Lower extremity amputation

INTRODUCTION — Lower extremity amputation is performed to remove ischemic, infected, necrotic tissue or locally unresectable tumor and, at times, is a life-saving procedure. Peripheral artery disease, alone or in combination with diabetes mellitus, contributes to more than one-half of all amputations; trauma is the second leading cause. The second Trans-Atlantic Inter-Society Consensus Working Group (TASC II) documented an incidence of major amputations due to peripheral artery disease ranging from 12 to 50 per 100,000 individuals per year [1]. The aging population is expected to increase this number by 50 percent in the next 15 years [2].

Factors that predict the need for lower extremity amputation in patients with extremity ischemia include tissue loss, end-stage kidney disease, poor functional status, and diabetes mellitus. Patients with diabetes have a 10-fold increased risk for lower extremity amputation compared with those who do not have diabetes. Amputees with diabetes are more likely to be severely disabled, experience their initial amputation at a younger age, progress to higher-level amputations, and die at a younger age compared with patients without diabetes [3].

The indications and techniques for lower extremity amputation, postoperative care, complications, and outcomes are reviewed here. Techniques for performing lower extremity amputation are discussed elsewhere. (See "Techniques for lower extremity amputation".)

TERMINOLOGY — Major amputation refers to any amputation performed above the level of the ankle. Foot amputations are those at or below the ankle.

Amputation performed without an attempt at limb salvage (eg, revascularization, bony repair, soft tissue coverage) is termed primary amputation, whereas amputation following a failed attempt at revascularization is termed secondary amputation. Traumatic amputation refers to limb loss that occurs in the field at the time of injury.

INDICATIONS FOR AMPUTATION — The majority of lower extremity amputations are performed for ischemia due to peripheral artery disease [2,4]. Trauma and malignancy account for the remainder of cases [2,4,5].

Amputation of the lower extremity is indicated for:

●An unsalvageable extremity due to critical limb ischemia in patients with vascular disease. Primary amputation may be the only option for patients without an anatomic option for revascularization or those with medical risk factors that contraindicate revascularization.

•Peripheral artery disease. (See "Management of chronic limb-threatening ischemia".)

•Acute arterial thrombosis or thromboembolism. (See "Clinical features and diagnosis of acute lower extremity ischemia".)

●Trauma resulting in a mangled extremity or failed attempt at limb salvage. (See "Severe lower extremity injury in the adult patient".)

●Severe infections with extensive soft tissue or bony destruction, or osteomyelitis. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities" and "Necrotizing soft tissue infections".)

●Locally unresectable malignant tumors of the musculoskeletal system [6]. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Extremity sarcomas' and "Surgical resection of primary soft tissue sarcoma of the extremities" and "Bone sarcomas: Preoperative evaluation, histologic classification, and principles of surgical management", section on 'Indications for amputation'.)

●Frostbite-related gangrene. (See "Frostbite: Emergency care and prevention".)

●Failed management of acute compartment syndrome. (See "Acute compartment syndrome of the extremities".)

●Failed management of Charcot's degenerative osteoarthropathy. (See "Diabetic neuroarthropathy".)

●Debilitating extremity paralysis, which can be unilateral but is frequently bilateral (eg, paraplegia), from infection or pressure-related complications.

PREOPERATIVE EVALUATION AND PREPARATION — Most indications for amputation are elective and should be preceded by preoperative evaluation and preparation of the patient, which includes evaluation of medical risk, nutrition assessment, prosthetic and rehabilitation consultation, and potentially psychological consultation.

In patients with a grossly infected extremity that cannot be brought under control by aggressive surgical drainage, debridement, and antibiotics (with or without systemic sepsis), or those with an unsalvageable mangled extremity, amputation is an emergency or urgent procedure that should proceed without delay.

Medical risk — Major amputations (below-knee amputation and higher) carry a significant risk of perioperative morbidity and mortality, particularly in patients with vascular disease. Identification of medical risk factors and appropriate pre- and postoperative medical care may decrease the rate of perioperative complications. In a five-year retrospective study, higher modified frailty index scores were predictors of 30 day readmission after lower extremity amputation [7]. (See "Evaluation of cardiac risk prior to noncardiac surgery" and "Strategies to reduce postoperative pulmonary complications in adults" and "Perioperative medication management".)

●Myocardial infarction is the most common cause of death following lower extremity amputation in patients with peripheral artery disease [8,9].

●Pulmonary complications, including atelectasis and pneumonia, complicate 5 percent of major lower extremity amputations [8].

●The incidence of new-onset renal failure after a lower extremity major amputation is 0.6 to 2.6 percent [8,9]. Renal failure is associated with increased operative and long-term mortality.

Psychological evaluation — Depression following amputation can result from an adjustment reaction to the surgery and to sudden disability. Risk factors for major depressive disorder following amputation include a young age at time of the amputation, pain, neurotic personality lifestyle, and poor coping skills [10,11]. (See "Screening for depression in adults".)

