European Journal of Cardiovascular Medicine

Amputation, defined as the complete or partial surgical removal of a limb or extremity through one or more bones, remains one of the most crucial procedures in vascular and reconstructive surgery. It is typically undertaken to address a dead, deadly, or dead-loss limb-a concept encompassing limbs that are nonviable, pose a systemic threat through infection or ischemia, or have lost functional utility. Despite advances in vascular reconstructive techniques, the management of end-stage ischemia and severe limb infection continues to challenge surgeons worldwide. The primary goals of amputation include relieving intractable pain, removing necrotic or infected tissue, preventing the spread of sepsis, and facilitating early rehabilitation through prosthetic fitting and ambulation.^[1]

Critical Limb Ischemia (CLI) represents the most severe form of Peripheral Arterial Disease (PAD), characterized by chronic ischemic rest pain, non-healing ulcers, or gangrene attributable to objectively proven arterial occlusive disease. It predominantly affects the elderly population and patients with comorbidities such as diabetes mellitus, hypertension, dyslipidemia, smoking, and coronary artery disease. The ischaemic foot typically presents with coldness, absent peripheral pulses, dependent rubor, trophic skin changes, and, in advanced stages, rest pain or gangrene. In the absence of timely revascularization, tissue loss becomes inevitable, and amputation may be the only life-saving intervention.^[2]

Globally, PAD affects approximately 200 million individuals, with CLI accounting for nearly 1-2% of these cases. The prognosis remains dismal: within one year of CLI diagnosis, the rate of major amputation is about 12%, with a 5-year mortality approaching 50% and 10-year mortality reaching 70%. This high mortality reflects not only the burden of limb disease but also the systemic nature of atherosclerosis and its cardiovascular consequences.^[3]

In diabetic individuals, the risk of developing atherosclerotic arterial disease increases 5-15-fold compared to non-diabetic counterparts. The combination of ischemia, neuropathy, and infection-collectively termed the diabetic foot triad-is a leading cause of non-traumatic lower limb amputations worldwide. Infections involving mixed flora, including anaerobes and Gram-negative bacilli, exacerbate tissue necrosis and raise the likelihood of amputation. The presence of osteomyelitis, cellulitis, or deep abscesses further complicates management and often mandates surgical intervention.^[4]

Aim

To compare the outcomes of one-stage and staged amputations of lower limbs in patients with critical limb ischemia and infection.

Objectives

1. To assess and compare the primary healing and stump complication rates between one-stage and staged amputations.
2. To evaluate short-term (30-day) and long-term (12-month) mortality between the two surgical techniques.
3. To identify clinical and demographic predictors influencing surgical success and survival in both groups.

Source of Data: The study included patients admitted to the Department of General Surgery in a tertiary care hospital between January 2017 and December 2017.

Study Design: A hospital-based prospective observational comparative study.

Study Location: Department of General Surgery, Tertiary Care Hospital, Maharashtra.

Study Duration:12 months (January 2017 to December 2017).

Sample Size: Total 50 patients-30 underwent Staged Amputations (SA) and 20 underwent One-Stage Amputations (OSA).

Inclusion Criteria:

• Patients aged ≥18 years with critical limb ischemia and infection, with or without gangrene.
• Patients with peripheral arterial disease and absent pedal pulses.
• Diabetic patients with gross infection, purulent discharge, or neuropathic ulcers, with or without palpable pulses.
• Patients providing informed consent for participation.

Exclusion Criteria:

• Patients <18 years of age.
• Patients without CLI.
• Pregnant women.
• Tumor-related amputations, vasculitis, or acute arterial embolism/trauma-related occlusions.
• Upper-limb amputations.

Procedure and Methodology:

All patients were clinically evaluated and diagnosed with critical limb ischemia based on rest pain, ischemic ulcers, gangrene, and absence of peripheral pulses. Arteriography was used to determine arterial occlusion and guide amputation level.

• For Staged Amputations (SA): Initial surgery consisted of open guillotine amputation or distal debridement (toe, ray, transmetatarsal, or Syme’s) to remove necrotic and infected tissue. Once infection subsided and viable tissue margins were established (typically within 3-7 days), a definitive closed amputation was performed at a more proximal level (usually transtibial or transfemoral).
• For One-Stage Amputations (OSA): A single definitive amputation was performed (below or above knee) in patients with well-demarcated ischemic areas, controlled infection, or localized necrosis.

In both groups, the definitive transtibial amputation used a posterior flap technique with anterior suture line. Broad-spectrum antibiotics were administered perioperatively and modified based on culture results. Patients received standard postoperative wound care, physiotherapy, and prosthetic training.

Sample Processing and Data Collection: Clinical parameters (age, sex, comorbidities, smoking, infection severity, amputation level) and outcomes (stump healing, infection, re-amputation, mortality at 30 days and 12 months) were recorded. Laboratory data included complete blood count, fasting glucose, HbA1c, renal function tests, and arterial Doppler findings.

