Role of regional tissue oxygen saturation (rSO₂) monitoring in lower limb ischemia during VA-ECMO: a retrospective case study

Role of regional tissue oxygen saturation (rSO₂) monitoring in lower limb ischemia during VA-ECMO: a retrospective case study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Role of regional tissue oxygen saturation (rSO₂) monitoring in lower limb ischemia during VA-ECMO: a retrospective case study Zhongzhi Xie, Shulin Xiang, Lin Han, Pang Jing, Zhenjia Liu, Huirong Shi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7417623/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and objectives VA-ECMO can provide circulatory support for critically ill patients with cardiogenic failure for periods ranging from several days to months; however, it may result in lower limb ischemia. This study aims to analyze and investigate the risk factors contributing to lower limb ischemia in VA-ECMO patients. Methods This study included 40 consecutive patients who received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support therapy and were admitted to the Intensive Care Unit (ICU) of the People's Hospital of Guangxi Zhuang Autonomous Region from May 2024 to May 2025. By analyzing and comparing differences in baseline characteristics, multivariate logistic regression analysis was applied to identify independent risk factors for lower extremity ischemia in patients treated with VA-ECMO. Results Among 40 VA-ECMO patients, 12 (30%) developed lower limb ischemia. Compared to the non-ischemia group, the ischemia group showed significantly lower values in regional oxygen saturation (rSO₂), bilateral lower limb rSO₂ difference, femoral catheter-to-artery diameter ratio (d/D), and antithrombin III (AT-III) levels (p Logistic regression analysis demonstrated that rSO₂ more accurately reflects the status of lower limb ischemia, with rSO₂, bilateral rSO₂ difference, d/D ratio, and AT-III all showing statistical significance. Multifactorial binary logistic regression analysis identified bilateral rSO₂ difference as an independent predictor of lower limb ischemia (OR = 1.692, p ROC curve analysis demonstrated that rSO₂ had a high predictive value for lower limb ischemia risk, with the highest predictive performance (AUC = 0.982) achieved through combined biomarker assessment. Conclusions rSO₂ monitoring enables early prediction of lower limb ischemia in VA-ECMO patients, demonstrating significant clinical value. When combined with complementary biomarkers, it further enhances predictive accuracy, offering high utility in clinical practice. Near-infrared spectroscopy Regional oxygen saturation Veno-arterial extracorporeal membrane oxygenation Acute lower limb ischemia Figures Figure 1 Background With the continuous advancement of medical technology and improvements in critical patient care, extracorporeal life support technologies have undergone rapid development in recent years. The utilization rate of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has shown exponential growth, driven by its increasing role in managing life-threatening cardiopulmonary failures[ 1 ]. In VA-ECMO, arterial cannulation sites include the femoral artery and the axillary artery. The femoral artery is often the preferred choice due to its superficial anatomical location and ease of access, making it a pragmatic option for rapid deployment in critical scenarios[ 2 ]. However, femoral artery cannulation in VA-ECMO may lead to acute limb ischemia in the ipsilateral extremity and even tissue necrosis.This has become a major complication of VA-ECMO technology, significantly and adversely affecting patient prognosis[ 3 ]. The current research focus is on preventing lower limb ischemia and optimizing distal blood perfusion in the lower extremities of VA-ECMO patients. Placing a distal perfusion catheter (DPC) in the limb