Key Points 1.

The incidence of surgical site infections can be reduced by appropriate patient preparation, timely perioperative antibiotic administration, maintenance of perioperative normothermia and normoglycemia, and appropriate wound management. 2. Principles relevant to appropriate antibiotic prophylaxis for surgery: (a) select an agent with activity against common organisms at the site of surgery, (b) the initial dose of the antibiotic should be given within 30 minutes of incision, (c) antibiotics should be redosed every 1 to 2 half-lives during surgery to ensure adequate tissue levels, and (d) antibiotics should not be continued for more than 24 hours after surgery for routine prophylaxis. 3. Source control is a key concept in the treatment of most surgically relevant infections. Infected or necrotic material must be drained or removed as part of the treatment plan in this setting. Delays in adequate source control are associated with worsened outcomes. 4. Sepsis is both the presence of infection and the host response to infection (systemic inflammatory response syndrome, SIRS). Sepsis is a clinical spectrum, ranging from sepsis (SIRS plus infection) to severe sepsis (organ dysfunction), to septic shock (hypotension requiring vasopressors). Outcomes in patients with sepsis are improved with an organized approach to therapy that includes rapid resuscitation, antibiotics, and source control. 5. When using antimicrobial agents for therapy of serious infection, several principles should be followed: (a) identify likely sources of infection, (b) choose an agent (or agents) that covers likely organisms for these sources, (c) remember that inadequate or delayed antibiotic therapy results in increased mortality, so it is important to begin therapy with broader coverage, (d) when possible, obtain cultures early and use results to tailor therapy, (e) if there is no infection identified after 3 days, strongly consider discontinuation of antibiotics, and (f) stop antibiotics after an appropriate course of therapy. 6. The keys to good outcomes in patients with necrotizing soft tissue infection are early recognition and appropriate débridement of infected tissue with

repeated débridement until no further signs of infection are present. 7. Transmission of HIV and other infections spread by blood and body fluid from patient to health care worker can be minimized by observation of universal precautions, which include routine use of barriers when anticipating contact with blood or body fluids, washing of hands and other skin surfaces immediately after contact with blood or body fluids, and careful handling and disposal of sharp instruments during and after use. Duration of antibiotic administration should be decided at the time the drug regimen is prescribed. As noted below in Surgical Site Infections, prophylaxis is limited to a single dose administered immediately before creating the incision. Empiric therapy should be limited to 3 to 5 days or less, and should be curtailed if the presence of a local site or systemic infection is not revealed.25 This precept is highlighted by a study in which patients in whom SIRS was identified were closely monitored for the presence of infection: Less than half of them were found to harbor infection

intestine, or incision through inflamed, albeit nonpurulent, tissue. Dirty wounds (class IV) include traumatic wounds in which a significant delay in treatment has occurred and in which necrotic tissue is present, those created in the presence of overt infection as evidenced by the presence of purulent material, and those created to access a perforated viscus accompanied by a high degree of contamination. The microbiology of SSIs is reflective of the initial host microflora such that SSIs following creation of a class I wound are invariable, due solely to skin microbes found on that portion of the body, while SSIs subsequent to a class II wound created for the purpose of elective colon resection may be caused by either skin microbes or colonic microflora, or both. Surgical management of the wound is also a critical determinant of the propensity to develop an SSI. In healthy individuals, class I and II wounds may be closed primarily, while skin closure of class III and IV wounds is associated with high rates of incisional SSIs (approximately 25 to 50%).

Surgical wounds are classified based on the presumed magnitude of the bacterial load at the time of surgery (Table 6-8).36 Clean wounds (class I) include those in which no infection is present; only skin microflora potentially contaminate the wound, and no hollow viscus that contains microbes is entered. Class ID wounds are similar except that a prosthetic device (e.g., mesh or valve) is inserted. Clean/contaminated wounds (class II) include those in which a hollow viscus such as the respiratory, alimentary, or genitourinary tracts with indigenous bacterial flora is opened under controlled circumstances without significant spillage of contents. Interestingly, while elective colorectal cases have classically been included as class II cases, a number of studies in the last decade have documented higher SSI rates (9 to 25%).37–39 One study identified two thirds of infections presenting after discharge from hospital, highlighting the need for careful follow-up of these patients.37 Infection is also more common in cases involving entry into the rectal space.39 Contaminated wounds (class III) include open accidental wounds encountered early after injury, those with extensive introduction of bacteria into a normally sterile area of the body due to major breaks in sterile technique (e.g., open cardiac massage), gross spillage of viscus contents such as from the

Infections of the Skin and Soft Tissue Infections of the skin and soft tissue can be classified according to whether surgical intervention is required. For example, superficial skin and skin structure infections, such as cellulitis, erysipelas, and lymphangitis, invariably are effectively treated with antibiotics alone, although a search for a local source of infection should be undertaken. Generally, drugs that possess activity against the gram-positive skin microflora that are causative are selected. Furuncles or boils may drain spontaneously or require surgical incision and drainage. Antibiotics are prescribed if significant cellulitis is present or if cellulitis does not rapidly resolve after surgical drainage. Key Points 1. Wound healing is a complex cellular and biochemical cascade that leads to restitution of integrity and function. 2. Although individual tissues may have unique healing characteristics, all tissues heal by similar mechanisms, and the process undergoes phases of inflammation, cellular migration, proliferation, matrix deposition, and remodeling.