Posttraumatic stress disorder (PTSD) is common (20 to 22 percent) after amputations for combat or accidental injury. For ischemia-related (nontraumatic) amputations, the incidence of PTSD is less than 5 percent. (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical features, assessment, and diagnosis".)

Perioperative antibiotics — Surgical site infection (SSI) rates following lower extremity amputation remain high. The risk of surgical site infection following amputation depends upon the severity of infection and duration of any prior wounds, as well as the presence of ischemia (see 'Infection' below). Antibiotic prophylaxis is recommended for all patients within one hour of the skin incision for lower extremity amputation, regardless of the clinical classification of the surgical wound (table 1) [12,13]. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults".)

A systematic review identified four randomized trials comparing prophylactic antibiotics with no antibiotics, or placebo, and three trials comparing the efficacy of specific antibiotics [14]. In the largest trial [15], the incidence of wound infection following amputation was significantly lower in 77 patients treated with prophylactic antibiotics compared with 75 treated with placebo (17 versus 38 percent); similar results were reported in the smaller trials [16-18].

Selection — For amputation that is not complicated by soft tissue or wound infection or gangrene, intravenous prophylactic antibiotics appropriate for skin flora (table 2) are adequate.

For any patient undergoing major amputation with clinical evidence of an infected wound with or without concomitant ischemia, broad-spectrum perioperative antibiotics (oral or intravenous) should be administered and are selected in accordance with the local antibiogram and adjusted in response to wound culture and sensitivities. Surveys of the bacteriology of amputation wound infections confirm a wide spectrum of microbial species [19]. Anaerobic coverage should be considered for diabetics.

In the systematic review, three trials compared the efficacy of specific antibiotics [14]. Among these (methicillin versus cephalothin, penicillin G versus cefuroxime, benzyl penicillin versus amoxicillin + clavulanic acid) [20-22], a significant difference in the incidence of wound infection was found only for benzyl penicillin versus amoxicillin + clavulanic acid (13 versus 77 percent) [22].

Duration — Prophylactic perioperative antibiotics are discontinued within 24 hours of the procedure. For patients who are being treated for infected wounds or cellulitis, antibiotics are re-dosed perioperatively and continued postoperatively.

●Contaminated/dirty wounds – For patients undergoing major amputation associated with wounds classified as "contaminated" or "dirty" (table 1), we re-dose therapeutic antibiotics perioperatively and then continue antibiotics into the postoperative period. Even when no residual infected tissue remains after amputation, the risk for infection likely persists (some feel due to involvement of the lymphatics), so it seems reasonable to continue antibiotics postoperatively. Unfortunately, there are few data to inform the optimal duration. We continue antibiotic therapy for five days starting the day of the amputation, or day of amputation completion in the case of staged amputation. A longer or shorter duration may be appropriate depending on the duration of the prior associated infected wounds as well as the clinical appearance of the tissues at the time of the amputation, the ongoing appearance of the wound after amputation, and the overall clinical course of the patient.

●Clean wounds – For patients undergoing lower extremity amputation without prior associated infection or wounds (clean wound (table 1)), while there is some evidence to support a longer duration of prophylactic antibiotics, we do not feel the potential benefit of reduced SSI outweighs the risks of secondary infection (eg, Clostridioides difficile) or the development of antimicrobial resistance. The surgical site should be monitored daily, and if SSI develops, it should be treated accordingly. (See "Overview of the evaluation and management of surgical site infection".)

Observational studies comparing perioperative antibiotics (<24 hours) to a longer course following vascular procedures and specifically lower extremity amputation appear to support a longer course of therapy [23-25]. In a study comparing a five-day course of broad-spectrum antibiotics with a three-dose regimen among two cohorts of consecutive amputations, the incidence of amputation wound infection was significantly lower for the five-day group (5 versus 22.5 percent) [23]. However, the incidence of Clostridioides difficile colon infection was higher for those receiving the five-day course of antibiotics (7.5 versus 0 percent).

In a later randomized trial, 161 vascular patients undergoing amputation (minor, major) without significant baseline infection were randomly assigned to a 24-hour or five-day course of prophylactic antibiotics [24]. The incidence of SSI was significantly lower for the five-day course (11.8 versus 39.5 percent; based on ASEPSIS scores [26]) as was the incidence of impaired wound healing at the surgical site (22.4 versus 58 percent; based on ASEPSIS scores). In addition, significantly fewer patients receiving the five-day course required revision of their amputation (6.6 versus 21 percent). On univariate analysis, the level of amputation was a significant other factor in determining the risk of SSI and for impaired wound healing. In multivariable logistic regression, with amputation level and other variables controlled, longer antibiotic duration remained significant for reducing SSI. One patient each developed Clostridioides difficile and methicillin-resistant Staphylococcus aureus infection. A limitation of this trial was the lack of blinding of the patient, surgeon, and anesthesiologist; however, the assessors of the primary outcome were blinded.

