++
Wounds are classified as either acute or chronic. Acute wounds heal in a predictable manner and time frame. The process occurs with few, if any, complications, and the end result is a well-healed wound. Surgical wounds can heal in several ways. An incised wound that is clean and closed by sutures is said to heal by primary intention. Often, because of bacterial contamination or tissue loss, a wound will be left open to heal by granulation tissue formation and contraction; this constitutes healing by secondary intention. Delayed primary closure, or healing by tertiary intention, represents a combination of the first two, consisting of the placement of sutures, allowing the wound to stay open for a few days, and the subsequent closure of the sutures (Fig. 9-6).
++
++
The healing spectrum of acute wounds is broad (Fig. 9-7). In examining the acquisition of mechanical integrity and strength during healing, the normal process is characterized by a constant and continual increase that reaches a plateau at some point postinjury. Wounds with delayed healing are characterized by decreased wound-breaking strength in comparison to wounds that heal at a normal rate; however, they eventually achieve the same integrity and strength as wounds that heal normally. Conditions such as nutritional deficiencies, infections, or severe trauma cause delayed healing, which reverts to normal with correction of the underlying pathophysiology. Impaired healing is characterized by a failure to achieve mechanical strength equivalent to normally healed wounds. Patients with compromised immune systems such as those with diabetes, chronic steroid usage, or tissues damaged by radiotherapy are prone to this type of impaired healing. The surgeon must be aware of these situations and exercise great care in the placement of incision and suture selection, postoperative care, and adjunctive therapy to maximize the chances of healing without supervening complications.
++
++
Normal healing is affected by both systemic and local factors (Table 9-6). The clinician must be familiar with these factors and should attempt to counteract their deleterious effects. Complications occurring in wounds with higher risk can lead to failure of healing or the development of chronic, nonhealing wounds.
++
+++
Factors Affecting Wound Healing
++
Most surgeons believe that aging produces intrinsic physiologic changes that result in delayed or impaired wound healing. Clinical experience with elderly patients tends to support this belief. Studies of hospitalized surgical patients show a direct correlation between older age and poor wound healing outcomes such as dehiscence and incisional hernia.57,58 However, these statistics fail to take into account underlying illnesses or diseases as a possible source of impaired wound healing in the elderly. The increased incidence of cardiovascular disease, metabolic diseases (diabetes mellitus, malnutrition, and vitamin deficiencies), and cancer, and the widespread use of drugs that impair wound healing may all contribute to the higher incidence of wound problems in the elderly. However, more recent clinical experience suggests that major operative interventions can be accomplished safely in the elderly.
++
The results of animal studies regarding the effects of aging on wound healing have yielded contradictory results. In healthy human volunteers, there was a significant delay of 1.9 days in the epithelialization of superficial skin defects in those older than 70 years of age when compared to younger volunteers.59 In the same volunteers, using a micro-model of fibroplasia, no difference in DNA or hydroxyproline wound accumulation could be demonstrated between the young and elderly groups; however, the young volunteers had a significantly higher amount of total α-amino nitrogen in their wounds, a reflection of total protein content of the wound. Thus, although wound collagen synthesis does not seem to be impaired with advanced age, noncollagenous protein accumulation at wounded sites is decreased with aging, which may impair the mechanical properties of scarring in elderly patients.
+++
Hypoxia, Anemia, and Hypoperfusion
++
Low oxygen tension has a profoundly deleterious effect on all aspects of wound healing. Fibroplasia, although stimulated initially by the hypoxic wound environment, is significantly impaired by local hypoxia. Optimal collagen synthesis requires oxygen as a cofactor, particularly for the hydroxylation steps. Increasing subcutaneous oxygen tension levels by increasing the fraction of inspired oxygen (Fio2) of inspired air for brief periods during and immediately following surgery results in enhanced collagen deposition and in decreased rates of wound infection after elective surgery.60,61,62
++
Major factors affecting local oxygen delivery include hypoperfusion either for systemic reasons (low volume or cardiac failure) or due to local causes (arterial insufficiency, local vasoconstriction, or excessive tension on tissues). The level of vasoconstriction of the subcutaneous capillary bed is exquisitely responsive to fluid status, temperature, and hyperactive sympathetic tone as is often induced by postoperative pain. Correction of these factors can have a remarkable influence on wound outcome, particularly on decreasing wound infection rates.61,62,63 Mild to moderate normovolemic anemia does not appear to adversely affect wound oxygen tension and collagen synthesis, unless the hematocrit falls below 15%.63
+++
Steroids and Chemotherapeutic Drugs
++
Large doses or chronic usage of glucocorticoids reduce collagen synthesis and wound strength.64 The major effect of steroids is to inhibit the inflammatory phase of wound healing (angiogenesis, neutrophil and macrophage migration, and fibroblast proliferation) and the release of lysosomal enzymes. The stronger the anti-inflammatory effect of the steroid compound used, the greater the inhibitory effect on wound healing. Steroids used after the first 3 to 4 days postinjury do not affect wound healing as severely as when they are used in the immediate postoperative period. Therefore, if possible, their use should be delayed, or alternatively, forms with lesser anti-inflammatory effects should be administered.
