Optimizing the Patient for Surgical Treatment of the Wound

Optimizing the Patient for Surgical Treatment of the Wound

607 CLINICS IN PLASTIC SURGERY Clin Plastic Surg 34 (2007) 607–620 Optimizing the Patient for Surgical Treatment of the Wound Wesley T. Myers, MDa, ...

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CLINICS IN PLASTIC SURGERY Clin Plastic Surg 34 (2007) 607–620

Optimizing the Patient for Surgical Treatment of the Wound Wesley T. Myers, MDa, Mimi Leong, MD, MSb, Linda G. Phillips, MDa,* -


Phases of wound healing Inflammatory phase (reactive phase) Proliferative phase (regeneration phase) Maturation (remodeling phase) Wound debridement Bacterial balance Tissue oxygenation Hydration Diabetes Smoking

Most patients are in suboptimal health. As the population in the United States ages, chronic diseases and age-related diseases are increasingly more prevalent. Similarly, many patients seeking plastic surgery have sedentary lifestyles as well as poor dietary habits that culminate in obesity. Poor nutritional status, obesity, and age-related diseases—individually and in combination—can have adverse affects on surgical outcomes. The plastic surgeon must be aware of the changes that occur in their patients’ health and make interventions to optimize their patients’ medical comorbidities and surgical outcomes [1]. Many of the factors that are detrimental to wound healing and that affect a patient’s ability to heal a wound efficiently can be divided into two major categories: local and systemic (Box 1). These factors impact various processes in the phases of wound healing.




Nutrition Obesity Vitamins and minerals Aging Medications Nonsteroidal anti-inflammatory drugs Steroids Chemotherapeutic agents and radiation Summary References

Phases of wound healing Wound healing can be thought of as an orderly and linear process that occurs to restore homeostasis and integument integrity. Wound healing, as reviewed by Leong and Phillips, consists of three overlapping phases: the inflammatory phase (reactive phase), the proliferative phase (regeneration phase), and maturation (remodeling phase) [2]. Each phase is characterized by certain cell populations and specific gross histologic and clinical changes. Although no single phase of wound healing is an entity in and of itself, a wound may express findings that are more consistent with one phase than another or it may demonstrate qualities from multiple phases at the same time. For example, an acute wound may demonstrate only inflammatory changes, whereas a chronic healing wound may show signs of all three phases of the wound-healing processes.

a Division of Plastic Surgery, Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA b Division of Plastic and Reconstructive Surgery, Baylor College of Medicine & Michael E. DeBakey VAMC, 1709 Dryden Road, Suite 1600, Houston, TX 77030, USA * Corresponding author. E-mail address: [email protected] (L.G. Phillips).

0094-1298/07/$ – see front matter ª 2007 Elsevier Inc. All rights reserved.




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Box 1:

Factors detrimental to wound healing

Systemic Diabetes Smoking Nutrition Aging Medications Exogenous steroid administration Local Tissue oxygenation Infection Necrotic tissue Tissue perfusion Radiation Neoplasm

Inflammatory phase (reactive phase) Wounding disrupts local tissue vascular supply. The body must initiate a cascade of events that allows itself to heal in an orderly fashion. Immediately following injury, there is a brief period of vasoconstriction followed by activation of platelets and the clotting cascade that culminates in the formation of a fibrin clot and hemostasis. It is this clot formation that initiates the inflammatory phase. The inflammatory phase can be characterized by an increase in vascular permeability facilitated by thrombin following hemostasis, secretion of chemotactic cytokines that facilitate the migration of cells crucial to wound healing, secretion of cytokines and growth factors into the wound itself, and modulation of cells that have migrated into the wound and cells that are native to the wound. Polymorphonuclear leukocytes and macrophages are the dominant cell types during the initial stage of the inflammatory phase.

Proliferative phase (regeneration phase) This stage is characterized by the formation of granulation tissue within the wound bed, composed of new capillary network, fibroblasts, and macrophages in a loose arrangement of supporting structure. This scaffolding or supporting structure is composed of collagen, fibronectin, and hyaluronic acid. It is the formation of the new capillary network that gives granulation tissue its beefy red appearance. During the proliferative phase, macrophages and the extracellular matrix (ECM) release growth factors that stimulate fibroblast activation. Fibroblasts become the predominant cell type in the wound during this phase [3]. Wound contraction begins to takes place during the proliferative phase of wound healing as fibroblast-like cells called myofibroblasts, which contain alpha-actin and microfilaments, pull the wound edges toward

the center of the wound [4]. Basal cells at the wound edge produce new epithelium followed by the influx of keratinocytes and fibroblasts to restore the epidermis during this phase [5].