Thromboprophylaxis — Thromboprophylaxis is administered prior to amputation depending upon individual patient risk, amputation level, and expected level of activity following amputation. Patients undergoing major lower extremity amputation are at high risk for thromboembolism due to the nature of the surgery (table 3) [27-31]. In addition, most patients undergoing amputation at the transmetatarsal level will have weight-bearing restrictions and will be immobilized postoperatively. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".)

Indirect evidence from large randomized trials of other orthopedic surgeries (eg, knee replacement) and two small trials and other observational studies in patients undergoing major lower extremity amputation support thromboprophylaxis [28,32-34]. For all major lower extremity amputations, we recommend thromboprophylaxis because it reduces the incidence of venous thromboembolism. In older reviews, deep vein thrombosis is reported in up to 50 percent of patients following major lower extremity amputation without prophylaxis [29,31]. With prophylaxis, venous thromboembolism occurs in 10 to 15 percent of patients [27,28,30,35]. In a randomized trial that compared low-molecular-weight heparin and unfractionated heparin for prophylaxis, the incidence of deep vein thrombosis was 10 percent with no differences between the groups [27].

LEVEL AND AMPUTATION TYPES

Amputation level — The level of the amputation is dictated by the extent of the disease, healing potential of the stump, and rehabilitation potential of the patient. Although preservation of limb length is desirable, removal of all nonviable and infected tissue is a higher priority.

The surgeon must be satisfied that sufficient arterial perfusion is present at the proposed amputation level to sustain healing. The level of amputation is determined by a combination of a thorough physical examination supplemented by objective testing in patients with clinical symptoms and signs of lower extremity ischemia. In one study, 68.4 percent of patients underwent objective arterial testing prior to nontraumatic amputation [36]. Older age, male sex, being a Black person, renal disease, diabetes mellitus, known peripheral artery disease, evaluation by a vascular specialist, and living in the East North Central region were associated with greater rates of preoperative arterial testing. (See "Noninvasive diagnosis of upper and lower extremity arterial disease".)

Determination of amputation level by means of physical examination and clinical judgment alone results in healing in 80 percent of below-knee amputations (BKAs) and 90 percent of above-knee amputations (AKAs) [37]. The presence of a palpable pulse proximal to the level of amputation is associated with a healing rate of nearly 100 percent. The absence of a palpable pulse does not necessarily imply wound healing failure of the amputation stump; however, the rate of revision following major amputation may be higher.

Various objective tests can supplement the clinical examination to assist the choice of amputation level. These include ankle pressures, toe pressures, transcutaneous oxygen measurements, and skin perfusion pressure. The sensitivity of these studies for predicting wound healing is low, ranging from 60 to 74 percent, and thus, these tests should not be used to replace clinical judgment [38,39].

It is also important that structural integrity of the bony architecture of the residual limb is adequate. As an example, for some patients with diabetes and Charcot's degenerative osteoarthropathy of the foot, ongoing instability of the metatarsals may favor transtibial amputation over complex foot salvage procedures.

Standard and osseointegrated amputations — Major standard amputations include hip disarticulation, AKA, knee disarticulation, and BKA. These amputations use a standard socket prosthesis. A variety of foot amputations are also available that can salvage the patient's ability to ambulate with orthotic modifications, including mid- and hindfoot amputation (eg, Lisfranc, Chopart, Syme), transmetatarsal amputation, and digit amputations. Major amputation and foot amputation techniques are discussed in detail elsewhere. (See "Techniques for lower extremity amputation".)

If the stump is short, or for patients who cannot tolerate or use a standard socket prosthesis, an alternative option to a standard amputation and socket prosthesis is the technique of osseointegration, which fundamentally involves integration of the prosthesis into the appendicular skeleton. This technique has been used in transfemoral as well as transtibial amputations in the lower extremity [40-42]. Most studies have been done in patients without significant peripheral artery disease or associated diabetes. The anchoring system is implanted directly into the bone using a two-stage procedure. The Osseoanchored Prostheses for the Rehabilitation of Amputees (OPRA) Implant System has been approved for use in the United States [43]. Other systems include the Integral Leg Prosthesis (ILP) [44] and the Osseointegrated Prosthetic Limb (OPL) [45].

POSTOPERATIVE CARE — Postoperative care of amputation patients requires multidisciplinary cooperation. Anesthesiology pain services, rehabilitation medicine, physical therapy, and psychiatry services each contribute to the patient's postoperative recovery.

More than one third of perioperative (<30 days) deaths after major amputation occur after discharge from acute care [46]. Patients who have an increased risk for mortality may benefit from continued hospitalization or, if discharged, close postoperative follow-up. (See 'Perioperative mortality' below.)

Wound care — Following amputation, the incision should be examined daily for signs of infection (erythema, excess warmth, wound drainage), particularly in patients with unexplained fever or excessive stump pain. Drains placed into the wound at the time of the surgery are maintained until volume in the drain reservoir is minimal; thereafter, the drain can be removed.

