Medical Therapy
The latest research on wound care has resulted in increased use of interactive and active dressings rather than passive dressings that cover and absorb. Interactive hydrocolloid dressings provide a controlled microenvironment for wound healing. Active dressings deliver substances such as growth factors, which are important in the healing cascade.
Interactive dressings are typically occlusive dressings. They provide important moisture and supply a favorable microenvironment for the growth of new tissue. The advantages of moist occlusive dressings are numerous. Exudate is controlled, while epithelial cell migration is encouraged. Eschar is liquefied and fibrin is lysed to allow convenient debridement. Infection is managed through wound fluid rich in leukocytes. These dressings are also believed to provide symptomatic relief, such as decreased pain and pruritus.
Dressings that deliver substances active in the healing process, such as growth factors, have been the subject of much recent investigation. While normal wounds heal because of epidermal division and migration within a neovascularized mesh of granulation tissue, resulting in a cover of new skin, chronic wounds typically show inadequate repair due to insufficient perfusion or wound infection.
Wounds caused by venous hypertension are commonly treated with multilayer compression dressings that assist the return of pooled blood to the central circulation. These dressings have shown good results, with 73% of wounds healing with no other intervention needed. [3]
A randomized, controlled study by Ashby et al suggested that two-layer compression hosiery is as effective as four-layer bandages in the treatment of venous leg ulcers and may reduce the incidence of ulcer recurrence. The study involved 457 adult patients with venous leg ulcers, all of whom were able to tolerate high compression. The investigators found that the time required for ulcers to heal was the same for both compression modalities. However, it took less time for ulcers to recur in the bandage group than in the group treated with compression hosiery. [14]
A study by Alvarez et al indicated that healing of a persistent venous leg ulcer can be expedited with intermittent pneumatic compression. Patients in the report had chronic venous insufficiency and a lower leg ulceration that was over 1 year old and over 20 cm2 in size. In measuring median time to wound closure by 9 months, the investigators found that in persons treated with a wound dressing and compression bandage along with intermittent pneumatic compression, healing occurred in 141 days. This was in comparison to 211 days for patients whose treatment did not include pneumatic compression. [15]
Topically applied growth factors are meant to assist the chronic wound with establishing healthy granulation tissue or epidermal cell function for improved healing. Several growth factors have been studied to this end. Platelet-derived growth factor has been shown to reduce the size of chronic ulcers by up to 70%, as compared to 17% for placebo, probably via acceleration of provisional wound matrix deposition. Epidermal growth factor supplementation was associated with healing of 8 of 9 wounds in which therapy had previously failed. Fibroblast growth factor has also been studied, but positive results have not yet been achieved.
In contrast to the above observations, a literature review by de Carvalho et al found that although positive healing outcomes were seen after growth factors (from platelet-rich plasma or in the form of epidermal growth factor) were employed against venous ulcers, the results tended to be of little statistical significance. [16]
Chronic wounds may be associated with active infection, such as cellulitis. Additionally, an occasional chronic wound may be the nidus for bacteremia and sepsis. In these cases, administer systemic antibiotics. Alternatively, the wound itself may be infected, without systemic effects. Take steps to lower the bacterial count of these wounds, including topical methods to encourage wound healing.
Edlich et al have shown that dressing changes alone usually lower the bacterial load, regardless of the type. [17] Silver sulfadiazine has been shown to almost universally reduce the bacterial load to levels acceptable for wound closure. It is a broad-spectrum antibiotic and does not cause pain, as has been noted with mafenide acetate (Sulfamylon). However, penetration of eschar is questionable with this antibiotic. Saline-dampened gauze dressing changes also reduce the bacterial load in the large majority of wounds, but not as effectively as silver sulfadiazine. Povidone-iodine solution (Betadine) has also been used as a topical antibiotic and is largely successful at reducing bacterial counts. However, a widely held belief is that this solution also kills granulation tissue, which significantly impairs healing of these wounds.