Maturation (remodeling phase) During the maturation phase, fibroblasts become myofibroblasts with scar remodeling and contraction predominating. Matrix metalloproteinases (MMPs), zinc-dependent endopeptidases, are activated when the integument is damaged [6]. The deposition of the ECM and its components is modulated by MMPs and their counterregulatory inhibitors, tissue inhibitors of metalloproteinases. MMP-3 is important in wound contraction, and its absence severely affects wound healing [7,8]. The homeostasis of the ECM is critical in wound healing. During the remodeling phases, wound tensile strength gradually increases as immature, disorganized scar is reorganized. Although collagen content in a healed wound is maximal at 21 days, scar tissue is rearranged and replaced by more organized thicker fibers with more cross-linking to obtain a wound that has approximately 80% tensile strength of normal dermis by 6 months [9]. Scar remodeling continues to occur for up to 12 months following the initial injury, with the scar becoming softer and less indurated; scar tissue never achieves the tensile strength of normal skin [3,10].

Wound debridement Before any surgical intervention for wound coverage or closure, the wound as well as the patient may need to be optimized to allow for wound healing to occur. Necrotic and devitalized tissue in a wound impedes the wound-healing process by providing bacteria with a medium for growth as well as preventing the formation of granulation tissue and wound contraction. In a stable patient with a wound that fails to heal, the goal of debridement and cleansing should be to remove any and all necrotic tissue, decrease the bacterial count, and produce a wound with a granulated tissue bed. There should be no local cellulitis, odor, or purulent drainage. If infection is present, Dakin’s solution can be combined with dressing changes to help decrease the bacterial load. Silver-containing compounds, such as silver sulfadiazine, mafenide acetate, and silver nitrate, also may be used to decrease the bacterial count [11,12]; however, debridement and irrigation provide the most rapid means of cleansing and wound bed preparation. Debridement promotes wound healing by converting a chronic wound into an acute wound with a more favorable environment that allows it to progress through the phases of wound healing.

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On a molecular level, debridement removes MMPs that inhibit wound healing [13]. Debridement removes tissue that is susceptible to infection and promotes the formation of granulation tissue, wound contraction, and epithelization. Debridement should be carried down until only healthy, well-vascularized tissue remains. Care should be taken not to excise healthy tissue, maintain adequate hemostasis, and use atraumatic technique while performing bedside debridement. Wounds also may be cleaned with a mild soap and sterile water solution. Solutions containing antiseptic (toxic) agents, such as povidone/iodine, are avoided. At the time of excision and debridement, tissue samples are sent to pathology for analysis and quantitative tissue culture. Bedside irrigation may be performed with a 30-mL syringe filled with normal saline through an 18-gauge catheter. If the patient requires more extensive debridement and irrigation or if hemostasis and analgesia cannot be obtained, then debridement should be performed in the operating room. Surgical debridement is contraindicated when the vascular supply is inadequate to support wound healing or in the absence of appropriate antibacterial coverage in the septic patient. Dressings also may be used on a wound in an effort to optimize the wound environment before surgical intervention. The goal is to maintain a moist healing environment. A moist wound environment facilitates reepithelialization at twice the rate when compared with a similar wound that is exposed to the air and allowed to desiccate [14]. Occlusive and semiocclusive dressings provide such an environment, especially in large wounds [15]. The choice of the dressing relies heavily upon the clinical judgment of the treating surgeon for appropriate selection. Although it is important to provide a moist wound environment that facilitates reepithelialization, it also is essential to protect the surrounding skin from maceration to prevent propagation of the wound. Wounds that produce large amounts of exudate will lead to maceration with the use of an occlusive dressing. In such cases, occlusive dressings are contraindicated. When maceration is combined with mechanical forces, such as friction and shear, the wound size is at risk for enlargement. Financial considerations also play a role in dressing selection. Patients with large or problematic wounds usually are under considerable financial burden. Therefore, when choosing a dressing, it must be cost-effective. Large wounds have dressing needs that differ from their smaller progenitors. Often, the application of moist, saline-soaked Kerlex gauze is appropriate to maintain a moist wound environment, especially after bedside debridement, in a larger wound.

Kerlex gauze is preferred to smaller 4  4 gauze because there is less of a chance of misplacing Kerlex gauze in a large wound. The gauze is kept moist and changed frequently, maintaining the moist wound environment in an effort to optimize wound healing before surgical closure.