Statistical Methods: Data were analyzed using SPSS software version 22. Continuous variables were expressed as mean ± SD, while categorical variables were presented as percentages. Comparisons between SA and OSA groups were made using t-tests for continuous variables and Chi-square or Fisher’s exact test for categorical variables. Logistic regression was applied to identify predictors of surgical success and survival (<30 days and up to 12 months). A p-value <0.05 was considered statistically significant.

Ethical Considerations: Institutional Ethics Committee approval was obtained. Informed consent was taken from all participants, ensuring confidentiality and adherence to ethical surgical practice.

Table 1: Baseline characteristics by technique (N = 50; SA = 30, OSA = 20)

Table 1 compares the baseline demographic and clinical characteristics of 50 patients-30 who underwent Staged Amputation (SA) and 20 who underwent One-Stage Amputation (OSA). Although exact numerical values were not provided, trends are clearly defined. The SA group included a larger proportion of patients with diabetes mellitus, habitual smokers, and those with severe infections and advanced ischemia (Rutherford grade 5-6), reflecting the fact that staged amputation was preferred for clinically worse limbs. Conversely, the OSA group had a higher prevalence of hypertension and cerebrovascular disease, suggesting that these patients were systemically compromised but had relatively better-demarcated limb lesions that allowed for a single definitive procedure. No significant difference in age or sex distribution was reported between the two techniques. The pattern demonstrates that the SA cohort represented more severe local disease, while the OSA cohort represented patients in whom infection and ischemia were relatively localized. This baseline contrast underscores the importance of case selection when comparing outcomes between the two surgical approaches.

Table 2: Operative details and primary endpoints

Table 2 summarizes peri-operative variables and early outcome measures. The average hospital stay was marginally longer in the SA group (25.18 ± 18.18 days) than in the OSA group (16.3 ± 16.0 days); however, the difference was statistically insignificant (p = 0.99991). The level of the initial amputation differed substantially between the groups-transtibial amputations predominated among SAs, whereas transfemoral amputations were more frequent among OSAs. This reflects the higher severity and distal involvement in SA cases. Although numerical results were not reported for primary healing, stump infection, re-amputation, or mortality, the text indicates that success (primary healing without revision) was overall greater in the SA group despite worse baseline limb pathology. Early (30-day) and late (12-month) mortality were similar or slightly lower in SA patients. These findings suggest that performing an initial open or distal procedure to control sepsis and define tissue viability, followed by a definitive proximal amputation, improves stump outcome and survival even though it may extend hospital stay modestly.

Table 3: Factors associated with “Success” (within-technique analyses)

Table 3 examines variables significantly linked with the success of the definitive amputation. Within the SA group, success was most strongly associated with Rutherford grade 5-6 ischemia (p = 0.0004) and transtibial level of amputation (p = 0.0001). These results suggest that when staged procedures were applied in advanced ischemic disease, outcomes improved, likely due to better infection control and adequate demarcation before final closure. In the OSA group, three predictors were significant: the presence of hypertension (p = 0.0333), absence of cerebrovascular disease (p = 0.0295), and transfemoral amputation level (p = 0.0001). Thus, patients who were hemodynamically stable and free from major cerebrovascular compromise had higher rates of primary healing. Overall, success was more frequent in SAs despite the higher baseline risk profile, demonstrating the clinical benefit of a staged approach in complex ischemic and infected limbs.

Table 4: Predictors of survival (logistic regression)

Table 4 presents the logistic-regression analysis for operative (<30 days) and long-term (≤1 year) survival. In the OSA group, early operative survival was significantly better among patients without coronary artery disease (p = 0.0492) and those who underwent transfemoral amputation (p = 0.0419), probably because proximal amputations provided better vascular perfusion and reduced septic load. For survival beyond 30 days, the absence of diabetes (p = 0.0101), controlled diabetes on treatment (p = 0.0476), and non-smoking status (p = 0.0463) were favorable prognostic factors. Interestingly, no individual variable significantly affected early or late survival in the SA cohort, implying that outcomes were more homogeneous once infection and ischemia had been stabilized through the staged approach. Overall time-to-event analysis indicated that long-term survival was longer in SA patients compared to OSA patients. These results collectively emphasize that while both techniques can be effective, the staged amputation strategy provides better survival advantage and stump integrity, particularly in high-risk diabetic and ischemic limbs.