Patients who undergo class II procedures benefit from a single dose of an appropriate antibiotic administered before the skin incision. Preoperative orders are written and reviewed. Dirty or infected cases often require the same antibiotic spectrum. For example. With the advent of minimal-access surgery. depending on the drug's halflife. such as laparoscopic hernia repair. Such an approach is taken in the setting of emergency abdominal surgery. although the patient's renal function may alter the timing ( Table 1212 ).. Informed consent after discussion with the patient and family members regarding the indication for the anticipated surgical procedure.3. A recent meta-analysis showed that both of these events are not decreased and may be increased with mechanical cleansing. Contaminated (class III) cases require mechanical preparation or parenteral antibiotics with both aerobic and anaerobic activity. and application of best practices and techniques. 5. including β-blockers and antiarrhythmics. Some drugs are associated with an increased risk for perioperative bleeding and are withheld before surgery.[25] Perioperative antibiotic prophylaxis generally is not continued beyond the day of surgery. The patient is asked to name all medications. in cases that result in prosthetic graft (i. or psychiatric drugs are advised to take their medications with a sip of water on the morning of surgery. however. Clinically. which represents an opportunity to ensure that all necessary and pertinent data have been obtained and appropriately interpreted. The ultimate goal of the partnership is to save lives by reducing the incidence of surgical complications by 25% by the year 2010. tissue engineering. the opposite is true. 4. and in trauma cases. The patient receives written instructions regarding the time of surgery and management of special perioperative issues such as fasting. and local factors play a major role.[26] Preoperative Mechanical Bowel Cleansing Mechanical bowel preparation with the addition of oral antibiotics was the standard of care for several decades for any intestinal surgery. 6. In addition. Two notable examples are the additional cardiovascular morbidity associated with the perioperative discontinuation of βblockers and rebound hypertension with abrupt cessation of the antihypertensive clonidine. although it seems intuitive that removal of bulk . and prophylactic antibiotics. mesh) placement. patients taking cardiac drugs. pancreatic. and technical conditions that the surgeon must take into account. excess healing can be as significant a problem as impaired healing. except in the setting of indwelling prosthesis placement or when bone is incised. routine antibiotic prophylaxis in patients undergoing laparoscopic cholecystectomy for symptomatic cholelithiasis is of questionable value. and to provide dosages and frequency. The Surgical Care Improvement Project (SCIP) is a national quality partnership of organizations committed to improving the safety of surgical care through a reduction in postoperative complications. pulmonary drugs such as inhaled or nebulized medications. It is important to return patients to their normal medication regimen as soon as possible. Antibiotic Prophylaxis Appropriate antibiotic prophylaxis in surgery depends on the most likely pathogens encountered during the surgical procedure. PREOPERATIVE CHECKLIST The preoperative evaluation concludes with a review of all pertinent studies and information obtained from investigative tests. Future advances in growth factor understanding. the goal is to appropriately use medications that control the patient's medical illnesses while minimizing the risk associated with anesthetic-drug interactions or the hematologic or metabolic effects of some commonly used medications and therapies. and medication use. [27] Review of Medications Careful review of the patient's home medications is a part of the preoperative evaluation before any operation. genetic. antihypertensives. Drugs that affect platelet function are withheld for variable periods: aspirin and clopidogrel (Plavix) are withheld for 7 to 10 days. Medications such as lipidlowering agents or vitamins can be omitted on the day of surgery. For abdominal (hepatobiliary. they probably need to be withheld for a period of 4 weeks preoperatively. gastroduodenal) cases.e. and alternative/herbal medications. fecal material would decrease the risk for anastomotic and infectious complications. usually 3 hours for abdominal cases or twice the half-life of the antibiotic. as well as its risks and proposed benefits. and dressing design are expected to increase the armamentarium in improving wound outcomes. technical. In general. Parenteral forms or substitutes are available for many drugs and may be used if the patient remains NPO for any significant period postoperatively.[28] The widespread use of herbal medications has prompted review of the The appropriate antibiotic is chosen before surgery and administered before the skin incision is made ( Table 12-11 ). including psychiatric drugs. Because the use of estrogen and tamoxifen has been associated with an increased risk for thromboembolism. hormones. as for suspected appendicitis. or anticonvulsants. bowel preparation. It may have a role. which can be continued into the postoperative period in the setting of ongoing infection or delayed treatment. the use of antibiotics seems less justified because the risk for wound infection is extremely low. The guidelines developed as part of SCIP will be monitored in every hospital ( Table 12-13 ). The preoperative checklist also gives the surgeon an opportunity to review the need for β-blockade. cefazolin is generally used. Oral antibiotics confer no benefit to the patient and may increase the risk for postoperative infection with Clostridium difficile. Optimal outcome of acute wounds relies on complete evaluation of the patient and of the wound. Prophylactic antibiotics are not generally required for clean (class I) cases. Documentation of this review is made in the chart. Factors that impede normal healing include local. [24] Repeat dosing occurs at an appropriate interval. whereas NSAIDs are withheld between 1 day (ibuprofen and indomethacin) and 3 days (naproxen and sulindac). More recent studies have evaluated the need for both oral antibiotics and mechanical cleansing. DVT prophylaxis. systemic. are documented in the chart. The type of operative procedure ( Table 12-10 ) is helpful in deciding the appropriate antibiotic spectrum and is considered before ordering or administering any preoperative medication.

It is stalled in the inflammatory phase as a result of a variety of causes and does not proceed to closure. or bacterial products. PMNs are also a major source of cytokines early during inflammation. these phases overlap in both time and activity. A chronic wound. Though not reported in all the trials. 9-2A). PMNs are the first infiltrating cells to enter the wound site. occur in every healing process regardless of the tissue type or the inciting injury. Increased vascular permeability.[29] Generally. oftentimes flawless repair is sacrificed because of the urgency to return to function. Once the wound is assessed as being ready for closure. however. Acute wounds proceed in an orderly and timely reparative process to achieve sustained restoration of structure and function. such as complement factors. Hemostasis and Inflammation Hemostasis precedes and initiates inflammation. When the literature was recently reviewed by the Cochrane group. Exposure of subendothelial collagen to platelets results in platelet aggregation. platelet factor 4. although important metabolic and hematologic effects can result from their regular use ( Table 12-14 ). closure. but this needs to be done with caution in patients who report the use of valerian. With the recent basic science discoveries of the 1980s and 1990s. tumor necrosis factor alpha (TNF). TGF . intention involves no active intent to seal the wound. is performed. there did not appear to be an increased risk for aspiration/regurgitation with a shortened period of fasting. During the effort to restore barriers to fluid loss and infection. with the ensuing release of chemotactic factors from the wound site (Fig. a) hemostasis and inflammation. a single wound may have regions that are in several different phases at once. However. and activation of the coagulation cascade. in lower organisms such as the stone crab and salamander. the exact mechanisms underlying wound healing are not completely understood. 