++
In addition to their effect on collagen synthesis, steroids also inhibit epithelialization and contraction and contribute to increased rates of wound infection, regardless of the time of administration.64 Steroid-delayed healing of cutaneous wounds can be stimulated to epithelialize by topical application of vitamin A.64,65 Collagen synthesis of steroid-treated wounds also can be stimulated by vitamin A.
++
All chemotherapeutic antimetabolite drugs adversely affect wound healing by inhibiting early cell proliferation and wound DNA and protein synthesis, all of which are critical to successful repair. Delay in the use of such drugs for about 2 weeks postinjury appears to lessen the wound healing impairment.66 Extravasation of most chemotherapeutic agents is associated with tissue necrosis, marked ulceration, and protracted healing at the affected site.67
++
Diabetes mellitus is the best known of the metabolic disorders contributing to increased rates of wound infection and failure.68 Uncontrolled diabetes results in reduced inflammation, angiogenesis, and collagen synthesis. Additionally, the large- and small-vessel disease that is the hallmark of advanced diabetes contributes to local hypoxemia. Defects in granulocyte function, capillary ingrowth, and fibroblast proliferation all have been described in diabetes. Obesity, insulin resistance, hyperglycemia, and diabetic renal failure contribute significantly and independently to the impaired wound healing observed in diabetics.69 In wound studies on experimental diabetic animals, insulin restores collagen synthesis and granulation tissue formation to normal levels if given during the early phases of healing.70 In clean, noninfected, and well-perfused experimental wounds in human diabetic volunteers, type 1 diabetes mellitus was noted to decrease wound collagen accumulation in the wound, independent of the degree of glycemic control. Type 2 diabetic patients showed no effect on collagen accretion when compared to healthy, age-matched controls.71 Furthermore, the diabetic wound appears to be lacking in sufficient growth factor levels, which signal normal healing. It remains unclear whether decreased collagen synthesis or an increased breakdown due to an abnormally high proteolytic wound environment is responsible.
++
Careful preoperative correction of blood sugar levels improves the outcome of wounds in diabetic patients. Increasing the inspired oxygen tension, judicious use of antibiotics, and correction of other coexisting metabolic abnormalities all can result in improved wound healing.
++
Uremia also has been associated with disordered wound healing. Experimentally, uremic animals demonstrate decreased wound collagen synthesis and breaking strength. The contribution of uremia alone to this impairment, rather than that of associated malnutrition, is difficult to assess.69 The clinical use of dialysis to correct the metabolic abnormalities and nutritional restoration should impact greatly on the wound outcome of such patients.
++
Obesity is the largest growing public health problem in the United States and the world. Over 60% of Americans are overweight or obese. Uncomplicated obesity (i.e., in the absence of comorbid conditions such as cardiovascular disease, diabetes, or respiratory insufficiency) has by itself significant deleterious effects on wound healing. Visceral adiposity is active metabolically and immunologically and, through generation of proinflammatory cytokines and adipokines, leads to the development of the metabolic syndrome. Many of these molecules have effects on cells participating in the healing response. In nondiabetic obese rodents, wounds are mechanically weaker, and there is less dermal and reparative scar collagen. Pre-adipocytes infiltrate the dermis, and although they can evolve into fibroblasts, their regulatory mechanisms appear different from those of dermal or wound fibroblasts. Many studies indicate that obese patients have high rates of perioperative complications, with estimates as high as 30% for wound dehiscence, 17% for surgical site infections, 30% for incisional hernias, 19% for seromas, 13% for hematomas, and 10% for fat necrosis.72,73,74 Increased subcutaneous fat was associated with a 10-fold increased risk of surgery-related complications including anastomotic leaks, abdominal collection, and wound infections.75 In many studies, obesity is a constant and major risk factor for hernia formation and recurrence after repair. The mechanism by which obesity impairs wound healing awaits complete delineation.