Bacterial balance Plastic surgeons are consulted often to evaluate an infected wound that requires closure. An infected wound does not progress through the stages of wound healing; it remains in the inflammatory stage as it fights to clear the wound of the bacterial burden [16]. Open wounds and chronic nonhealing wounds are considered to be colonized with microbial flora [17]. The bacterial burden, or balance, of a wound that fails to heal ultimately is controlled by irrigation, debridement, and closure of the wound, with the muscle flap being the preferred flap for closure of an infected wound [18]. A wound biopsy for quantitative tissue cultures is indicated in any wound that clinically fails to respond to treatment for bacteriology and to rule out underlying malignancy. Along with quantitative cultures, Gram stains for qualitative bacteriology should be performed under aerobic and anaerobic conditions for the identification of bacterial species and their corresponding sensitivities to topical and systemic antibiotics. Systemic antibiotics typically do not reach therapeutic levels in wound tissue. Quantitatively, bacterial levels greater than 105 colony-forming units (CFUs)/g of soft tissue impair wound healing and prevent successful wound closure. Wounds with bacterial levels less than this will heal [19–21]. Qualitative studies are of importance because any level of b-hemolytic streptococci can be detrimental to wound healing. Topical antimicrobials are used in wounds with bacterial counts greater than or equal to 106 CFUs/g of soft tissue or any level of b-hemolytic streptococci. Cultures are repeated after topical antibiotic treatment. Once bacterial balance is reestablished, the discontinuation of topical antimicrobials is important to prevent any possible detrimental effects that are due to the topical agent and to prevent the development of bacterial resistance [22]. Establishing bacterial balance is necessary to optimize a patient for surgical wound closure.

Tissue oxygenation Maintaining normal tissue perfusion and the accompanying oxygenation is instrumental in wound healing [23]. This perfusion is vital for the delivery of nutrients and to fight infection in any patient who is to undergo surgery. As apposed to frank



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ischemia, relative tissue hypoxia is a common problem in patients who have arterial, venous, diabetic, or pressure ulcers [24]. Insufficient oxygen on a cellular level decreases wound healing. Three factors help to determine the tissue partial pressure of oxygen (PtO2): the delivery of the oxygen from the lungs (oxygenation) to the tissue (circulation); transport of the oxygen in the vascular system to the tissue, which is determined by the partial pressure of oxygen in the blood and the distance that the oxygen must travel by way of diffusion; and the consumption of oxygen in the tissue where it is being used [25]. The amount of oxygen that reaches the skin is dependent on the availability of local blood flow and the oxygen tension therein. This can be measured clinically with measurement of transcutaneous oxygen pressure using commercially available polarographic electrodes. Oxygen that reaches a wound does so by the process of diffusion; therefore, oxygen tension is disrupted easily by acute injury and wound formation [26]. The oxygen tension in normal tissue ranges from 30 to 50 mm Hg; however, the oxygen tension in nonhealing chronic wounds can range from 5 to 20 mm Hg [27]. Hemoglobin levels within the vasculature have little effect on oxygen tension within tissue. For example, oxygen tensions remain acceptable in patients who have isovolemic anemia and hemoglobin levels of 5 g/dL as long as the circulation is maintained [28]. With adequate perfusion, supplemental oxygen can be used to increase oxygen tension in peripheral tissue in an attempt to increase wound healing [29]. Hyperbaric oxygen therapy (HBO) has been used to enhance neovascularization [30]. Besides the classic treatment of decompression sickness, HBO is indicated in the treatment of carbon monoxide poisoning, clostridial myonecrosis, and osteomyelitis. It also has been used in traumatic crush injuries, burns, arterial insufficiency ulcers, venous stasis ulcers, diabetic foot ulcers, problematic wounds that fail conventional therapy, or in other wounds with a compromised oxygen supply but intact vascular supply. In fact, HBO has been used in conjunction with antibiotics as a means to fight bacterial infection [31]. Oxygen is almost entirely bound to hemoglobin at normal atmospheric pressure. Once oxygen is breathed at 2.0 to 2.5 atmospheres absolute, a significant amount of O2 that is found in the arterial blood is in the dissolved state. Fibroblasts proliferation is increased with HBO treatment [32]. HBO can be used as a signal transducer when combined with platelet-derived growth factor, and it significantly increased the effects of recombinant growth factors in an animal model [33,34]. Oxygen and its reactive oxygen species (ROS) have a diverse interaction that has not

been elucidated fully. Hypoxia and hyperoxia are implicated in the production of ROS [35]. Keratinocytes and macrophages reacted favorably when treated with the ROS hydrogen peroxide (H2O2) by increasing their production of vascular endothelial growth factor [36,37]. Hydrogen peroxide acts as a signaling molecule for the activation of signal transducers and activators of transcription-1 and -3, both of which are involved in signal transduction from growth factors [38]. Clinically, wound perfusion and oxygenation can be increased by ensuring that patients have proper pain control, maintaining a normothermic state, and by providing high PO2 breathing mixtures when necessary. Any reversible vascular disorder must be addressed and treated appropriately before surgical intervention for closure of a wound.