8-1 ). A key concept in wound healing is that all tissues proceed through the same series of events. Preoperative Fasting The standard order of “NPO past midnight” for preoperative patients is based on the theory of reduction of volume and acidity of the stomach contents during surgery. Recently. is perfect restoration of the preexisting tissue architecture in the absence of scar formation. . Wounding by definition disrupts tissue integrity. especially TNF. skin graft placement. leading to division of blood vessels and direct exposure of extracellular matrix to platelets. Closure by secondary. or spontaneous. or in certain tissue compartments such as bone and liver. such as closure of the wound at the end of a surgical procedure. it is found only in embryonic development. guidelines have recommended a shift to allow a period of restricted fluid intake up to a few hours before surgery. systemic or topical antibiotics. platelet-activating factor. this type of repair is associated with a highly contaminated wound and will close by reepithelialization. the wounds are sealed immediately with simple suturing. the use of herbal medications is stopped preoperatively. degranulation. and restore the mechanical integrity of the injured system. skin graft placement. TISSUE INJURY AND RESPONSE Wound repair is the effort of injured tissues to restore their normal function and structural integrity after injury. 9-1). interleukin-1 (IL-1). these events are divided into specific stages. surgical intervention. The postulated primary role of neutrophils is phagocytosis of bacteria and tissue debris. reestablish normal blood and lymphatic flow patterns. Cellular infiltration after injury follows a characteristic. that is. all stimulate neutrophil migration. In addition to achieving hemostasis. The ASA recommends that adults stop intake of solids for at least 6 hours and clear fluids for 2 hours.effects of some commonly used preparations and their potential adverse outcomes in the perioperative period. All wounds undergo the same basic steps of repair. the fibrin clot serves as scaffolding for the migration into the wound of inflammatory cells such as polymorphonuclear leukocytes (PMNs. The surgical and anesthetic advances of the 18th and 19th centuries resulted in improved surgical outcomes. fibronectin. and for ease of understanding. or negative pressure wound therapy for several days to control infection. such as platelet-derived growth factor (PDGF). Regeneration. which results in contraction of the wound. In primary. obese. and tertiary repair ( Fig. in contrast. does not proceed to restoration of functional integrity. Wound closure by tertiary intention is also referred to as delayed primary closure. Platelet -granules release a number of wound-active substances. neutrophils) and monocytes. transforming growth factor beta (TGF ). elderly. In wound healing in adult humans. Knowledge of the steps involved allows physicians to manipulate wounds to achieve optimal results in a short period. or flap closure. Generally. physicians can now manipulate the wound with cellular and molecular biology techniques and thus improve outcomes. peaking at 24 to 48 hours. Although regeneration is the goal of wound healing. or those with stomach disorders). [39] [40] Surgeons and anesthesiologists should evaluate the evidence and consider adjusting their standard fasting policies. Wound closure types are divided into primary. in the same order. Even with recent advances. and (c) maturation and remodeling. which may be associated with a benzodiazepine-like withdrawal syndrome. such as suturing. they found 22 trials in healthy adults that provided 38 controlled comparisons. Very few trials investigated the fasting routine in patients at higher risk for regurgitation/aspiration (pregnant. The same events. or flap design.[30] There was no evidence that the volume or pH of gastric contents differed with the length and type of fasting. or first-intention. and the presence of chemotactic substances. (b) proliferation. local prostaglandin release. A contaminated wound is initially treated by repeated débridement. These substances may fail to be recorded in the preoperative evaluation. the accuracy of regeneration is sacrificed for the speed of repair. predetermined sequence (see Fig.3 which may have a significant influence on CHAPTER 8 – Wound Healing The treatment and healing of wounds are some of the oldest subjects discussed in the medical literature. and serotonin. in contrast. secondary. There is also increasing evidence that preoperative carbohydrate supplementation is safe and may improve a patient's response to perioperative stress.

Depletion of most wound T lymphocytes decreases wound strength and collagen content. neutrophil factors have been implicated in delaying the epithelial closure of wounds. This effect is lost if the cells are physically separated. Type III. maturation. and new capillary tubule formation are under the influence of such cytokines and growth factors as TNF.7 Macrophages also play a significant role in regulating angiogenesis and matrix deposition and remodeling (Table 9-1). On the contrary. as well as directly by cell– cell interaction and intercellular adhesion molecules. macrophages represent a major source in the healing wound.4 The second population of inflammatory cells that invades the wound consists of macrophages.19 Matrix Synthesis Biochemistry of Collagen Collagen. Although known to be essential to wound healing. each chain of collagen is composed of a glycine residue in every third position. The macrophage's most pivotal function is activation and recruitment of other cells via mediators such as cytokines and growth factors. Its deposition.16. Although it is clear that the cytokine-rich wound environment plays a significant role in this phenotypic alteration and activation. the exact mediators are only partially characterized. 9-2C).9 whereas selective depletion of the CD8+ suppressor subset of T lymphocytes enhances wound healing. plays a critical role in the successful completion of adult wound healing. Extracellularly. Three -helical chains entwine to form a right-handed superhelical structure called procollagen. the protocollagen chain is also glycosylated by the linking of galactose and glucose at specific hydroxylysine residues. PMNs also release proteases such as collagenases. Less numerous than macrophages.14. macrophages regulate cell proliferation. Endothelial cells migrate from intact venules close to the wound. In the endoplasmic reticulum.5 Derived from circulating monocytes. It is during this phase that tissue continuity is re-established. imposing steric changes that force the protocollagen chain to assume an -helical configuration. epithelial growth factor. which is also normally present in skin. and then become activated.13 Upon entering the wound environment. Tlymphocyte numbers peak at about 1 week postinjury and truly bridge the transition from the inflammatory to the proliferative phase of healing. the procollagen molecule becomes much stronger by the covalent cross-linking of lysine residues. suggesting that extracellular matrix synthesis is regulated not only via soluble factors but also by direct cell–cell contact between lymphocytes and fibroblasts. these cells do not appear to play a role in collagen deposition or acquisition of mechanical wound strength. 9-2C). and lactate.18. to carry out their primary function of matrix synthesis remodeling. a process essential to successful wound healing.12. These steps of hydroxylation and glycosylation alter the hydrogen bonding forces within the chain. and IL-1. recruited fibroblasts first need to proliferate. and the procollagen strands undergo further polymerization and cross-linking. By releasing such mediators as TGF . However. the nonhelical registration peptides are cleaved by a procollagen peptidase. the main ones of interest to wound repair are types I and III.15 Additionally. Their migration. Although many cells produce VEGF. T lymphocytes comprise another population of inflammatory/immune cells that routinely invades the wound. matrix synthesis. Macrophages. the lymphocytes' role in wound healing is not fully defined. Type I collagen is the major component of extracellular matrix in skin. this structure contains nonhelical peptide domains called registration peptides. Fibroblasts and endothelial cells are the last cell populations to infiltrate the healing wound. which accumulates in significant amounts in the wound environment over time (~10 mmol). and ascorbic acid (vitamin C) as an electron donor. and the strongest chemotactic factor for fibroblasts is PDGF. and angiogenesis. and they actively carry out matrix contraction. Fibroblasts isolated from wounds synthesize more collagen than nonwound fibroblasts. and VEGF receptors are located specifically on endothelial cells. Release of protocollagen into the endoplasmic reticulum results in the hydroxylation of proline to hydroxyproline and of lysine to hydroxylysine by specific hydroxylases (Fig. The second position in the triplet is made up of proline or lysine during the translation process. is a potent regulator of collagen synthesis through a mechanism involving adenosine 5'-diphosphate– ribosylation. lactate. participate in wound débridement via phagocytosis and contribute to microbial stasis via oxygen radical and nitric oxide synthesis (see Fig. TNF. . TGF . which participate in matrix and ground substance degradation in the early phase of wound healing.subsequent angiogenesis and collagen synthesis (see Fig. Although there are at least 18 types of collagen described. like neutrophils. Although initially joined by weak. At both ends. and VEGF. the most abundant protein in the body. replication.8 A significant body of data supports the hypothesis that T lymphocytes play an active role in the modulation of the wound environment. Other than their role in limiting infections. they proliferate less. Biochemically. This activation is mediated mainly by the cytokines and growth factors released from wound macrophages.11 Proliferation The proliferative phase is the second phase of wound healing and roughly spans days 4 through 12 (see Fig. The polypeptide chain that is translated from messenger RNA (mRNA) contains approximately 1000 amino acid residues and is called protocollagen. 