ipsilateral to the arterial cannula is the primary method for preventing and mitigating ischemia in VA-ECMO patients[ 4 ]. However, this does not provide complete prevention. An ideal monitoring method should enable early detection of lower limb ischemia.The '6 Ps' are commonly used clinical indicators for observation, including pain, pallor, pulselessness, paresthesia, paralysis, and poikilothermia. These constitute the classic presentation of lower limb ischemia[ 5 ]. However, there are certain limitations. Alternatively, methods such as lower limb vascular color Doppler ultrasonography and biomarker tests—including hemoglobin, platelets, troponin, and myocardial enzymes—may be employed for prediction. However, these approaches fail to deliver accuracy, objectivity, and real-time capability, substantially compromising the clinical outcomes of patients with lower limb ischemia. There is an urgent clinical need for a convenient, rapid, non-invasive, and effective monitoring method to provide early warning for lower limb hemorrhage and ischemic adverse events in VA-ECMO patients.Near-infrared spectroscopy (NIRS) is a non-invasive and convenient technique that can effectively and rapidly monitor regional oxygen saturation (rSO₂). This mature technology has been routinely applied to monitor cerebral perfusion during cardiopulmonary bypass in cardiac surgery[ 6 ]. Studies have reported that when rSO₂ falls below 50% or decreases by more than 20% from baseline values, interventions to ensure adequate cerebral blood and oxygen supply should be initiated. Conversely, rSO₂ levels above 50% may indicate adequate limb perfusion[ 7 – 8 ]. Based on a retrospective summary and analysis of lower limb rSO₂ levels monitored by NIRS technology in VA-ECMO patients and related data, this study provides relevant clinical evidence for the association between rSO₂ levels and lower limb ischemia. Materials and methods Patients and study design This study enrolled 40 patients who received VA-ECMO treatment in the Intensive Care Unit of Guangxi Zhuang Autonomous Region People's Hospital between May 2024 and May 2025. Based on the diagnostic criteria for acute lower limb ischemia[ 9 ], patients were categorized into the ischemia group and the non-ischemia group. This study enrolled 40 patients who received VA-ECMO treatment. Inclusion criteria: (1) Patients receiving VA-ECMO support, aged 23–71 years; (2) SOFA score between 2 and 8 points; (3) Absence of lower extremity vascular diseases or traumatic injuries. Exclusion criteria: (1) Patients with pre-existing lower extremity fractures or vascular pathologies; (2) Patients who withdrew from ECMO therapy or died during the study period. This study received approval from the Ethics Committee of Guangxi Zhuang Autonomous Region People's Hospital (No. : KY-ZC-2025-001), and informed consent was waived due to the retrospective nature of the research. rSO₂Monitoring After cleansing the dorsal foot skin of the patients, NIRS monitoring probes (Cerebral and Regional Tissue Oxygen Saturation Monitor, Model: 01-06-X100, Jiangxi EluDeli Medical Technology Co., Ltd.) were placed. The rSO₂ value was recorded after 2 minutes of signal stabilization. For all patients undergoing VA-ECMO, dynamic monitoring was conducted over 24 hours, with values recorded every 6 hours. The lowest value was selected as the target value, and the bilateral rSO₂ difference was calculated (ΔrSO₂). Data collection Data regarding age, sex, smoking history, the ratio of arterial catheter diameter to femoral artery diameter (d/D), cannulated-side arterial rSO₂ (rSO₂), bilateral rSO₂ difference (ΔrSO₂), and the results of the first laboratory tests were obtained after the patient was admitted to the Intensive Care Unit (ICU) for treatment: white blood cell count (WBC), red blood cell count (RBC), hematocrit (HCT), hemoglobin (Hb), platelet count (PLT), blood lactate (Lac), creatine kinase (CK), myoglobin (Mb), D-dimer, interleukin-6 (IL-6), antithrombin III (AT-III), and fibrinogen (Fib). Statistical methods Statistical analysis was performed using SPSS 26.0 software. For continuous variables, the t-test was used if the data followed a normal distribution and were expressed as mean ± standard deviation (x̄ ± SD); otherwise, the rank-sum test was used, and the data were expressed as median and quartiles [Q (P25, P75)]. For categorical variables, the chi-square test was used and results were expressed as n (%). To identify independent risk factors, multivariable logistic regression analysis was performed using all variables that showed significant differences. The Receiver Operating Characteristic (ROC) curve was used to analyze the diagnostic performance of clinical indicators for lower limb ischemia after VA-ECMO, where an Area Under the Curve (AUC) of 0.5 indicated no predictive value, and an AUC closer to 1 indicated higher accuracy. Statistical significance was defined as P < 0.05. Results General information of the two patient groups A cohort of 40 VA-ECMO patients was included, among whom 12 developed lower limb ischemia (with outcomes: 10 resolved after intervention, 1 required amputation, and 1 discontinued treatment), resulting in an ischemia incidence rate of 30%. Comparison between the ischemic and non-ischemic groups revealed no significant differences in gender, age, smoking history, WBC, RBC, HCT, Hb, PLT, Lac, CK, Mb, D-dimer, IL-6, and Fib (P > 0.05). However, rSO₂, ΔrSO₂, d/D, and AT-III in the ischemic group were significantly lower than those of patients in the non-ischemic group (P See Table 1 for details. Independent risk factors associated with lower limb ischemia in VA-ECMO patients. Univariate binary logistic regression analysis was performed with significantly different indicators as independent variables and ischemia occurrence as the dichotomous dependent variable, and the results showed that d/D (adjusted OR 1.060; 95% CI, 1.009–1.113; P = 0.019), rSO₂ (adjusted OR 0.644; 95% CI, 0.496–0.864; P = 0.003), ΔrSO₂ (adjusted OR 1.983; 95% CI, 1.324–2.971; P = 0.001), and AT-III (adjusted OR 0.943; 95% CI, 0.895–0.995; P = 0.031) were all statistically significant. These independent variables were subsequently analyzed using multivariate binary logistic regression, revealing that ΔrSO₂ (adjusted OR 1.692; 95% CI, 1.033–2.772; P = 0.037) is an independent influencing factor for VA-ECMO-associated lower limb ischemia. See Table 2 for details. The ROC curve demonstrates that the area under the curve for rSO₂ was 0.952 (P < 0.001; 95% CI, 0.893–1.000), indicating high predictive value, and the four-marker panel demonstrated superior diagnostic accuracy, with an area under the curve of 0.982 (P < 0.001; 95% CI, 0.951–1.000). See Table 3 for details and Fig. 1 . Table 1 General information of the two patient groups Characteristics Non ischemic(n = 28) Ischemic(n = 12) p Age (years) 52.97 ± 13.28 47.41 ± 17.93 0.283 Male,gender (n,%) 20(71.43) 8(66.67) 0.763 Smoking History (n,%) 8(28.57) 2(16.67) 0.426 d/D(%) 68.71 ± 16.52 84.00 ± 15.77 0.010 rSO2(%) 58.00 ± 7.35 43.58 ± 4.21 0.000 ΔrSO2(%) 7(6.0,9.0) 16.5(16.0,17.5) 0.000 WBC(x10 9 /L) 12.53(10.12,17.47) 15.35(7.51,27.11) 0.555 RBC(x10 12 /L) 3.36 ± 1.05 3.35 ± 1.35 0.979 HCT(%) 29.17 ± 8.81 29.52 ± 10.65 0.913 Hb(g/L) 93.96 ± 27.20 94.50 ± 35.40 0.959 PLT(x10 9 /L) 125.50(63.50,195.00) 148.00(79.50,212.50) 0.745 Lac(mmol/L) 5.50(3.80, ,11.00) 9.40(3.10,16.75) 0.712 Mb(ng/mL) 457.50(102.95, 1206.00) 1027.40(221.00,3000.00) 0.123 ck(u/L) 336.50(106.00,4852.50) 492.50(114.00,2737.00) 1.000 D-Dimer(mg/L) 9.34(2.95,18.85) 13.32(8.35,19.37) 0.364 AL-6(pg/mL) 210.00(85.27,1034.00) 604.50(108.88,4171.50) 0.281 AT-III(%) 58.82 ± 17.22 45.75 ± 11.74 0.022 Fib 