Diabetic Wounds of the Lower Extremity
Diabetic foot wounds represent a problem of significant and increasing importance within our society and health care system. The incidence of new cases of diabetes tripled between 1990 and 201016 and the prevalence of diagnosed cases of diabetes in American adults and children is estimated to be 25.8 million as of 2011.17 More than 60% of nontraumatic lower extremity amputations occur in people with diabetes, and in 2006 approximately 65,700 individuals with diabetes underwent such amputations. In addition, it has been reported that 10% to 15% of diabetics will have at least one foot ulcer at some point in their lives, so the stage is set for an epidemic of diabetic foot ulcers in our communities (FIGURE 18-21).16
Annual number of U.S. adults aged 18–79 years with diagnosed diabetes, 1980–2000
The prevalence of diabetes has increased dramatically over the last 3 decades, making it a major problem for the health care system. HBO2 has been shown to significantly decrease the number of amputations in patients with diabetes and improve healing rates.
Over the years, a number of clinical trials have been done in an effort to define the role of HBO2 in the treatment of diabetic foot ulceration. A 2004 Cochrane Review18 of randomized controlled clinical trials of HBO2 treatment in chronic wounds concluded that “in people with foot ulcers due to diabetes, HBO treatment significantly reduced the risk of major amputation and may improve the chance of healing at 1 year. The application of HBO treatment to these patients may be justified where HBO facilities are available; however economic evaluations should be undertaken.” In 2007, Fife et al conducted a retrospective, multicenter case series of 1144 patients and reported positive outcomes in 75.6% of subjects, all of whom had pretreatment hypoxic transcutaneous oximetry values.19 In 1996, Faglia et al studied 70 hospitalized patients with severe, ischemic, infected diabetic foot ulcers.31 All patients underwent initial evaluation, radical surgical debridement, culture-directed antibiotic therapy, vascular evaluation, and revascularization if indicated. The subjects were then randomized with 35 in the hyperbaric arm and 33 in the control arm (no HBO2). After a number of weeks, all were evaluated for major amputation by a surgeon unaware of their treatment status. There were fewer amputation, 3 out of 35, in the HBO2 group than in the control group (11 out of 33); this difference was statistically significant (p = 0.016). Kalani et al, in their 2002 Swedish study, reported increased healing and decreased overall amputation rate with HBO2 in their 12-week study.32 The next year, Abidia et al in the United Kingdom also reported improved healing with the use of HBO2. Unfortunately, statistical analyses were not performed on either of these two studies.
On April 1, 2003, the Centers for Medicare and Medicaid Services (CMS) made effective its decision to cover treatment of diabetic wounds of the lower extremities with hyperbaric oxygen in patients meeting the following criteria:
The patient has type I or II diabetes and has a lower-extremity wound due to diabetes.
The patient has a wound classified as Wagner grade III or higher.
The patient has failed an adequate course of standard wound therapy, defined as 30 days of standard treatment that includes the following components: assessment and correction of vascular abnormalities, optimization of nutritional status and glycemic control, debridement, moist wound dressing, offloading, and treatment of infection.
In order for HBO2 to continue, reevaluation at 30-day intervals must show continued progress toward healing. FIGURES 18-22 and 18-23 illustrate a diabetic foot ulcer at initial presentation and 8 weeks later following surgical debridement, appropriate wound care, offloading, and hyperbaric oxygen therapy.
Presentation of a diabetic foot wound prior to initiation of standard care plus HBO2 therapy.
Presentation of the same wound after 8 weeks of standard care plus HBO2 therapy. The wound is in the remodeling phase of healing.
Arterial Insufficiency Ulcers
The primary objective in the treatment of a wound due to arterial insufficiency is restoration of adequate arterial flow. If revascularization for an ischemic wound has failed, or is not possible for any combination of reasons, HBO2 may be beneficial as correction of tissue hypoxia with HBO2 leads to fibroblast proliferation, collagen synthesis, angiogenesis, and the production of granulation tissue.
When arterial insufficiency is the suspected etiology of a lower-extremity wound, transcutaneous oxygen measurement (TcPO2) should be performed to assess oxygen delivery to the periwound tissues. If the baseline TcPO2 levels are abnormal, or if their history and/or clinical presentations suggest critical limb ischemia, the patient should be referred immediately for invasive arterial testing such as angiography or MRA. If revascularization is successful and tissue hypoxia is reversed, wound healing may then be expected to occur with quality moist wound care. If revascularization is unsuccessful or not possible due to medical concerns, HBO2 may be beneficial in this critical limb-salvage situation. Before committing the patient to a full course of HBO2 in this scenario, in-chamber TcPO2 should be performed and a minimum value of 200 mm at treatment depth observed in order for efficacy to be expected. FIGURE 18-24 illustrates an arterial insufficiency ulceration on the lateral lower leg with exposed tendon. (Refer to Chapter 4, Vascular Wounds, for more details on treating ischemic wounds.)