9-2B). These cells participate in the formation of new capillaries (angiogenesis). Prolyl hydroxylase requires oxygen and iron as cofactors.and intermolecular covalent bonds. vascular endothelial growth factor (VEGF). ketoglutarate as cosubstrate. macrophages achieve significant numbers in the wound by 48 to 96 hours postinjury and remain present until wound healing is complete. insulin-like growth factor. and subsequent remodeling are essential to the functional integrity of the wound. 9-3).17 Endothelial cells also proliferate extensively during this phase of healing. ionic bonds.6. depletion of the CD4+ helper subset has no effect. The resulting collagen monomer is further polymerized and cross-linked by the formation of intra. becomes more prominent and important during the repair process. which are recognized as being essential to successful healing.10 Lymphocytes also exert a downregulating effect on fibroblast collagen synthesis by cellassociated interferon.

but may take substantially longer in the case of larger wounds. PDGF) or for their initially identified function (e. There is a net shift toward collagen synthesis and eventually the reestablishment of extracellular matrix composed of a relatively acellular collagen-rich scar. basic fibroblast growth factor.24. glycosaminoglycans and proteoglycans represent the next significant matrix components. the presence of sufficient nutrients (amino acids and carbohydrates) and cofactors (vitamins and trace metals). epithelial growth factor. it appears that the process is mediated by a combination of a loss of contact inhibition. in which there is a significant epidermal/dermal defect.23 Re-epithelialization is complete in less than 48 hours in the case of approximated incised wounds. proliferation. The interaction between collagen and proteoglycans is being actively studied. increasing their concentration greatly during the first 3 weeks of healing. If only the epithelium and superficial dermis are damaged. avascular. or in an endocrine manner (in which the effect of the substance is distant to the site of . and increase their mitotic activity. Marginal basal cells at the edge of the wound lose their firm attachment to the underlying dermis. which is usually sulfated. and the local wound environment (vascular supply and lack of infection). Maturation and Remodeling The maturation and remodeling of the scar begins during the fibroplastic phase.20 Fibril formation and fibril cross-linking result in decreased collagen solubility. they couple with proteins to form proteoglycans. PDGF. However. where it acts on the immediately neighboring cells). and the net wound collagen content is the result of a balance between collagenolysis and collagen synthesis. As scar collagen is deposited. gradually resulting in a mature. Furthermore. and cytokines produced by immune mononuclear cells. and these cells appear to migrate by moving over one another in a leapfrog fashion until the defect is covered. as well as during normal tissue homeostasis.. as well as posttranslational modifications. fibroblast growth factor). and insulin-like growth factor I have been shown to promote epithelialization. The disaccharide composition of proteoglycans varies from about 10 units in the case of heparan sulfate to as much as 2000 units in the case of hyaluronic acid. Scar remodeling continues for many (6 to 12) months postinjury. enlarge.21 This balance of collagen deposition and degradation is the ultimate determinant of wound strength and integrity. become more columnar in shape. and is characterized by a reorganization of previously synthesized collagen. The stimuli for reepithelialization remain incompletely defined. There is a constant turnover of collagen in the extracellular matrix. Epithelialization While tissue integrity and strength are being re-established. Wound strength and mechanical integrity in the fresh wound are determined by both the quantity and quality of the newly deposited collagen. the external barrier must also be restored. Collagenolysis is the result of collagenase activity. Collagen is broken down by matrix metalloproteinases. and begin to migrate across the surface of the provisional matrix. a paracrine manner (by release into the extracellular environment. Addressing these factors and reversing nutritional deficiencies can optimize collagen synthesis and deposition. Proteoglycan Synthesis Glycosaminoglycans comprise a large portion of the "ground substance" that makes up granulation tissue. the content of proteoglycans gradually diminishes. Role of Growth Factors in Normal Healing Growth factors and cytokines are polypeptides produced in normal and wounded tissue that stimulate cellular migration. Fibroblasts synthesize these compounds. Both collagen synthesis and lysis are strictly controlled by cytokines and growth factors. however.g. The process begins within 1 day of injury and is seen as thickening of the epidermis at the wound edge. platelet-derived growth factor. both in the healing wound. and increased resistance to enzymatic degradation of the collagen matrix. They may act in an autocrine manner (in which the growth factor acts on the cell producing it). the proteoglycans are incorporated into the collagen scaffolding. with scar maturation and collagen remodeling. For example. a class of matrix metalloproteinases that require activation. These names are often misleading. The major glycosaminoglycans present in wounds are dermatan and chondroitin sulfate.Collagen synthesis. The polysaccharide chain is made up of repeating disaccharide units composed of glucuronic or iduronic acid and a hexosamine. Most growth factors are extremely potent and produce significant effects in nanomolar concentrations. It is thought that the assembly of collagen subunits into fibrils and fibers is dependent on the lattice provided by the sulfated proteoglycans. it appears that the extent of sulfation is critical in determining the configuration of the collagen fibrils. and acellular scar. Fixed basal cells in a zone near the cut edge undergo a series of rapid mitotic divisions. By several weeks postinjury the amount of collagen in the wound reaches a plateau. then repair consists primarily of reepithelialization with minimal or no fibroplasia and granulation tissue formation.22 Once the defect is bridged.25 In particular. TGF . and function. They often are named for the cells from which they were first derived (e. TGF increases new collagen transcription and also decreases collagen breakdown by stimulating synthesis of tissue inhibitors of metalloproteinase..g. the migrating epithelial cells lose their flattened appearance. but the tensile strength continues to increase for several more months. because growth factors have been demonstrated to have multiple functions. The deposition of matrix at the wound site follows a characteristic pattern: Fibronectin and collagen type III constitute the early matrix scaffolding. 9-4). The mechanical strength of the scar never achieves that of the uninjured tissue. such as occurs in splitthickness skin graft donor sites or in superficial second-degree burns. Rarely found free. increased strength. particularly fibronectin. Some factors affect both aspects of collagen remodeling. exposure to constituents of the extracellular matrix. Layering of the epithelium is re-established. and collagen type I is the final matrix. is highly dependent on systemic factors such as an adequate oxygen supply. and the surface layer eventually keratinizes. This process is characterized primarily by proliferation and migration of epithelial cells adjacent to the wound (Fig.

