Surgery_Schwartz

Surgery_Schwartz. to the concentration of the growth factor, the timing of release is as important to determine their effective-ness. As these growth factors exert their effects by cell-surface receptor binding, the appropriate receptor on the responding cells must be present at the time of release in order for the bio-logic effect to occur. Table 9-2 summarizes the principal growth factors found in healing wounds and their known effects on cells participating in the healing process. Growth factors have diver-gent actions on different cells; they can be chemoattractive to one cell type while stimulating replication of a different cell type. Little is known about the ratio of growth factor concentra-tions, which may be as important as the absolute concentration of individual growth factors.Growth factors act on cells via surface receptor binding. Various receptor types have been described, such as ion chan-nels, G-protein linked, or enzyme linked. The response elicited in the cell is usually one of


Surgery_Schwartz

Surgery_Schwartz. act on cells via surface receptor binding. Various receptor types have been described, such as ion chan-nels, G-protein linked, or enzyme linked. The response elicited in the cell is usually one of phosphorylation or dephosphoryla-tion of second-messenger molecules through the action of phos-phatases or kinases, resulting in activation or deactivation of proteins in the cytosol or nucleus of the target cell. Phosphoryla-tion of nuclear proteins is followed by the initiation of transcrip-tion of target genes.26 The signal is stopped by internalization of the receptor-ligand complex.Wound ContractionAll wounds undergo some degree of contraction. For wounds that do not have surgically approximated edges, the area of the wound will be decreased by this action (healing by secondary intention). The myofibroblast has been postulated as the major cell responsible for contraction, and it differs from the normal fibroblast in that it possesses a cytoskeletal structure. Typically this cell


Surgery_Schwartz

Surgery_Schwartz. The myofibroblast has been postulated as the major cell responsible for contraction, and it differs from the normal fibroblast in that it possesses a cytoskeletal structure. Typically this cell contains α-smooth muscle actin in thick bundles called stress fibers, giving myofibroblasts contractile capability.27 The α-smooth muscle actin is undetectable until day 6, and then it is increasingly expressed for the next 15 days of wound healing.28 After 4 weeks, this expression fades, and the cells are believed to undergo apoptosis.29 A puzzling point is that the identification of myofibroblasts in the wound does not correspond directly to the initiation of wound contraction, which starts almost immedi-ately after injury. It is believed that fibroblasts might play a role in contraction. In vitro, fibroblasts placed in a collagen lattice actively move in the lattice and contract it without expressing stress fibers. It is postulated that the movement of cells with concomitant reorganization


Surgery_Schwartz

Surgery_Schwartz. fibroblasts placed in a collagen lattice actively move in the lattice and contract it without expressing stress fibers. It is postulated that the movement of cells with concomitant reorganization of the cytoskeleton is responsible for contraction.30HERITABLE DISEASES OF CONNECTIVE TISSUEHeritable diseases of connective tissue consist of a group of generalized, genetically determined, primary disorders of one of the elements of connective tissue: collagen, elastin, or muco-polysaccharide. Five major types, Ehlers-Danlos syndrome, Marfan’s syndrome, osteogenesis imperfecta, epidermolysis bullosa, and acrodermatitis enteropathica, will be discussed, as each provides unique challenges to the surgeon.Ehlers-Danlos SyndromeEhlers-Danlos syndrome (EDS) is a group of 10 disorders that present as a defect in collagen formation. Over half of the Hair follicleSweat glandBlood vesselsWoundEpidermisDermisRegeneratingepitheliumEpithelialislandEpidermisDermisHair follicleSweat glandBlood


Surgery_Schwartz

Surgery_Schwartz. present as a defect in collagen formation. Over half of the Hair follicleSweat glandBlood vesselsWoundEpidermisDermisRegeneratingepitheliumEpithelialislandEpidermisDermisHair follicleSweat glandBlood vesselsEpidermisDermisFigure 9-4. The healing by epithelialization of superficial cutane-ous wounds.Brunicardi_Ch09_p0271-p0304.indd 27601/03/19 4:50 PM 277WOUND HEALINGCHAPTER 9Table 9-2Growth factors participating in wound healingGROWTH FACTORWOUND CELL ORIGINCELLULAR AND BIOLOGIC EFFECTSPDGFPlatelets, macrophages, monocytes, smooth muscle cells, endothelial cellsChemotaxis: fibroblasts, smooth muscle, monocytes, neutrophilsMitogenesis: fibroblasts, smooth muscle cellsStimulation of angiogenesisStimulation of collagen synthesisEnhance reepithelizationModulate tissue remodelingFGFFibroblasts, endothelial cells, keratinocytes, smooth muscle cells, chondrocytesStimulation of angiogenesis (by stimulation of endothelial cell proliferation and migration)Mitogenesis: mesoderm and


Surgery_Schwartz

Surgery_Schwartz. endothelial cells, keratinocytes, smooth muscle cells, chondrocytesStimulation of angiogenesis (by stimulation of endothelial cell proliferation and migration)Mitogenesis: mesoderm and neuroectodermHGFFibroblastsStimulates fibroblasts, keratinocytes, chondrocytes, myoblastsSuppresses inflammation, granulation tissue formation, angiogenesis, reepithelializationKeratinocyte growth factorKeratinocytes, fibroblastsSignificant homology with FGF; stimulates keratinocytesEGFPlatelets, macrophages, monocytes (also identified in salivary glands, duodenal glands, kidney, and lacrimal glands)Stimulates proliferation and migration of all epithelial cell typesTGF-αKeratinocytes, platelets, macrophagesHomology with EGF; binds to EGF receptorMitogenic and chemotactic for epidermal and endothelial cellsTGF-β (three isoforms: β1, β2, β3)Platelets, T lymphocytes, macrophages, monocytes, neutrophils, fibroblasts, keratinocytesStimulates angiogenesisStimulates leukocyte chemotaxisTGF-β1 stimulates wound


Surgery_Schwartz

Surgery_Schwartz. (three isoforms: β1, β2, β3)Platelets, T lymphocytes, macrophages, monocytes, neutrophils, fibroblasts, keratinocytesStimulates angiogenesisStimulates leukocyte chemotaxisTGF-β1 stimulates wound matrix production (fibronectin, collagen glycosaminoglycans); regulation of inflammationTGF-β3 inhibits scar formationInsulin-like growth factors (IGF-1, IGF-2)Platelets (IGF-1 in high concentrations in liver; IGF-2 in high concentrations in fetal growth); likely the effector of growth hormone actionPromote protein/extracellular matrix synthesisIncrease membrane glucose transportVascular endothelial growth factorMacrophages, fibroblasts, endothelial cells, keratinocytesMitogen for endothelial cells (not fibroblasts)Stimulates angiogenesisProinflammatoryIL-1IL-4IL-6ActivinAngiopoitein-1/-2CX3CL1Macrophages, leukocytes, keratinocytes, fibroblastsLeukocytesFibroblasts, endothelial cells, macrophages, keratinocytesKeratinocytes, fibroblastsEndothelial cellsMacrophages, endothelial


Surgery_Schwartz

Surgery_Schwartz. leukocytes, keratinocytes, fibroblastsLeukocytesFibroblasts, endothelial cells, macrophages, keratinocytesKeratinocytes, fibroblastsEndothelial cellsMacrophages, endothelial cellsProinflammatoryStimulates angiogenesis, reepithelialization, tissue remodelingEnhances collagen synthesisStimulates inflammation, angiogenesis, reepithelialization, collagen deposition, tissue remodelingStimulates granulation tissue formation, keratinocyte differentiation, reepithelializationStimulates angiogenesisStimulates inflammation, angiogenesis, collagen depositionGranulocyte-macrophage colony-stimulating factorMacrophage/monocytes, endothelial cells, fibroblastsStimulates macrophage differentiation/proliferationCX3CL1 = chemokine (C-X3-C motif) ligand; EGF = epidermal growth factor; FGF = fibroblast growth factor; HGF = hepatocyte growth factor; IL = interleukin; PDGF = platelet-derived growth factor; TGF = transforming growth factor.Brunicardi_Ch09_p0271-p0304.indd 27701/03/19 4:50 PM 278BASIC


Surgery_Schwartz

Surgery_Schwartz. factor; HGF = hepatocyte growth factor; IL = interleukin; PDGF = platelet-derived growth factor; TGF = transforming growth factor.Brunicardi_Ch09_p0271-p0304.indd 27701/03/19 4:50 PM 278BASIC CONSIDERATIONSPART Iaffected patients manifest genetic defects encoding α-chains of collagen type V, causing it to be either quantitatively or struc-turally defective. These changes lead to “classic” EDS with phenotypic findings that include thin, friable skin with promi-nent veins, easy bruising, poor wound healing, atrophic scar formation, recurrent hernias, and hyperextensible joints. Gas-trointestinal problems include bleeding, hiatal hernia, intesti-nal diverticulae, and rectal prolapse. Small blood vessels are fragile, making suturing difficult during surgery. Large vessels may develop aneurysms, varicosities, or arteriovenous fistulas or may spontaneously rupture.31-33 Table 9-3 presents a descrip-tion of EDS subtypes, including a recently recognized autoso-mal recessive form


Surgery_Schwartz

Surgery_Schwartz. aneurysms, varicosities, or arteriovenous fistulas or may spontaneously rupture.31-33 Table 9-3 presents a descrip-tion of EDS subtypes, including a recently recognized autoso-mal recessive form characterized by tenascin-X deficiency. The defect is a quantitative loss of protein, resulting in phenotypic changes similar to those observed in other types of EDS.EDS must be considered in every child with recurrent her-nias and coagulopathy, especially when accompanied by platelet abnormalities and low coagulation factor levels. Inguinal her-nias in these children resemble those seen in adults. Great care should be taken to avoid tearing the skin and fascia. The trans-versalis fascia is thin, and the internal ring is greatly dilated. Like adults, hernia repair in these patients with the use of mesh or felt may result in a lower incidence of recurrence.34Closing wounds in patients with EDS might represent a major challenge to the surgeon. Dermal wounds should be closed in two layers,


Surgery_Schwartz

Surgery_Schwartz. use of mesh or felt may result in a lower incidence of recurrence.34Closing wounds in patients with EDS might represent a major challenge to the surgeon. Dermal wounds should be closed in two layers, approximated with the sutures under ten-sion, and the stitches should be left in place twice as long as usual. In addition, external fixation with adhesive tape can help reinforce the scar and prevent stretching.35Marfan’s Syndrome. Patients with Marfan’s syndrome have tall stature, arachnodactyly, lax ligaments, myopia, sco-liosis, pectus excavatum, and aneurysm of the ascending aorta. Patients who suffer from this syndrome also are prone to her-nias. Skin may be hyperextensible but shows no delay in wound healing.36,37The genetic defect associated with Marfan’s syndrome is a mutation in the FBN1 gene, which encodes for fibrillin. Pre-viously, it was thought that structural alteration of the micro-fibrillar system was responsible for the phenotypic changes seen with the disease. However,