An arterial wound with exposed tendon. The TcPO2 at exposed depth is used as a criteria to determine if arterial wounds will benefit from HBO2 therapy; a minimum value of 200 mmHg is the predictor of efficacy.
Delayed Radiation Injury—Soft Tissue and Bony Necrosis
Soft-tissue radionecrosis and osteoradionecrosis typically develop months to years following exposure to external-beam radiation therapy. This type of radiation therapy has been part of various cancer treatment protocols for a number of years and continues its prominent role in cancer treatment. In spite of numerous technological advances in the formulas and delivery of radiation therapy, the incidence of radiation injury is not declining.
Both soft-tissue and bony radionecrosis develop as a result of radiation therapy. During radiation treatment, a beam of radiation is directed at the site of malignancy. It is impossible, however, for the beam to strike only the cancerous target without affecting the surrounding tissue. With subsequent exposures the radiation slowly obliterates the end arteries supplying the surrounding tissues leaving hypoxic, fibrotic tissue as a result. This tissue has been referred to as “triple H” tissue: denotes hypoxic, hypovascular, and hypocellular (FIGURE 18-25).
Irradiated tissue has been described as Triple H because of the effects of the radiation. The loss of vascularity and oxygenation make the tissue vulnerable to both acute and chronic wounds that have been shown to respond to HBO2 therapy.
With osteoradionecrosis, the causative radiation is usually radiation therapy for cancers of the head and neck region. The zone of the radiation beam extends outward from the target beam and commonly affects the lower jaw (mandible). The affected bone becomes hypoxic, hypovascular, and hypocellular. The affected portion of the mandible may not become problematic for a number of years until a dental problem or oral surgery disrupts the bone, at which point healing of the bone will fail and the mandible may disintegrate. In more severe cases, the mandible may actually disintegrate spontaneously and the patient may present for dental care with exposed and fragmented bone.37 Marx and his colleagues at the University of Miami have studied this extensively and authored the treatment paradigms known as the Marx Protocols, which remain in use at this time.25,27,28,30
In the case of soft-tissue radionecrosis, the mechanism of injury remains the same but the target tissues are typically different. External beam radiotherapy is commonly used on pelvic malignancies such as uterine and ovarian cancer in women and prostate cancer in men. It is also commonly employed in breast cancer treatment both before and after surgical intervention, depending on type and size of the breast cancer. When a pelvic cancer is irradiated, the soft tissues typically affected are bowel and bladder, leading to conditions known as radiation proctitis and radiation cystitis. These are commonly uncomfortable if not painful conditions characterized by episodic bleeding from the bladder or bowel. Clarke et al published results of a randomized, controlled trial in 2008 establishing the efficacy of HBO2 in the treatment of radiation proctitis.31 While this level of evidence does not yet exist for radiation cystitis, the mechanism is similar and the treatment similarly accepted. Another relatively common location for soft-tissue radionecrosis is the breast. Radiation therapy may be used preoperatively to reduce tumor size prior to surgery or postoperatively with or without concomitant chemotherapy. Wound-related problems arise most frequently when surgery such as lumpectomy or mastectomy is performed in a previously irradiated field where, due to the impairment in tissue vascularity and cellularity, normal healing is not able to take place. FIGURES 18-26 and 18-27 illustrate such a wound that had failed to heal in the 15 months following surgery in spite of good wound care. With a combination of appropriate topical wound care, negative-pressure wound therapy, and HBO2 the wound progressed to complete closure in 20 weeks.
Soft tissue necrosis with resulting non-healing wound in radiated tissue. Note the pale granulation tissue that is indicative of the Triple H phenomenon.
The chronic radiation wound after 20 weeks of standard care and HBO2 therapy.
Gas gangrene is an uncommon condition caused by an anaerobic, gram-positive, spore-forming bacillus named Clostridium perfringens. This organism produces a toxin that creates a rapidly progressive, necrotizing infection of the muscles leading to grave illness, extensive tissue death, and production of gas, which can be palpated in the tissues and seen on x-ray. HBO2 is used as an adjunct to surgery in the treatment of gas gangrene to attenuate toxicity and spread of infection. Exposure to HBO2 halts the production of the α-toxin and is also bactericidal. HBO2 has been shown to reduce morbidity and mortality and to lessen the degree of amputation due to tissue loss.