Open wounds (eg, open amputation, soft tissue defect, stump breakdown) are managed with moist saline dressings. Once the wounds have stabilized and no necrotic debris is apparent, negative pressure wound therapy may be useful [47]. (See "Basic principles of wound management", section on 'Wound dressings' and "Negative pressure wound therapy".)

Preventing wound contamination from urine and stool can be challenging following hip disarticulation and above-knee amputation. A urinary drainage catheter is typically placed at the time of major amputation and can be maintained for a few days postoperatively if a problem is anticipated but should be removed as soon as possible. (See "Placement and management of urinary bladder catheters in adults", section on 'Catheter removal'.)

The skin overlying the sacrum and other bony protuberances should be inspected frequently for signs of decubitus ulcer. (See "Prevention of pressure-induced skin and soft tissue injury".)

Stump pain — Acute stump pain following amputation gradually subsides over a one- to three-week period of time. Optimal management of preoperative and postoperative pain in patients undergoing amputation may be important for reducing the risk of phantom limb pain [48]. Multimodality pain management is the cornerstone of successful amputation rehabilitation and consists of a combination of epidural, intravenous, and oral analgesics [48,49]. Depression may complicate the treatment of pain in many amputees [49]. A detailed discussion of the management of postoperative pain is found elsewhere. (See "Approach to the management of acute pain in adults".)

Chronic pain, to some degree, is reported by up to 95 percent of amputees [49]. Persistent pain may be a sign of stump ischemia, neuroma formation, infection, or a manifestation of phantom limb syndrome.

●Ischemic stump pain may be difficult to detect by physical examination alone but can be confirmed by a transcutaneous oxygen tension less than 20 mmHg at the level of the stump. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Transcutaneous oxygen measurements'.)

●Neuroma can develop at the site of transection of virtually any peripheral nerve, and is relatively common [50,51]. The pain is usually well localized to the site of injury and can be transiently blocked with anesthetic injection. Heterogeneity on T2 weighted magnetic resonance imaging may indicate that a neuroma is likely to be symptomatic [52].

●Pressure points that develop over bone spurs or pathologic bone formation can also be a source of localized pain and can be identified by obtaining a plain radiograph of the stump.

●Infection (osteomyelitis, residual graft infection) can also be a source of chronic postoperative pain.

●Phantom limb syndrome is a diagnosis of exclusion after the other causes of stump pain listed above have been eliminated. (See 'Phantom limb pain' below.)

Weight bearing and ambulation — The duration of non-weight-bearing in the residual limb depends upon the level of the amputation and whether there are any anticipated wound healing issues. Patients who are nonambulatory should receive prophylaxis for deep vein thrombosis until their activity restriction is lifted. (See 'Thromboprophylaxis' above.)

For amputations that are related to lower extremity ischemia, no weight bearing is allowed until the wound is thoroughly healed, which can take up to six weeks for major amputations. Younger patients undergoing major amputation for other indications may be candidates for immediate postoperative prostheses and ambulation. (See 'Immediate postoperative prosthesis' below.)

An elastic stump "shrinker" is applied after adequate wound healing of major amputation stumps to reduce edema and facilitate molding of the stump for a future prosthetic. Ambulation on a prosthetic is undertaken gradually under the direction of a multidisciplinary rehabilitation team.

For toe amputation, a rocker-bottom shoe with a metatarsal bar can be used in selected patients and allows ambulation while eliminating pressure to the toe wound. Older patients and patients with diabetes often find it difficult to maintain their balance using these shoes.

Following transmetatarsal and proximal foot amputation, weight bearing is allowed after six weeks provided the wounds are adequately healed. With an appropriate orthotic, the patient can be expected to ambulate with an almost imperceptible alteration in their gait once healing is complete.

●Transmetatarsal amputation: Shoe-filler and normal shoe

●Lisfranc amputation: Shoe-filler with an ankle-high lace-up shoe

●Chopart: Custom-fitted ankle foot orthosis with a filler, and ankle-high lace-up shoe

●Syme: Syme amputation prosthesis

Immediate postoperative prosthesis — Immediate postoperative prosthesis (IPOP) was developed to reduce the time to ambulation with a prosthetic [53]. Advocates of IPOP report that more patients are able to achieve earlier ambulation on a prosthetic compared with conventional rehabilitation [53,54]. Disadvantages of IPOP are that the rigid prosthetic limits access to the wound for examination, and that the skilled multidisciplinary team needed for its implementation is not universally available [55,56]. IPOP may play a role in elective amputation in patients who have no vascular issues, but it is generally not useful for patients with peripheral artery disease due to the frequency of stump complications.

Alternative prostheses

●An alternative to a standard socket prosthesis after lower extremity amputation is an osseointegrated prosthesis. (See 'Standard and osseointegrated amputations' above.)