Surgery_Schwartz

Surgery_Schwartz. FBN1 gene, which encodes for fibrillin. Pre-viously, it was thought that structural alteration of the micro-fibrillar system was responsible for the phenotypic changes seen with the disease. However, recent research indicates an intricate role that FBN1 gene products play in TGF-β signal-ing. These extracellular matrix molecules normally bind and regulate TGF-β signaling; abnormal FBN1 gene function may cause an increase in TGF-β signaling, particularly in the aortic wall.38Osteogenesis ImperfectaPatients with osteogenesis imperfecta (OI) have brittle bones, osteopenia, low muscle mass, hernias, and ligament and joint laxity. OI is a result of a mutation in type I collagen. Mutations in prolidase, an enzyme responsible for cleaving c-terminal pro-line and hydroxyproline, may have a role in the disease. There are four major OI subtypes with mild to lethal manifestations. Patients experience dermal thinning and increased bruisability. Scarring is normal, and the skin is not


Surgery_Schwartz

Surgery_Schwartz. a role in the disease. There are four major OI subtypes with mild to lethal manifestations. Patients experience dermal thinning and increased bruisability. Scarring is normal, and the skin is not hyperextensible. Surgery can be successful but difficult in these patients, as the bones fracture easily under minimal stress.31,34 Table 9-4 lists the vari-ous features associated with the clinical subtypes of OI.Table 9-3Clinical, genetic, and biochemical aspects of Ehlers-Danlos subtypesTYPECLINICAL FEATURESINHERITANCEBIOCHEMICAL DEFECTISkin: soft, hyperextensible, easy bruising, fragile, atrophic scars; hypermobile joints; varicose veins; premature birthsADNot knownIISimilar to type I, except less severeADNot knownIIISkin: soft, not hyperextensible, normal scars; small and large joint hypermobilityADNot knownIVSkin: thin, translucent, visible veins, normal scarring, no hyperextensibility; no joint hypermobility; arterial, bowel, and uterine ruptureADType III collagen defectVSimilar to


Surgery_Schwartz

Surgery_Schwartz. knownIVSkin: thin, translucent, visible veins, normal scarring, no hyperextensibility; no joint hypermobility; arterial, bowel, and uterine ruptureADType III collagen defectVSimilar to type IIXLRNot knownVISkin: hyperextensible, fragile, easy bruising; hypermobile joints; hypotonia; kyphoscoliosisARLysyl hydroxylase deficiencyVIISkin: soft, mild hyperextensibility, no increased fragility; extremely lax joints with dislocationsADType I collagen gene defectVIIISkin: soft, hyperextensible, easy bruising, abnormal scars with purple discoloration; hypermobile joints; generalized periodontitisADNot knownIXSkin: soft, lax; bladder diverticula and rupture; limited pronation and supination; broad clavicle; occipital hornsXLRLysyl oxidase defect with abnormal copper useXSimilar to type II with abnormal clotting studiesARFibronectin defectTNxHypermobile joints, skin fragilityARAbsence of tenascin X proteinAD = autosomal dominant; AR = autosomal recessive; XLR = X-linked recessive.Reproduced with


Surgery_Schwartz

Surgery_Schwartz. clotting studiesARFibronectin defectTNxHypermobile joints, skin fragilityARAbsence of tenascin X proteinAD = autosomal dominant; AR = autosomal recessive; XLR = X-linked recessive.Reproduced with permission from Cohen IK, Diegelmann RF, Lindblad WJ: Wound Healing: Biochemical and Clinical Aspects. Philadelphia, PA: WB Saunders/Elsevier; 1992.Brunicardi_Ch09_p0271-p0304.indd 27801/03/19 4:50 PM 279WOUND HEALINGCHAPTER 9Epidermolysis BullosaEpidermolysis bullosa (EB) is classified into four major sub-types: EB simplex, junctional EB, dystrophic EB, and Kindler’s syndrome. The first three are determined by location in various skin layers; the last can present as multiple blisters throughout different layers of skin. There are identified genetic defects for each subtype, but the overall phenotype is remarkably similar. The disease manifestations include impairment in tissue adhe-sion within the epidermis, basement membrane, or dermis, resulting in tissue separation and blistering with


Surgery_Schwartz

Surgery_Schwartz. is remarkably similar. The disease manifestations include impairment in tissue adhe-sion within the epidermis, basement membrane, or dermis, resulting in tissue separation and blistering with minimal trauma. Characteristic features of EB are blistering and ulceration. The recessively inherited dystrophic type is characterized by defects in the COL7A1 gene, encoding type 7 collagen, important for connecting the epidermis to the dermis, and therefore pheno-typically resulting in blistering.39 Management of nonhealing wounds in patients with EB is a challenge, as their nutritional status is compromised because of oral erosions and esophageal obstruction. Surgical interventions include esophageal dilata-tion and gastrostomy tube placement. Dermal incisions must be meticulously placed to avoid further trauma to skin.34,40 The skin requires nonadhesive pads covered by a “bulky” dressing to avoid blistering.Acrodermatitis EnteropathicaAcrodermatitis enteropathica (AE) is an autosomal


Surgery_Schwartz

Surgery_Schwartz. avoid further trauma to skin.34,40 The skin requires nonadhesive pads covered by a “bulky” dressing to avoid blistering.Acrodermatitis EnteropathicaAcrodermatitis enteropathica (AE) is an autosomal recessive disease of children that causes an inability to absorb sufficient zinc from breast milk or food. The AE mutation affects zinc uptake in the intestine by preventing zinc from binding to the cell surface and its translocation into the cell. Recently, the genetic defect has been localized on chromosome 8q24.3 identi-fied as the SLC39A4 gene, expressed in the intestinal lumen and upregulated based on zinc stores.41 Zinc deficiency is associated with impaired granulation tissue formation, as zinc is a neces-sary cofactor for DNA polymerase and reverse transcriptase, and its deficiency may impair healing due to inhibition of cell proliferation.AE is characterized by impaired wound healing as well as erythematous pustular dermatitis involving the extremities and the areas around the


Surgery_Schwartz

Surgery_Schwartz. may impair healing due to inhibition of cell proliferation.AE is characterized by impaired wound healing as well as erythematous pustular dermatitis involving the extremities and the areas around the bodily orifices. Diagnosis is confirmed by the presence of an abnormally low blood zinc level (<100 mg/dL). Oral supplementation with 100 to 400 mg zinc sulfate orally per day is curative for impaired healing.42,43HEALING IN SPECIFIC TISSUESGastrointestinal TractRepair and healing of the gastrointestinal tract is essential for the normal functions of the GI tract such as absorptive, bar-rier, and motor functions. Full-thickness GI injury healing remains an unresolved clinical issue. Healing of full-thickness GI wounds begins with a surgical or mechanical reapposition of the bowel ends, which is most often the initial step in the repair process. Sutures or staples are principally used, although various other means such as buttons, plastic tubes, and various wrappings have been attempted


Surgery_Schwartz

Surgery_Schwartz. is most often the initial step in the repair process. Sutures or staples are principally used, although various other means such as buttons, plastic tubes, and various wrappings have been attempted with variable success. Failure of healing results in dehiscence, leaks, and fistulas, which carry significant morbidity and mortality. Conversely, excessive heal-ing can be just as troublesome, resulting in stricture formation and stenosis of the lumen.The gross anatomic features of the GI tract are remarkably constant throughout most of its length. Within the lumen, the epithelium is supported by the lamina propria and underlying muscularis mucosa. The submucosa lies radially and circumfer-entially outside of these layers, is comprised of abundant col-lagenous and elastic fibers, and supports neural and vascular structures. Further toward the peritoneal surface of the bowel are the inner and outer muscle layers and ultimately a peritoneal extension, the serosa. The submucosa is the layer


Surgery_Schwartz

Surgery_Schwartz. neural and vascular structures. Further toward the peritoneal surface of the bowel are the inner and outer muscle layers and ultimately a peritoneal extension, the serosa. The submucosa is the layer that imparts the greatest tensile strength and greatest suture-holding capac-ity, a characteristic that should be kept in mind during surgical repair of the GI tract. Additionally, serosal healing is essential for quickly achieving a watertight seal from the luminal side of the bowel. The importance of the serosa is underscored by the significantly higher rates of anastomotic failure observed clinically in segments of bowel that are extraperitoneal and lack serosa (i.e., the esophagus and rectum).Injuries to all parts of the GI tract undergo the same sequence of healing as cutaneous wounds. However, there are some significant differences (Table 9-5). Mesothelial (serosal) and mucosal healing can occur without scarring. The early integ-rity of the anastomosis is dependent on formation of a


Surgery_Schwartz

Surgery_Schwartz. there are some significant differences (Table 9-5). Mesothelial (serosal) and mucosal healing can occur without scarring. The early integ-rity of the anastomosis is dependent on formation of a fibrin seal on the serosal side, which achieves water tightness, and on the suture-holding capacity of the intestinal wall, particularly the sub-mucosal layer. There is a significant decrease in marginal strength during the first week due to an early and marked collagenolysis. The lysis of collagen is carried out by collagenase derived from neutrophils, macrophages, and intraluminal bacteria. Recently, it has been shown that strains of Pseudomonas aeruginosa undergo phenotypic shifts characterized by higher collagenase secretion in an injured/anastomosed bowel environment.44 Collagenase activ-ity occurs early in the healing process, and during the first 3 to 5 days, collagen breakdown far exceeds collagen synthesis. The integrity of the anastomosis represents equilibrium between col-lagen lysis,


Surgery_Schwartz

Surgery_Schwartz. early in the healing process, and during the first 3 to 5 days, collagen breakdown far exceeds collagen synthesis. The integrity of the anastomosis represents equilibrium between col-lagen lysis, which occurs early, and collagen synthesis, which takes a few days to initiate (Fig. 9-5). Collagenase is expressed following injury in all segments of the GI tract, but it is much more marked in the colon compared to the small bowel. Colla-gen synthesis in the GI tract is carried out by both fibroblasts and smooth muscle cells. Colon fibroblasts produce greater amounts of collagen than skin fibroblasts, reflecting different phenotypic features, as well as different responses to cytokines and growth factors among these different fibroblast populations. Ultimate anastomotic strength is not always related to the absolute amount of collagen, and the structure and arrangement of the collagen matrix may be more important.45Table 9-4Osteogenesis imperfecta: clinical and genetic featuresTYPECLINICAL


Surgery_Schwartz

Surgery_Schwartz. to the absolute amount of collagen, and the structure and arrangement of the collagen matrix may be more important.45Table 9-4Osteogenesis imperfecta: clinical and genetic featuresTYPECLINICAL FEATURESINHERITANCEIMild bone fragility, blue scleraDominantII“Prenatal lethal”; crumpled long bones, thin ribs, dark blue scleraDominantIIIProgressively deforming; multiple fractures; early loss of ambulationDominant/recessiveIVMild to moderate bone fragility; normal or gray sclera; mild short statureDominantReproduced with permission from Cohen IK, Diegelmann RF, Lindblad WJ: Wound Healing: Biochemical and Clinical Aspects. Philadelphia, PA: WB Saunders/Elsevier; 1992.Brunicardi_Ch09_p0271-p0304.indd 27901/03/19 4:50 PM 280BASIC CONSIDERATIONSPART ITechnical Considerations. Traditional teaching holds that in order for an anastomosis to heal without complications it must be tension free, have an adequate blood supply, receive adequate nutrition, and be free of sepsis. Although sound