++
The importance of nutrition in the recovery from traumatic or surgical injury has been recognized by clinicians since the time of Hippocrates. Poor nutritional intake or lack of individual nutrients significantly alters many aspects of wound healing. The clinician must pay close attention to the nutritional status of patients with wounds, since wound failure or wound infections may be no more than a reflection of poor nutrition. Although the full interaction of nutrition and wound healing is still not fully understood, efforts are being made to develop wound-specific nutritional interventions and institute the pharmacologic use of individual nutrients as modulators of wound outcomes.
++
Experimental rodents fed either a 0% or 4% protein diet have impaired collagen deposition with a secondary decrease in skin and fascial wound-breaking strength and increased wound infection rates. Induction of energy-deficient states by providing only 50% of the normal caloric requirement leads to decreased granulation tissue formation and matrix protein deposition in rats. Acute fasting in rats markedly impairs collagen synthesis while decreasing procollagen mRNA.76
++
Clinically, it is extremely rare to encounter pure energy or protein malnutrition, and the vast majority of patients exhibit combined protein-energy malnutrition. Such patients have diminished hydroxyproline accumulation (an index of collagen deposition) into subcutaneously implanted polytetrafluoroethylene tubes when compared to normally nourished patients (Fig. 9-8). Furthermore, malnutrition correlates clinically with enhanced rates of wound complications and increased wound failure following diverse surgical procedures. This reflects impaired healing response as well as reduced cell-mediated immunity, phagocytosis, and intracellular killing of bacteria by macrophages and neutrophils during protein-calorie malnutrition.76
++
++
Two additional nutrition-related factors warrant discussion. First, the degree of nutritional impairment need not be long-standing in humans, as opposed to the experimental situation. Thus patients with brief preoperative illnesses or reduced nutrient intake in the period immediately preceding the injury or operative intervention will demonstrate impaired fibroplasias.77,78 Second, brief and not necessarily intensive nutritional intervention, either via the parenteral or enteral route, can reverse or prevent the decreased collagen deposition noted with malnutrition or with postoperative starvation.79
++
The possible role of single amino acids in enhanced wound healing has been studied for the last several decades. Arginine appears most active in terms of enhancing wound fibroplasia. Arginine deficiency results in decreased wound-breaking strength and wound-collagen accumulation in chow-fed rats. Rats that are given 1% arginine HCl supplementation, and therefore are not arginine-deficient, have enhanced wound-breaking strength and collagen synthesis when compared to chow-fed controls.80 Studies have been carried out in healthy human volunteers to examine the effect of arginine supplementation on collagen accumulation. Young, healthy, human volunteers (aged 25–35 years) were found to have significantly increased wound-collagen deposition following oralsupplementation with either 30 g of arginine aspartate (17 g of free arginine) or 30 g of arginine HCl (24.8 g of free arginine) daily for 14 days.81 In a study of healthy older humans (aged 67–82 years), daily supplements of 30 g of arginine aspartate for 14 days resulted in significantly enhanced collagen and total protein deposition at the wound site when compared to controls given placebos. There was no enhanced DNA synthesis present in the wounds of the arginine-supplemented subjects, suggesting that the effect of arginine is not mediated by an inflammatory mode of action.82 In this and later studies, arginine supplementation, whether administered orally or parenterally, had no effect on the rate of epithelialization of a superficial skin defect. This further suggests that the main effect of arginine on wound healing is to enhance wound collagen deposition. Recently, a dietary supplemental regimen of arginine, β-hydroxy-β-methyl butyrate, and glutamine was found to significantly and specifically enhance collagen deposition in elderly, healthy human volunteers when compared to an isocaloric, isonitrogenous supplement (Fig. 9-9).83 As increases in breaking strength during the first weeks of healing are directly related to new collagen synthesis, arginine supplementation may result in an improvement in wound strength as a consequence of enhanced collagen deposition.