Chronic Refractory Osteomyelitis
Chronic osteomyelitis, refractory to conventional treatment, may benefit from HBO2. Both chronicity and failure to respond to appropriate treatment must be documented. Oxygen levels in infected bone are usually significantly lower (20 mmHg) as compared to 30 to 40 mmHg as seen in healthy tissues. Adjunct HBO2, along with appropriate antibiotic and surgical management, can elevate bone oxygen levels to near-normal levels, stimulate osteogenesis, and catalyze the development of new capillary vasculature.
In a prospective trial of 32 patients designed to evaluate the efficacy of HBO2 on postoperative sternal infections after median sternotomy, Barili et al showed that relapse rates were lower, duration of antibiotic therapy was shorter, and hospital stays were less than in the non-HBO2 treated group.32 Although the two groups were not strictly randomized, they appeared well matched from the perspective of their surgical as well as infection-related characteristics.
While there are presently no randomized trials to support or refute the efficacy of HBO2 in chronic refractory osteomyelitis, there is a robust collection of animal studies, human case series, and prospective clinical trials supporting the safety and efficacy of adjunct HBO2 in its management. The available evidence appears to support a reduction in the need for surgical procedures, antibiotic therapy, and overall health-care expenditure (FIGURE 18-28).
Chronic osteomyelitis Blistering and other signs of chronic infection in the soft tissue are indicators of underlying osteomyelitis. In addition, any wound that can be probed to bone has a high probability of having osteomyelitis.
Compromised Skin Grafts and Flaps
HBO2 has proven to be extremely useful in the preservation and salvage of compromised or ischemic tissue flaps. There have, however, been no studies to support the use of HBO2 for healthy, viable grafts and flaps. HBO2 therapy has been studied extensively in grafts that are compromised by tissue hypoxia or involve previously irradiated tissue.
There are many causes for flap compromise, most resulting in an impairment of both blood flow and oxygenation to the flap. These causes range from arterial inflow compromise to edema caused by venous congestion. Ischemia-reperfusion injury can also lead to the compromise and ultimate failure of flaps. This is the condition in which a flap is exposed to a prolonged period of ischemia followed by reperfusion. Zamboni et al examined and reported on the effect of HBO2 during and immediately after ischemic periods in skin flaps in a rat model and found beneficial effects of HBO2 when compared to the non-HBO2 group.33 These skin-flap studies were followed and supported by skeletal muscle studies, which in fact may be more important, as skeletal muscle is more sensitive to ischemia-reperfusion injury than is skin.34
Whatever the etiology of the ischemic insult, prompt recognition of the problem remains the most important factor in determining what measures can be taken. In some cases, surgical reexploration will be able to identify and correct the cause but in others there may be no identifiable cause. In these cases the prompt initiation of HBO2 may assist in the salvage of a flap that otherwise may fail. The vasoconstrictive effects of HBO2 leading to edema reduction and the saturation of tissues with oxygen are the primary protective hyperbaric mechanisms at work here. FIGURE 18-29 illustrates amputation and ray resection of toes 2-5; FIGURE 18-30 shows the surgical flap that has become totally nonviable.
Surgical incision after amputation and ray resection of toes 2-5. The blanching periwound skin and incisional necrosis are signs of hypoxia in the forefoot that may respond well to HBO2 therapy.
The same surgical incision will become a larger necrotic wound if the hypoxia cannot be reversed in time for the soft tissue to recover.
Hyperbaric oxygen therapy is indicated in the treatment of serious burns, defined as those covering more than 20% total body surface area and/or involving of the hands, face, feet, or perineum, and that are deep-partial or full-thickness injury.10 The burn wound is a complex and evolving injury characterized by a central area of coagulation due to capillary occlusion, with a surrounding area of stasis and a border of erythema. (Refer to Chapter 10 on Burns for more details.) Local microcirculation appears to be maximally compromised in the 12 to 24 hours postburn and the central area of coagulation can increase by a factor of 10 over the first 48 hours. Burns are in this evolution process for up to 72 hours following the initial injury.35
In 1997, Niezgoda et al demonstrated reduced wound size, laser Doppler measured hyperemia, and wound exudate in a UV-irradiated blister wound model. This was the first prospective, randomized, controlled, double-blind trial comparing HBO2 with sham controls in a human burn model. In a 2005 rat model study, deep second-degree burns were created, treated with silver sulfadiazine and then assigned to either a normoxic placebo group or a 2.5 ATA HBO2 group. The results were decreased burn edema, increased neoangiogenesis, an increased number of regenerative skin follicles, and reduced time to healing.36 In addition to the studies cited, there have been numerous others in both animal and human models supporting edema reduction, decreased need for grafting, faster healing, and shorter hospital stays.
While adjunct HBO2 appears to markedly reduce the healing time in burn injuries, especially in deep second-degree injuries, more carefully controlled human studies are necessary in order to more completely define the role of HBO2 in thermal burn injuries.