Surgery_Schwartz

Surgery_Schwartz. teaching holds that in order for an anastomosis to heal without complications it must be tension free, have an adequate blood supply, receive adequate nutrition, and be free of sepsis. Although sound prin-ciples for all wound healing, there are several considerations unique to GI anastomotic healing. From a technical viewpoint, the ideal method of suturing two ends of bowel together has not yet been identified. Although debate exists concerning meth-ods of creating an anastomosis, clinically there has been no convincing evidence that any given technique has any advan-tage over another (i.e., hand-sutured vs. stapled, continuous vs. interrupted sutures, absorbable vs. nonabsorbable sutures, or singlevs. two-layer closure). A recent meta-analysis revealed that stapled ileocolic anastomoses have fewer leak rates than hand-constructed ones, but this might not apply to colo-colic or small bowel anastomoses.46Fluid third spacing, tissue edema, and increased intraab-dominal pressure


Surgery_Schwartz

Surgery_Schwartz. have fewer leak rates than hand-constructed ones, but this might not apply to colo-colic or small bowel anastomoses.46Fluid third spacing, tissue edema, and increased intraab-dominal pressure secondary to overzealous fluid administration can result in blood flow compromise in small vessels at the edge of anastomosis and thus interfere with GI healing.47,48BoneFollowing any type of injury to bone, several changes take place at the site of injury to restore structural and functional integrity. Most of the phases of healing resemble those observed in der-mal healing, but some notable individual characteristics apply to Table 9-5Comparison of wound healing in the gastrointestinal tract and skin GI TRACTSKINWound environmentpHVaries throughout GI tract in accordance with local exocrine secretionsUsually constant except during sepsis or local infection MicroorganismsAerobic and anaerobic, especially in the colon and rectum; problematic if they contaminate the peritoneal cavitySkin


Surgery_Schwartz

Surgery_Schwartz. secretionsUsually constant except during sepsis or local infection MicroorganismsAerobic and anaerobic, especially in the colon and rectum; problematic if they contaminate the peritoneal cavitySkin commensals rarely cause problems; infection usually results from exogenous contamination or hematogenous spread Shear stressIntraluminal bulk transit and peristalsis exert distracting forces on the anastomosisSkeletal movements may stress the suture line but pain usually acts as a protective mechanism preventing excess movement Tissue oxygenationDependent on intact vascular supply and neocapillary formationCirculatory transport of oxygen as well as diffusionCollagen synthesisCell typeFibroblasts and smooth muscle cellsFibroblasts Lathyrogensd-Penicillamine has no effect on collagen cross-linkingSignificant inhibition of cross-linking with decreased wound strength SteroidsContradictory evidence exists concerning their negative effect on GI healing; increased abscess in the anastomotic line


Surgery_Schwartz

Surgery_Schwartz. inhibition of cross-linking with decreased wound strength SteroidsContradictory evidence exists concerning their negative effect on GI healing; increased abscess in the anastomotic line may play a significant roleSignificant decrease in collagen accumulationCollagenase activity—Increased presence throughout GI tract after transection and reanastomosis; during sepsis, excess enzyme may promote dehiscence by decreasing suture-holding capacity of tissueNot as significant a role in cutaneous woundsWound strength—Rapid recovery to preoperative level.Less rapid than GI tissueScar formationAgeDefinite scarring seen in fetal wound sitesUsually heals without scar formation in the fetusDaysTensile strengthResultant curveStrength of newcollagen increaseswith synthesisStrength of collagendecreases due tolysisFigure 9-5. Diagrammatic representation of the concept of GI wound healing as a fine balance between collagen synthesis and collagenolysis. The “weak” period when collagenolysis exceeds


Surgery_Schwartz

Surgery_Schwartz. due tolysisFigure 9-5. Diagrammatic representation of the concept of GI wound healing as a fine balance between collagen synthesis and collagenolysis. The “weak” period when collagenolysis exceeds col-lagen synthesis can be prolonged or exacerbated by any factors that upset the equilibrium. (Reproduced with permission from Dunphy JE: Fundamentals of Wound Management in Surgery. New York, NY: Chirurgecom, Inc.; 1976.)Brunicardi_Ch09_p0271-p0304.indd 28001/03/19 4:50 PM 281WOUND HEALINGCHAPTER 9bone injuries. The initial stage of hematoma formation consists of an accumulation of blood at the fracture site, which also con-tains devitalized soft tissue, dead bone, and necrotic marrow. The next stage accomplishes the liquefaction and degradation of nonviable products at the fracture site. The normal bone adja-cent to the injury site can then undergo revascularization, with new blood vessels growing into the fracture site. This is similar to the formation of granulation in soft tissue.


Surgery_Schwartz

Surgery_Schwartz. The normal bone adja-cent to the injury site can then undergo revascularization, with new blood vessels growing into the fracture site. This is similar to the formation of granulation in soft tissue. The symptoms associated with this stage are characteristic of inflammation, with clinical evidence of swelling and erythema.Three to 4 days following injury, soft tissue forms a bridge between the fractured bone segments in the next stage (soft callus stage). The soft tissue is deposited where neovasculariza-tion has taken place and serves as an internal splint, preventing damage to the newly laid blood vessels and achieving a fibrocar-tilaginous union. The soft callus is formed externally along the bone shaft and internally within the marrow cavity. Clinically, this phase of healing is characterized by the cessation of pain and inflammatory signs.The next phase consists of mineralization of the soft callus and conversion to bone (hard callus stage). This may take up to 2 to 3 months and


Surgery_Schwartz

Surgery_Schwartz. by the cessation of pain and inflammatory signs.The next phase consists of mineralization of the soft callus and conversion to bone (hard callus stage). This may take up to 2 to 3 months and leads to complete bony union. The bone is now considered strong enough to allow weight bearing and will appear healed on radiographs. Then remodeling phase follows, in which the excessive callus is reabsorbed and the marrow cav-ity is recanalized. Remodeling allows for the correct transmis-sion of forces and restores the contours of the bone.As in dermal healing, the process of osseous union is mediated by soluble growth factors and cytokines. The most extensively studied group is the bone morphogenic proteins (BMPs), which belong to the TGF-β superfamily. By stimulat-ing the differentiation of mesenchymal cells into chondroblasts and osteoblasts, BMPs directly affect bone and cartilage repair. Other growth factors such as PDGF, TGF-β, TNF-α, and bFGF also participate in bony repair by mediating


Surgery_Schwartz

Surgery_Schwartz. cells into chondroblasts and osteoblasts, BMPs directly affect bone and cartilage repair. Other growth factors such as PDGF, TGF-β, TNF-α, and bFGF also participate in bony repair by mediating the inflammatory and proliferative phases of healing.CartilageCartilage consists of cells (chondrocytes) surrounded by an extracellular matrix made up of several proteoglycans, colla-gen fibers, and water. Unlike bone, cartilage is very avascular and depends on diffusion for transmittal of nutrients across the matrix. Additionally, the hypervascular perichondrium contrib-utes substantially to the nutrition of the cartilage. Therefore, injuries to cartilage may be associated with permanent defects due to tenuous blood supply.The healing response of cartilage depends on the depth of injury. In a superficial injury, there is disruption of the pro-teoglycan matrix and injury to the chondrocytes. There is no inflammatory response, but an increase in synthesis of proteo-glycan and collagen dependent


Surgery_Schwartz

Surgery_Schwartz. injury, there is disruption of the pro-teoglycan matrix and injury to the chondrocytes. There is no inflammatory response, but an increase in synthesis of proteo-glycan and collagen dependent entirely on the chondrocyte. The healing power of cartilage is often inadequate, and over-all regeneration is incomplete. Therefore, superficial cartilage injuries are slow to heal and often result in persistent structural defects.In contrast to superficial injuries, deep injuries involve the underlying bone and soft tissue. This leads to the exposure of vascular channels of the surrounding damaged tissue that may help in the formation of granulation tissue. Hemorrhage allows for the initiation of the inflammatory response and the subse-quent mediator activation of cellular function for repair. As the granulation tissue is laid down, fibroblasts migrate toward the wound and synthesize fibrous tissue that undergoes chondrifica-tion. Gradually, hyaline cartilage is formed, which restores the


Surgery_Schwartz

Surgery_Schwartz. As the granulation tissue is laid down, fibroblasts migrate toward the wound and synthesize fibrous tissue that undergoes chondrifica-tion. Gradually, hyaline cartilage is formed, which restores the structural and functional integrity of the injured site.TendonTendons and ligaments are specialized structures that link mus-cle and bone, and bone and bone, respectively. They consist of parallel bundles of collagen interspersed with spindle cells. Tendons and ligaments can be subjected to a variety of injuries, such as laceration, rupture, and contusion. Due to the mobility of the underlying bone or muscles, the damaged ends usually separate. Tendon and ligament healing progresses in a similar fashion as in other areas of the body (i.e., through hematoma formation, organization, laying down of reparative tissue, and scar formation). Matrix is characterized by accumulation of types I and III collagen along with increased water, DNA, and glycosaminoglycan content. As the collagen fibers


Surgery_Schwartz

Surgery_Schwartz. of reparative tissue, and scar formation). Matrix is characterized by accumulation of types I and III collagen along with increased water, DNA, and glycosaminoglycan content. As the collagen fibers are orga-nized, transmission of forces across the damaged portion can occur. Restoration of the mechanical integrity may never be equal to that of the undamaged tendon.Tendon vasculature has a clear effect on healing. Hypovas-cular tendons tend to heal with less motion and more scar for-mation than tendons with better blood supply. The specialized cells, tenocytes, are metabolically very active and retain a large regenerative potential, even in the absence of vascularity. Cells on the tendon surface are identical to those within the sheath and play a role in tendon healing as well.NerveNerve injuries are very common, with an estimated 200,000 repairs performed every year in the United States. Peripheral nerves are a complex arrangement of axons, nonneuronal cells, and extracellular


Surgery_Schwartz

Surgery_Schwartz. injuries are very common, with an estimated 200,000 repairs performed every year in the United States. Peripheral nerves are a complex arrangement of axons, nonneuronal cells, and extracellular elements. There are three types of nerve inju-ries: neurapraxia (focal demyelination), axonotmesis (interrup-tion of axonal continuity but preservation of Schwann cell basal lamina), and neurotmesis (complete transection). Following all types of injury, the nerve ends progress through a predictable pattern of changes involving three crucial steps: (a) survival of axonal cell bodies; (b) regeneration of axons that grow across the transected nerve to reach the distal stump; and (c) migration and connection of the regenerating nerve ends to the appropriate nerve ends or organ targets.Phagocytes remove the degenerating axons and myelin sheath from the distal stump (Wallerian degeneration). Regen-erating axonal sprouts extend from the proximal stump and probe the distal stump and the surrounding