●Another option is the use of a powered exoskeleton [57-60]. In an evaluation of six individuals with an above-knee amputation, use of an autonomous powered hip exoskeleton significantly improved metabolic walking economy by 16 percent [58].

COMPLICATIONS — Complications following lower extremity amputation are common and include medical complications related to preexisting cardiac and pulmonary conditions and local complications related to the surgery, which is discussed below.

Cardiopulmonary complications are a common cause of morbidity and mortality, which is not surprising given the incidence of cardiovascular disease, diabetes, and smoking in patients with peripheral artery disease. A retrospective review of 959 major amputations reported a cardiac complication rate of 10.2 percent. Complications included arrhythmias (2.6 percent), heart failure (4.2 percent), and myocardial infarction (3.4 percent) [8]. Another study of 154 patients undergoing 172 major amputations found that 63 percent of perioperative deaths were due to cardiac disease [9]. Identification of risk factors for cardiovascular and pulmonary disease and institution of preventive strategies are important to limit these complications and reduce mortality associated with them. (See 'Medical risk' above.)

For below-knee amputation, a review of the National Surgical Quality Improvement Program (NSQIP) database identified a 34 percent incidence of perioperative (30 day) complications in 2911 patients. The most common major complications were return to the operating room in 15.6 percent of patients, wound infection in 9.3 percent, and postoperative sepsis in 9.3 percent [61]. A history of sepsis, alcohol use, glucocorticoid use, cardiac disease, renal insufficiency, and contaminated/infected wounds independently predicted the development of one or more complications.

Another analysis of the NSQIP database evaluated wound occurrences defined as superficial infection, deep infection, and/or wound disruption following below-knee (2309 patients) or above-knee amputation (1941 patients) [62]. Wound occurrences were present in 10.4 percent of below-knee amputations and 7.2 percent of above-knee amputations. Independent predictors of wound occurrence in patients with below-knee amputation included age and elevated international normalized ratio (INR; odds ratio [OR] 1.5 for each integer increase in INR, 95% CI 1.1-1.93). For above-knee amputation, predictors of wound occurrence included a history of smoking within the year (OR 1.9, 95% CI 1.31-2.74) and increasing body mass index (OR 1.3 for every 10 kg/m² increase, 95% CI 1.01-1.05). In a separate review, risk factors associated with unplanned operation after above-knee amputation included prior revascularization, multiple indications for amputation, wound breakdown, and hematoma [63].

Deep vein thrombosis — Deep vein thrombosis (DVT) has been reported in up to 50 percent of patients following major lower extremity amputation without prophylaxis [31]. The incidence of DVT is higher for above-knee amputation compared with below-knee amputation (37.5 versus 21.2 percent, respectively) [64]. This difference may contribute to the increased incidence of sudden death due to thromboembolism in patients with above-knee amputation. Thus, it is important to provide thromboprophylaxis. (See 'Thromboprophylaxis' above and 'Perioperative mortality' below.)

Stump hematoma — Postoperative bleeding that requires reoperation occurs in 3 to 9 percent of major lower extremity amputations, and stump hematoma may lead to stump wound breakdown [9,65]. Patients on antithrombotic therapy, including DVT prophylaxis, are at a higher risk for stump hematoma. Patients with stump hematoma causing pain and stump swelling with or without drainage should have the wound opened partially, the hematoma evacuated, and the wound washed out and packed with a moist saline dressing.

Infection — Wound infection following major lower extremity amputation occurs in 13 to 40 percent of patients [19,23,66]. Patients with diabetes, preoperative wound infection, malnutrition, malignancy, advanced age, wound hematoma, and prior prosthetic bypass grafts have an increased risk for stump wound infection. In patients with prior lower extremity bypass graft, stump infection rates are reduced by complete removal of synthetic graft material [67].

Superficial wound infections are treated by removing the skin sutures and initiating broad-spectrum antibiotics, which are adapted to reflect the results of wound culture and sensitivities. Deeper wound infection requires operative management with removal of skin and fascial sutures, drainage and washout of the wound, and debridement of any nonviable tissue (picture 1).

Need for re-amputation — The rate of revision following major amputation remains high despite the availability of a variety of methods to select amputation level. (See 'Amputation level' above.)

The need for re-amputation at a more proximal level is inversely related to the level of the index amputation. Following toe amputation (picture 2), 25 to 50 percent of patients eventually undergo additional amputations compared with 10 to 20 percent of patients undergoing below-knee amputation (BKA) [3,8,9,68-73]. Patients with diabetes are almost twice as likely to require re-amputation as patients without diabetes [68,72]. In one study, the one-, three-, and five-year ipsilateral re-amputation rates for patients with diabetes were 23, 40, and 52 percent for toe amputations; 29, 41, and 50 percent for ray amputations; 19, 33, and 43 percent for midfoot amputations; and 5, 12, and 13 percent for major amputations [68]. In a study analyzing factors that predict long-term resource utilization and survival after major amputation, complicated diabetes, renal failure, and index below-knee amputation were each associated with an increased need for additional amputation-related procedures [74]. In a review of 8878 amputations at a variety of levels, independent risk factors associated with early amputation failure included emergency operation, transmetatarsal amputation, sepsis, septic shock, end-stage kidney disease, systemic inflammatory response syndrome, intraoperative surgical trainee participation, body mass index ≥30, and ongoing tobacco use [75,76].