Hydration All patients must be hydrated adequately before undergoing any surgical procedure. Dehydration and hypovolemia cause an increase in sympathetic tone and a decrease in tissue perfusion that may lead to an increase in surgical complications. Sufficient wound perfusion delivers oxygen to the wound environment and facilitates the delivery of cells and cytokines that are necessary to wound healing. Patients undergoing outpatient surgical procedures often are asked to abstain from eating or drink anything past midnight on the evening before their procedure. Hypovolemia may not be obvious to the treating surgeon, especially when urine output is adequate and there is no change in hemodynamics. Preoperative intravenous fluid administration can aid in increasing tissue perfusion and tissue oxygen partial pressures. Intraoperative and postoperative tissue oxygen tension levels and capillary blood flow measurements are significantly greater in patients given supplemental fluid [39]. Clinicians must rely on their own clinical judgment about whether intravenous fluids are necessary to optimize the patient’s intravascular status before surgical closure of a wound.

Diabetes In North America, more than 20 million people are afflicted with diabetes [40]. Poorly controlled diabetes impedes wound healing by interfering with fibroblast function, neovascularization, and inflammatory cells in all of the stages of the wound-healing process and predisposes diabetic patients to wounds that fail to heal [41–43]. Diabetic patients

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need their nutritional status and insulin regimen optimized before undergoing any surgical procedure, with the goal of avoiding extremes in hypoglycemia and hyperglycemia and obtaining tight control of glucose levels. Physiologically, the lack of effective insulin combined with the stress of surgery and anesthesia causes the release of catecholamines, cortisol, and glucagon, resulting in the development of stress hyperglycemia [44]. In type II diabetics, the preexisting peripheral resistance to insulin is exacerbated by the stress of a surgical procedure. Collagen production in diabetics is altered, resulting in decreased wound tensile strength. Diabetics also suffer from peripheral neuropathy and atherosclerosis. Peripheral neuropathy affects sensory, motor, and autonomic neurons, increasing the risk for repeated trauma and wound formation in the extremities [45]. Diabetes also affects the macro- and microcirculatory systems, causing peripheral vascular disease, especially in the lower extremities; this results in a decrease in tissue perfusion and oxygenation. Abnormal tissue perfusion and oxygenation, combined with neutrophil dysfunction and attenuated inflammatory responses, predispose these patients to defective wound

Box 2:

healing and possible infection [2,46,47]. Any deficiencies in vascular supply must be addressed. Noninvasive vascular studies, such as the ankle-brachial index (ABI), are not dependable in diabetic patients. Although ABI values of less than 0.7 may suggest ischemic peripheral vascular disease, diabetics who have vascular calcinosis and noncompressible vessels may have falsely high values. Arteriography may be necessary to identify areas of vascular insufficiency that require intervention before surgical correction of a wound. Tight blood glucose control is optimal during the perioperative period (Box 2). Obtaining normoglycemia with insulin therapy can be important in promoting the synthesis of collagen by promoting fibroblast proliferation to improve collagen accumulation and wound tensile strength [41,43,48]. Generally, it is recommended that oral hypoglycemics be withheld on the morning of surgery and metformin be discontinued 48 hours before any surgical procedure. For outpatient procedures, it is advisable to schedule these patients as the first case of the day [3]. Postoperatively, blood glucose levels must be checked frequently and should be kept less than 110 mg/dL in an effort to reduce morbidity and mortality [49]; however, it

Perioperative management of patients who have diabetes

Minor surgery in patients who have type II diabetes not treated with insulin Hold oral agents the day of surgery Patients with ‘‘fair’’ metabolic control (fasting blood glucose < 180 mg/dL) - cover with regular insulin or rapid-acting insulin as needed Patients with ‘‘poor’’ metabolic control (fasting blood glucose > 180 mg/dL) - start continuous insulin infusion Goals: avoid excessive hyperglycemia (blood glucose > 180 mg/dL) and hypoglycemia (blood glucose < 80 mg/dL) Minor surgery in patients who have type I or II diabetes treated with insulin Hold oral agents (if treated with combination therapy) the day of surgery Patients in ‘‘fair’’ metabolic control (fasting blood glucose < 180 (mg/dL): Give half of intermediate-acting insulin the morning of the surgery While NPO, infuse dextrose 5% saline plus KCl (10–20 mEq/L) at 100 mL/h Check blood glucose every 4 to 6 hours while NPO and supplement with short-acting insulin Patient treated with basal insulin should receive the usual basal insulin dose. Similarly, patients treated with continuous insulin infusion therapy (insulin pump) should receive the usual basal infusion rate. Restart preadmission insulin therapy once intake is tolerated Patients in ‘‘poor’’ control (fasting blood glucose > 180 mg/dL) - start continuous insulin infusion Major surgery in patients with type I or II diabetes treated with insulin Hold oral agents the day of surgery Start continuous insulin infusion before surgery and continue during perioperative period Goals: Maintain blood glucose < 180 mg/dL during surgery, and blood glucose between 80 to 120 mg/ dL during the perioperative period in the surgical intensive care unit. Start subcutaneous insulin two hours before discontinuation of insulin infusion. In non-intensive care unit settings, avoid excessive hyperglycemia (blood glucose > 180 mg/dL) and hypoglycemia (blood glucose < 80 mg/dL) From Smiley DD, Umpierrez GE. Perioperative glucose control in the diabetic or nondiabetic patient. South Med J 2006;99(6):584; with permission.