++
++
The vitamins most closely involved with wound healing are vitamin C and vitamin A. Scurvy or vitamin C deficiency leads to a defect in wound healing, particularly via a failure in collagen synthesis and cross-linking. Biochemically, vitamin C is required for the conversion of proline and lysine to hydroxyproline and hydroxylysine, respectively. Vitamin C deficiency has also been associated with an increased incidence of wound infection, and if wound infection does occur, it tends to be more severe. These effects are believed to be due to an associated impairment in neutrophil function, decreased complement activity, and decreased walling-off of bacteria secondary to insufficient collagen deposition. The recommended dietary allowance is 60 mg daily. This provides a considerable safety margin for most healthy nonsmokers. In severely injured or extensively burned patients, this requirement may increase to as high as 2 g daily. There is no evidence that excess vitamin C is toxic; however, there is no evidence that supertherapeutic doses of vitamin C are of any benefit.84
++
Vitamin A deficiency impairs wound healing, while supplemental vitamin A benefits wound healing in nondeficient humans and animals. Vitamin A increases the inflammatory response in wound healing, probably by increasing the lability of lysosomal membranes. There is an increased influx of macrophages, with an increase in their activation and increased collagen synthesis. Vitamin A directly increases collagen production and epidermal growth factor receptors when it is added in vitro to cultured fibroblasts. As mentioned before, supplemental vitamin A can reverse the inhibitory effects of corticosteroids on wound healing. Vitamin A also can restore wound healing that has been impaired by diabetes, tumor formation, cyclophosphamide, and radiation. Serious injury or stress leads to increased vitamin A requirements. In the severely injured patient, supplemental doses of vitamin A have been recommended. Doses ranging from 25,000 to 100,000 IU per day have been advocated.
++
The connections between specific minerals and trace elements and deficits in wound healing are complex. Frequently, deficiencies are multiple and include macronutrient deficiencies. As with some of the vitamins described earlier, the specific trace element may function as a cofactor or part of an enzyme that is essential for homeostasis and wound healing. Clinically, preventing deficiencies is often easier to accomplish than diagnosing them.
++
Zinc is the most well-known element in wound healing and has been used empirically in dermatologic conditions for centuries. It is essential for wound healing in animals and humans. There are over 150 known enzymes for which zinc is either an integral part or an essential cofactor, and many of these enzymes are critical to wound healing.85 With zinc deficiency, there is decreased fibroblast proliferation, decreased collagen synthesis, impaired overall wound strength, and delayed epithelialization. These defects are reversed by zinc supplementation. To date, no study has shown improved wound healing with zinc supplementation in patients who are not zinc deficient.86
++
Wound infections continue to represent a major medical problem, both in terms of how they affect the outcome of surgical procedures (surgical site infections), and for their impact on the length of hospital stay and medical costs.87 Many otherwise successful surgical operations fail because of the development of wound infections. The occurrence of infections is of major concern when implants are used, and their occurrence may lead to the removal of the prosthetic material, thus subjecting the patient to further operations and severe risk of morbidity and mortality. Infections can weaken an abdominal closure or hernia repair and result in wound dehiscence or recurrence of the hernia. Cosmetically, infections can lead to disfiguring, unsightly, or delayed closures.
++
Exhaustive studies have been undertaken that examine the appropriate prophylactic treatment of operative wounds. Bacterial contaminants normally present on skin are prevented from entry into deep tissues by intact epithelium. Surgery breaches the intact epithelium, allowing bacteria access to these tissues and the bloodstream. Antibiotic prophylaxis is most effective when adequate concentrations of antibiotic are present in the tissues at the time of incision, and assurance of adequate preoperative antibiotic dosing and timing has become a significant hospital performance measure.88 Addition of antibiotics after operative contamination has occurred clearly is ineffective in preventing postoperative wound infections.
++
Studies that compare operations performed with and without antibiotic prophylaxis demonstrate that class II, III, and IV procedures (see below) treated with appropriate prophylactic antibiotics have only one third the wound infection rate of previously reported untreated series.89 More recently, repeat dosing of antibiotics has been shown to be essential in decreasing postoperative wound infections in operations with durations exceeding the biochemical half-life (t1/2) of the antibiotic or in which there is large-volume blood loss and fluid replacement.90,91 In lengthy cases, those in which prosthetic implants are used, or when unexpected contamination is encountered, additional doses of antibiotic may be administered for 24 hours postoperatively.