examples include:  taper (needle body is round and tapers smoothly to a point)  cutting (needle body is triangular and has a sharpened cutting edge on the inside)  reverse cutting (cutting edge on the outside)  trocar point or tapercut (needle body is round and tapered. The original sutures were made from biological materials. compound curve. G-protein linked. thus the name traumatic. The timing of release may be as important as concentration in determining the effectiveness of growth factors. the appropriate receptor on the responding cells must be present at the time of release for the biologic effect to occur. or enzyme linked.26 The signal is stopped by internalization of the receptor-ligand complex. but ends in a small triangular cutting point)  blunt points for sewing friable tissues  side cutting or spatula points (flat on top and bottom with a cutting edge along the front to one side) for eye surgery Finally. The suture manufacturer swages the suture thread to the eyeless atraumatic needle at the factory. 1/4 circle. Needles may also be classified by their point geometry. Table 9-2 summarizes the principal growth factors found in healing wounds and their known effects on cells participating in the healing process. There are several advantages to having the needle pre-mounted on the suture. The myofibroblast has been postulated as being the major cell responsible for contraction. they can be chemoattractive to one cell type while stimulating replication of a different cell type.release. and the substance is carried to the effector site through the bloodstream). 5/8 circle. 1/2 circle. and it differs from the normal fibroblast in that it possesses a cytoskeletal structure. Growth factors act on cells via surface receptor binding.28 After 4 weeks this expression fades. Most modern sutures are synthetic. Various receptor types have been described. and the cells are believed to undergo apoptosis. where instruments are inserted into the abdominal cavity through narrow cannulas. When passing through the tissues. Absorbable suture materials . and polydioxanone as well as the non-absorbablesnylon and polypropylen e. as is done when sewing at home. the area of the wound will be decreased by this action (healing by secondary intention). which may be as important as the absolute concentration of individual growth factors. and then is increasingly expressed for the next 15 days of wound healing. 3/8 circle. including the absorbables polyglycolic acid. [citation needed] Sutures come in very specific sizes and may be either absorbable (naturally biodegradable in the body) or non-absorbable. As these polypeptides exert their effects by cell-surface receptor binding. giving myofibroblasts contractile capability. and half curved at both ends of a straight segment (also known as canoe). the suture end of a swaged needle is smaller than the needle body.30 Needles Traumatic needles are needles with holes or eyes which are supplied to the hospital separate from their suture thread.29 A puzzling point is that the identification of myofibroblasts in the wound does not correspond directly to the initiation of wound contraction. The doctor or the nurse does not have to spend time threading the suture on the needle. Sutures must be strong enough to hold tissue securely but flexible enough to be knotted.27 The -smooth muscle actin is undetectable until day 6. [edit]Absorbability All sutures are classified as either absorbable or non-absorbable depending on whether the body will naturally degrade and absorb the suture material over time. Growth factors have divergent actions on different cells. Wound Contraction All wounds undergo some degree of contraction. polylactic acid. where each suture is only passed once and then tied. Little is known about the ratio of growth factor concentrations. Materials Suture thread is made from numerous materials. They must behypoallergenic and avoid the "wick effect" that would allow fluids and thus infection to penetrate the body along the suture tract. These include straight. this type of suture rips the tissue to a certain extent. such as catgut suture and silk. These "pop-offs" are commonly used for interrupted sutures. Newer still is the idea of coating sutures with antimicrobial substances to reduce the chances of wound infection. Atraumatic needles with sutures comprise an eyeless needle attached to a specific length of suture thread. More importantly. resulting in activation or deactivation of proteins in the cytosol or nucleus of the target cell. half curved (also known as ski). the shortening of the scar itself results in contracture. such as ion channels. Phosphorylation of nuclear proteins is followed by the initiation of transcription of target genes. The ski and canoe needle design allows curved needles to be straight enough to be used in laparoscopic surgery. Fibroblasts placed in a collagen lattice in vitro actively move in the lattice and contract it without expressing stress fibers. For wounds that do not have surgically approximated edges. In traumatic needles with eyes. which starts almost immediately after injury. The suture must be threaded on site. Typically this cell contains -smooth muscle actin in thick bundles called stress fibers. the thread comes out of the needle's hole on both sides. It is postulated that the movement of cells with concomitant reorganization of the cytoskeleton is responsible for contraction. atraumatic needles may be permanently swaged to the suture or may be designed to come off the suture with a sharp straight tug. There are several shapes of surgical needles. Nearly all modern sutures feature swaged atraumatic needles. The response elicited in the cell is usually one of phosphorylation or dephosphorylation of second-messenger molecules through the action of phosphatases or kinases.