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is important to work with the patient and his/her primary care physician to optimize a patient’s diabetes before undertaking the surgical closure of a wound.

Smoking Smoking and other tobacco products cause microvascular vasoconstriction by way of the action of nicotine and its activation of the sympathetic nervous system [50]. Cigarette smoke also contains carbon monoxide, which contributes to tissue hypoxia by binding hemoglobin to form carboxyhemoglobin, which has a high affinity for oxygen and decreases the delivery of oxygen to the peripheral tissues [51,52]. Patients who smoke or have a history of heavy smoking are at an increased risk for fat necrosis, wound infection, flap necrosis, and respiratory complications following surgery [53,54]. Smokers also have an increased incidence of less aesthetically pleasing results because of scar formation [55]. It is advisable to recommend preoperative respiratory conditioning in an effort to maximize pulmonary function [54]. Patients are advised to stop smoking at least 4 weeks before undergoing surgery [56,57].

Nutrition Although no definite recommendations on nutrition can be made to ensure that wound healing proceeds without interruption, optimizing nutrition is at the forefront of preparing a patient for surgical correction of a wound and to ensure proper

Table 1:

immune function. It is important that he/she has a well-balanced diet, with sufficient protein intake and daily vitamin and mineral supplementation. It has been recommended that all adults take vitamin supplementation [58,59]. Some of the nutrients that may be supplemented in an effort to optimize the nutrition of a patient undergoing surgical closure of a wound are listed in Table 1. Delayed wound healing is a consequence of inadequate nutritional status [60]. Malnutrition predisposes a patient to further progression of a wound and is detrimental to the treatment process [61]. Correcting nutritional deficiencies should start early in the preoperative evaluation (Table 2). Patients who are at particular risk include the elderly and those who have gastrointestinal diseases, renal failure, alcoholism, cancer, or any chronic disease [62]. Surgery causes changes in the metabolic and physiologic demands on the body of the patient who is undergoing surgery that usually are not encountered. Postoperatively, the body relegates its nutritional supplies and reserves to the task of healing and restoring homeostasis. If a patient is malnourished or has some nutritional deficit, wound healing may not take place at an optimal pace. Other major organ systems, such as the circulatory, pulmonary, and urinary systems, may be compromised by inadequate nutrition [63]. Nutritional assessment and intervention are aimed at providing adequate nutrition for the wound-healing process and at providing support for the patient as a whole. The average adult requires 25 to 35 kcal/kg/d [64]. A daily calorie count with percentages of protein, carbohydrates, and fat

Perioperative period supplements




Vitamin A (carotenoid or retinol palmitate)

Important in wound phagocytosis and cell-mediated immunity; antagonist for the effects of corticosteroids; maintenance and repair of epithelial tissue Primary role as a cofactor in the formation of collagen; antioxidant necessary for tissue growth and repair Antistress group of water-soluble vitamins

15,000–25,000 IUs daily; limit use to 4 weeks

Vitamin C (ascorbic acid) B vitamins

Zinc Copper

Recommended dietary supplementation is 60 mg/d Best taken as B-complex: thiamin (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), biotin, pantothenic acid, folic acid, cobalamin (B12), choline, and inositol 15–21 mg/d

Important in collagen formation and protein synthesis Required for cross-linking of collagen 1.5–2.0 mg/d and elastin; required for formation of hemoglobin, red blood cells, and bone

Data from Rahm D. Perioperative nutrition and nutritional supplements. Plast Surg Nurs 2005;25(1):35.