++
Selection of antibiotics for use in prophylaxis should be tailored to the type of surgery to be performed, operative contaminants that might be encountered during the procedure, and the profile of resistant organisms present at the institution where the surgery is performed. The continuing widespread appearance of methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) has significantly restricted the selection of these agents for routine use. Surgery-specific treatment guidelines are provided in Table 9-7.90
++
++
Patients with prosthetic heart valves or any implanted vascular or orthopedic prostheses should receive antibiotic prophylaxis prior to any procedure in which significant bacteremia is anticipated. Dental procedures require prophylaxis with broad-spectrum penicillins or amoxicillin, while urologic instrumentation should be pretreated with a second-generation cephalosporin. Patients with prostheses who undergo gastrointestinal surgery should receive anaerobic coverage combined with a cephalosporin. Nasal screening and decolonization for Staphylococcus aureus carriers is recommended for selected procedures (i.e., cardiac, orthopedic, neurosurgical procedures with implants).
++
The incidence of wound infection is about 5% to 10% nationwide and has not changed during the last few decades. Quantitatively, it has been shown that if the wound is contaminated with >105 microorganisms, the risk of wound infection is markedly increased, but this threshold may be much lower in the presence of foreign materials. The source of pathogens for the infection is usually the endogenous flora of the patient’s skin, mucous membranes, or from hollow organs. The most common organisms responsible for wound infections in order of frequency are Staphylococcus species, coagulase-negative Streptococcus, enterococci, and Escherichia coli. The incidence of wound infection bears a direct relationship to the degree of contamination that occurs during the operation from the disease process itself (clean—class I, clean contaminated—class II, contaminated—class III, and dirty—class IV). Many factors contribute to the development of postoperative wound infections. Most surgical wound infections become apparent within 7 to 10 days postoperatively, although a small number manifest years after the original operative intervention. With the hospital stay becoming shorter and shorter, many infections are detected in the outpatient setting, leading to underreporting of the true incidence of wound infections absent intensive surveillance. There has been much debate about the actual definition of wound infection. The narrowest definition would include wounds that drain purulent material with bacteria identified on culture. The more broad definition would include all wounds draining pus, whether or not the bacteriologic studies are positive; wounds that are opened by the surgeon; and wounds that the surgeon considers infected.92
++
Anatomically, wound infections can be classified as superficial incisional, deep incisional, and organ/space wound infections, involving fascia, muscle, or the abdominal cavity. About three fourths of all wound infections are superficial, involving skin and subcutaneous tissue only. Clinical diagnosis is easy when a postoperative wound looks edematous and erythematous and is tender. Often the presentation is more subtle, and development of postoperative fever, usually low-grade; development of a mild and unexplained leukocytosis; or the presence of undue incisional pain should direct attention to the wound. Inspection of the wound is most useful in detecting subtle edema around the suture or staple line, manifested as a waxy appearance of the skin, which characterizes the early phase of infection. If a wound infection is suspected, several stitches or staples around the most suspicious area should be removed with insertion of a cotton-tipped applicator into the subcutaneous area to open a small segment of the incision. This causes minimal if any discomfort to the patient. Presence of pus mandates further opening of the subcutaneous and skin layers to the full extent of the infected pocket. Samples should be taken for aerobic and anaerobic cultures, with very few patients requiring antibiotic therapy. Patients who are immunosuppressed (diabetics and those on steroids or chemotherapeutic agents), who have evidence of tissue penetration or systemic toxicity, or who have had prosthetic devices inserted (vascular grafts, heart valves, artificial joints, or mesh) should be treated with systemic antibiotics.92
++
Deep wound infections arise immediately adjacent to the fascia, either above or below it, and often have an intra-abdominal component. Most intra-abdominal infections do not, however, communicate with the wound. Deep infections present with fever and leukocytosis. The incision may drain pus spontaneously, or the intra-abdominal extension may be recognized following the drainage of what was thought to be a superficial wound infection, but pus draining between the fascial sutures will be noted. Sometimes wound dehiscence will occur.
