The first utilization of limb amputation was as an implement of punishment or torture. Hippocrates is credited with performing the first amputation for therapeutic purposes. Well into the 20th century, toe or forefoot gangrene was associated with limb loss. Leland McKittrick’s publication of his technique for transmetatarsal amputation (TMA) in 1949 led to thousands of spared limbs. For decades, however, a TMA was much more likely to succeed when infection was the indication rather than ischemia. As recently as the 1970s, up to 70% of the patients who underwent minor amputation progressed to limb loss within three years. Better understanding of microbiology, risk factor modification, and an enthusiasm for performing femoral to popliteal and tibial artery bypass grafts have led to contemporary limb salvage rates approximating 80% at 5 years.

In the United States, hospital admissions for foot ulceration increase yearly. One of the most important and overlooked aspects of successful limb salvage in these patients is a properly timed and executed minor amputation. Currently, minor amputations are performed twice as frequently as major amputations. Avoidance of major amputation is critical for a myriad of reasons. Trans-tibial and trans-femoral amputations result in inefficient ambulation. The increase in metabolic cost after these procedures is proportional to the number of functional joints that are lost. Increased oxygen consumption leads to reduced metabolic reserve and a dramatically altered exercise capacity. Adverse consequences of major amputation are decline in quality of life, difficulty maintaining independence, and high medical costs. Body image issues, depression, and shortened life expectancy are other sequelae. The risk of amputation is approximately three times higher after the age of 80 years, which is precisely the population most at the risk for loss of independence.

Currently, there are over 25 million diabetics in the United States and the prevalence continues to rise alarmingly. The CDS reports the percentage of US citizens with diabetes increased from 4.9% in 1990 to 7.3% in 2001. In the risk regions, the numbers are often
much higher. According to the 2009 Louisiana Health Report Card prepared by the Department of Health and Hospitals, the prevalence of diabetes in Louisiana is 10.7% and rises to 23.2% among the individuals of 65 years and older. Additionally, these numbers fail to account for occult cases whose population may be equal to that of known diabetics. Surveying health maintenance routines is no more reassuring. In Louisiana, nearly 30% of diabetics failed to perform a daily blood glucose check and 28% had not had a foot exam within the past year.

Diabetes mellitus is the leading cause of lower extremity amputation worldwide. European studies demonstrate the incidence of amputation among diabetics is almost 250 per 100,000 population, a rate 30 to 40 times higher than non-diabetics. Approximately 85% of all lower extremity amputations are precipitated by foot ulceration. The overall prevalence of foot ulcers in diabetics in the United States is 12% with a 20 year cumulative incidence approaching 10% and a lifetime incidence up to 25%, most of whom will require hospitalization for this condition. Indeed, foot ulcerations are the most frequent cause of diabetes-related hospital admission. The length of stay is significantly longer than that of other diabetes-associated complications with a yearly cost in the tens of billions of dollars. After amputation, diabetics heal at a rate similar to that of non-diabetics but their overall survival is significantly worse.

The continued development of our understanding of the pathophysiology of foot ulceration in diabetics has led to numerous advances in limb salvage. In the past, microvascular arterial obliteration or “small vessel disease” was thought to result in poor skin perfusion and necrosis. Thus, feeling powerless to improve tissue perfusion, the physician usually resorted to primary amputation. We now understand ulceration to be a result of a complex interplay between various sequelae of diabetes mellitus.

Nerve damage in diabetics can result in a severe sensory dysfunction. The loss of protective sensation in the foot leads to injury from abnormal repetitive stress, poorly applied footwear, and even undetected hazards such as a foreign object in a shoe. Diabetics with reduced sensation are more likely to injure their feet and are less likely to notice injuries, resulting in delayed treatment. Peripheral neuropathy can also lead to changes in foot structure. Denervation of the intrinsic arch muscles can cause the toes to be pulled back by the now-unopposed long tendons, leading to hammertoe formation. Plantar and intrinsic muscle atrophies result in prominent metatarsal heads and less foot surface area overall to bear weight, a common source of pressure ulceration. Repetitive injury to a malformed insensitive foot leads to ligament laxity and further abnormal pressure points such as those seen in Charcot deformity. Autonomic neuropathy produces dry skin and decreased sweating. Callus formation is thus initiated, triggering abnormal pressure points and ulcer formation.

Tissue ischemia also plays a large role in ulcer pathogenesis. Rather than microvascular obliteration, atherosclerosis in diabetics occurs in large vessels just as in non-diabetics. The difference is that atherosclerosis in diabetics tends to be more aggressive, rapidly progressive, and more often involves the tibial vessels. Additionally, functional changes in the microcirculation prevent maximal vasodilation causing the diabetic foot to be more susceptible to ischemia. The dorsalis pedis vessel is usually spared from extensive atherosclerosis and calcification, making it a useful target in many limb salvage cases.

In diabetics, the combination of sensory loss, autonomic neuropathy, altered foot structure, increased sensitivity to changes in perfusion, and tibial occlusive disease conspire to establish the perfect milieu for ulceration, infection, and tissue loss.

