A Closer Look At Mortality After Lower Extremity Amputation

A Closer Look At Mortality After Lower Extremity Amputation

Are we saving lives by preventing major amputation? Does major amputation hasten death in patients with diabetes in comparison to limb salvage?

Currently, it is evident that ulceration and amputation are associated with increased mortality. Five-year mortality following a first-time ulceration is approximately 40 percent in patients with diabetes and ranges from 52 to 80 percent after major amputation. In addition, proximal amputation is associated with death in multiple studies.

If one directly compares these rates, it superficially appears that major amputation does hasten death. It even seems that the more proximal the amputation, the higher the mortality. However, the aforementioned data were not part of a randomized trial, and for ethical reasons, there will likely never be a randomized trial. These were observational studies, meaning the burden of disease (diabetes and its associated comorbid conditions) was also likely to be higher in these patients.

Patients with renal disease, increased age and peripheral arterial disease (PAD) have exhibited overall higher mortality rates after amputation, demonstrating that patients’ health status heavily influences their outcome. Furthermore, cardiovascular disease is the major cause of death in these individuals. Cause and effect become impossible to elucidate in this tangle of confounders.

As limb salvage experts, we are not alone in this conundrum. Endocrinologists find this same dilemma with insulin and increased mortality. In fact, an increased dose of insulin is also associated with increased mortality. Certainly, one could argue that insulin is increasing mortality but a more plausible explanation seems to be that those who require insulin (and higher doses of insulin) are not as healthy. Likewise, amputation may also be guilty by association rather than the true culprit in mortality.  

Why Does Amputation Lead To Increased Mortality?

If amputation is implicated in the demise of a patient, then the next question is why?

One theory is that body mass loss after amputation results in altered cardiorespiratory function. After traumatic amputations, a reduction in myocardial contractility can be apparent. In addition, the metabolic demand is higher after major amputation although this may not be a factor in young and physically active patients. Aside from the many methodological shortcomings inherent to the research supporting this theory, a more logical review recognizes this theory may not fully explain increased mortality. This research seems to suggest patients will merely slow ambulation down in order to compensate.  

Ambulatory status may have merit as a link to death, a finding indicated by several studies. Approximately one-third of patients will not walk again following major amputation and an even higher percentage in the elderly and renally compromised will never walk again after major amputation. Researchers have found the five-year mortality rate in those who are able to walk after major amputation to be 30 percent in comparison to 69 percent in those unable to ambulate. Interestingly, this study also noted an overall increase in ambulatory status from 45 percent preoperative to 63 percent postoperative in patients who had a major amputation. Unlike PAD or renal disease, improving ambulation status may be an aspect in which physicians can intervene and improve mortality. Recognizing that ambulation may be a critical influential factor in mortality may lead to different choices. Sometimes this may mean more limb salvage attempts while other cases may be more conducive to early amputation.

Objective review of the facts may aid in our decision making but emotional experience can also influence our choices. Take, for example, the case of an elderly gentleman with end-stage renal disease (ESRD), diabetes and calcaneal osteomyelitis. Magnetic resonance imaging (MRI) revealed that nearly half of the posterior calcaneus appeared to be infected. We offered him aggressive partial calcaneal resection versus major amputation. As most patients often do, he chose to undergo a limb sparing surgery despite the potential risk for losing limb function with an aggressive resection.

Postoperatively, he did have continued pain, which required narcotics, and was essentially bedridden in the hospital while receiving antibiotics. However, he developed pneumonia and subsequently died from complications associated with the respiratory affliction.

One can recognize the intent to help this patient but one may also wonder if major amputation would have led to a more expeditious recovery and better pain control, thus reducing respiratory depression and reducing the risk of pneumonia. We will never be certain if we should have pushed harder for major amputation as this very well may have made no difference.

It is easy to see the consequences of lack of ambulation. Intuitively, it seems we already know this in our “use it or lose it” idiom. Activity reduction in patients who already lead a sedentary lifestyle may be the final straw. It is interesting to note that Wukich and colleagues noted a five-year mortality rate of 30 percent in patients who were ambulatory after major amputation, which is quite similar to the approximately 40 percent mortality rate after ulceration prior to any amputation.

If non-ambulatory status is the sentinel event rather than amputation, then one must consider this as part of treatments. We frequently recommend prolonged non-weightbearing following surgery in this population. Minor amputations, such as transmetatarsal amputations, frequently exhibit poor healing and a higher occurrence of re-amputations. However, transmetatarsal amputations also have high rates of ambulation if the procedures are successful.

Thus, with proper patient selection, a minor amputation is usually preferable in patients who were previously ambulatory. Conversely, if the risk of failure following minor amputation would be very high, then one may consider a primary major amputation to give the patient the best shot at postoperative ambulation rather than prolonged non-weightbearing due to failed salvage attempts. Charcot arthropathy is particularly troubling as all treatment options require prolonged non-weightbearing.

In the future, interventions aimed at increasing mobility during the treatment phase may not only be able to improve ambulatory status but may also yield improvements in mortality.