Complete healing of a major amputation may be quite protracted. One retrospective review found that at 100 days postoperatively, 45 percent of transtibial and 24 percent of transfemoral amputations were not yet completely healed [9]. Approximately 20 to 30 percent of wounds fail to heal primarily, and of these, only about 50 percent are salvaged at the same level [3,8,9,69]. Re-amputation at the transfemoral level is needed in 10 to 20 percent of patients who initially underwent below-knee amputation [3,8,9,69-71,73]. Between 9 and 17 percent of patients undergoing transtibial amputation will require contralateral major amputation within 12 months [3,8,69,70,73,77].

Following foot or ankle amputation, approximately 35 percent of patients progress to a higher-level amputation within one year [3,68,78-82].

For toe amputations, wound failure occurs in approximately 25 percent [68]. Of patients who require revision of toe amputation, approximately 40 percent are performed at the transtibial level [3].

Phantom limb pain — True phantom limb pain is a complex, poorly understood pain syndrome that is described as burning, aching, or electric-type pain in the amputated limb [49]. There is no clear consensus on the mechanisms of this disorder and no standard treatment [83]. The diagnosis of phantom pain should only be made after other causes of stump pain have been eliminated, including ischemia, infection, neuroma, and pressure-related wounds. (See 'Stump pain' above.)

The incidence of phantom pain widely varies in the literature, ranging from 50 to 85 percent depending upon the diagnostic criteria used to define the syndrome [84,85]. Inadequate control of preoperative and postoperative pain may increase the risk of chronic amputation pain [86]. The use of preemptive epidural anesthesia may reduce the incidence and severity of phantom pain [48,87].

Systematic reviews have identified low-to-moderate-quality trials using a variety of pharmacologic agents (eg, gabapentin, memantine, ketamine, amitriptyline, mexiletine, or lidocaine) or other treatments (mirror therapy, virtual reality, peripheral nerve stimulation) to manage phantom limb pain after upper limb, lower limb, and digit amputations [88-94]. Most trials were small, and it is unclear whether the reported outcomes constituted a meaningful reduction in phantom limb pain. A novel approach incorporating sensory feedback from a specialized prosthetic may help reduce the perception of pain [95,96]. Another promising approach is target muscle reinnervation (TMR) [97]. The principles of TMR are similar for the lower and upper extremity. (See "Upper extremity amputation", section on 'Target muscle reinnervation'.)

In the absence of specific data to suggest better efficacy for treating phantom limb pain over other types of pain, we approach therapy in a manner similar to treatment of other conditions leading to chronic neuropathic pain, which is discussed in more detail separately. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Pharmacologic therapy for neuropathic pain, or nociplastic or centralized pain'.)

Flexion contracture — Flexion contracture at the hip or knee joint (15° limitation) occurs in 3 to 5 percent of major lower extremity amputations. Although up to 15° hip contracture can be accommodated with prosthetic alignment, a more than 25° contracture will cause compensatory lumbar lordosis, leading to low back pain. Contractures are more likely to develop in older patients, particularly those with dementia or prior ipsilateral stroke. Failure to provide adequate postoperative analgesia may also result in flexion contracture. Once a significant contracture develops, it may not be possible to correct it with physical therapy or surgery [98].

Hip flexion contracture can be retarded with prone positioning; however, patients may not tolerate this position.

Because a fixed flexion contracture can limit prosthetic ambulation, preventive measures are undertaken immediately following amputation. A rigid, removable dressing is applied intraoperatively and maintained postoperatively to straighten the knee, and an aggressive postoperative knee exercise program is undertaken as soon as allowable, taking into account the patient pain threshold and healing of the wound. (See "Techniques for lower extremity amputation", section on 'Dressings and drains'.)

FUNCTIONAL OUTCOMES — A good functional outcome can be achieved in most patients but may be largely dependent upon the patient's preoperative functional status, other comorbidities, and the level of the amputation.

Near-normal ambulation with conventional footwear is likely following toe, ray, and transmetatarsal amputation. Shoe fillers and simple orthotics are usually sufficient to allow ambulation for the majority of patients [78-80,99-101].

Following amputation of the proximal foot, patients can expect to ambulate with almost imperceptible gait alteration with the use of appropriate orthotics. However, because Lisfranc and Chopart amputations cause dramatic alterations in normal foot biomechanics, the durability of these amputations may be limited, particularly in patients with diabetes.

