Acute Wounds

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

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

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.

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).

FIGURE 60-6 Compression with a multilayered wrap is useful to reduce edema, if there is adequate perfusion. An ankle-brachial index greater than 0.8 or an ankle pressure greater than 80 mm Hg is recommended to use three- or four-layer wraps, because they create 30-40 mm Hg of pressure.

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.

TABLE 60-2 Selecting Methods of Wound Debridement