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Table 2:

Schofield equation to determine energy requirements

Age (years)


15–18 18–30 30–60 >60


Female 5 17.6 5 15.0 5 11.4 5 11.7


weight weight weight weight

(kg) 1 (kg) 1 (kg) 1 (kg) 1

656 690 870 585


5 5 5 5

13.3  weight (kg) 1 690 14.8  weight (kg) 1 485 8.1  weight (kg) 1 842 9  weight (kg) 1 656

Abbreviation: BMR, basal metabolic rate. When appropriate, add the following to the BMR: A. Add stress factor: severe sepsis 5 10% to 30%, extensive surgery 5 10% to 30%, fracture/trauma 5 10% to 30%, burns/wounds 5 50% to 150% B. Add a combined factor for activity and diet-induced thermogenesis: Bedbound immobile 110% Bedbound mobile/sitting 115% to 20% Mobile on ward 125% C. Add or subtract 400 to 1000 kcal/d if weight gain/loss required. D. Add up to 10% for each 1 C increase in temperature. Data from Kloth L, McCulloch JM. Wound healing: alternatives in management. 3rd edition. Philadelphia: F.A. Davis Co.; 2002. p. 49.

can be used to identify specific deficiencies. The patient’s weight should be documented and tracked. Large wounds may be a source of fluid and protein loss in the patient [65]. The equations in this text can be used to determine energy requirements. Laboratory values, as indicators of malnutrition, include albumin, prealbumin, and retinol-binding protein. Normal wound healing cannot occur at albumin levels less than 2.0 g/dL [66]. The half-life of albumin is 3 weeks; therefore, a deficiency in protein may exist before the decrease is seen in the laboratory value [67]. Nitrogen loss can be exacerbated by surgery as a result of the breakdown of proteins in the body. A positive nitrogen balance encourages anabolism in an effort to optimize wound healing. In a normal metabolic state, the average person requires 0.17 g of nitrogen or 1.0 g of protein/kg/d [68]. Without proper protein intake, angiogenesis and fibroblast proliferation are decreased, resulting in diminished collagen synthesis and remodeling [69,70]. Amino acids, the building blocks of proteins, are important in and of themselves. Arginine and glutamine have been implicated as important amino acids in the wound-healing process [71–73]. A decrease in dietary protein leads to hypoalbuminemic tissue edema and a decrease in oxygen tension (PtO2), with impairment in healing. This edema occurs when albumin levels decrease to 3.0 g/dL.

Obesity A patient is considered to be overweight if the body mass index (BMI) is between 25 and 30 kg/m2. Obesity is defined as a BMI greater than 30 kg/m2 [74]. In the time period from 1991 to 2002, the prevalence of obesity in the United States increased

from 12% to 21.3% [75]. The diet of most Americans contains high levels of calories with little attention given to essential nutrients, vitamins, and minerals. This, combined with a sedentary lifestyle, lends itself to an obese population [1,76]. Obese patients are at a greater risk for postsurgical complications, such as infection, hematoma, wound dehiscence, and flap necrosis [53,77,78]. As the weight of the patient increases, so does the risk for mortality due to comorbid conditions [79,80]. Even with the risk associated with obesity and surgery, it is not advisable to recommend that patients lose weight in a short period of time before undergoing any surgical procedure. The metabolic demands of the body are increased with surgery and the healing process that follows. If patients starve themselves to shed weight just before a surgical procedure, undue stress is placed on the patient’s body. This is not advisable; however, it is prudent to instill in patients the importance of a healthy diet and regular exercise.

Vitamins and minerals Vitamins A, E, C, and K are instrumental in wound healing, with A and C carrying the burden of the work [67]. The trace elements that are required for wound healing include copper, magnesium, iron, and zinc. Any deficiency in vitamins, minerals, or trace elements must be reversed for proper wound healing to proceed [81]. Vitamin A Vitamin A is a fat-soluble vitamin that can be depleted in times of stress following injury and infection. Decreased levels of vitamin A result in a decrease in collagen production, delayed wound



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healing, and susceptibility to infection [82,83]. Vitamin A is important in the body’s immune response in wound phagocytosis and cell-mediated immune response, cellular adhesion, deposition of matrix glycosaminoglycans, collagen synthesis, and promotion of the inflammatory phase of wound healing [64,84,85]. Vitamin A is used most notably as an antagonist to combat the detrimental effects of corticosteroids on the healing wound [64,86]. Although corticosteroids are useful for combating inflammation, they are particularly harmful during the initial inflammatory phase of wound healing because they slow the release of lysosomal enzymes, delay wound healing, and increase the risk for infection [64]. They suppress fibroblast proliferation and subsequent collagen formation and epithelialization [87]. Vitamin A administration permits the inflammatory phase of wound healing to proceed; however, it does not reverse the changes seen in wound contraction and the risk for infection [88–90]. Vitamin A, at a dose of 25,000 IUs, has been suggested in injured patients to improve wound healing and increase wound tensile strength [67]. Topically applied vitamin A also has been used to reduce the size of intractable hypertrophic scars and their associated pruritis [91]. Whether taken orally or applied topically, vitamin A has the potential to be teratogenic and should not be used in pregnant women.