Surgery_Schwartz

Surgery_Schwartz. the degenerating axons and myelin sheath from the distal stump (Wallerian degeneration). Regen-erating axonal sprouts extend from the proximal stump and probe the distal stump and the surrounding tissues. Schwann cells envelope and help in remyelinating the regenerating axons. Functional units are formed when the regenerating axons con-nect with the appropriate end targets. Several factors play a role in nerve healing, such as growth factors, cell adhesion mol-ecules, and nonneuronal cells and receptors. Growth factors include nerve growth factor, brain-derived neurotrophic factor, basic and acidic fibroblastic growth factors, and neuroleukin. Cell adhesion molecules involved in nerve healing include nerve adhesion molecule, neuron-glia adhesion molecule, myelin adhesion glycoprotein, and N-cadherin. This complex interplay of growth factors and adhesion molecules helps in nerve regeneration.Fetal Wound HealingThe main characteristic that distinguishes the healing of fetal wounds from


Surgery_Schwartz

Surgery_Schwartz. N-cadherin. This complex interplay of growth factors and adhesion molecules helps in nerve regeneration.Fetal Wound HealingThe main characteristic that distinguishes the healing of fetal wounds from that of adult wounds is the lack of scar forma-tion. Understanding how fetal wounds achieve integrity without Brunicardi_Ch09_p0271-p0304.indd 28101/03/19 4:50 PM 282BASIC CONSIDERATIONSPART Ievidence of scarring holds promise for the possible manipula-tion of unwanted fibrosis or excessive scar formation in adults.Although early fetal healing is characterized by the absence of scarring and resembles tissue regeneration, there is a phase of transition during gestational life when a more adult-like healing pattern emerges. This so-called “transition wound” occurs at the beginning of the third trimester, and during this period, there is scarless healing; however, there is a loss of the ability to regenerate skin appendages.49 Eventually a classic, adult-patterned healing with scar


Surgery_Schwartz

Surgery_Schwartz. third trimester, and during this period, there is scarless healing; however, there is a loss of the ability to regenerate skin appendages.49 Eventually a classic, adult-patterned healing with scar formation occurs exclusively, although overall healing continues to be faster than in adults.There are a number of characteristics that may influence the differences between fetal and adult wounds. These include wound environment, inflammatory responses, differential growth factor profiles, and wound matrix.Wound Environment. The fetus is bathed in a sterile, tem-perature-stable fluid environment, although this alone does not explain the observed differences. Experiments have demon-strated that scarless healing may occur outside of the amniotic fluid environment, and conversely, scars can form in utero.50,51Inflammation. The extent and robustness of the inflammatory response correlates directly with the amount of scar formation in all healing wounds. Reduced fetal inflammation due to the


Surgery_Schwartz

Surgery_Schwartz. in utero.50,51Inflammation. The extent and robustness of the inflammatory response correlates directly with the amount of scar formation in all healing wounds. Reduced fetal inflammation due to the immaturity of the fetal immune system may partially explain the lack of scarring observed. Not only is the fetus neutrope-nic, but fetal wounds also contain lower numbers of PMNs and macrophages.52Growth Factors. Fetal wounds are notable for the absence of TGF-β, which may have a significant role in scarring. Blocking TGF-β1 or TGF-β2 using neutralizing antibodies considerably reduces scar formation in adult wounds. Exogenous application of TGF-β3 downregulates TGF-β1 and TGF-β2 levels at the wound site with a resultant reduction in scarring.53 Thus, the balance between the concentration and/or activity of TGF-β iso-forms may be important for regulating scar production.Wound Matrix. The fetal wound is characterized by excessive and extended hyaluronic acid production, a


Surgery_Schwartz

Surgery_Schwartz. concentration and/or activity of TGF-β iso-forms may be important for regulating scar production.Wound Matrix. The fetal wound is characterized by excessive and extended hyaluronic acid production, a high-molecular-weight glycosaminoglycan that is produced primarily by fibro-blasts. Although adult wounds also produce hyaluronic acid, its synthesis is sustained only in the fetal wound. Components of amniotic fluid, most specifically fetal urine, have a unique abil-ity to stimulate hyaluronic acid production.54 Fetal fibroblasts produce more collagen than adult fibroblasts, and the increased level of hyaluronic acid may aid in the orderly organization of collagen. As a result of these findings, hyaluronic acid is used topically to enhance healing and to inhibit postoperative adhesion formation.55 The collagen pattern of fetal wounds is reticular in nature and resembles surrounding tissue, while adult patterns express large bundles of parallel collagen fibrils ori-ented perpendicular to


Surgery_Schwartz

Surgery_Schwartz. The collagen pattern of fetal wounds is reticular in nature and resembles surrounding tissue, while adult patterns express large bundles of parallel collagen fibrils ori-ented perpendicular to the surface.56CLASSIFICATION OF WOUNDSWounds are classified as either acute or chronic. By definition, an acute wound becomes chronic if healing is not achieved after 4 weeks of treatment. Acute wounds heal in a predictable man-ner and time frame as previously mentioned. The process occurs with few, if any, complications, and the end result is a well-healed wound. Surgical wounds can heal in several ways. An incised wound that is clean and closed by sutures is said to heal by primary intention. Often, because of bacterial contamination or tissue loss, a wound will be left open to heal by granula-tion tissue formation and contraction; this constitutes healing by secondary intention. Delayed primary closure, or healing by tertiary intention, represents a combination of the first two, con-sisting


Surgery_Schwartz

Surgery_Schwartz. tissue formation and contraction; this constitutes healing by secondary intention. Delayed primary closure, or healing by tertiary intention, represents a combination of the first two, con-sisting of the placement of sutures, allowing the wound to stay open for a few days, and the subsequent closure of the sutures (Fig. 9-6).The healing spectrum of acute wounds is broad (Fig. 9-7). In examining the acquisition of mechanical integrity and strength during healing, the normal process is characterized by a con-stant and continual increase that reaches a plateau at some point after injury. In regular wounds, the maximal wound strength is reached after about 6 weeks of healing. A fully healed wound achieves only 75% to 80% of a normal tissue. Wounds with delayed healing are characterized by decreased wound-breaking strength in comparison to wounds that heal at a normal rate; however, they eventually achieve the same integrity and strength as wounds that heal normally. Conditions such as


Surgery_Schwartz

Surgery_Schwartz. decreased wound-breaking strength in comparison to wounds that heal at a normal rate; however, they eventually achieve the same integrity and strength as wounds that heal normally. Conditions such as nutritional deficiencies, infections, or severe trauma cause delayed heal-ing, which reverts to normal with correction of the underlying pathophysiology. Impaired healing is characterized by a failure to achieve mechanical strength equivalent to normally healed wounds. Patients with compromised immune systems such as those with diabetes, chronic steroid usage, or tissues damaged by radiotherapy are prone to this type of impaired healing. The surgeon must be aware of these situations and exercise great care in the placement of incision and suture selection, postop-erative care, and adjunctive therapy to maximize the chances of healing without supervening complications.In general, wounds heal by a combination of mecha-nisms, including connective tissue deposition, contraction, and Primary


Surgery_Schwartz

Surgery_Schwartz. therapy to maximize the chances of healing without supervening complications.In general, wounds heal by a combination of mecha-nisms, including connective tissue deposition, contraction, and Primary IntentionSecondary IntentionTertiary IntentionContractionContractionConnective TissueRepairConnective TissueRepairEpithelializationEpithelializationFigure 9-6. Different clinical approaches to the closure and heal-ing of acute wounds.Brunicardi_Ch09_p0271-p0304.indd 28201/03/19 4:50 PM 283WOUND HEALINGCHAPTER 9epithelialization, depending on wound type. Surgically closed wounds need mostly epithelialization for healing, while open wounds require a combination of tissue contraction, connective tissue deposition, and epithelialization to a lesser extent. Chronic ulcers heal by secondary intention similar to open wounds.Normal healing is affected by both systemic and local fac-tors (Table 9-6). The clinician must be familiar with these fac-tors and should attempt to counteract their


Surgery_Schwartz

Surgery_Schwartz. intention similar to open wounds.Normal healing is affected by both systemic and local fac-tors (Table 9-6). The clinician must be familiar with these fac-tors and should attempt to counteract their deleterious effects. Complications occurring in wounds with higher risk can lead to failure of healing or the development of chronic, nonhealing wounds.Factors Affecting Wound HealingAdvanced Age. Most surgeons believe that aging produces intrinsic physiologic changes that result in delayed or impaired wound healing. Clinical experience with elderly patients tends to support this belief. Studies of hospitalized surgical patients show a direct correlation between older age and poor wound healing outcomes such as dehiscence and incisional hernia.57,58 However, these statistics fail to take into account underlying illnesses or diseases as a possible source of impaired wound healing in the elderly. The increased incidence of cardiovascu-lar disease, metabolic diseases (diabetes mellitus,


Surgery_Schwartz

Surgery_Schwartz. into account underlying illnesses or diseases as a possible source of impaired wound healing in the elderly. The increased incidence of cardiovascu-lar disease, metabolic diseases (diabetes mellitus, malnutrition, and vitamin deficiencies), and cancer, and the widespread use of drugs that impair wound healing may all contribute to the higher incidence of wound problems in the elderly. However, more recent clinical experience suggests that major operative interventions can be accomplished safely in the elderly.The results of animal studies regarding the effects of aging on wound healing have yielded contradictory results. In healthy human volunteers, there was a significant delay of 1.9 days in the epithelialization of superficial skin defects in those older than 70 years of age when compared to younger volunteers.59 In the same volunteers, using a micro-model of fibroplasia, no dif-ference in DNA or hydroxyproline wound accumulation could be demonstrated between the young and elderly


Surgery_Schwartz

Surgery_Schwartz. to younger volunteers.59 In the same volunteers, using a micro-model of fibroplasia, no dif-ference in DNA or hydroxyproline wound accumulation could be demonstrated between the young and elderly groups; how-ever, the young volunteers had a significantly higher amount of total α-amino nitrogen in their wounds, a reflection of total protein content of the wound. Thus, although wound collagen synthesis does not seem to be impaired with advanced age, non-collagenous protein accumulation at wounded sites is decreased with aging, which may impair the mechanical properties of scar-ring in elderly patients. Generally, in a relatively healthy person age will cause a delay in healing rather than nonhealing.Hypoxia, Anemia, and Hypoperfusion. Low oxygen tension has a profoundly deleterious effect on all aspects of wound heal-ing. Fibroplasia, although stimulated initially by the hypoxic wound environment, is significantly impaired by local hypoxia. Optimal collagen synthesis requires oxygen as


Surgery_Schwartz

Surgery_Schwartz. all aspects of wound heal-ing. Fibroplasia, although stimulated initially by the hypoxic wound environment, is significantly impaired by local hypoxia. Optimal collagen synthesis requires oxygen as a cofactor, partic-ularly for the hydroxylation steps. Increasing subcutaneous oxy-gen tension levels by increasing the fraction of inspired oxygen (Fio2) of inspired air for brief periods during and immediately following surgery results in enhanced collagen deposition and in decreased rates of wound infection after elective surgery.60-62Major factors affecting local oxygen delivery include hypoperfusion either for systemic reasons (low volume or car-diac failure) or due to local causes (arterial insufficiency, local vasoconstriction, or excessive tension on tissues). The level of vasoconstriction of the subcutaneous capillary bed is exquisitely responsive to fluid status, temperature, and hyperactive sympa-thetic tone as is often induced by postoperative pain. Correction of these factors