The majority of patients who require lower extremity amputation will present initially with a foot ulcer. A thorough history and physical examination is the cornerstone for developing an effective treatment plan and limiting the extent of amputation required. Pertinent questions include a history of previous ulceration and length of healing involved. How long has the current ulcer been present? Does it appear to be healing? Signs of infection including fever, chills, and difficulty with glucose control should be solicited. If the patient has been recently hospitalized or immobilized, a pressure etiology must be suspected, especially for ulcers in the posterior heel location. The patient’s functional status and capacity for independence will also help determine the ideal amputation level. Comorbid conditions such as tobacco abuse and diabetes mellitus can lead to ulcer formation. If the patient is a known diabetic, glycosylated hemoglobin should be sent. If the patient states he is not diabetic, our preference is to perform a screening fasting glucose level according to the American Diabetes Association guidelines (Table 1). In our experience, nearly half of the patients who present with a foot ulcer and are not a known diabetic will test positive for occult diabetes or prediabetes. The patient must be asked whether they suffer from complications of diabetes including neuropathy, retinopathy, and nephropathy. The presence of severe coronary artery disease and/or congestive heart failure may preclude extensive attempts at open revascularization. A history of lower extremity bypass or angioplasty will readily identify a patient as having peripheral vascular disease. Symptoms of claudication or rest pain should also be elicited. The existence of end-stage renal disease (ESRD) will negatively affect the patient’s ability to heal as well as dramatically reduce his or her overall life expectancy.

Physical examination of the involved extremity is obviously informative. Pulses should be inspected manually, and with handheld Doppler as necessary, in the femoral, popliteal, posterior tibial, and dorsalis pedis locations. In the foot itself, look for any structural deformity, which is simply defined as a contracture that cannot be manually reduced. Limited joint mobility is a marker for diabetes and a risk factor for ulcer formation. Fissures and calluses may mask underlying wounds. Simple callus removal will usually reduce plantar pressures and can be curative. The performance of a 10-g Semmes–Weinstein monofilament test on 10 ipsilateral foot sites by an experienced physician is an extremely sensitive test for peripheral neuropathy. Sequela of motor neuropathy may include hammertoe formation and a high plantar arch with decreased soft tissue bulk. All toenails should be inspected for both fungal infection and as a possible source of pressure ulceration.

The location and characteristics of the wound must be carefully examined and recorded. Constant low pressure such as that caused by ill-fitting footwear usually leads to medial ulceration. Plantar ulcers suggest repetitive stress to abnormal pressure points such as the metatarsal heads or the
midfoot in the case of Charcot deformity. Circumferential involvement of the distal toes is suggestive of ischemic gangrene rather than trophic ulceration. Finally, examine the patient’s footwear itself as a potential culprit. Wound depth and size should be vigilantly measured, the latter preferably using wound tracing or digital planimetric assessment since manual measurements are notoriously inconsistent. Signs of infection such as drainage and erythema should be sought. Osteomyelitis can be assumed if bone is contacted during exploration of the ulcer with a sterile probe. The use of a documented ulcer classification system has many benefits including standardized communication among involved physicians, monitoring of wound healing, and as a tool to validate investigational treatment methods. Though the most popular system is the Wagner Ulcer Classification System (Table 2), the authors’ prefer the University of Texas Wound Classification System as it accounts for wound penetration as well as presence of ischemia and/or infection (Table 3).

If osteomyelitis is missed during the initial assessment of the patient, ascending infection and limb loss can readily occur. Though a simple probe exam will uncover many cases of osteomyelitis, in nearly one-third of patients it will be non-diagnostic. Therefore, if bone is not readily encountered during the sterile probe exam, the next step is to obtain plain X-ray imaging of the foot. Classic findings of osteomyelitis on plain film are demineralization, periosteal reaction, and bony destruction, whereas lesser signs include effacement of fat planes and soft tissue edema. It is important to note that these findings may be delayed or absent in early cases. Additionally, osteomyelitis is rare without a point of entry; if bone degradation is present with intact skin, osteoarthropathy should be suspected. Clinically, osteoarthropathy occurs in a midfoot location and is polyarticular in nature, whereas osteomyelitis is found most frequently as a focal cortical lesion in the toes or metatarsal heads. If X-ray imaging is negative, MRI or triple-phase bone scanning may be helpful as both become positive within 48 hours of infection. Both are highly sensitive with a high negative predictive value. The presence of neuroarthropathy or chronic bone changes due to trauma, surgery, or arthritis will adversely affect the sensitivity and specificity of MRI and bone scanning. Other diagnostic modalities include tagged white blood cell scanning and CT imaging, but the authors would recommend open or image-guided bone biopsy as the next diagnostic step if the presence of osteomyelitis remains in doubt.

Investigation of the circulatory status of the patient begins with the history and physical examination and now proceeds to the non-invasive laboratory. Ankle brachial indices are obtained first with normal findings usually defined as >0.95. Unfortunately, the calcified arterial media in many diabetics lead to falsely elevated readings; therefore, we augment our investigation with pulse volume recordings and toe pressures when possible. Transcutaneous oximetry (TcPO₂) has been advocated by many practitioners as both a screening test for peripheral vascular disease as well as a marker for determining healing potential. It is important to note that oximetry measures oxygen partial pressure in the adjacent skin and not in the wound itself. Also, after revascularization the maximum measured increase in TcPO₂ may be delayed by as much as 72 hours. Dr. Fife et al. published a consensus statement from the June 2007 workshop “Transcutaneous Oximetry: Art, Science and Practice.” A summary is listed in Table 4. The authors do not find that the routine use of TcPO₂ provides improved clinical outcomes for experienced vascular surgeons in the setting of tissue loss.

Once vascular insufficiency has been demonstrated in the face of tissue loss, the authors recommend proceeding with angiography even if the ulcer is believed to be pressure induced. We perform selective angiography with digital subtraction imaging. Anterior and posterior foot vessel imaging is routinely obtained. A 60-mg intra-arterial papaverine injection can help identify potential target vessels. The use of high-speed acquisition rates allows for a lower volume of contrast. Lesions amenable to endovascular therapy are usually treated at the same setting to minimize delays. In some cases, a patent pedal artery may not be readily identified by traditional angiography and an MRA may be beneficial.