3.48(2.67,5.44) 3.74(1.76,4.70) 0.488 Note: d/D(Ratio of arterial catheter diameter to femoral artery diameter), rSO₂(Cannulated-Side Arterial rSO₂),ΔrSO₂(Bilateral rSO₂difference), WBC (White blood cell count), RBC (Red blood cell count), HCT (Hematocrit), Hb (Hemoglobin), PLT (Platelet count), Lac (Lac blood lactate), CK (Creatine kinase), MB (Myoglobin), IL-6 (Interleukin-6 ), AT-III (Antithrombin III), Fib (fibrinogen) Table 2 Univariate and multivariable analysis of ischemic complications in VA-ECMO patients Variables Univariate analysis Multivariable analysis OR 95% Cl p OR 95% Cl p d/D(%) 1.060 1.009–1.113 0.019 1.039 0.952–1.134 0.390 rSO 2 (%) 0.644 0.497–0.864 0.003 0.709 0.454–1.109 0.132 ΔrSO 2 (%) 1.983 1.324–2.971 0.001 1.692 1.033–2.772 0.037 AT-III(%) 0.943 0.895–0.995 0.031 0.966 0.851–1.096 0.598 Note: d/D(Ratio of arterial catheter diameter to femoral artery diameter), rSO₂(Cannulated-Side Arterial rSO₂),ΔrSO₂(Bilateral rSO₂difference), AT-III (Antithrombin III) Table 3 ROC Curve analysis results demonstrating diagnostic performance for lower limb ischemia in VA-ECMO patients Variables AUC SE P 95%CL d/D(%) 0.757 0.080 0.011 0.601–0.914 rSO 2 (%) 0.952 0.031 0.000 0.893−1.000 ΔrSO 2 (%) 0.940 0.058 0.000 0.827−1.000 AT-III(%) 0.722 0.082 0.028 0.561–0.883 four-marker panel 0.982 0.016 0.000 0.951−1.000 Note: d/D(Ratio of arterial catheter diameter to femoral artery diameter), rSO₂(Cannulated-Side Arterial rSO₂),ΔrSO₂(Bilateral rSO₂difference), AT-III (Antithrombin III) Discussion VA-ECMO technology involves withdrawing venous blood from the patient, oxygenating it via an artificial membrane lung, and returning the oxygenated blood to the arterial circulation. This system provides partial circulatory support for patients with refractory circulatory failure, sustaining vital perfusion for periods ranging from days to months[ 10 ]. This technology is also indicated for extracorporeal cardiopulmonary resuscitation (ECPR) in patients with cardiac arrest of varied etiologies[ 11 ]. With continuous technological advancements, the clinical applications of VA-ECMO are expanding rapidly across diverse medical scenarios[ 12 ]. Complications, including hemolysis, hemorrhage, infection, renal impairment, and lower limb ischemia, have been frequently reported in patients on VA-ECMO support. VA-ECMO cannulation approaches are categorized into central and peripheral techniques based on anatomical insertion sites. Central cannulation is typically indicated for transitioning from cardiopulmonary bypass to VA-ECMO support following open-heart surgery.Peripheral cannulation is more widely applied in clinical practice. The femoral vessels provide superficial anatomical positioning and ample operative space, allowing rapid bedside cannulation under color Doppler guidance with high procedural success rates—establishing this approach as the predominant cannulation strategy for adult VA-ECMO. However, patients on VA-ECMO support often present with circulatory failure and hemodynamic instability, necessitating vasoactive agents to maintain hemodynamic stability. Vasoactive agents induce potent vasoconstriction, reducing arterial lumen diameter and slowing intravascular flow. This hemodynamic alteration, when compounded by arterial cannulation, further impairs perfusion—potentially culminating in flow cessation—which predisposes patients to the development or exacerbation of lower limb ischemia[ 13 ]. Several studies have reported [ 14 – 15 ] that lower limb ischemia occurs in 10–70% of patients undergoing VA-ECMO support via peripheral cannulation, with 1.9–4.7% of these cases progressing to limb amputation. During VA-ECMO support, non-pulsatile blood flow, vascular endothelial injury, and thrombogenesis collectively contribute to distal hypoperfusion in the lower extremities.These pathophysiological alterations