Surgery_Schwartz

Surgery_Schwartz. of the subcutaneous capillary bed is exquisitely responsive to fluid status, temperature, and hyperactive sympa-thetic tone as is often induced by postoperative pain. Correction of these factors can have a remarkable influence on wound out-come, particularly on decreasing wound infection rates.61-63 Mild to moderate normovolemic anemia does not appear to adversely affect wound oxygen tension and collagen synthesis. However, profound anemia with 15% less hematocrit can interfere with wound healing.63Steroids and Chemotherapeutic Drugs. Large doses or chronic usage of glucocorticoids reduce collagen synthesis and wound strength.64 The major effect of steroids is to inhibit the inflammatory phase of wound healing (angiogenesis, neutro-phil and macrophage migration, and fibroblast proliferation) and the release of lysosomal enzymes. The stronger the anti-inflammatory effect of the steroid compound used, the greater the inhibitory effect on wound healing. Steroids used after the first 3 to


Surgery_Schwartz

Surgery_Schwartz. and the release of lysosomal enzymes. The stronger the anti-inflammatory effect of the steroid compound used, the greater the inhibitory effect on wound healing. Steroids used after the first 3 to 4 days after injury do not affect wound healing as severely as when they are used in the immediate postoperative 3Normal healingDelayed healingImpaired healing chronicTimeWound mechanical strengthFigure 9-7. The acquisition of wound mechanical strength over time in normal, delayed, and impaired healing.Table 9-6Factors affecting wound healingSystemic Age Nutrition Trauma Metabolic diseases Immunosuppression Connective tissue disorders SmokingLocal Mechanical injury Infection Edema Ischemia/necrotic tissue Topical agents Ionizing radiation Low oxygen tension Foreign bodiesBrunicardi_Ch09_p0271-p0304.indd 28301/03/19 4:50 PM 284BASIC CONSIDERATIONSPART Iperiod. Therefore, if possible, their use should be delayed, or alternatively, forms with lesser anti-inflammatory effects should be


Surgery_Schwartz

Surgery_Schwartz. 28301/03/19 4:50 PM 284BASIC CONSIDERATIONSPART Iperiod. Therefore, if possible, their use should be delayed, or alternatively, forms with lesser anti-inflammatory effects should be administered.In addition to their effect on collagen synthesis, steroids also inhibit epithelialization and contraction and contribute to increased rates of wound infection, regardless of the time of administration.64 Steroid-delayed healing of cutaneous wounds can be stimulated to epithelialize by topical application of vitamin A.64,65 Collagen synthesis of steroid-treated wounds also can be stimulated by vitamin A.All chemotherapeutic antimetabolite drugs adversely affect wound healing by inhibiting early cell proliferation, wound DNA and protein synthesis, attenuation of the inflamma-tory phase, decrease fibrin deposition, and delay wound contrac-tion, all of which are critical to successful healing. The effect is worse if these agents are given preoperatively; so a delay in the use of such drugs


Surgery_Schwartz

Surgery_Schwartz. fibrin deposition, and delay wound contrac-tion, all of which are critical to successful healing. The effect is worse if these agents are given preoperatively; so a delay in the use of such drugs for about 2 weeks after injury appears to lessen wound healing impairment.66 Extravasation of most che-motherapeutic agents is associated with tissue necrosis, marked ulceration, and protracted healing at the affected site.67Metabolic Disorders. Diabetes mellitus is the best known of the metabolic disorders contributing to increased rates of wound infection and failure.68 Uncontrolled diabetes results in reduced inflammation, angiogenesis, and collagen synthe-sis. Additionally, the largeand small-vessel disease that is the hallmark of advanced diabetes contributes to hypoperfusion and local hypoxemia. Defects in granulocyte function, capillary ingrowth, and fibroblast proliferation all have been described in diabetes. Obesity, insulin resistance, hyperglycemia, and dia-betic renal failure


Surgery_Schwartz

Surgery_Schwartz. Defects in granulocyte function, capillary ingrowth, and fibroblast proliferation all have been described in diabetes. Obesity, insulin resistance, hyperglycemia, and dia-betic renal failure contribute significantly and independently to the impaired wound healing observed in diabetics.69 In wound studies on experimental diabetic animals, insulin restores colla-gen synthesis and granulation tissue formation to normal levels if given during the early phases of healing.70 In clean, nonin-fected, and well-perfused experimental wounds in human dia-betic volunteers, type 1 diabetes mellitus was noted to decrease wound collagen accumulation in the wound, independent of the degree of glycemic control. Type 2 diabetic patients showed no effect on collagen accumulation when compared to healthy, age-matched controls.71 Furthermore, the diabetic wound appears to be lacking in sufficient growth factor levels, which signal normal healing. It remains unclear whether decreased collagen synthesis or


Surgery_Schwartz

Surgery_Schwartz. controls.71 Furthermore, the diabetic wound appears to be lacking in sufficient growth factor levels, which signal normal healing. It remains unclear whether decreased collagen synthesis or an increased breakdown due to an abnormally high proteolytic wound environment is responsible.Careful preoperative correction of blood sugar levels improves the outcome of wounds in diabetic patients. Increas-ing the inspired oxygen tension, judicious use of antibiotics, and correction of other coexisting metabolic abnormalities all can result in improved wound healing. Additionally, revasculariza-tion to local areas with chronic ulcers will aid in the healing process.Uremia also has been associated with disordered wound healing and impairs defenses for infection. Experimentally, uremic animals demonstrate decreased wound collagen synthe-sis and breaking strength, causing delayed healing of intestinal anastomosis and abdominal wounds. The contribution of uremia alone to this impairment, rather than


Surgery_Schwartz

Surgery_Schwartz. decreased wound collagen synthe-sis and breaking strength, causing delayed healing of intestinal anastomosis and abdominal wounds. The contribution of uremia alone to this impairment, rather than that of associated malnutri-tion, is difficult to assess.69 The clinical use of dialysis to correct the metabolic abnormalities and nutritional restoration should impact greatly on the wound outcome of such patients. In some uremic patients, wounds might be associated with abnormal deposition of calcium and phosphate in the tissue leading to uremic gangrene syndrome (calciphylaxis). In such patients, the wounds are extremely painful and difficult to heal.Obesity is the largest growing public health problem in the United States and the world. Over 60% of Americans are overweight or obese. Uncomplicated obesity (i.e., in the absence of comorbid conditions such as cardiovascular disease, diabetes, or respiratory insufficiency) has by itself significant deleterious effects on wound healing.


Surgery_Schwartz

Surgery_Schwartz. obesity (i.e., in the absence of comorbid conditions such as cardiovascular disease, diabetes, or respiratory insufficiency) has by itself significant deleterious effects on wound healing. Visceral adiposity is active metaboli-cally and immunologically and, through generation of proin-flammatory cytokines and adipokines, leads to the development of the metabolic syndrome. Many of these molecules have effects on cells participating in the healing response. In nondia-betic obese rodents, wounds are mechanically weaker, and there is less dermal and reparative scar collagen. Preadipocytes infil-trate the dermis, and although they can evolve into fibroblasts, their regulatory mechanisms appear different from those of dermal or wound fibroblasts. Many studies indicate that obese patients have high rates of perioperative complications, with estimates as high as 30% for wound dehiscence, 17% for surgi-cal site infections, 30% for incisional hernias, 19% for seromas, 13% for hematomas, and 10%


Surgery_Schwartz

Surgery_Schwartz. rates of perioperative complications, with estimates as high as 30% for wound dehiscence, 17% for surgi-cal site infections, 30% for incisional hernias, 19% for seromas, 13% for hematomas, and 10% for fat necrosis.72-74 Increased subcutaneous fat was associated with a tenfold increased risk of surgery-related complications including anastomotic leaks, abdominal collection, and wound infections.75 In many studies, obesity is a constant and major risk factor for hernia formation and recurrence after repair. The mechanism by which obesity impairs wound healing awaits complete delineation.Nutrition. The importance of nutrition in the recovery from traumatic or surgical injury has been recognized by clinicians since the time of Hippocrates. Poor nutritional intake or lack of individual nutrients significantly alters many aspects of wound healing. The clinician must pay close attention to the nutritional status of patients with wounds, since wound failure or wound infections may be no more


Surgery_Schwartz

Surgery_Schwartz. significantly alters many aspects of wound healing. The clinician must pay close attention to the nutritional status of patients with wounds, since wound failure or wound infections may be no more than a reflection of poor nutrition. Although the full interaction of nutrition and wound healing is still not fully understood, efforts are being made to develop wound-specific nutritional interventions and institute the phar-macologic use of individual nutrients as modulators of wound outcomes.Experimental rodents fed either a 0% or 4% protein diet have impaired collagen deposition with a secondary decrease in skin and fascial wound-breaking strength and increased wound infection rates. Induction of energy-deficient states by providing only 50% of the normal caloric requirement leads to decreased granulation tissue formation and matrix protein deposition in rats. Acute fasting in rats markedly impairs collagen synthesis while decreasing procollagen mRNA.76Clinically, it is extremely rare


Surgery_Schwartz

Surgery_Schwartz. granulation tissue formation and matrix protein deposition in rats. Acute fasting in rats markedly impairs collagen synthesis while decreasing procollagen mRNA.76Clinically, it is extremely rare to encounter pure energy or protein malnutrition, and the vast majority of patients exhibit combined protein-energy malnutrition. Such patients have diminished hydroxyproline accumulation (an index of collagen deposition) into subcutaneously implanted polytetrafluoroeth-ylene tubes when compared to normally nourished patients (Fig. 9-8). Furthermore, malnutrition correlates clinically with enhanced rates of wound complications and increased wound failure following diverse surgical procedures. This reflects impaired healing response as well as reduced cell-mediated immunity, phagocytosis, and intracellular killing of bacte-ria by macrophages and neutrophils during protein-calorie malnutrition.76Two additional nutrition-related factors warrant discus-sion. First, the degree of nutritional


Surgery_Schwartz

Surgery_Schwartz. intracellular killing of bacte-ria by macrophages and neutrophils during protein-calorie malnutrition.76Two additional nutrition-related factors warrant discus-sion. First, the degree of nutritional impairment need not be Brunicardi_Ch09_p0271-p0304.indd 28401/03/19 4:50 PM 285WOUND HEALINGCHAPTER 9long-standing in humans, as opposed to the experimental situa-tion. Thus, patients with brief preoperative illnesses or reduced nutrient intake in the period immediately preceding the injury or operative intervention will demonstrate impaired fibroplasias.77,78 Second, brief and not necessarily intensive nutritional interven-tion, either via the parenteral or enteral route, can reverse or prevent the decreased collagen deposition noted with malnutri-tion or with postoperative starvation.79The possible role of single amino acids in enhanced wound healing has been studied for the last several decades. Arginine appears most active in terms of enhancing wound fibroplasia. Arginine