[edit]Sizes Suture sizes are defined by the United States Pharmacopeia (U. they will hold the body tissues together long enough to allow healing.a medicinal grade super glue. Then if ordered. The most common is the simple interrupted stitch. polylactic acid.P. Sutures should bring together the wound edges. polydioxanone."[cite this quote] [edit]Expansions A pledgeted suture is one that is supported by a pledget.). #0 was added to the suture diameters. They must be removed after a certain time.P. Sutures were originally manufactured ranging in size from #1 to #6. The vertical and horizontal mattress stitch are also interrupted but are more complex and specialized for everting the skin and distributing tension. The chest drain stitch and corner stitch are variations of the horizontal mattress. A #4 suture would be roughly the diameter of a tennis racquet string. If a small area remains unhealed. Non-absorbable sutures are used either on skin wound closure.k. Non-absorbable sutures are made of special silk or the synthetics polypropylene. sutures in . and thus are used where cosmetic outcome is important. but the distance between each suture generally should be equal to the distance from the suture to the wound edge. advanced along the trajectory of the needle's curve until it emerges.[3] [4] Sutured skin should roll slightly outward from the wound (eversion). Stainless steel wires are commonly used in orthopedic surgery and for sternal closure in cardiac surgery. [edit]Removal While some sutures are intended to be permanent. a small flat absorbent pad or piece of cloth. remove sutures from the healed area only. Occasionally. a. These may or may not have coatings to enhance their performance characteristics. but will disintegrate so that they do not leave foreign material or require further procedures.[cite this quote] "Not all stitches must be removed. Atraumatic needles are manufactured in all shapes for most sizes. that is. notify the health care practitioner. Examples include the heart (with its constant pressure and movement) or the bladder (with adverse chemical conditions). Non-absorbable sutures often cause less scarring because they provoke less immune response. Other stitches include the Figure 8 stitch and subcuticular stitch. As the procedures improved. They are broken down by various processes includinghydrolysis (polyglycolic acid) and proteolytic enzymatic degradation. The running or continuous stitch is quicker but risks failing if the suture is cut in just one place. have been used in combination with. and others in specialized cases may be kept in place for an extended period of many weeks. in order to protect a wound. or in stressful internal environments where absorbable sutures will not suffice.[7] [edit]Tissue adhesives In recent years. limbs 10–14 days. trunk of the body 7–10 days. usually a square knot or surgeon's knot. did not allow thinner diameters. The actual diameter of thread for a given U.S.[3] Placement varies based on the location.polyester or nyl on. Depending on the material. derived at the beginning from the production of musical strings. size differs depending on the suture material class. scalp wound 7–10 days. topical cyanoacrylate adhesi ves ("liquid stitches").S. [2] since the blood supply may be impeded and thus increase infection and scarring.[4][5] Many different techniques exist. as a rule sutures are a short term device to allow healing of a trauma or wound. or as an alternative to. Common time to remove stitches will vary: facial wounds 3–5 days. thinner and thinner threads were manufactured.include the original catgut as well as the newer synthetics polyglycolic acid (Biovek). the process can be from ten days to eight weeks. which were identified as #00 (#2-0 or #2/0) to #000000 (#6-0 or #6/0). and caprolactone. The trailing thread is then tied into a knot. The needle point is pressed into the flesh. where the sutures can be removed after a few weeks. and later. They are used in patients who cannot return for suture removal. Ukuran benang 2-0 < 0 . In both cases. absorbable sutures can cause inflammation and be rejected by the body rather than absorbed. the continuous locking stitch is in some ways a more secure version. in accordance with Jenkin's Rule. or left permanently. 1> 0 [edit]Placement Sutures are placed by mounting a needle with attached suture into a needle holder.[6] it is indeed the simplest to perform and is called "interrupted" because the suture thread is cut between each individual stitch. but should not cause indenting or blanching of the skin. with #1 being the smallest. joints 14 days. and the depth and width of the sutured flesh should be roughly equal. and pulled through. or in internal body tissues. "Different parts of the body heal at different speed. Modern sutures range from #5 (heavy braided suture for orthopedics) to #11-0 (fine monofilament suture for ophthalmics). The manufacturing techniques.

FloraSeal.56. Optimal collagen synthesis requires oxygen as a cofactor. Cyanoacrylate is the generic name for cyanoacrylate based fast-acting glues such as methyl-2cyanoacrylate. The tissue adhesive has been shown to act as a barrier to microbial penetration as long as the adhesive film remains intact. their use should be delayed or. such as LiquiBand. forms with lesser anti-inflammatory effects should be administered. In healthy human volunteers there was a significant delay of 1. metabolic diseases (diabetes mellitus. and vitamin deficiencies). after which it cures (polymerizes) and forms a flexible film that bonds to the underlying surface.57 Collagen synthesis of steroid-treated wounds also can be stimulated by vitamin A. The use of common household super glue is not advisable. particularly on decreasing wound infection rates. 2octyl cyanoacrylate. is significantly impaired by local hypoxia. although wound collagen synthesis does not seem to be impaired with advanced age. SurgiSeal.wound closure. particularly for the hydroxylation steps. alternatively. Correction of these factors can have a remarkable influence on wound outcome.52–54 Major factors affecting local oxygen delivery include hypoperfusion either for systemic reasons (low volume or cardiac failure) or due to local causes (arterial insufficiency.49. steroids also inhibit epithelialization and contraction and contribute to increased rates of wound infection. and hyperactive sympathetic tone as is often induced by postoperative pain. Hypoxia. Limitations of tissue adhesives include contraindications to use near the eyes and a mild learning curve on correct usage. The increased incidence of cardiovascular disease. the young volunteers had a significantly higher amount of total -amino nitrogen in their wounds. if possible. cancer. In addition to their effect on collagen synthesis. It is available under various trade names. Studies of hospitalized surgical patients show a direct correlation between older age and poor wound healing outcomes such as dehiscence and incisional hernia. These have the advantages of being more flexible. The level of vasoconstriction of the subcutaneous capillary bed is exquisitely responsive to fluid status. 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. the greater the inhibitory effect on wound healing. a reflection of total protein content of the wound. is the preferred medical grade glue.9 days in the epithelialization of superficial skin defects in those older than 70 years of age when compared to younger volunteers. for example octyl and butyl forms.51 In the same volunteers. However. and being easier to use. temperature. or excessive tension on tissues). and Hypoperfusion Low oxygen tension has a profoundly deleterious effect on all aspects of wound healing. Nowadays. These worked well but had the disadvantage of having to be stored in the refrigerator. which may impair the mechanical properties of scarring in elderly patients.56 The major effect of steroids is to inhibit the inflammatory phase of wound healing (angiogenesis. and the bond was brittle. making a stronger bond.55 Steroids and Chemotherapeutic Drugs Large doses or chronic usage of glucocorticoids reduce collagen synthesis and wound strength. and fibroblast proliferation) and the release of lysosomal enzymes. and Dermabond. Increasing subcutaneous oxygen tension levels by increasing the fraction of inspired oxygen (FiO2) of inspired air for brief periods during and immediately after surgery results in enhanced collagen deposition and in decreased rates of wound infection after elective surgery. and the widespread use of drugs that impair wound healing may all contribute to the