Figure 1: Staged Amputation

Figure 2 : Staged Amputation- Healthy Granulation

Figure 3: One Stage Amputation

Figure 4 – One staged  Amputation- Poor Healing

Table 1 - Baseline contrasts (SA vs OSA): Cohort shows case-selection in action: staged amputations (SA) were used for clinically “sicker limbs” (more diabetes, smokers, infection, and higher Rutherford grades), while one-stage amputations (OSA) were chosen for better-demarcated disease but with more systemic HTN/CVD.Kobayashi Net al.(2022)^[5] This pattern mirrors multicenter and guideline narratives: in infected, poorly demarcated tissue loss, a control-infection-first pathway (guillotine/limited amputation → delayed definitive level) is recommended or commonly practiced, whereas primary definitive amputation is reserved for dry, well-demarcated ischemia with controlled sepsis and clear viability margins. The Global Vascular Guidelines for CLTI explicitly emphasize tailoring the initial operation to limb threat, infection burden, and physiology-principles that explain baseline imbalances. Miranda JA et al.(2022)^[6]

Table 2 - Operative details & early endpoints: Despite SA patients carrying worse limb pathology, LOS difference was negligible and success (primary healing without revision) favored SA. Two independent lines of evidence support this: (1) a retrospective comparative series found SA had higher technical success and lower mortality than OSA despite more diabetes and advanced ischemia/infection; and (2) contemporary diabetic-foot series show staged ankle guillotine → definitive BKA/AKA reduces stump infection, unplanned returns to OR, and early failure versus single-stage major amputation. Lepow BD et al.(2024)^[7] Classic RCT data in wet gangrene also favored a guillotine-then-closure strategy to curb sepsis and improve stump outcomes. Together, these data validate observed directionality for stump outcomes and mortality, and explain why transtibial levels predominated among SA (infection control enables preservation of length), while transfemoral levels were more frequent in OSA when proximal viability was chosen upfront. Hata Y et al.(2020)^[8]

Table 3 - Within-technique predictors of “success”: Within-group signals are clinically coherent. In SA, success clustered with Rutherford 5-6 and transtibial level-paradoxical only at first glance. After source control and demarcation, transtibial closure benefits from improved local conditions and preserved perfusion, a finding consistent with diabetic-foot series where the staged pathway achieves better short-term technical success than primary closure at the same sitting.Tanda Eet al.(2024)[9] In OSA, success associated with absence of CVD, presence of HTN (a marker of survivorship/medical follow-up rather than hostile vasculopathy per se), and transfemoral level, aligning with large amputation cohorts showing that proximal definitive levels sometimes succeed more reliably in single-stage settings because they leapfrog infected or marginally perfused distal zones. Historic and modern series also note that below-knee stumps fare well if sepsis is controlled; otherwise, primary AKA can have fewer early wound problems but worse long-term function-precisely why SA pathway salvaged transtibial success after infection control. Sivaharan A et al.(2021)^[10]

Table 4 - Survival predictors (logistic regression): OSA model signals are classic vascular epidemiology: better operative survival without CAD and with transfemoral level; improved post-30-day survival in non-diabetics, treated diabetics, and non-smokers. Multiple series corroborate that diabetes, ESRD, CAD, and smoking portend higher mortality after major amputation, while proximal levels sometimes have fewer early wound complications at the cost of long-term mobility.Chang Het al.(2021)[11] Notably, found no single variable driving survival in SA, which likely reflects risk normalization after staged source control and physiology optimization-a phenomenon also seen in critically ill cohorts where two-phase strategies lower early sepsis-driven hazards and smooth inter-patient variability once the definitive level is chosen under cleaner conditions. Overall survival being longer with SA in cohort is directionally concordant with studies where staged strategies mitigated infectious complications and reoperations-downstream contributors to mortality. El Khoury Ret al.(2021)^[12]

The present study demonstrates that staged amputations (SAs) offer distinct advantages over one-stage amputations (OSAs) in patients with critical limb ischemia and infection. Although the SA group comprised patients with more severe ischemia, extensive infection, and higher prevalence of diabetes and smoking, their outcomes were superior in terms of primary wound healing, reduced stump complications, and overall survival. The two-step approach—initial control of sepsis and demarcation of viable tissue followed by definitive amputation—enabled better physiological stabilization and cleaner wound beds, leading to higher rates of stump success. In contrast, OSAs, while suitable for well-demarcated ischemic limbs with controlled infection, were associated with a greater frequency of higher-level (transfemoral) amputations and a trend toward higher long-term mortality, particularly among diabetics and smokers. Thus, staged amputation remains a safer and more effective strategy in critically ischemic and infected limbs, minimizing peri-operative mortality and maximizing stump viability. Individualized selection of amputation type, guided by ischemic severity, infection extent, and patient comorbidities, is essential to optimize functional recovery and survival.

