Risk Factors Associated with In-hospital Poor Outcomes in Patients with Acute Limb Ischemia

Acute limb ischemia (ALI) is a vascular emergency characterized by a sudden reduction in limb perfusion, most commonly caused by thromboembolism or in situ thrombosis over an atherosclerotic plaque.^1–4 In recent years, various minimally invasive treatment methods have been proposed, including catheter-directed thrombolysis (CDT),5 percutaneous thromboaspiration,⁶ and percutaneous mechanical thrombectomy.⁷ However, the reported results have been inconsistent. Furthermore, a metaanalysis by Enezate et al.,⁸ which included six clinical trials, compared the short- and medium-term outcomes of endovascular versus surgical interventions and found no significant differences in postoperative results. Notably, during the COVID-19 pandemic, an increase in thromboembolic events and ALI cases has been reported.^9–12

Several risk factors have been associated with poor outcomes after revascularization, including advanced clinical stages,^13,14 elevated systemic inflammation,^13–17 heart failure,¹⁷ and renal failure.¹⁷ Although multiple biomarkers have been investigated for their potential to predict short- and long-term outcomes in patients with ALI, none have yet been integrated into clinical practice.^13–17

The primary aim of this study was to identify and analyze risk factors associated with major amputation and inhospital mortality among patients with ALI.

In total, 177 patients were enrolled in the study, with a mean age of 71.37 ± 14.48 years, comprising 90 men (50.85%) and 87 women (49.15%). The most common comorbidity was hypertension, present in 133 patients (75.14%), followed by ischemic heart disease in 88 patients (49.72%), atrial fibrillation in 77 patients (43.50%), and diabetes mellitus in 50 patients (28.25%) (Table 1). Regarding surgical interventions, 156 patients (88.14%) underwent embolectomy using a Fogarty catheter, 14 patients (7.91%) required bypass grafting, and 7 patients (3.95%) underwent endarterectomy. In terms of anesthesia, the majority of patients (56.50%) received general anesthesia, one-third (33.33%) underwent local anesthesia, and 6.12% received regional block anesthesia. During hospitalization, 27 patients (15.25%) underwent major amputation, and 22 patients (12.43%) died (Table 1).

We observed that patients with lower limb ALI were significantly older than those with upper limb ALI (73.0 ± 14.19 vs. 68.21 ± 14.63 years; p = 0.041). Additionally, patients with lower limb ALI had a higher prevalence of ischemic heart disease (55.56% vs. 38.33%; p = 0.030), chronic heart failure (28.21% vs. 11.67%; p = 0.013), and peripheral arterial disease (30.77% vs. 5.0%; p < 0.001) (Table 1). Regarding laboratory parameters, patients with lower limb ALI had significantly red blood cell count (p = 0.034), hemoglobin (p = 0.010), and hematocrit (p = 0.011), along with higher levels of creatin kinase (p = 0.013), neutrophils (p = 0.017), and monocytes (p = 0.034) (Table 1). Although the types of surgical interventions did not differ significantly between groups, patients with lower limb ALI underwent local anesthesia less frequently (17.95% vs. 63.33%; p < 0.001) and general anesthesia more frequently (72.65% vs. 25.0%; p < 0.001).

Regarding thrombosis localization, in the upper limb, the brachial artery was most commonly affected, with involvement in 45 patients (75.0%), followed by the radial artery in 32 patients (53.33%) and again the radial artery in 30 patients (50.0%). Thrombosis of the axillary artery occurred in 15 patients (25.0%) and of the subclavian artery in 6 patients (10.0%) (Table 2). In the lower limb, the popliteal artery was most frequently involved, affecting 95 patients (81.19%), followed by the superficial femoral artery in 88 patients (75.21%) and the common femoral artery in 49 patients (41.88%). Thrombosis also involved the deep femoral artery in 33 patients (28.20%), the external iliac artery in 25 patients (21.36%), and the common iliac artery in 20 patients (17.09%) (Table 2).

Furthermore, univariate analysis identified several predictive factors associated with major amputation and in-hospital mortality. As shown in Table 3, peripheral arterial disease (OR 2.45; p = 0.046), elevated baseline WBC count (OR 1.92; p = 0.001), increased monocyte levels (OR: 1.67, p = 0.007), and platelet count (OR 1.51; p = 0.031) were significantly associated with an increased risk of major amputation during hospitalization.

Regarding in-hospital mortality, univariate analysis revealed that chronic heart failure (OR 2.77; p = 0.033), history of myocardial infarction (OR 3.85; p = 0.024), and diabetes mellitus (OR 3.23; p = 0.012) were significantly associated with poor postoperative outcomes. In addition, elevated baseline WBC count (OR 1.51; p = 0.041) and neutrophil levels (OR 1.98; p < 0.001) were also predictive of mortality (Table 4).

This study investigated the risk factors linked to major amputation and in-hospital mortality in patients with ALI affecting both upper and lower limbs. We provided a detailed analysis of the affected arterial segments, anesthesia methods, and surgical interventions performed at our center. Our short-term clinical outcomes, summarized in Table 1, revealed an amputation-free survival rate of 84.75% and a post-revascularization survival rate of 87.57%. Notably, among cardiovascular comorbidities, peripheral arterial disease was associated with an increased risk of major amputation, while chronic heart failure, previous myocardial infarction, and diabetes mellitus were correlated with higher in-hospital mortality rates. Therefore, stringent management of these comorbidities and preventive measures against their onset and progression might lower the long-term risk of ALI.

In a recent study published by El-Sayed et al.²³, the authors analyzed technical success, functional limb outcomes, and amputation risk in a cohort of 96 patients with upper limb ischemia, reporting a technical success rate of 76.4% and an in-hospital mortality rate of 7.3%. Similarly, in our cohort, patients with upper limb ischemia had a 6.67% rate of major amputation and in-hospital mortality. Additionally, Bae et al.²⁴ identified prolonged symptom duration (OR 1.251; p = 0.046) and elevated lactate dehydrogenase levels (OR 1.001; p = 0.031) as predictors of functional sequelae in patients with ALI. Regarding revascularization strategies in ALI, numerous studies have compared surgical, endovascular, and hybrid treatments, with inconsistent findings regarding short- and long-term benefits.^25–30 While Taha et al.,²⁷ Kolte et al.,²⁸ and Grip et al.³⁰ reported a higher short-term amputation rate following open revascularization compared to endovascular treatment, Davis et al.²⁵ and Veenstra et al.²⁶ found no significant differences between the two approaches.

This study has several limitations. Firstly, it was conducted on a relatively small patient cohort from a single tertiary center, which may limit the generalizability of the findings. Future research should include prospective, multicenter studies to assess whether addressing the identified risk factors can improve long-term outcomes. Secondly, patient follow-up was restricted to the in-hospital period; we aim to extend this in future studies to incorporate medium- and long-term outcomes. Additionally, the study exclusively included patients who underwent surgical revascularization, excluding those treated with endovascular approaches. Consequently, our findings cannot be generalized to all patients with ALI, highlighting the need for additional studies with larger patient groups.

Poor outcomes following surgical revascularization for both upper and lower limb ischemia are strongly associated with underlying cardiovascular comorbidities, including peripheral arterial disease, chronic heart failure, diabetes mellitus, and prior myocardial infarction. These findings underscore the importance of aggressive management of cardiovascular risk factors in patients with ALI to improve outcomes following surgical revascularization.