Surgery_Schwartz

Surgery_Schwartz. possible role of single amino acids in enhanced wound healing has been studied for the last several decades. Arginine appears most active in terms of enhancing wound fibroplasia. Arginine deficiency results in decreased wound-breaking strength and wound-collagen accumulation in chow-fed rats. Rats that are given 1% arginine HCl supplementation, and there-fore are not arginine-deficient, have enhanced wound-breaking strength and collagen synthesis when compared to chow-fed controls.80 Studies have been carried out in healthy human vol-unteers to examine the effect of arginine supplementation on collagen accumulation. Young, healthy, human volunteers (age 25–35 years) were found to have significantly increased wound-collagen deposition following oral supplementation with either 30 g of arginine aspartate (17 g of free arginine) or 30 g of argi-nine Hall (24.8 g of free arginine) daily for 14 days.81 In a study of healthy older humans (age 67–82 years), daily supplements of 30 g of


Surgery_Schwartz

Surgery_Schwartz. arginine aspartate (17 g of free arginine) or 30 g of argi-nine Hall (24.8 g of free arginine) daily for 14 days.81 In a study of healthy older humans (age 67–82 years), daily supplements of 30 g of arginine aspartate for 14 days resulted in significantly enhanced collagen and total protein deposition at the wound site when compared to controls given placebos. There was no enhanced DNA synthesis present in the wounds of the arginine-supplemented subjects, suggesting that the effect of arginine is not mediated by an inflammatory mode of action.82 In this and later studies, arginine supplementation, whether administered orally or parenterally, had no effect on the rate of epithelializa-tion of a superficial skin defect. This further suggests that the main effect of arginine on wound healing is to enhance wound collagen deposition. Recently, a dietary supplemental regimen of arginine, β-hydroxy-β-methyl butyrate, and glutamine was found to significantly and specifically enhance collagen


Surgery_Schwartz

Surgery_Schwartz. is to enhance wound collagen deposition. Recently, a dietary supplemental regimen of arginine, β-hydroxy-β-methyl butyrate, and glutamine was found to significantly and specifically enhance collagen depo-sition in elderly, healthy human volunteers when compared to an isocaloric, isonitrogenous supplement (Fig. 9-9).83 As increases in breaking strength during the first weeks of healing are directly related to new collagen synthesis, arginine supple-mentation may result in an improvement in wound strength as a consequence of enhanced collagen deposition.The vitamins most closely involved with wound healing are vitamin C and vitamin A. Scurvy or vitamin C deficiency leads to a defect in wound healing, particularly via a failure in collagen synthesis and cross-linking. Biochemically, vitamin C is required for the conversion of proline and lysine to hydroxy-proline and hydroxylysine, respectively. Vitamin C deficiency has also been associated with an increased incidence of wound infection,


Surgery_Schwartz

Surgery_Schwartz. is required for the conversion of proline and lysine to hydroxy-proline and hydroxylysine, respectively. Vitamin C deficiency has also been associated with an increased incidence of wound infection, and if wound infection does occur, it tends to be more severe. These effects are believed to be due to an associated impairment in neutrophil function, decreased complement activ-ity, and decreased walling-off of bacteria secondary to insuffi-cient collagen deposition. The recommended dietary allowance is 60 mg daily. This provides a considerable safety margin for most healthy nonsmokers. In severely injured or extensively burned patients, this requirement may increase to as high as 2 g daily. There is no evidence that excess vitamin C is toxic; however, there is no evidence that supratherapeutic doses of vitamin C are of any benefit.84Vitamin A deficiency impairs wound healing, while sup-plemental vitamin A benefits wound healing in nondeficient humans and animals. Vitamin A increases


Surgery_Schwartz

Surgery_Schwartz. doses of vitamin C are of any benefit.84Vitamin A deficiency impairs wound healing, while sup-plemental vitamin A benefits wound healing in nondeficient humans and animals. Vitamin A increases the inflammatory OHP (nmol/mg)1.52.01.00.50.0Adequatefood intakeInadequatefood intake1.51.00.5OHP (µg/cm)0.0WellnourishedMalnourishedFigure 9-8. Effect of malnutrition on collagen deposition in exper-imental human wounds. OHP = hydroxyproline.54321ASPLYSOHPExperimentalControl˜ANFigure 9-9. Ratios of 14-day to 7-day values for aspartate (ASP), lysine (LYS), hydroxyproline (OHP), and α-amino nitrogen (αAN) in volunteers given dietary supplements of arginine, β-hydroxy-β-methylbutyrate, and glutamine. P <.05. (Reproduced with per-mission from Williams JZ, Abumrad NN, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition, Ann Surg. 2002 Sep;236(3):369-374.)Brunicardi_Ch09_p0271-p0304.indd 28501/03/19 4:50 PM 286BASIC CONSIDERATIONSPART Iresponse in wound healing,


Surgery_Schwartz

Surgery_Schwartz. amino acid mixture on human collagen deposition, Ann Surg. 2002 Sep;236(3):369-374.)Brunicardi_Ch09_p0271-p0304.indd 28501/03/19 4:50 PM 286BASIC CONSIDERATIONSPART Iresponse in wound healing, probably by increasing the labil-ity of lysosomal membranes. There is an increased influx of macrophages, with an increase in their activation and increased collagen synthesis. Vitamin A directly increases collagen pro-duction and epidermal growth factor receptors when it is added in vitro to cultured fibroblasts. As mentioned before, supple-mental vitamin A can reverse the inhibitory effects of cortico-steroids on wound healing. Vitamin A also can restore wound healing that has been impaired by diabetes, tumor formation, cyclophosphamide, and radiation. Serious injury or stress leads to increased vitamin A requirements. In the severely injured patient, supplemental doses of vitamin A have been recom-mended. Doses ranging from 25,000 to 100,000 IU per day have been advocated.The connections


Surgery_Schwartz

Surgery_Schwartz. vitamin A requirements. In the severely injured patient, supplemental doses of vitamin A have been recom-mended. Doses ranging from 25,000 to 100,000 IU per day have been advocated.The connections between specific minerals and trace ele-ments and deficits in wound healing are complex. Frequently, deficiencies are multiple and include macronutrient deficien-cies. As with some of the vitamins described earlier, the specific trace element may function as a cofactor or part of an enzyme that is essential for homeostasis and wound healing. Clinically, preventing deficiencies is often easier to accomplish than diag-nosing them.Zinc is the most well-known element in wound heal-ing and has been used empirically in dermatologic conditions for centuries. It is essential for wound healing in animals and humans. There are over 150 known enzymes for which zinc is either an integral part or an essential cofactor, and many of these enzymes are critical to wound healing.85 With zinc deficiency, there


Surgery_Schwartz

Surgery_Schwartz. and humans. There are over 150 known enzymes for which zinc is either an integral part or an essential cofactor, and many of these enzymes are critical to wound healing.85 With zinc deficiency, there is decreased fibroblast proliferation, decreased collagen synthesis, impaired overall wound strength, and delayed epithe-lialization. These defects are reversed by zinc supplementation. To date, no study has shown improved wound healing with zinc supplementation in patients who are not zinc deficient.86Infections. Wound infections continue to represent a major medical problem, both in terms of how they affect the outcome of surgical procedures (surgical site infections), and for their impact on the length of hospital stay and medical costs.87 Many otherwise successful surgical operations fail because of the development of wound infections. The occurrence of infections is of major concern when implants are used, and their occur-rence may lead to the removal of the prosthetic material, thus


Surgery_Schwartz

Surgery_Schwartz. because of the development of wound infections. The occurrence of infections is of major concern when implants are used, and their occur-rence may lead to the removal of the prosthetic material, thus subjecting the patient to further operations and severe risk of morbidity and mortality. Infections can weaken an abdominal closure or hernia repair and result in wound dehiscence or recur-rence of the hernia. Cosmetically, infections can lead to disfig-uring, unsightly, or delayed closures.Exhaustive studies have been undertaken that examine the appropriate prophylactic treatment of operative wounds. Bacte-rial contaminants normally present on skin are prevented from entry into deep tissues by intact epithelium. Surgery breaches the intact epithelium, allowing bacteria access to these tissues and the bloodstream. Antibiotic prophylaxis is most effective when adequate concentrations of antibiotic are present in the tissues at the time of incision, and assurance of adequate pre-operative


Surgery_Schwartz

Surgery_Schwartz. and the bloodstream. Antibiotic prophylaxis is most effective when adequate concentrations of antibiotic are present in the tissues at the time of incision, and assurance of adequate pre-operative antibiotic dosing and timing has become a significant hospital performance measure.88 The addition of antibiotics after operative contamination has occurred clearly is ineffective in preventing postoperative wound infections.Studies that compare operations performed with and without antibiotic prophylaxis demonstrate that classes II, III, and IV procedures (see below) treated with appropriate prophylactic antibiotics have only one third the wound infection rate of previously reported untreated series.89 More recently, repeat dosing of antibiotics has been shown to be essential in decreasing postoperative wound infections in operations with durations exceeding the biochemical half-life (t1/2) of the anti-biotic or in which there is large-volume blood loss and fluid replacement.90,91 In


Surgery_Schwartz

Surgery_Schwartz. postoperative wound infections in operations with durations exceeding the biochemical half-life (t1/2) of the anti-biotic or in which there is large-volume blood loss and fluid replacement.90,91 In lengthy cases, those in which prosthetic implants are used, or when unexpected contamination is encoun-tered, additional doses of antibiotic may be administered for 24 hours postoperatively.Selection of antibiotics for use in prophylaxis should be tailored to the type of surgery to be performed, operative con-taminants that might be encountered during the procedure, and the profile of resistant organisms present at the institution where the surgery is performed. The continuing widespread appear-ance of methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) has significantly restricted the selection of these agents for routine use. Surgery-specific treatment guidelines are provided in Table 9-7.90Patients with prosthetic heart valves or any implanted


Surgery_Schwartz

Surgery_Schwartz. has significantly restricted the selection of these agents for routine use. Surgery-specific treatment guidelines are provided in Table 9-7.90Patients with prosthetic heart valves or any implanted vascular or orthopedic prostheses should receive antibiotic prophylaxis prior to any procedure in which significant bac-teremia is anticipated. Dental procedures require prophylaxis with broad-spectrum penicillins or amoxicillin, while urologic instrumentation should be pretreated with a second-generation cephalosporin. Patients with prostheses who undergo gastroin-testinal surgery should receive anaerobic coverage combined with a cephalosporin. Nasal screening and decolonization for S aureus carriers are recommended for selected procedures (i.e., cardiac, orthopedic, neurosurgical procedures with implants).The incidence of wound infection is about 5% to 10% nationwide and has not changed during the last few decades. Quantitatively, it has been shown that if the wound is contami-nated with