New investigations have focused on nonsurgical methods of improving the microcirculation of the healing wound. The use of low-intensity ultrasonic stimulation of venous ulcers has shown a significant improvement in the rate of wound healing from 29% in a control group to 63% in the experimental group. This increased rate of healing is thought to be mediated by stimulation of signal-transduction pathways directly involved in angiogenesis, leukocyte adhesion, and growth factor production. [18]
The results of a Cochrane Database of Systematic Reviews study found that intermittent pneumatic compression (IPC) may increase healing compared with no compression in the treatment of venous leg ulcers and limb swelling due to lymphedema. Further trials are needed to determine whether IPC increases healing when used in conjunction with bandage treatment or if it can be used as an alternative to compression bandages. [19]
Even though hyperbaric oxygen therapy is considered an important adjunct in wound healing, it is always important to revisit the evidence in the literature. The authors of a recent Cochrane summary reviewed relevant trials and concluded that in people with foot ulcers due to diabetes, hyperbaric oxygen therapy significantly improves ulcer healing in the short term but not in the long term. More studies are needed to properly evaluate hyperbaric oxygen therapy in patients with chronic wounds. [20]
Investigations have highlighted the possibility of using injected low molecular weight heparin to speed healing in neurotrophic ulcers in the setting of occlusive peripheral artery disease. The rationale for this therapy is to improve the microcirculation of the healing wound by thinning the blood and increasing the flow of capillary flow of blood to the injured tissues. Data published by Kalani et al show 67% wound healing in patients treated with dalteparin compared to 47% healing in individuals treated with placebo. [21] This medication also showed benefit in a lower rate of amputation, from 19% amputation rate in the placebo group to 5% rate of amputation in the dalteparin group. [21] Oral therapies under investigation reportedly decrease the symptoms of chronic venous insufficiency but remain experimental at this time. [22]
Surgical Therapy
When considering surgical therapy for chronic vascular ulcers, consider which is more appropriate for the patient: (1) revascularization and/or coverage of the wound, (2) ligation of incompetent venous perforators, or (3) primary amputation and rehabilitation. The plastic surgeon has several options when choosing operative coverage of an ulcer.
As always, basic surgical principles should be followed. All chronic wounds need to be debrided to convert them into an acute wound to allow for the normal wound healing cycle to resume. In addition, a formal debridement removes the biofilm that has been built up during the chronic phase. The colonized bacteria are removed and cytoprotective cytokines are secreted to start the inflammatory phase of wound healing.
When the ulcer is caused by venous reflux in the superficial venous system, the problem can be addressed with minimally invasive procedures commonly practiced by vascular surgeons. These surgeries include saphenofemoral junction disconnection, stripping of the long saphenous vein to below the knee, calf varicosity avulsions, and saphenopopliteal junction disconnection. The rate of wound healing for those treated with surgery is not significantly higher than that of patients who are treated conservatively, but the resultant diminished rate of wound recurrence is a benefit. [3]
A literature review by Goldschmidt et al indicated that nonhealing venous ulcers can successfully be treated with ongoing compression therapy combined with ablative treatment of incompetent perforating veins and superficial venous reflux. With the elimination of superficial reflux, persistent ulcers ranged in frequency from 2.3% at 2 years post intervention to 21.1% at 1-year follow-up. [23]
Ligation of superficial venous perforators has been shown to reduce the 4-year recurrence rate of vascular ulcers, from 56% in ulcers treated by compression alone to 31% in ulcers treated by compression plus surgery (P< .01). [4] This is a tremendous leap forward, as the natural history of these wounds is one of frequent recurrence. In the case of ulcers not caused by venous hypertension, other approaches must be considered.
A literature review by de Carvalho, however, found that three of the four studies used in the review reported healing rates for venous leg ulcers treated with compression therapy alone to be the same as those for ulcers managed with a combination of compression and surgery. Moreover, although most of the studies found a lower rate of recurrence for venous ulcers treated with the compression/surgery combination versus with compression alone, the difference was not statistically significant. [24]
Revision of the wound followed by split-thickness skin graft (STSG) has long been an option for chronic wound management. Once a clean, granulating wound bed has been established through debridement, placement of a skin graft is usually all that is required to attain closure. Skin grafting can be effective for coverage of venous ulcers, but attention must be paid to extremity elevation during healing. Ischemic wounds located in areas that are difficult to treat also may be closed with skin grafting; studies have reported closure rates of 40% for diabetic foot wounds.
Often, the wound bed is not suitable for grafting or a structure such as a bone or tendon is exposed. Under these circumstances, consider pedicled or free flaps. These flaps are desirable for several reasons. Healing is promoted even in a suboptimal bed. All diseased tissue, including bone, may be debrided or excised. Neovascularization of the ischemic bed from the flap may occur, and vascular graft patency may be improved by the vascular runoff provided by free tissue transfer.
Microvascular flap coverage of chronic ulcers has met with much success in the treatment of arterial ulcers. Colen performed 10 such transfers in patients with peripheral vascular disease; 7 of these patients had revascularization prior to the procedure. [25] All anastomoses were successful, although 1 patient underwent amputation after sepsis and its cardiovascular sequelae. Ciresi and coworkers reported successful salvage of limb length and function in 5 of 7 patients who underwent free tissue transfer for ischemic ulcers. [26]
Recently, plastic surgeons have begun treating venous ulcers with free tissue transfer, with mixed results. Steffe and Caffee report a 43% complication rate after tissue transfer to venous wounds and the development of new ulcers in all patients at approximately 17 months. [27] Alternatively, Kumins et al [28] and Weinzweig and Schuler [29] reported good success using free muscle flaps and skin grafting to cover venous ulcers. In the first study, all ulcers were healed, and the second study reports a 90% success rate. Both studies were notable for a low recurrence of ulceration and an acceptable complication rate.