Following major amputation for injury or malignancy in otherwise healthy patients, ambulation with a prosthetic can generally be expected. The outcomes for patients with severe extremity trauma depend upon the integrity of each of the functional components of the extremity (nerves, vessels, bones, soft tissues). These outcomes are discussed elsewhere. (See "Surgical management of severe lower extremity injury", section on 'Amputation and functional outcomes'.)

Successful ambulation with a prosthetic is less likely in patients who have undergone major amputation for peripheral artery disease [9,102-104]. The outcomes of rehabilitation vary widely depending on the definition of success. Only approximately 25 percent of major lower extremity amputees due to peripheral artery disease ambulate with a prosthetic outside the home. Patients are not able to use a prosthetic for a variety of reasons, including mental illness, poor cardiopulmonary reserve, inadequate balance, and stump-related issues.

Significant preoperative patient factors that are independently associated with an increased risk of not being able to use a prosthetic include the following [104]:

●Nonambulatory before amputation (odds ratio [OR] 9.5, 95% CI 4.5-20.2)

●Above-knee amputation (OR 4.4, 95% CI 2.6-7.4)

●Age >70 years (OR 3.0, 95% CI 1.5-5.8)

●Homebound but ambulatory status (OR 3.0, 95% CI 1.6-6.2)

●Dementia (OR 2.4, 95% CI 1.3-4.1)

●End-stage kidney disease (OR 2.3, 95% CI 1.5-3.7)

●Coronary artery disease (OR 2.0, 95% CI, 1.3-3.2)

The energy required for ambulation with an above-knee amputation (AKA) is approximately 50 percent higher than after below-knee amputation (BKA). Fewer than 10 percent of elderly vascular amputees can be expected to ambulate effectively after AKA [9,69,102,104,105].

Despite the fact that few patients with peripheral artery disease ambulate with a prosthetic outside the home, most amputees maintain their preoperative living status. Thus, most patients living independently prior to major amputation remain independent postoperatively. Highly motivated patients, as evidenced by commitment to a strict rehabilitation program including smoking cessation and weight loss, are more likely to achieve long-term success [106]. Patients with financial resources that allow participation in a well-organized rehabilitation program are also more likely to be successful. The following preoperative factors were found to be significantly associated with an increased risk of being unable to maintain independent living status following amputation [104]:

●Age ≥70 years (hazard ratio [HR] 4.0, 95% CI 1.7-9.5)

●Age 60 to 69 (HR 2.7, 95% CI 1.1-6.5)

●Above-knee amputation (HR 1.8, 95% CI 1.2-2.8)

●Homebound status (HR 1.6, 95% CI 1.1-2.6)

●Dementia (HR 1.6, 95% CI 1.1-2.4)

A later study that evaluated the effect of rehabilitation setting on functional outcomes of 297 patients found that those who received postoperative care at an acute inpatient rehabilitation facility had better functional outcome at six months compared with patients who were treated at a skilled nursing facility or at home [107].

PERIOPERATIVE MORTALITY — Mortality in the immediate postoperative period is related to the indication for the amputation, associated medical comorbidities (eg, peripheral artery disease, diabetes), and complicating infection [108]. The most common causes of death following amputation for peripheral artery disease are cardiac complications, sepsis, and pneumonia [8,9]. Another important cause of mortality following amputation is thromboembolism from deep vein thrombosis. Mortality related directly to the operation, such as due to blood loss or postoperative infection, is much less common. (See 'Deep vein thrombosis' above.)

Mortality rates as high as 40 percent have been reported following major amputation in the past [109-111], but in contemporary series, 30 day mortality rates for major amputation range from 3 to 18 percent [3,8,9,69-71,73,112-118]. A higher level of amputation correlates with increased mortality and may reflect the severity of systemic cardiovascular disease, or differences in the incidence of thromboembolism rather than the magnitude of the procedure [112]. Mortality for above-knee amputation (AKA) ranges from 11 to 18 percent compared with 4 to 9 percent for below-knee amputation (BKA) [3,8,9,61,62,69-71,73,112-116,119]. In a study of 9368 patients from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database, perioperative (30 day) mortality was 12.8 percent for AKA and 6.5 percent for BKA [118]. Mortality following amputation of the foot (total or partial) is 2 to 7 percent [78-81,99,120,121].

Factors that increase the risk for mortality following major amputation include age over 80, dependent functional status, dialysis, glucocorticoid use, preoperative sepsis, delirium, thrombocytopenia, coagulopathy, and renal insufficiency [61,62,117-119,122,123]. Additional factors for mortality include heart failure, dyspnea, low body mass index for AKA, and chronic obstructive pulmonary disease and previous cardiac surgery for BKA [118]. In a separate study, renal failure increased the incidence of death (62 percent) in patients undergoing BKA more than threefold over the second most important independent risk factor, which was cardiac disease [61]. A study found that preoperative septic shock and thrombocytopenia were independent risk factors for perioperative (30 day) mortality after AKA, while burn etiology, leukocytosis, and guillotine amputation contributed to prolonged length of stay [124].

