Discussion
This study was designed to determine the survival distribution of all-level reamputations to both the ipsilateral and contralateral limbs and to assess whether reamputation rates are improving over time. We found high incidence rates for both categories of reamputation. At 1 year, the reamputation rate for all contralateral and ipsilateral reamputations was found to be 19% (IQR=5.1%–31.6%), and at 5 years, it was found to be 37.1% (IQR=27.0%–47.2%). The contralateral reamputation rate at 5 years was found to be 20.5% (IQR=13.3%–27.2%). There was no evidence of a trend in the reamputation rates over the period spanned by the studies in the meta-analysis (p=0.4; Kendall τ=−0.11).
Our results reflect the high recidivism rates following index amputations documented throughout the literature: for many patients with diabetes after an initial partial-foot amputation, a subsequent proximal amputation is required, sometimes at the transfemoral level.16 53 Murdoch et al42 reported that 1 year after index amputation, 60% of all patients had a second amputation, 21% had a third amputation, and 7% had a fourth amputation. Similarly, Kono and Muder34 reported that approximately 50% of patients required ipsilateral reamputation by 3 years after the index amputation. In addition to the reamputation rates, the reoperation rate has also remained high. A chart review of 52 patients found a total of 85 additional operations required, with some patients undergoing as high as four additional operations,64 although some patients included in this study had prior amputation history, so the subsequent amputations could be confounded by the progression of other underlying health conditions and thereby contribute to an overestimation of the reamputation rate. Nonetheless, evidence has suggested that patients with diabetes are at high risk of perioperative death,13 14 21 and therefore, any additional operations would presumably impose additional risk of mortality.
Our results suggest there has been no major change in the reamputation rate over a prolonged period. Follow-up work should investigate whether the incidence of reamputation is changing relative to the incidence of index amputation, but this more sophisticated analysis was outside the scope of the present investigation. Improvements in reamputation rate may be impeded by challenges of selecting the optimal level of index amputation, poor surgical wound healing and rehabilitation following amputation, and likelihood of recurrence of diabetic foot wounds particularly with the introduction of further foot deformity and gait deviation post amputation. Routinely, the most distal location is chosen for wounds in order to preserve the integrity of the remaining foot, resulting in an amputation of the digits. However, some studies have demonstrated that a lower level of index amputation is associated with higher risks of re-ulceration and a lower rate of healing.65 In addition, persons with diabetes can also experience a significant progression of the underlying disease process.21 This in turn leads to a higher risk of more proximal ipsilateral reamputation or amputation of the contralateral limbs.
Our review identified inconsistent anatomic definitions used among the studies, making comparisons across studies challenging. For example, a contralateral amputation was defined as amputation at or proximal to the transmetatarsal level on the opposite lower limb,30 any amputation of the contralateral foot or leg,8 42 or a new amputation at a lower level than the index amputation.56 Other studies either did not provide a precise definition21 or further divided subsequent amputations on the contralateral side by anatomical levels.19 38 Standardized definitions are needed for future research to mitigate the methodological discrepancies and allow for a more accurate comparison of published results regarding index and reamputation status.
We executed a comprehensive search strategy without any date restrictions and extracted articles that were cited by each of the identified studies. This allowed us to retrieve a high volume of articles and facilitated our examination of changes in the reamputation rate over time. The main strength of this study is that by reviewing and synthesizing the extant literature, we were able to provide an estimate of survival from reamputation for both limbs and for the contralateral limb. In addition, our review primarily focused on patients with diabetes, and therefore the results are relevant to clinical decision making and selection of the appropriate measures used to prevent reamputation in people with diabetes at high risk of future foot complications. This work contributes to existing knowledge of the high re-ulceration rate of the ipsilateral and contralateral limb. It has been estimated that after ulcer healing, 40% of patients have a recurrence within 1 year, and as high as 65% within 5 years. Taken together, the current evidence suggests the tremendous financial as well as the medical burden of foot complications on the diabetic population and highlights the importance of diabetic ulcer prevention.
This study had several limitations. First, like most meta-analyses, ours was limited by publication bias of the studies underlying our analysis. We believe that this limitation is somewhat mitigated in our case by the fact that we are not analyzing the results from the intervention groups of randomized studies but instead relying on data observational studies. Second, many studies identified were retrospective studies and thereby lacked granularity on the progression of reamputation status per year, which limited the amount of data available for our meta-analysis. This limited literature evidence revealed a need for more prospective research with extended follow-up periods, in order to synthesize long-term results and investigate the key determinants of the performance of different diabetic care systems. Finally, we did not perform a formal assessment of risks of bias because all papers included in this review were observational in nature and have a low risk of bias for our purposes.
The incidence of lower extremity reamputation is high among patients with diabetes who have undergone initial amputations secondary to diabetes. Long-term reamputation-free survival decreased with longer follow-up, and patients with diabetes are at a distinctly higher risk of reamputation at any follow-up lengths. For all-level or contralateral reamputation rates, the lack of significant downward trends over the past 50 years calls for improved prevention efforts. This systematic review and meta-analysis revealed high heterogeneity in study design and confirmed the need to standardize outcome reporting methods in future studies. Additional focus on prevention for those with recent amputations is necessary to reduce overall incidence of LEA.