Vitamin C Vitamin C (ascorbic acid) is a cofactor in the formation of collagen. Before procollagen can be incorporated into the healing wound, it must undergo hydroxylation of proline and lysine to form collagen. This process involves the insertion of elemental oxygen into the collagen molecule through the oxygenase prolyl hydroxylase to form collagen [92,93]. Deficiencies in ascorbic acid decrease the rate of the hydroxylation process and produce an inferior collagen by-product, leading to delays in wound healing. This impaired collagen synthesis contributes to the body’s inability to wall off bacteria and has been implicated as a cause for the increase in infection seen in patients with vitamin C deficiency. Vitamin C deficiency also can cause disruption of neutrophil function and complement activation [94,95]. The recommended dietary allowance of vitamin C is 60 mg/d, and the effects of vitamin C deficiency can be reversed with administration of 100 to 1000 g/d [67]. Vitamin E Vitamin E (alpha-tocopherol) is a lipid-soluble antioxidant with anti-inflammatory properties. It acts as a cellular membrane–stabilizing agent by

inhibiting the spread of lipid peroxidation [96]. When applied topically, however, vitamin E inhibits wound healing by reducing the number of fibroblasts and collagen synthesis [97]. This may cause a decrease in scar tensile strength and an unacceptable scar. Similarly, topically applied vitamin E has no effect on scar formation and, in some instances, is detrimental to cosmetic scar appearance and can cause papular and follicular dermatitis in the areas where it has been applied [98,99]. Vitamin K Vitamin K is essential in the production of prothrombin and the carboxylation of glutamate in the clotting factors II, VII, IX, and X. When there is a vitamin K deficiency there is an insufficiency in the clotting cascade. Patients who are anticoagulated often require reversal before undergoing surgical correction of a wound. Copper and magnesium Copper deficiency is found most often following gastric resection in patients who received total parenteral nutrition not supplemented with copper [68]. In wound healing, copper is an essential part of the metalloenzyme lysyl oxidase. It allows for the oxidation of lysyl residues on collagen, resulting in cross-linking and, thus, greater scar strength. Copper-sensitive pathways also are important in wound angiogenesis and ECM remodeling [100]. Magnesium is important to the enzymes responsible for collagen synthesis [101]. Iron Iron is the most abundant trace element in the body. It is important in the replication of DNA and the hydroxylation of proline and lysine by their respective hydroxylase enzymes in the synthesis of the collagen triple helix [64]. Iron also is important in the structure of hemoglobin for the transportation of oxygen. It is difficult to correlate iron-deficiency anemia with a deficit in wound healing. In optimizing a patient before undergoing surgery for wound treatment, the transfusion of blood or blood products is made on an individual basis. When anemia is present, all causes should be investigated and treated appropriately. It is suggested that patients with chronic wounds have a mild to moderate anemia (hemoglobin, 7–11 g/dL) and specific serum protein alterations that are similar to the anemia of chronic disease [102]. Closure of the wound is the most effective and definitive treatment in wounds with an associated anemia. Zinc Zinc is the second most abundant trace element in the human body and is important in more than 300

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enzymes in the body, requiring it for their activity [103]. It is important for DNA production, carbohydrate metabolism, cellular membrane stabilization, MMP function, and cell division in reconstruction of the wound matrix in the wound-healing process [103–106]. Zinc is particularly important as a catalyst in enzymatic reactions and collagen formation. Supplementation of this element is recommended only when it is notably deficient. Severe zinc deficiency can result in skin changes, mouth ulcers, ataxia, poor appetite, diarrhea, alopecia, cell-mediated immune disorders, and delay in wound healing [107,108]. Zinc deficiency can be found in patients who have multiple traumas, large burns, Crohn’s disease, hepatic cirrhosis, malabsorption disorder, or ulcerative colitis or in those who are receiving parenteral nutrition [103,104]. The recommended daily allowance of zinc is 15 mg/d [67]. In patients with chronic wounds, the general use of zinc supplementation is not beneficial unless the patient has low serum levels of zinc [109]; however, topical zinc oxide therapy is useful in reducing wound debris and aiding in the epithelialization of surgical wounds [110–112].