++
The most dangerous of the deep infections is necrotizing fasciitis. It results in high mortality, particularly in the elderly. This is an invasive process that involves the fascia and leads to secondary skin necrosis. Pathophysiologically, it is a septic thrombosis of the vessels between the skin and the deep layers. The skin demonstrates hemorrhagic bullae and subsequent frank necrosis, with surrounding areas of inflammation and edema. The fascial necrosis is usually wider than the skin involvement or than the surgeon estimates on clinical grounds. The patient is toxic and has high fever, tachycardia, and marked hypovolemia, which if uncorrected, progresses to cardiovascular collapse. Bacteriologically, this is a mixed infection, and samples should be obtained for Gram stain smears and cultures to aid in diagnosis and treatment. As soon as bacteriologic studies have been obtained, high-dose penicillin treatment needs to be started (20–40 million U/d intravenously) due to concern over the presence of Clostridia perfringens and other related species; broad-spectrum antibiotics should be added and the regimen modified based on culture results. Cardiovascular resuscitation with electrolyte solutions, blood, and/or plasma is carried out as expeditiously as possible prior to induction of anesthesia. The aim of surgical treatment is thorough removal of all necrosed skin and fascia. If viable skin overlies necrotic fascia, multiple longitudinal skin incisions can be made to allow for excision of the devitalized fascia. Although removal of all necrotic tissue is the goal of the first surgical intervention, the distinction between necrotic and simply edematous tissue often is difficult. Careful inspection every 12 to 24 hours will reveal any new necrotic areas, and these need further débridement and excision. When all necrotic tissue has been removed and the infection has been controlled, the wounds may be covered with homo- or xenografts until definitive reconstruction and autografting can take place.
++
The mere presence of bacteria in an open wound, either acute or chronic, does not constitute an infection, because large numbers of bacteria can be present in the normal situation. In addition, the bacteria identified by cultures may not be representative of the bacteria causing the actual wound infection. There seems to be confusion as to what exactly constitutes wound infection. For purposes of clarity, we have to differentiate between contamination, colonization, and infection. Contamination is the presence of bacteria without multiplication, colonization is multiplication without host response, and infection is the presence of host response in reaction to deposition and multiplication of bacteria. The presence of a host response helps to differentiate between infection and colonization as seen in chronic wounds. The host response that helps in diagnosing wound infection comprises cellulitis, abnormal discharge, delayed healing, change in pain, abnormal granulation tissue, bridging, and abnormal color and odor.
++
As discussed previously, neutrophils play a major role in preventing wound infections. Chronic granulomatous disease (CGD) comprises a genetically heterogeneous group of diseases in which the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxide enzyme is deficient. This defect impairs the intracellular killing of microorganisms, leaving the patient liable to infection by bacteria and fungi. Afflicted patients have recurrent infections and form granulomas, which can lead to obstruction of the gastric antrum and genitourinary tracts and poor wound healing. Surgeons become involved when the patient develops infectious or obstructive complications.
++
The nitroblue tetrazolium (NBT) reduction test is used to diagnose CGD. Normal neutrophils can reduce this compound, while neutrophils from affected patients do not, facilitating the diagnosis via a colorimetric test. Clinically, patients develop recurrent infections such as pneumonia, lymphadenitis, hepatic abscess, and osteomyelitis. Organisms most commonly responsible are Staphylococcus aureus, Aspergillus, Klebsiella, Serratia, or Candida. When CGD patients require surgery, a preoperative pulmonary function test should be considered since they are predisposed to obstructive and restrictive lung disease. Wound complications, mainly infection, are common. Sutures should be removed as late as possible since the wounds heal slowly. Abscess drains should be left in place for a prolonged period until the infection is completely resolved.93
++
Hyperglycemia has been shown to be a significant risk factor of postoperative infections.94 Tight blood glucose control, beginning preoperatively and continued into the operating room and beyond, has been associated with significant reduction in infectious complications, in particular following cardiac surgery.95,96 Too tight of a glycemic control (80–100 mg/dL) appears to be associated with more complications and is as effective, if not less than, moderate control (120–180 mg/dL).97,98
++
Another host factor that has been implicated in the development of superficial surgical site infection relates to the state of the subcutaneous capillary bed. Thomas K. Hunt had shown through several decades of work that this capillary bed is exquisitely sensitive to hypovolemia,99 hypothermia,100 and stress, leading to rapid vasoconstriction with secondary impaired oxygen delivery and increased rates of infection.61 Maintenance of euvolemia, core temperature above 36 to 36.5°C, and pain control have all been shown singly and additively to reduce rates of wound infections.63 Another suggestion has been to increase inspired Fio2 to 0.8 for the duration of the operation and in the immediate postoperative period, as a means of increasing subcutaneous tissue oxygen delivery. Although successful in most studies,62,101 there have also been negative results from such a single approach102; this suggests that addressing volume, temperature, pain control, and oxygen delivery in concert may be the more fruitful approach to reduce surgical wound infections.
