is the limb ischemic, and does it have adequate blood flow to heal the wound? Adequate tissue oxygenation must be present for wound healing. Oxygen is available bound to hemoglobin and dissolved in plasma. In chronic wounds, plasma dissolved oxygen can be adequate for wound healing, assuming that perfusion of the tissue is satisfactory.
Assessment of the large vessel vascular supply is a critical component of the examination. A palpable pulse indicates a blood pressure of greater than 80 mm Hg in the foot and 70 mm Hg in the hand.28 If a pulse is not easily palpable, use of a vascular laboratory examination is essential. Doppler waveforms and ankle-brachial index (ABI) as well as plethysmography (Figure 60-5) can be used with transcutaneous pressure of oxygen (TcPO2) and skin perfusion pressure to determine the adequacy of blood supply. In patients with falsely elevated “stiff” arteries (high ABI with poor Doppler signals), pulse volume recordings, Doppler waveforms, and toe pressures are more reliable.
FIGURE 60-5 Physiologic studies of the lower limb are useful to determine the likelihood of wound healing. An ankle-brachial index (ABI) greater than 0.6 and biphasic or triphasic Doppler waveforms suggests a high likelihood of healing, whereas an ABI less than 0.4 and monophasic waveforms makes the likelihood of healing low.
Normal acute wounds usually have oxygen tensions (TcPO2) of 60 to 90 mm Hg, whereas chronic nonhealing wounds are most often associated with varying degrees of hypoxia because of low oxygen tension and poor blood perfusion. A tissue oxygen tension of greater than 40 mm Hg is adequate for wound healing. Tissue oxygen levels of less than 20 mm Hg in the wound bed are usually associated with failure to heal. When there is inadequate blood flow or perfusion pressure for wound healing, then treatment must be directed at increasing the perfusion by revascularization.
Treatment of Nonhealing Wounds
Elimination of Edema
Edema reduces microvascular blood flow and the clearance of bacteria and protein from the wound. It eliminates or reduces the likelihood of healing, and other management is often futile until edema is eliminated. The most challenging wounds are those with edema and ischemia, because patients with limb ischemia often place the limb in a dependent position to relieve ischemic rest pain. Prolonged dependency increases the limb edema and reduces perfusion, which paradoxically lead to an additional need for dependency. In ischemic limbs, the best method to reduce edema is to elevate the limb above the heart. Compression using sequential devices (e.g., Lymphopress, wraps [Unna boot or Profore], or support hose at 20 to 40 mm Hg pressure) should be limited to patients with a documented normal ankle brachial index of greater than 0.80 (Figure 60-6).
Debridement
The presence of necrotic tissue in a wound is the most obvious marker of a chronic wound. Reestablishing the balance of cytokines, proteases, and growth factors should be the focus of wound treatment. Efficient removal of devitalized tissue (necrotic burden) is an essential step in chronic wound management. The underlying pathogenic abnormalities in chronic wounds cause a continual buildup of necrotic tissue, and regular debridement is necessary to reduce the necrotic burden and achieve healthy granulation tissue. Debridement of devitalized tissue reduces tissue damage and destruction, removes bioburden, and exposes dead space that can harbor bacteria. Debridement can be accomplished in several different ways (Table 60-2), and the method chosen should be dictated by the condition of the wound and the skill of the practitioner, as well as the patient situation.
Autolytic Debridement
Autolytic debridement uses the body’s own natural enzymes to dissolve necrotic tissue within the wound and occurs spontaneously to some extent in all wounds. The macrophages and endogenous proteolytic enzymes liquefy and spontaneously separate necrotic tissue and eschar from healthy tissue. Autolytic debridement is most effective in a moist wound environment. Dressings most commonly used for this method include hydrogels and hydrocolloids, both of which can produce a more effective environment for destruction and phagocytosis of the necrotic tissue. Dressings that are occlusive or semiocclusive facilitate contact between the necrotic tissue and the enzymes within the wound. This method of debridement is selective with little discomfort, but it is often slow. If there is not improvement in the wound bed within 72 hours, another method of debridement should be used. This method is inappropriate for a wound that has a significant amount of necrotic debris or is heavily infected.
Enzymatic Debridement
Enzymatic debridement uses the application of topical agents to the surface of the wound, which chemically disrupts or digests devitalized extracellular proteins present in wound. There are two main preparations used in enzymatic debridement: collagenase (Santyl) and papain urea (Accuzyme). Collagenase is a partially purified preparation of collagenase derived from Clostridium histolyticum. Collagenase has been shown to have specificity for collagen types I and II. It cleaves glycine in endogenous collagen and digests collagen, but is not active against keratin, fat, or fibrin. Papain urea is composed of papain (from papaya fruit) mixed with a chemical agent, urea. Papain digests necrotic tissue by liquefaction of fibrinous debris, but is inactive against collagen. Urea is an activator for the papain. Urea also digests nonviable protein, making it more susceptible to proteolysis. Studies have demonstrated that the combination of papain urea is approximately twofold more effective than the enzyme alone.
Alvarez and colleagues showed that the papain urea product achieved a better wound response than did collagenase, but there was not a significant difference in wound closure between the two groups.28a Some patients complain of burning when the papain urea is applied, and this may limit its use in some patients.
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