Surgery_Schwartz

Surgery_Schwartz. implants).The incidence of wound infection is about 5% to 10% nationwide and has not changed during the last few decades. Quantitatively, it has been shown that if the wound is contami-nated with >105 microorganisms per gram of tissue, the risk of wound infection is markedly increased, but this threshold may be much lower in the presence of foreign materials. The source of pathogens for the infection is usually the endogenous flora of the patient’s skin, mucous membranes, or from hollow organs. The most common organisms responsible for wound infections in order of frequency are Staphylococcus species, coagulase-negative Streptococcus, enterococci, and Escherichia coli. The incidence of wound infection bears a direct relationship to the degree of contamination that occurs during the operation from the disease process itself (clean—class I, clean contaminated—class II, contaminated—class III, and dirty—class IV). Many factors contribute to the development of postoperative wound


Surgery_Schwartz

Surgery_Schwartz. operation from the disease process itself (clean—class I, clean contaminated—class II, contaminated—class III, and dirty—class IV). Many factors contribute to the development of postoperative wound infections. Most surgical wound infections become apparent within 7 to 10 days postoperatively, although a small number manifest years after the original operative intervention. With the hospital stay becoming shorter and shorter, many infections are detected in the outpatient setting, leading to underreporting of the true incidence of wound infections absent intensive sur-veillance. There has been much debate about the actual defini-tion of wound infection. The narrowest definition would include wounds that drain purulent material with bacteria identified on culture. The broader definition would include all wounds drain-ing pus, whether or not the bacteriologic studies are positive; wounds that are opened by the surgeon; and wounds that the surgeon considers infected.92Anatomically, wound


Surgery_Schwartz

Surgery_Schwartz. include all wounds drain-ing pus, whether or not the bacteriologic studies are positive; wounds that are opened by the surgeon; and wounds that the surgeon considers infected.92Anatomically, wound infections can be classified as superficial incisional, deep incisional, and organ/space wound infections, involving fascia, muscle, or the abdominal cavity. Brunicardi_Ch09_p0271-p0304.indd 28601/03/19 4:50 PM 287WOUND HEALINGCHAPTER 9Table 9-7Antimicrobial prophylaxis for surgeryNATURE OF OPERATIONCOMMON PATHOGENSRECOMMENDED ANTIMICROBIALSADULT DOSAGE BEFORE SURGERY1CardiacStaphylococcus aureus, S. epidermidisCefazolin orCefuroxime orVancomycin41–2 g IV2,31.5 g IV31 g IVGastrointestinalEsophageal/gastroduodenalEnteric gram-negative bacilli, gram-positive cocciHigh risk5 only: cefazolin61–2 g IV2Biliary tractEnteric gram-negative bacilli, enterococci, clostridiaHigh risk7 only: cefazolin6,81–2 g IV2ColorectalEnteric gram-negative bacilli, anaerobes, enterococciOral: neomycin +


Surgery_Schwartz

Surgery_Schwartz. g IV2Biliary tractEnteric gram-negative bacilli, enterococci, clostridiaHigh risk7 only: cefazolin6,81–2 g IV2ColorectalEnteric gram-negative bacilli, anaerobes, enterococciOral: neomycin + erythromycin base9 or metronidazole9Parenteral: cefoxitin6 orCefotetan6 orCefazolin +Metronidazole6 orAmpicillin/sulbactamsee note 91–2 g IV1–2 g IV1–2 g IV20.5 g IV3 g IVAppendectomy, nonperforated11Same as for colorectalCefoxitin6 or cefotetan6 orCefazolin6 +Metronidazole1–2 g IV1–2 g IV20.5 g IVGenitourinaryCystoscopy aloneEnteric gram-negative bacilli, enterococciHigh risk only12: ciprofloxacin10 orTrimethoprim-sulfamethoxazole500 mg PO or 400 mg IV1 DS tabletCystoscopy with manipulation or upper tract instrumentation13Enteric gram-negative bacilli, enterococciCiprofloxacin10 orTrimethoprim-sulfamethoxazole500 mg PO or 400 mg IV1 DS tabletOpen or laparoscopic surgery14Enteric gram-negative bacilli, enterococciCefazolin61–2 g IV2Gynecologic and obstetricVaginal, abdominal, or laparoscopic


Surgery_Schwartz

Surgery_Schwartz. mg PO or 400 mg IV1 DS tabletOpen or laparoscopic surgery14Enteric gram-negative bacilli, enterococciCefazolin61–2 g IV2Gynecologic and obstetricVaginal, abdominal, or laparoscopic hysterectomyEnteric gram-negative bacilli, anaerobes, group B streptococci, enterococciCefazolin6 or cefoxitin6 or cefotetan6 or Ampicillin/sulbactam6,101–2 g IV23 g IVCesarean sectionSame as for hysterectomyCefazolin61–2 g IV2Abortion, surgicalSame as for hysterectomyDoxycycline300 mg PO15Head and neck surgeryIncisions through oral or pharyngeal mucosaAnaerobes, enteric gram-negative bacilli, S. aureusClindamycin orCefazolin +Metronidazole orAmpicillin/sulbactam10600–900 mg IV1–2 g IV20.5 g IV3 g IVNeurosurgeryS. aureus, S. epidermidisCefazolin1–2 g IV2OphthalmicS. epidermidis, S. aureus, streptococci, enteric gram-negative bacilli, Pseudomonas spp.Gentamicin, tobramycin, ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, ofloxacin or neomycin-gramicidin-polymyxin BOR cefazolinMultiple drops


Surgery_Schwartz

Surgery_Schwartz. enteric gram-negative bacilli, Pseudomonas spp.Gentamicin, tobramycin, ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, ofloxacin or neomycin-gramicidin-polymyxin BOR cefazolinMultiple drops topically over 2 to 24 hours100 mg subconjuctivallyOrthopedicS. aureus, S. epidermidisCefazolin16 or Vancomycin2,161–2 g IV2, 1 g IVThoracic (noncardiac)S. aureus, S. epidermidis, streptococci, enteric gram-negative bacilliCefazolin orAmpicillin/sulbactam10 or Vancomycin41–2 g IV23 g IV1 g IV(Continued)Brunicardi_Ch09_p0271-p0304.indd 28701/03/19 4:50 PM 288BASIC CONSIDERATIONSPART IAbout three-fourths of all wound infections are superficial, involving skin and subcutaneous tissue only. Clinical diagnosis is easy when a postoperative wound looks edematous and ery-thematous and is tender. Often the presentation is more subtle, and the development of postoperative fever, usually low-grade; the development of a mild and unexplained leukocytosis; or the presence of undue incisional pain


Surgery_Schwartz

Surgery_Schwartz. Often the presentation is more subtle, and the development of postoperative fever, usually low-grade; the development of a mild and unexplained leukocytosis; or the presence of undue incisional pain should direct attention to the wound. Inspection of the wound is most useful in detecting sub-tle edema around the suture or staple line, manifested as a waxy appearance of the skin, which characterizes the early phase of infection. If a wound infection is suspected, several stitches or staples around the most suspicious area should be removed with insertion of a cotton-tipped applicator into the subcutane-ous area to open a small segment of the incision. This causes minimal if any discomfort to the patient. Presence of pus man-dates further opening of the subcutaneous and skin layers to the full extent of the infected pocket. Samples should be taken for aerobic and anaerobic cultures, with very few patients requir-ing antibiotic therapy. Patients who are immunosuppressed (diabetics and


Surgery_Schwartz

Surgery_Schwartz. full extent of the infected pocket. Samples should be taken for aerobic and anaerobic cultures, with very few patients requir-ing antibiotic therapy. Patients who are immunosuppressed (diabetics and those on steroids or chemotherapeutic agents), who have evidence of tissue penetration or systemic toxicity, or who have had prosthetic devices inserted (vascular grafts, heart valves, artificial joints, or mesh) should be treated with systemic antibiotics.92Deep wound infections arise immediately adjacent to the fascia, either above or below it, and often have an intra-abdominal component. Most intra-abdominal infections do not, however, communicate with the wound. Deep infections present with fever and leukocytosis. The incision may drain pus spon-taneously, or the intra-abdominal extension may be recognized following the drainage of what was thought to be a superficial wound infection, but pus draining between the fascial sutures will be noted. Sometimes wound dehiscence will occur.The


Surgery_Schwartz

Surgery_Schwartz. may be recognized following the drainage of what was thought to be a superficial wound infection, but pus draining between the fascial sutures will be noted. Sometimes wound dehiscence will occur.The most dangerous of the deep infections is necrotizing fasciitis. It results in high mortality, particularly in the elderly. This is an invasive process that involves the fascia and leads to secondary skin necrosis. Pathophysiologically, it is a septic thrombosis of the vessels between the skin and the deep layers. Table 9-7Antimicrobial prophylaxis for surgeryNATURE OF OPERATIONCOMMON PATHOGENSRECOMMENDED ANTIMICROBIALSADULT DOSAGE BEFORE SURGERY1VascularArterial surgery involving a prosthesis, the abdominal aorta, or a groin incisionS. aureus, S. epidermidis, enteric gram-negative bacilliCefazolin orVancomycin41–2 g IV21 g IVLower extremity amputation for ischemiaS. aureus, S. epidermidis, enteric gram-negative bacilli, clostridiaCefazolin or Vancomycin41–2 g IV21 g IV1Parenteral


Surgery_Schwartz

Surgery_Schwartz. orVancomycin41–2 g IV21 g IVLower extremity amputation for ischemiaS. aureus, S. epidermidis, enteric gram-negative bacilli, clostridiaCefazolin or Vancomycin41–2 g IV21 g IV1Parenteral prophylactic antimicrobials can be given as a single IV dose begun within 60 min before the operation. For prolonged operations (>3 h) or those with major blood loss, or in patients with extensive burns, additional intraoperative doses should be given at intervals 1–2 times the half-life of the drug (ampicillin/sulbactam q2 h, cefazolin q4 h, cefuroxime q4 h, cefoxitin q2 h, clindamycin q6 h, vancomycin q12 h) for the duration of the procedure in a patient with normal renal function. If vancomycin or a fluoroquinolone is used, the infusion should be started 60–120 min before the initial incision to minimize the possibility of an infusion reaction close to the time of induction of anesthesia and to have adequate tissue levels at the time of incision.2The recommended dose of cefazolin is 1 g for patients


Surgery_Schwartz

Surgery_Schwartz. the possibility of an infusion reaction close to the time of induction of anesthesia and to have adequate tissue levels at the time of incision.2The recommended dose of cefazolin is 1 g for patients who weigh 80 kg and 2 g for those >80 kg. Morbidly obese patients may need higher doses.3Some experts recommend an additional dose when patients are removed from bypass during open heart surgery.4Vancomycin can be used in hospitals in which methicillin-resistant Staphylococcus aureus (MRSA) and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillin or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 min, hypotension may occur; treatment with diphenhydramine (Benadryl and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of


Surgery_Schwartz

Surgery_Schwartz. the drug is given over 60 min, hypotension may occur; treatment with diphenhydramine (Benadryl and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of vancomycin to patients weighing more than 75 kg up to a maximum of 1.5 g with a slower infusion rate (90 min for 1.5 g). For procedures in which gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside (gentamicin, tobramycin, or amikacin), aztreonam, or a fluoroquinolone.5Morbid obesity, GI obstruction, decreased gastric acidity or gastrointestinal motility, gastric bleeding, malignancy or perforation, or immunosuppression.6For patients allergic to penicillin and cephalosporins, clindamycin or vancomycin with either gentamicin, ciprofloxacin, levofloxacin, or aztreonam is a reasonable alternative. Fluoroquinolones should not be used for prophylaxis in cesarean section.7Age >70 y, acute cholecystitis, nonfunctioning gallbladder, obstructive