++
Chronic wounds are defined as wounds that have failed to proceed through the orderly process that produces satisfactory anatomic and functional integrity or that have proceeded through the repair process without producing an adequate anatomic and functional result. The majority of wounds that have not healed in 3 months are considered chronic. Skin ulcers, which usually occur in traumatized or vascular compromised soft tissue, are also considered chronic in nature, and proportionately are the major component of chronic wounds. In addition to the factors discussed earlier that can delay wound healing, other causative mechanisms may also play a role in the etiology of chronic wounds. Repeated trauma, poor perfusion or oxygenation, and/or excessive inflammation contribute to the causation and the perpetuation of the chronicity of wounds.
++
Unresponsiveness to normal regulatory signals also has been implicated as a predictive factor of chronic wounds. This may come about as a failure of normal growth factor synthesis,103 and thus an increased breakdown of growth factors within a wound environment that is markedly proteolytic because of overexpression of protease activity or a failure of the normal antiprotease inhibitor mechanisms.104 Fibroblasts from chronic wounds also have been found to have decreased proliferative potential, perhaps because of senescence105 or decreased expression of growth factor receptors.106 Chronic wounds occur due to various etiologic factors, and several of the most common are discussed later.
++
Malignant transformation of chronic ulcers can occur in any long-standing wound (Marjolin’s ulcer). Any wound that does not heal for a prolonged period of time is prone to malignant transformation. Malignant wounds are differentiated clinically from nonmalignant wounds by the presence of overturned wound edges (Fig. 9-10). In patients with suspected malignant transformations, biopsy of the wound edges must be performed to rule out malignancy. Cancers arising de novo in chronic wounds include both squamous and basal cell carcinomas.
++
+++
Ischemic Arterial Ulcers
++
These wounds occur due to a lack of blood supply and are painful at presentation. They usually are associated with other symptoms of peripheral vascular disease, such as intermittent claudication, rest pain, night pain, and color or trophic changes. These wounds commonly are present at the most distal portions of the extremities such as the interdigital clefts, although more proximal locations are also encountered. On examination, there may be diminished or absent pulses with decreased ankle-brachial index and poor formation of granulation tissue. Other signs of peripheral ischemia, such as dryness of skin, hair loss, scaling, and pallor can be present. The wound itself usually is shallow with smooth margins, and a pale base and surrounding skin may be present. The management of these wounds is two-pronged and includes revascularization and wound care.107 Nonhealing of these wounds is the norm unless successful revascularization is performed. After establishing adequate blood supply, most such wounds progress to heal satisfactorily.
++
A strategy of prevention is extremely important in the approach to patients with limb ischemia. In bedridden patients, especially those who are sedated (in the intensive care unit), demented, or with peripheral neural compromise (neuropathy or paraplegia), pressure ulcers develop rapidly and often unecessarily. Removal of restrictive stockings (in patients with critical ischemia), frequent repositioning, and surveillence are vital to preventing these ulcers.108
++
Although there is unanimous agreement that venous ulcers are due to venous stasis and hydrostatic back pressure, there is less consensus as to what are the exact pathophysiologic pathways that lead to ulceration and impaired healing. On the microvascular level, there is alteration and distention of the dermal capillaries with leakage of fibrinogen into the tissues; polymerization of fibrinogen into fibrin cuffs leads to perivascular cuffing that can impede oxygen exchange, thus contributing to ulceration. These same fibrin cuffs and the leakage of macromolecules such as fibrinogen and α2-macroglobulin trap growth factors and impede wound healing.103 Another hypothesis suggests that neutrophils adhere to the capillary endothelium and cause plugging with diminished dermal blood flow. Venous hypertension and capillary damage lead to extravasation of hemoglobin. The products of this breakdown are irritating and cause pruritus and skin damage. The resulting brownish pigmentation of skin combined with the loss of subcutaneous fat produces characteristic changes called lipodermatosclerosis. Regardless of the pathophysiologic mechanisms, the clinically characteristic picture is that of an ulcer that fails to re-epithelialize despite the presence of adequate granulation tissue.
++
Venous stasis occurs due to the incompetence of either the superficial or deep venous systems. Chronic venous ulcers usually are due to the incompetence of the deep venous system and are commonly painless. Stasis ulcers tend to occur at the sites of incompetent perforators, the most common being above the medial malleolus, over Cockett’s perforator. Upon examination, the typical location combined with a history of venous incompetence and other skin changes is diagnostic. The wound usually is shallow with irregular margins and pigmented surrounding skin.