Guillotine amputation, which is often used to manage sepsis, is also associated with increased mortality. In one study, the 30 day mortality rate was 14 percent for guillotine amputation compared with 8 percent for elective amputation [8].

Patients presenting with extremity injury who require amputation have lower mortality rates compared with patients with peripheral artery disease and are more likely to die from associated injuries (eg, traumatic brain injury, abdominal injury). (See "Surgical management of severe lower extremity injury", section on 'Mortality'.)

LONG-TERM SURVIVAL — Long-term survival following major lower extremity amputation in patients with peripheral artery disease has improved but remains significantly lower than age-matched controls [65,112,114,125-127]. In one study, the overall survival after above-knee amputation was 78 percent at one year and 55 percent at three years [9].

Long-term survival is worse for patients with more proximal amputation, diabetes, and renal dysfunction but does not appear to be related to previous revascularization procedures, gender, or a history of hypertension [5,128,129]. Whether there are any ethnic or racial differences remains unsettled [114,130,131].

●One-year survival is 50 to 60 percent following above-knee amputation and 65 to 80 percent for below-knee amputation (figure 1) [3,8,71,112,113,116,126].

●Long-term survival for patients with diabetes is generally worse compared with patients without diabetes. In a review of 788 patients, five-year survival for patients with diabetes was 31 percent compared with 51 percent for patients without diabetes [8]. In another study, the median time to death was 27 months in patients with diabetes compared with 47 months following amputation [72].

●In a review of 788 patients who underwent major amputation, one-year survival was 52 percent for dialysis-dependent patients compared with 75 percent in patients with normal renal function [8]. For patients who were not dialysis dependent but had a preoperative serum creatinine >2 mg/dL, one-year survival was not significantly different (56 versus 52 percent) compared with dialysis-dependent patients.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Severe blunt or penetrating extremity trauma" and "Society guideline links: Soft tissue sarcoma".)

SUMMARY AND RECOMMENDATIONS

●Lower extremity amputation – Lower extremity amputation is indicated for a variety of reasons to remove ischemic, infected, or necrotic tissue or locally unresectable tumor and, at times, may be lifesaving. Peripheral artery disease and diabetes are the leading causes of nontraumatic lower extremity amputation in the United States. (See 'Introduction' above and 'Indications for amputation' above.)

●Preoperative preparation – Prior to amputation, medical, prosthetic, rehabilitation, and, potentially, psychological consultation should be obtained. (See 'Preoperative evaluation and preparation' above.)

•For all patients undergoing lower extremity amputation who are not already receiving antibiotics for associated soft tissue infection, we recommend perioperative prophylactic antibiotics (Grade 1A). Prophylactic antibiotics significantly reduce the incidence of amputation wound infection. The choice of antibiotic therapy and duration depend upon the clinical situation. (See 'Perioperative antibiotics' above.)

•We recommend thromboprophylaxis for all patients undergoing major lower extremity amputation (transtibial and above) (Grade 1B). Patients undergoing major lower extremity amputation are at high risk for thromboembolism. Without prophylaxis, deep vein thrombosis (DVT) has been reported in up to 50 percent of patients following major lower extremity amputation. Pharmacologic prophylaxis reduces the incidence of DVT to approximately 10 percent. (See 'Thromboprophylaxis' above.)

●Amputation level – The level of the amputation is dictated by the extent of the disease, healing potential of the stump, and rehabilitation potential of the patient. The presence of a palpable pulse proximal to the level of amputation is associated with a healing rate of nearly 100 percent, but the absence of a palpable pulse does not imply that the incision will not heal. Although various objective tests can supplement the clinical examination, these tests have a wide variability in their sensitivity and should not be used to replace good clinical judgment. (See 'Amputation level' above.)

●Complications – Complications following lower extremity amputation are common and include medical complications related to preexisting conditions and local complications related to the surgery, which include stump hematoma, infection, need for repeat amputation, phantom limb syndrome, and flexion contracture. The need for re-amputation at a more proximal level is inversely related to the level of the index amputation, with more proximal amputations less likely to require revision. (See 'Complications' above.)

●Mortality – Perioperative mortality rates for major amputation in patients with peripheral artery disease range from 3 to 18 percent and are related to the patient's medical comorbidities (eg, cardiac disease, pulmonary disease). Mortality related directly to the operation is less common. (See 'Perioperative mortality' above and 'Long-term survival' above.)

•Mortality is 11 to 18 percent for above-knee amputation (AKA), 4 to 9 percent for below-knee amputation (BKA), and 2 to 7 percent for foot amputation (total or partial).

•Mortality rates for amputation performed for nonvascular indications are lower.

•Patients with diabetes have a 10-fold increased risk for lower extremity amputation compared with those who do not have diabetes, and patients with diabetes are almost twice as likely to require re-amputation as patients without diabetes. Long-term mean survival is also reduced in patients with diabetes.