Surgery_Schwartz

Surgery_Schwartz. or aztreonam is a reasonable alternative. Fluoroquinolones should not be used for prophylaxis in cesarean section.7Age >70 y, acute cholecystitis, nonfunctioning gallbladder, obstructive jaundice, or common duct stones.8Cefotetan, cefoxitin, and ampicillin/sulbactam are reasonable alternatives.9In addition to mechanical bowel preparation, 1 g of neomycin plus 1 g of erythromycin at 1 p.m., 2 p.m., and 11 p.m. or 2 g of neomycin plus 2 g of metronidazole at 7 p.m. and 11 p.m. the day before an 8 a.m. operation.10Due to increasing resistance of E. coli to fluoroquinolones and ampicillin/sulbactam, local sensitivity profiles should be reviewed prior to use.11For a ruptured viscous, therapy is often continued for about 5 d.12Urine culture positive or unavailable, preoperative catheter, transrectal prostate biopsy, or placement of prosthetic material.13Shock wave lithotripsy, ureteroscopy.14Including percutaneous renal surgery, procedures with entry into the urinary tract, and those


Surgery_Schwartz

Surgery_Schwartz. transrectal prostate biopsy, or placement of prosthetic material.13Shock wave lithotripsy, ureteroscopy.14Including percutaneous renal surgery, procedures with entry into the urinary tract, and those involving implantation of a prosthesis. If manipulation of bowel is involved, prophylaxis is given according to colorectal guidelines.15Divided into 100 mg before procedure and 200 mg after.16If a tourniquet is to be used in the procedure, the entire dose of antibiotic must be infused prior to its inflation.Reprinted with special permission from Treatment Guidelines from The Medical Letter, October 2012; Vol. 10(122):73. www.medicalletter.org.(Continued)Brunicardi_Ch09_p0271-p0304.indd 28801/03/19 4:50 PM 289WOUND HEALINGCHAPTER 9The skin demonstrates hemorrhagic bullae and subsequent frank necrosis, with surrounding areas of inflammation and edema. The fascial necrosis is usually wider than the skin involvement or than the surgeon estimates on clinical grounds. The patient is toxic


Surgery_Schwartz

Surgery_Schwartz. necrosis, with surrounding areas of inflammation and edema. The fascial necrosis is usually wider than the skin involvement or than the surgeon estimates on clinical grounds. The patient is toxic and has high fever, tachycardia, and marked hypovo-lemia, which if uncorrected, progresses to cardiovascular col-lapse. Bacteriologically, this is a mixed infection, and samples should be obtained for Gram stain smears and cultures to aid in diagnosis and treatment. As soon as bacteriologic studies have been obtained, high-dose penicillin treatment needs to be started (20–40 million U/d intravenously) due to concern over the presence of Clostridia perfringens and other related species; broad-spectrum antibiotics should be added and the regimen modified based on culture results. Cardiovascular resuscitation with electrolyte solutions, blood, and/or plasma is carried out as expeditiously as possible prior to induction of anesthesia. The aim of surgical treatment is thorough removal of all


Surgery_Schwartz

Surgery_Schwartz. resuscitation with electrolyte solutions, blood, and/or plasma is carried out as expeditiously as possible prior to induction of anesthesia. The aim of surgical treatment is thorough removal of all necrosed skin and fascia. If viable skin overlies necrotic fascia, multiple longitudinal skin incisions can be made to allow for excision of the devitalized fascia. Although removal of all necrotic tissue is the goal of the first surgical intervention, the distinction between necrotic and simply edematous tissue often is difficult. Careful inspection every 12 to 24 hours will reveal any new necrotic areas, and these need further debridement and excision. When all necrotic tissue has been removed and the infection has been controlled, the wounds may be covered with homoor xeno-grafts until definitive reconstruction and autografting can take place.The mere presence of bacteria in an open wound, either acute or chronic, does not constitute an infection, because large numbers of bacteria can


Surgery_Schwartz

Surgery_Schwartz. reconstruction and autografting can take place.The mere presence of bacteria in an open wound, either acute or chronic, does not constitute an infection, because large numbers of bacteria can be present in the normal situation. In addition, the bacteria identified by cultures may not be repre-sentative of the bacteria causing the actual wound infection. There seems to be confusion as to what exactly constitutes wound infection. For purposes of clarity, we have to differ-entiate between contamination, colonization, and infection. Contamination is the presence of bacteria without multiplica-tion, colonization is multiplication without host response, and infection is the presence of host response in reaction to depo-sition and multiplication of bacteria. The presence of a host response helps to differentiate between infection and coloniza-tion as seen in chronic wounds. The host response that helps in diagnosing wound infection comprises cellulitis, abnormal discharge, delayed healing,


Surgery_Schwartz

Surgery_Schwartz. to differentiate between infection and coloniza-tion as seen in chronic wounds. The host response that helps in diagnosing wound infection comprises cellulitis, abnormal discharge, delayed healing, change in pain, abnormal granula-tion tissue, bridging, and abnormal color and odor.As discussed previously, neutrophils play a major role in preventing wound infections. Chronic granulomatous disease (CGD) comprises a genetically heterogeneous group of dis-eases in which the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxide enzyme is deficient. This defect impairs the intracellular killing of microorganisms, leav-ing the patient liable to infection by bacteria and fungi. Afflicted patients have recurrent infections and form granulomas, which can lead to obstruction of the gastric antrum and genitourinary tracts and poor wound healing. Surgeons become involved when the patient develops infectious or obstructive complications.The nitro blue tetrazolium (NBT)


Surgery_Schwartz

Surgery_Schwartz. of the gastric antrum and genitourinary tracts and poor wound healing. Surgeons become involved when the patient develops infectious or obstructive complications.The nitro blue tetrazolium (NBT) reduction test is used to diagnose CGD. Normal neutrophils can reduce this com-pound, while neutrophils from affected patients do not, facili-tating the diagnosis via a colorimetric test. Clinically, patients develop recurrent infections such as pneumonia, lymphadenitis, hepatic abscess, and osteomyelitis. Organisms most commonly responsible are S. aureus, Aspergillus, Klebsiella, Serratia, or Candida. When CGD patients require surgery, a preoperative pulmonary function test should be considered since they are predisposed to obstructive and restrictive lung disease. Wound complications, mainly infection, are common. Sutures should be removed as late as possible since the wounds heal slowly. Abscess drains should be left in place for a prolonged period until the infection is completely


Surgery_Schwartz

Surgery_Schwartz. infection, are common. Sutures should be removed as late as possible since the wounds heal slowly. Abscess drains should be left in place for a prolonged period until the infection is completely resolved.93Hyperglycemia has been shown to be a significant risk factor of postoperative infections.94 Tight blood glucose con-trol, beginning preoperatively and continued into the operating room and beyond, has been associated with significant reduc-tion in infectious complications, in particular following cardiac surgery.95,96 Too tight of a glycemic control (80–100 mg/dL) appears to be associated with more complications and is as effec-tive, if not less than, moderate control (120–180 mg/dL).97,98Another host factor that has been implicated in the devel-opment of superficial surgical site infection relates to the state of the subcutaneous capillary bed. Thomas K. Hunt had shown through several decades of work that this capillary bed is exqui-sitely sensitive to hypovolemia,99


Surgery_Schwartz

Surgery_Schwartz. site infection relates to the state of the subcutaneous capillary bed. Thomas K. Hunt had shown through several decades of work that this capillary bed is exqui-sitely sensitive to hypovolemia,99 hypothermia,100 and stress, leading to rapid vasoconstriction with secondary impaired oxy-gen delivery and increased rates of infection.61 Maintenance of euvolemia, core temperature above 36°C to 36.5°C, and pain control have all been shown singly and additively to reduce rates of wound infections.63 Another suggestion has been to increase inspired Fio2 to 0.8 for the duration of the operation and in the immediate postoperative period, as a means of increasing sub-cutaneous tissue oxygen delivery. Although successful in most studies,62,101 there have also been negative results from such a single approach102; this suggests that addressing volume, tem-perature, pain control, and oxygen delivery in concert may be the more fruitful approach to reduce surgical wound infections.Chronic


Surgery_Schwartz

Surgery_Schwartz. a single approach102; this suggests that addressing volume, tem-perature, pain control, and oxygen delivery in concert may be the more fruitful approach to reduce surgical wound infections.Chronic WoundsChronic wounds are defined as wounds that have failed to pro-ceed through the orderly process that produces satisfactory ana-tomic and functional integrity or that have proceeded through the repair process without producing an adequate anatomic and functional result. The majority of wounds that have not healed in 3 months are considered chronic, although a duration as low as 4 weeks has been used to indicate chronicity. Skin ulcers, which usually occur in traumatized or vascular compromised soft tis-sue, are also considered chronic in nature, and proportionately are the major component of chronic wounds. In addition to the factors discussed earlier that can delay wound healing, other causative mechanisms may also play a role in the etiology of chronic wounds. Repeated trauma, poor


Surgery_Schwartz

Surgery_Schwartz. of chronic wounds. In addition to the factors discussed earlier that can delay wound healing, other causative mechanisms may also play a role in the etiology of chronic wounds. Repeated trauma, poor perfusion or oxygen-ation, and/or excessive inflammation contribute to the causation and the perpetuation of the chronicity of wounds.Unresponsiveness to normal regulatory signals also has been implicated as a predictive factor of chronic wounds. This may come about as a failure of normal growth factor synthesis,103 and thus an increased breakdown of growth factors within a wound environment that is markedly proteolytic because of overexpression of protease activity or a failure of the normal antiprotease inhibitor mechanisms.104 Fibroblasts from chronic wounds also have been found to have decreased proliferative potential, perhaps because of senescence105 or decreased expres-sion of growth factor receptors.106 Chronic wounds occur due to various etiologic factors, and several of the most


Surgery_Schwartz

Surgery_Schwartz. proliferative potential, perhaps because of senescence105 or decreased expres-sion of growth factor receptors.106 Chronic wounds occur due to various etiologic factors, and several of the most common are discussed later.Brunicardi_Ch09_p0271-p0304.indd 28901/03/19 4:50 PM 290BASIC CONSIDERATIONSPART IMalignant transformation of chronic ulcers can occur in any long-standing wound (Marjolin’s ulcer). Any wound that does not heal for a prolonged period of time is prone to malig-nant transformation. Malignant wounds are differentiated clini-cally from nonmalignant wounds by the presence of overturned wound edges (Fig. 9-10). In patients with suspected malignant transformations, biopsy of the wound edges must be performed to rule out malignancy. Cancers arising de novo in chronic wounds include both squamous and basal cell carcinomas.Ischemic Arterial Ulcers. These wounds occur due to a lack of blood supply and are typically extremely painful in patients with pure ischemic ulcers. They