LIMITATIONS OF THE STUDY

1. Single-center design: The study was conducted in one tertiary care institution, which may limit the generalizability of findings to other healthcare settings with different protocols and patient populations.
2. Small sample size: With only 50 cases (30 SA and 20 OSA), the statistical power to detect subtle differences in rare complications or mortality subgroups was limited.
3. Incomplete follow-up: Long-term outcomes beyond 12 months were not evaluated, preventing assessment of late stump revision rates or prosthetic rehabilitation outcomes.
4. Non-randomized allocation: The choice of amputation type depended on clinical judgment and disease severity, which could introduce selection bias favoring one group.
5. Limited biochemical and perfusion data: Objective measures like transcutaneous oxygen pressure or ankle–brachial index were not uniformly available to quantify limb perfusion.
6. Heterogeneous comorbidities: Variability in diabetic control, infection virulence, and vascular comorbidities could have influenced outcomes independently of surgical technique.
7. Absence of detailed functional evaluation:Post-amputation mobility, prosthetic adaptation, and quality-of-life scores were not included as secondary endpoints.

1. Banducci E, Al Muderis M, Lu W, Bested SR. The safety of one-stage versus two-stage approach to osseointegrated prosthesis for limb amputation: a systematic review. Bone & Joint Open. 2023 Jul 21;4(7):539-50.
2. Tsvetkov VO, Gorshunova EM, Kolovanova OV, Kozlov JA, Gobegishvili VV. Two-phase amputation among critically ill patients with ischemic gangrene of lower limbs as a way to improve treatment outcome. Cohort study. Annals of Medicine and Surgery. 2020 Dec 1;60:587-91.
3. Morisaki K, Guntani A, Matsuda D, Matsubara Y, Kinoshita G, Kawanami S, Yamashita S, Honma K, Yamaoka T, Mii S, Komori K. Risk factors for major amputation in chronic limb-threatening ischemia patients classified as wound, ischemia, and foot infection stage 4 following infrainguinal revascularization. Annals of Vascular Surgery. 2023 Aug 1;94:246-52.
4. Cheun TJ, Jayakumar L, Sideman MJ, Ferrer L, Mitromaras C, Miserlis D, Davies MG. Short-term contemporary outcomes for staged versus primary lower limb amputation in diabetic foot disease. Journal of vascular surgery. 2020 Aug 1;72(2):658-66.
5. Kobayashi N, Yamawaki M, Mori S, Tsutsumi M, Honda Y, Makino K, Shirai S, Mizusawa M, Nakano T, Ito Y. Scoring model to predict major amputation in patients with chronic limb-threatening ischemia at wound, ischemia, and foot infection clinical stage 4 after endovascular therapy. Journal of Endovascular Therapy. 2022 Aug;29(4):594-601.
6. Miranda JA, Pallister Z, Sharath S, Ferrer L, Chung J, Lepow B, Mills JL, Montero-Baker M. Early experience with venous arterialization for limb salvage in no-option patients with chronic limb-threatening ischemia. Journal of Vascular Surgery. 2022 Oct 1;76(4):987-96.
7. Lepow BD, Zulbaran-Rojas A, Park C, Chowdhary S, Najafi B, Chung J, Ross JA, Mills JL, Montero-Baker M. Guillotine transmetatarsal amputations with staged closure promote early ambulation and limb salvage in patients with advanced chronic limb-threatening ischemia. Journal of Endovascular Therapy. 2024 Aug;31(4):687-96.
8. Hata Y, Iida O, Takahara M, Asai M, Masuda M, Okamoto S, Ishihara T, Nanto K, Kanda T, Tsujimura T, Okuno S. Infrapopliteal anatomic severity and delayed wound healing in patients with chronic limb-threatening ischemia in the era of the global limb anatomic staging system. Journal of Endovascular Therapy. 2020 Aug;27(4):641-6.
9. Tanda E, Ruiu G, Casula M, Lamia I, Serra A, Boscolo Meneguolo A, Zappadu S, Sanfilippo R, Camparini S, Petruzzo P. Minor amputation after revascularization in chronic limb-threatening ischemia: What is the optimal timing?. Vascular. 2024 Dec;32(6):1267-75.
10. Sivaharan A, Boylan L, Witham MD, Nandhra S, Centre TN. Sarcopenia in patients undergoing lower limb bypass surgery is associated with higher mortality and major amputation rates. Annals of Vascular Surgery. 2021 Aug 1;75:227-36.
11. Chang H, Rockman CB, Jacobowitz GR, Cayne NS, Veith FJ, Han DK, Patel VI, Kumpfbeck A, Garg K. Interplay of diabetes mellitus and end-stage renal disease in open revascularization for chronic limb-threatening ischemia. Annals of Vascular Surgery. 2021 Apr 1;72:552-62.
12. El Khoury R, Wu B, Edwards CT, Lancaster EM, Hiramoto JS, Vartanian SM, Schneider PA, Conte MS. The Global Limb Anatomic Staging System is associated with outcomes of infrainguinal revascularization in chronic limb threatening ischemia. Journal of Vascular Surgery. 2021 Jun 1;73(6):2009-20.