++
The cornerstone of treatment of venous ulcers is compression therapy, although the best method to achieve it remains controversial. Compression can be accomplished via rigid or flexible means. The most commonly used method is the rigid, zinc oxide–impregnated, nonelastic bandage. Others have proposed a four-layered bandage approach as a more optimal method of obtaining graduated compression.109 Wound care in these patients focuses on maintaining a moist wound environment, which can be achieved with hydrocolloids. Other, more modern approaches include use of vasoactive substances and growth factor application, as well as the use of skin substitutes. Recently, sprayed allogeneic keratinocytes and fibroblasts plus four-layer bandages have been shown to hasten healing when compared to compression alone.110 Most venous ulcers can be healed with perseverance and by addressing the venous hypertension.109 Unfortunately, recurrences are frequent despite preventative measures, largely because of patients’ lack of compliance.111
++
Ten percent to 25% of diabetic patients run the risk of developing ulcers. There are approximately 50,000 to 60,000 amputations performed in diabetic patients each year in the United States. The major contributors to the formation of diabetic ulcers include neuropathy, foot deformity, and ischemia. It is estimated that 60% to 70% of diabetic ulcers are due to neuropathy, 15% to 20% are due to ischemia, and another 15% to 20% are due to a combination of both. The neuropathy is both sensory and motor and is secondary to persistently elevated glucose levels. The loss of sensory function allows unrecognized injury to occur from ill-fitting shoes, foreign bodies, or other trauma. The motor neuropathy or Charcot’s foot leads to collapse or dislocation of the interphalangeal or metatarsophalangeal joints, causing pressure on areas with little protection. There is also severe micro- and macrovascular circulatory impairment.
++
Once ulceration occurs, the chances of healing are poor. The treatment of diabetic wounds involves local and systemic measures.112 Achievement of adequate blood sugar levels is very important. Most diabetic wounds are infected, and eradication of the infectious source is paramount to the success of healing. Treatment should address the possible presence of osteomyelitis and should employ antibiotics that achieve adequate levels both in soft tissue and bone. Wide débridement of all necrotic or infected tissue is another cornerstone of treatment. Off-loading of the ulcerated area by using specialized orthotic shoes or casts allows for ambulation while protecting the fragile wound environment. Topical application of PDGF and granulocyte-macrophage colony-stimulating factor has met with limited but significant success in achieving closure.113 The application of engineered skin allograft substitutes, although expensive, also has shown some significant success.114 Prevention and specifically foot care play an important role in the management of diabetics.115
+++
Decubitus or Pressure Ulcers
++
The incidence of pressure ulcers ranges from 2.7% to 9% in the acute care setting, in comparison to 2.4% to 23% in long-term care facilities. A pressure ulcer is a localized area of tissue necrosis that develops when soft tissue is compressed between a bony prominence and an external surface. Excessive pressure causes capillary collapse and impedes the delivery of nutrients to body tissues. Pressure ulcer formation is accelerated in the presence of friction, shear forces, and moisture. Other contributory factors in the pathogenesis of pressure ulcers include immobility, altered activity levels, altered mental status, chronic conditions, and altered nutritional status. The four stages of pressure ulcer formation are as follows: stage I, nonblanching erythema of intact skin; stage II, partial-thickness skin loss involving epidermis or dermis or both; stage III, full-thickness skin loss, but not through the fascia; and stage IV, full-thickness skin loss with extensive involvement of muscle and bone.
++
The treatment of established pressure ulcers is most successful when carried out in a multidisciplinary manner by involving wound care teams consisting of physicians, nurses, dietitians, physical therapists, and nutritionists. Care of the ulcer itself comprises débridement of all necrotic tissue, maintenance of a favorable moist wound environment that will facilitate healing, relief of pressure, and addressing host issues such as nutritional, metabolic, and circulatory status. Débridement is most efficiently carried out surgically, but enzymatic proteolytic preparations and hydrotherapy also are used. The wound bed should be kept moist by employing dressings that absorb secretions but do not desiccate the wound.116 Operative repair, usually involving flap rotation, has been found to be useful in obtaining closure. Unfortunately, recurrence rates are extremely high, owing to the population at risk and the inability to fully address the causative mechanisms.117