Mortality increases with more proximal amputations but so does the prevalence of other risk factors associated with death. Ambulatory status may instead be the culprit of hastened death in these individuals. This reordering of priorities may change the way we address limb salvage in the interest of the patient. Thus, to improve postoperative ambulation and in turn mortality, consideration for perioperative physical therapy prior to and immediately following lower extremity amputations may be the next step. We anxiously await research to dispute or validate this possibility.

Dr. Thorud is board-certified by the American Board of Podiatric Medicine, and is a Fellow of the American College of Foot and Ankle Surgeons. Dr. Thorud is affiliated with Mercy Health System in Illinois.

Joslin Seidel is a fourth-year medical student at the Kent State College of Podiatric Medicine.

1.    Jupiter DC, Thorud JC, Buckley CJ, Shibuya N. The impact of foot ulceration and amputation on mortality in diabetic patients. I: From ulceration to death, a systematic review. Int Wound J.2016;13(5):892-903. 2.    Thorud JC, Plemmons B, Buckley CJ, Shibuya N, Jupiter DC. Mortality after nontraumatic major amputation among patients with diabetes and peripheral vascular disease: a systematic review. J Foot Ankle Surg. 2016;55(3):591-9. 3.    Larsson J, Agardh CD, Apelqvist J, Stenstrom A. Long-term prognosis after healed amputation in patients with diabetes. Clin Orthop Relat Res. 1998; 350:149–158. 4.    Hambleton IR, Jonnalagadda R, Davis CR, Fraser HS, Chaturvedi N, Hennis AJ. All cause mortality after diabetes-related amputation in Barbados: a prospective case control study. Diabetes Care. 2009; 32(8):306–307. 5.    Heikkinen M, Saarinen J, Suominen VP, Virkkunen J, Salenius J. Lower limb amputations: differences between the genders and long-term survival. Prosthet Orthot Int. 2007; 31(3):277–286. 6.    Sandnes DK, Sobel M, Flum DR. Survival after lower-extremity amputation. J Am Coll Surg. 2004; 199(3):394–402. 7.    Mayfield JA, Reiber GE, Maynard C, Czerniecki JM, Caps MT, Sangeorzan BJ. Survival following lower-limb amputation in a veteran population. J Rehabil Res Dev.2001; 38(3):341–345. 8.    Jones RN, Marshall WP. Does the proximity of an amputation, length of time between foot ulcer development and amputation, or glycemic control at the time of amputation affect the mortality rate of people with diabetes who undergo an amputation? Adv Skin Wound Care. 2008; 21(3):118–123. 9.    Subramaniam B, Pomposelli F, Talmor D, Park KW. Perioperative and long-term morbidity and mortality after above-knee and below-knee amputations in diabetics and nondiabetics. Anesth Analg. 2005; 100(5):1241–1247. 10.    Lavery LA, Hunt NA, Ndip A, Lavery DC, Van Houtum W, Boulton AJ. Impact of chronic kidney disease on survival after amputation in individuals with diabetes. Diabetes Care. 2010; 33(11):2365–2369. 11.    Thorud JC, Jupiter DC, Lorenzana J, Nguyen TT, Shibuya N. Reoperation and reamputation after transmetatarsal amputation: a systematic review and meta-analysis. J Foot Ankle Surg. 2016;55(5):1007-12 12.    Adler AI. Guilt, or guilt by association? Insulin therapy in type 2 diabetes and death. Lancet Diabetes Endocrinol. 2017;5(1):7-8. 13.    Holden SE, Jenkins-Jones S, Morgan CL, Schernthaner G, Currie CJ. Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer. Diabetes Obes Metab. 2015;17(4):350-62. 14.    Kurdibaylo SF. Cardiorespiratory status and movement capabilities in adults with limb amputation. J Rehabil Res Dev. 1994;31(3):222-35. 15.    Gailey RS, Wenger MA, Raya M, Kirk N, Erbs K, Spyropoulos P, Nash MS. Energy expenditure of trans-tibial amputees during ambulation at self-selected pace. Prosthet Orthot Int. 1994;18(2):84-91. 16.    Esposito ER, Rodriguez KM, Ràbago CA, Wilken JM. Does unilateral transtibial amputation lead to greater metabolic demand during walking? J Rehabil Res Dev. 2014;51(8):1287-96. 17.    Serizawa F, Sasaki S, Fujishima S, Akamatsu D, Goto H, Amada N. Mortality rates and walking ability transition after lower limb major amputation in hemodialysis patients. J Vasc Surg. 2016;64(4):1018-25. 18.    Wukich DK, Ahn J, Raspovic KM, Gottschalk FA, La Fontaine J, Lavery LA. Comparison of transtibial amputations in diabetic patients with and without end-stage renal disease. Foot Ankle Int. 2017; 38(4):388–96. 19.    Frykberg RG, Arora S, Pomposelli FB Jr, LoGerfo F. Functional outcome in the elderly following lower extremity amputation. J Foot Ankle Surg. 1998;37(3):181-5; discussion 261. 20.    Mandolfino T, Canciglia A, Salibra M, Ricciardello D, Cuticone G. Functional outcomes of transmetatarsal amputation in the diabetic foot: timing of revascularization, wound healing and ambulatory status. Updates Surg. 2016;68(4):401-405.

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