The use of negative pressure wound therapy has also been used in these wounds. This can help twofold. First, the wound can be temporized while waiting for additional studies to determine the etiology of disease or while optimizing the patient (ie, optimizing intrinsic, extrinsic, and iatrogenic factors); second, this therapy can serve as destination therapy or a bridging therapy to surgery. In addition, if a wound is skin grafted, negative pressure wound therapy (VAC therapy, KCI) should be used for improved take of the graft. [30]
Preoperative Details
Familiarity with the perfusion and vascular supply to the lower extremity is critical to the surgeon for operative planning. Studies estimating perfusion can help predict healing of the wound or flap. Specific knowledge of the arterial supply is invaluable when performing either pedicled or free tissue transfer. Angiography yields detailed visualization of the vessels. Colen and Musson advocate using duplex imaging to select both the recipient vessel and the region of the vessel most suitable for vascular anastomosis. [31]
Intraoperative Details
Normally, vascular ulcers are treated conservatively with nonoperative techniques. When treated surgically, STSG to the affected areas is the usual procedure.
Applying a skin graft to a vascular ulcer requires the same techniques as grafting to other wounds or burns. Varying degrees of ulcer debridement may be required prior to grafting.
Harvest a graft from an area of healthy tissue; it may be left in its contracted state or meshed for greater surface-area coverage. Then, apply the graft to the clean, granulating ulcer. It may be secured in place using sutures or skin staples. Grafts also adhere without suturing or stapling if protected well from disruptive forces.
Pedicled and free flaps also may be used for coverage of a vascular ulcer. A wide array of choices may be used, based on the location of the ulcer and the status of the vessels perfusing the various pedicled flaps. The patency of the vessel providing inflow for a free flap is also a consideration. The details for performing flap coverage of a chronic ulcer are best studied in a text dedicated to tissue flaps (eg, Flaps, Random Skin Flaps).
Complications
The greatest risk of complications in surgical coverage of vascular ulcers lies with tissue transfer. An obvious source of postoperative concern with regard to successful free tissue transfer is the vascular supply to the flap. The rate of vascular complications in flaps transferred to vascularly compromised tissue is not known, but Rieck et al report a 16% rate of vascular complications out of 631 cases of free tissue transfers. [32] Yajima et al experienced 39 complications in 250 similar cases. [33]
The complication rate in patients with ischemic ulcers is expected to be higher than these rates because of the patients' primary diseases. Indeed, Lepantalo and Tukiainen observed vascular patency rates of 68% in their study. [34] Ciresi et al report minor wound complications in 4 of 7 patients studied. [26]
Complication rates among cases of tissue transfer for venous ulceration are less well defined. Weinzweig and Schuler report a loss of 2 of 20 flaps, both due to vasospasm, although one occurred in a patient with a history of cocaine abuse. [29] They also noted 3 cases of infection with partial flap and/or graft loss and 2 cases of partial graft loss. Steffe and Caffee experienced a loss of 2 of 14 flaps, caused by venous thrombosis. [27] Two patients had partial flap necrosis in their study, while another 2 had partial graft loss.
Outcome and Prognosis
A study by Furuyama et al indicated that in patients with critical limb ischemia who undergo arterial revascularization, a white blood cell count of over 10,000, the presence of a major defect following débridement, and endovascular therapy hamper the ability of ulcers to heal within 90 days post-revascularization. The report also found that ulcer healing was significantly hindered in study patients who did not undergo treatment with the platelet inhibitor/vasodilator cilostazol. In addition, the investigators determined that the presence of ischemic heart disease, albumin levels below 3 g/dL, lack of cilostazol use, and the presence of a major defect following débridement reduce the likelihood of amputation-free survival. [35]
Care of chronic ulcers can be accomplished by an array of medical and surgical modalities. Regardless of the method of choice, the primary goal of treating vascular ulcers is preservation of limb length and function. The etiology of the patient's disease and the choice of treatment both play an important role in reaching a successful outcome. The patient's goals and expectations should be taken into account, and the approach should be multidisciplinary in nature.
Finally, practitioners must understand that without adequate perfusion to the extremity, healing stalls at a chronic inflammatory phase. For wound healing to advance to the next phase of the cycle, adequate perfusion to the wound should be present, which is essential in delivering the appropriate proliferative and remodeling cells and cytokines necessary for healing. In addition, nutrition and oxygen are delivered for pertinent biochemical reactions to take place locally. The wound healing market is saturated with many "potions," but the clinician must rely on his or her own discretion to understand the underlying pathophysiology and recommend optimal care.
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Vascular ulcers. Arterial ulcer with characteristic features.
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Vascular ulcers. Venous ulcer with characteristic features.