higher incidence of wound problems in the elderly. unless the hematocrit falls below 15%.56 Steroid-delayed healing of cutaneous wounds can be stimulated to epithelialize by topical application of vitamin A. using a micro-model of fibroplasia. The results of animal studies regarding the effects of aging on wound healing have yielded contradictory results. more recent clinical experience suggests that major operative interventions can be accomplished safely in the elderly. Skin glues like Indermil and Histoacryl were the first medical grade tissue adhesives to be used. The adhesive remains liquid until exposed to water or watercontaining substances/tissue.50 However. neutrophil and macrophage migration. Therefore.53–55 Mild to moderate normovolemic anemia does not appear to adversely affect wound oxygen tension and collagen synthesis. the longer chain polymer. malnutrition. Thus. . ethyl-2cyanoacrylate (commonly sold under trade names like Superglue and Krazy Glue) and n-butyl-cyanoacrylate. regardless of the time of administration. these statistics fail to take into account underlying illnesses or diseases as a possible source of impaired wound healing in the elderly. and these are composed of nbutyl cyanoacrylate. no difference in DNA or hydroxyproline wound accumulation could be demonstrated between the young and elderly groups. although stimulated initially by the hypoxic wound environment. Fibroplasia. The stronger the anti-inflammatory effect of the steroid compound used. noncollagenous protein accumulation at wounded sites is decreased with aging. however. Anemia. also reduce tissue reaction. local vasoconstriction. Clinical experience with elderly patients tends to support this belief. were exothermic so they stung the patient. The longer side chain types.[citation needed] Factors Affecting Wound Healing Advanced Age Most surgeons believe that aging produces intrinsic physiologic changes that result in delayed or impaired wound healing.

a dietary supplemental regimen of arginine. Defects in granulocyte function. arginine supplementation had no effect on the rate of epithelialization of a superficial skin defect. insulin resistance. Furthermore. The clinician must pay close attention to the nutritional status of patients with wounds. as opposed to the experimental situation. can reverse or prevent the decreased collagen deposition noted with malnutrition or with postoperative starvation.8 g of free arginine) daily for 14 days.59 Metabolic Disorders Diabetes mellitus is the best known of the metabolic disorders contributing to increased rates of wound infection and failure. Nutrition The importance of nutrition in the recovery from traumatic or surgical injury has been recognized by clinicians since the time of Hippocrates. isonitrogenous supplement (Fig. Thus. the large. Careful preoperative correction of blood sugar levels improves the outcome of wounds in diabetic patients. malnutrition correlates clinically with enhanced rates of wound complications and increased wound failure after diverse surgical procedures. It remains unclear whether decreased collagen synthesis or an increased breakdown due to an abnormally high proteolytic wound environment is responsible. healthy human volunteers when compared to an isocaloric.65. Arginine deficiency results in decreased woundbreaking strength and wound collagen accumulation in chow-fed rats.61 In wound studies on experimental diabetic animals. Young. human volunteers (aged 25 to 35 years) were found to have significantly increased wound collagen deposition after oral supplementation with either 30 g of arginine aspartate (17 g of free arginine) or 30 g of arginine HCl (24. Type II diabetic patients showed no effect on collagen accretion when compared to healthy.63 Furthermore. angiogenesis. The contribution of uremia alone to this impairment. First. brief and not necessarily intensive nutritional intervention. uremic animals demonstrate decreased wound collagen synthesis and breaking strength. 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. Such patients have diminished hydroxyproline accumulation (an index of collagen deposition) into subcutaneously implanted polytetrafluoroethylene tubes when compared to normally nourished patients (Fig. Arginine appears most active in terms of enhancing wound fibroplasia. suggesting that the effect of arginine is not mediated by an inflammatory mode of action. 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.68 Studies have been carried out in healthy human volunteers to examine the effect of arginine supplementation on collagen accumulation. noninfected. hyperglycemia.62 In clean. all of which are critical to successful repair. capillary ingrowth.All chemotherapeutic antimetabolite drugs adversely affect wound healing by inhibiting early cell proliferation and wound DNA and protein synthesis. Rats that are given 1% arginine HCl supplementation. 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. phagocytosis. Additionally. have enhanced wound-breaking strength and collagen synthesis when compared to chow-fed controls. marked ulceration. Although the full interaction of nutrition and wound healing is still not fully understood.64 Two additional nutrition-related factors warrant discussion. the degree of nutritional impairment need not be long- standing in humans. and collagen synthesis. and diabetic renal failure contribute significantly and independently to the impaired wound healing observed in diabetics.66 Second. Delay in the use of such drugs for about 2 weeks postinjury appears to lessen the wound healing impairment. and intracellular killing of bacteria by macrophages and neutrophils during protein-calorie malnutrition. Obesity.61 The clinical use of dialysis to correct the metabolic abnormalities and nutritional restoration should impact greatly on the wound outcome of such patients. and correction of other coexisting metabolic abnormalities all can result in improved wound healing. efforts are being made to develop woundspecific nutritional interventions and the pharmacologic use of individual nutrients as modulators of wound outcomes. judicious use of antibiotics. and are therefore not arginine-deficient.71 As increases in breaking strength during the first weeks of healing are directly related to new collagen synthesis. and fibroblast proliferation all have been described in diabetes. and the vast majority of patients exhibit combined protein-energy malnutrition.67 The possible role of single amino acids in enhanced wound healing has been studied for the last several decades. Increasing the inspired oxygen tension. .and small-vessel disease that is the hallmark of advanced diabetes contributes to local hypoxemia. healthy. as wound failure or wound infections may be no more than a reflection of poor nutrition. and protracted healing at the affected site. which signal normal healing. age-matched controls. insulin restores collagen synthesis and granulation tissue formation to normal levels if given during the early phases of healing. the diabetic wound appears to be lacking in sufficient growth factor levels. is difficult to assess. - hydroxy-methylbutyrate. and glutamine was found to significantly and specifically enhance collagen deposition in elderly. 9-8).60 Uncontrolled diabetes results in reduced inflammation. either via the parenteral or enteral route. patients with brief preoperative illnesses or reduced nutrient intake in the period immediately preceding the injury or operative intervention will demonstrate impaired fibroplasias.64 Clinically.58 Extravasation of most chemotherapeutic agents is associated with tissue necrosis.70 In this study. independent of the degree of glycemic control. 9-9). This reflects impaired healing response as well as reduced cellmediated immunity. rather than that of associated malnutrition. type I diabetes mellitus was noted to decrease wound collagen accumulation in the wound. There was no enhanced DNA synthesis present in the wounds of the argininesupplemented subjects. it is extremely rare to encounter pure energy or protein malnutrition. Poor nutritional intake or lack of individual nutrients significantly alters many aspects of wound healing. Acute fasting in rats markedly impairs collagen synthesis while decreasing procollagen mRNA. Uremia also has been associated with disordered wound healing. Experimentally. Recently.69 In a study of healthy older humans (aged 67 to 82 years). and wellperfused experimental wounds in human diabetic volunteers. This further suggests that the main effect of arginine on wound healing is to enhance wound collagen deposition.