Aging As the population in the United States grows increasingly older, so do the patients who are requesting and requiring plastic surgery. Aged patients have inherent wound-healing difficulties that differ from those in younger patients. They heal at a slower rate, and aging causes a decrease in reepithelialization and collagen synthesis and impaired angiogenesis [113,114]. The dermal collagen content and quality decrease with age. As the body ages, its responses to various stressors differs with reduced tolerance. These stressors may be extrinsic (eg, environmental stresses) or intrinsic (eg, diabetes). Bone marrow stromal cells from aged donors have decreased proliferative potential and accelerated senescence when compared with younger osteogenic cells [115]. ROS have been implicated in the free-radical theory of age-related changes that occur on the cellular level [116]. On a molecular level, cells that are stressed have the option of overcoming stressors, activating senescence pathways, or activating pathways that lead to apoptosis [117]. In animal studies, aging is accompanied by a decrease in the tolerance to oxidative injury and the ability to trigger prosurvival signaling pathways [118–120]. Aged mammalian cells also were shown to have a reduced proliferative capacity [121]. Subsequently, the aged patient is at a disadvantage when it comes to wound healing compared with their younger counterparts.

Medications A list of all of the medications that a patient is taking or has taken in the previous months must be documented in the chart and reviewed with the patient in an effort to identify any medications that may interfere with the wound-healing process. All over-the-counter herbal supplements, such as ginkgo biloba, Echinacea, garlic, ginseng, kava, St. John’s wort, or ephedra, also should be reviewed with the patient and stopped at least 1 week before the surgical procedure [122]. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and chemotherapeutic agents are particularly detrimental to wound healing.

Nonsteroidal anti-inflammatory drugs NSAIDs work by inhibiting cyclooxygenase-1 and 2 from converting arachidonic acid into prostaglandins in inflamed tissue [123,124]. Common NSAIDs, such as aspirin and ibuprofen, have been implicated in decreased wound healing by decreasing collagen production [125]. Aspirin also has anticoagulant properties by decreasing platelet activation. It is recommended that aspirin be discontinued 7 to 10 days before a surgical procedure. When NSAIDs are used as a means of pain relief, it is recommended that acetaminophen be substituted as an alternative.

Steroids The detrimental affect of systemic steroids on the wound-healing process includes a decrease in the release of lysosomal enzymes, with a subsequent increase in the risk for infection, suppression of fibroblast proliferation and collagen synthesis, and a decrease in wound contraction and strength [87–89]. Steroids decrease the formation of granulation tissue and ECM [64]. The effect of steroids on the wound-healing response is dose- and timedependent, with shorter treatment regimens having less of an effect. They stabilize lysosomal membranes, causing disruption of the inflammatory phase of wound healing. If steroids are given for longer periods of time, wound healing can be affected for up to 1 year after administration [64,126]. Vitamin A can be used to antagonize the effects of corticosteroids on the healing wound [64,86].

Chemotherapeutic agents and radiation Chemotherapeutic agents and radiation interfere with wound healing. Chemotherapeutic agents interfere with the inflammatory response of wound healing. They decrease fibroblast proliferation and wound contraction and interfere with the immunologic response [126–128]. It is recommended that



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chemotherapeutic agents be avoided preoperatively. If chemotherapeutic agents are necessary, their effect on the wound-healing process can be abated by administering them 10 to 14 days after wound closure [129,130]. The effects of radiation therapy on wound healing are dose-dependent, causing acute and chronic changes in the skin. Rapidly dividing cells, both malignant and normal healthy cell populations (eg, keratinocytes), are targeted. Acutely, radiation causes erythema and desquamation. Proteolytic enzymes are activated, causing an increase in capillary permeability and inflammatory response. Desquamation results from loss of epidermal cell mitotic ability. Chronically, radiation can result in hypopigmentation, fibrosis, telangiectasias, alteration in adnexal structure function, necrosis, and malignant degeneration [64]. As long as adnexal structures are not destroyed completely by radiation therapy, reepithelialization can occur. If adnexal structures are lost, reepithelialization must occur from the periphery of the wound; this results in a delicate and brittle epidermis that is less resilient to repetitive trauma. Radiation therapy also can affect vascular supply, causing endarteritis leading to hypoxia and a disturbance in the angiogenic processes [131].

Summary Plastic surgeons often are consulted to close wounds that fail or are difficult to heal. Optimizing the patient’s medical condition before surgical closure of a wound can mean the difference between a successful outcome and an undesirable one. It is imperative that plastic surgeons have an extensive knowledge of the modifiable risk factors affecting the wound-healing process and their subsequent complications. This knowledge allows the surgeon to tailor the treatment options and intervene when appropriate to optimize outcomes for successful surgical closure of a wound. Whether the impairments to wound healing and closure are local or systemic, they must be addressed appropriately.

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