leads to a defect in wound healing. there is no evidence that supertherapeutic doses of vitamin C are of any benefit. thus subjecting the patient to further operations and severe risk of morbidity and mortality. The vitamins most closely involved with wound healing are vitamin C and vitamin A.77 More recently. The continuing widespread appearance of methicillin-resistant Staphylococcus aureus and vancomycinresistant enterococci has significantly restricted the selection of these agents for routine use.000 IU per day have been advocated. Bacterial contaminants normally present on skin are prevented from entry into deep tissues by intact epithelium. vitamin C is required for the conversion of proline and lysine to hydroxyproline and hydroxylysine. Biochemically. Doses ranging from 25. infections can lead to disfiguring. As mentioned in the section Steroids and Chemotherapeutic Drugs. To date. or vitamin C deficiency. The recommended dietary allowance is 60 mg daily. the specific trace element may function as a cofactor or part of an enzyme that is essential for homeostasis and wound healing. and many of these enzymes are critical to wound healing. or when unexpected contamination is encountered. tumor formation. Vitamin A also can restore wound healing that has been impaired by diabetes. The occurrence of infections is of major concern when implants are used. Scurvy. The connections between specific minerals and trace elements and deficits in wound healing are complex. particularly via a failure in collagen synthesis and cross-linking. These effects are believed to be due to an associated impairment in neutrophil function. Infections can weaken an abdominal closure or hernia repair and result in wound dehiscence or recurrence of the hernia. Serious injury or stress leads to increased vitamin A requirements. Vitamin A increases the inflammatory response in wound healing. and if wound infection does occur. There is no evidence that excess vitamin C is toxic. Frequently. supplemental vitamin A can reverse the inhibitory effects of corticosteroids on wound healing. and their occurrence may lead to the removal of the prosthetic material. and radiation. deficiencies are multiple and include macronutrient deficiencies.76 Addition of antibiotics after operative contamination has occurred is clearly ineffective in preventing postoperative wound infections. and for their impact on the length of hospital stay and medical costs. impaired overall wound strength.000 to 100. An example of surgeryspecific treatment guidelines is provided in Table 9-7. It is essential for wound healing in animals and humans.74 Infections Wound infections continue to represent a major medical problem. and assurance of adequate preoperative antibiotic dosing and timing has become a significant hospital performance measure. These defects are reversed by zinc supplementation. allowing bacteria access to these tissues and the bloodstream.78.75 Many otherwise successful surgical operations fail because of the development of wound infections.arginine supplementation may result in an improvement in wound strength as a consequence of enhanced collagen deposition.72 Vitamin A deficiency impairs wound healing. There is an increased influx of macrophages. and decreased walling-off of bacteria secondary to insufficient collagen deposition. and IV procedures (see below) treated with appropriate prophylactic antibiotics have only one third the wound infection rate of previously reported untreated series.78 . respectively. with an increase in their activation and increased collagen synthesis. and the profile of resistant organisms present at the institution where the surgery is performed. Cosmetically. Selection of antibiotics for use in prophylaxis should be tailored to the type of surgery to be performed. and delayed epithelialization. supplemental doses of vitamin A have been recommended. those in which prosthetic implants are used. Studies that compare operations performed with and without antibiotic prophylaxis demonstrate that class II. decreased collagen synthesis. operative contaminants that might be encountered during the procedure. This provides a considerable safety margin for most healthy nonsmokers. III. both in terms of how they affect the outcome of surgical procedures (surgical site infections). Vitamin C deficiency has also been associated with an increased incidence of wound infection. There are more than 150 known enzymes for which zinc is either an integral part or an essential cofactor. Clinically. preventing deficiencies is often easier to accomplish than diagnosing them. Vitamin A directly increases collagen production and epidermal growth factor receptors when it is added in vitro to cultured fibroblasts. Zinc is the most well-known element in wound healing and has been used empirically in dermatologic conditions for centuries. cyclophosphamide. it tends to be more severe. repeat dosing of antibiotics has been shown to be essential in decreasing postoperative wound infections in operations with durations exceeding the biochemical halflife (t1/2) of the antibiotic or in which there is large-volume blood loss and fluid replacement. Exhaustive studies have been undertaken that examine the appropriate prophylactic treatment of operative wounds. Antibiotic prophylaxis is most effective when adequate concentrations of antibiotic are present in the tissues at the time of incision. In severely injured or extensively burned patients this requirement may increase to as high as 2 g daily. probably by increasing the lability of lysosomal membranes. or delayed closures. additional doses of antibiotic may be administered for 24 hours postoperatively. unsightly. Surgery breaches the intact epithelium.73 With zinc deficiency there is decreased fibroblast proliferation. however. As with some of the vitamins described above. no study has shown improved wound healing with zinc supplementation in patients who are not zinc deficient. whereas supplemental vitamin A benefits wound healing in nondeficient humans and animals. In the severely injured patient.79 In lengthy cases. decreased complement activity.