precipitate the development of limb ischemia, which not only severely compromise patients' quality of life but are also associated with elevated mortality rates[ 16 ]. Consequently, early identification, timely detection, and prompt intervention for lower limb ischemia are critical strategies to halt progression to irreversible ischemic damage in VA-ECMO patients. Early and effective surveillance methods are imperative for preventing irreversible complications. Although the "6P" syndrome (Pain, Pallor, Pulselessness, Paresthesia, Paralysis, Poikilothermia) remains a valuable clinical assessment tool, its utility is limited in patients with confounding factors such as edema, jaundice, or hypothermia—conditions that impede accurate evaluation of skin color and temperature. Pain assessment is not applicable in sedated and analgesized patients. Furthermore, the diagnostic latency inherent in clinical symptoms and physical signs (typically 6–24 hours post-ischemia onset) renders conventional monitoring modalities suboptimal for early detection of lower limb ischemia in VA-ECMO patients.These pathophysiological alterations precipitate the development of limb ischemia. While color Doppler ultrasonography enables anatomical vascular patency assessment, its diagnostic reliability is significantly compromised during VA-ECMO support due to the prevalent non-pulsatile flow characteristic of extracorporeal circulation. NIRS technology operates on the Lambert-Beer Law principle, quantifying rSO₂ by measuring differential light absorption between deoxygenated and oxygenated hemoglobin in the near-infrared spectrum (700–900 nm), where the attenuation of incident versus diffusely reflected light intensities correlates directly with tissue oxygenation states. Jobsis pioneered the application of near-infrared spectroscopy (NIRS) for regional tissue oxygen saturation (rSO₂) monitoring in 1977, as documented in his seminal Science publication [ 17 ]. Patton-Rivera et al. [ 18 ] demonstrated that NIRS-measured lower limb rSO₂ at 4 minutes predicted VA-ECMO-associated limb ischemia with 100% sensitivity and 95% specificity. Crucially, they established that an rSO₂ decline of ≥ 25% from baseline necessitates immediate clinical intervention.Consistent with our findings, the mean rSO₂ in the ischemic cohort of this study was 43.58% ± 4.21% (SD), representing a critical hypoperfusion threshold validated by current literature. Simultaneous bilateral near-infrared spectroscopy (NIRS) monitoring provides critical etiological differentiation for lower limb ischemia during ECMO support. An absolute rSO₂ difference > 15% between limbs strongly suggests cannulation-induced ischemia (sensitivity 92%, specificity 88%), whereas differences ≤ 15% indicate systemic hypoperfusion or microcirculatory failure, requiring distinct management strategies[19]. This study shows that rSO₂ has high value in predicting the risk of lower extremity ischemia (AUC = 0.952), and indicates that rSO₂, ΔrSO₂, d/D, and AT-III are all significant in predicting lower extremity ischemia. Combined detection has the highest predictive value, with a maximum AUC of 0.982. Conclusion IIn summary, this study included 40 patients treated with VA-ECMO, with the incidence of lower extremity ischemia being 30%. Lower extremity ischemia is caused by multiple factors, among which rSO₂ has a high predictive value for lower extremity ischemia. Monitoring rSO₂ can help identify patients with lower extremity ischemia at an early stage during VA-ECMO treatment, providing a basis for medical staff to formulate early treatment plans, reduce or halt the progression of lower extremity ischemic events, and improve the quality of treatment and patient satisfaction. Due to the small number of cases in this study, the research results need to be further verified. Declarations Acknowledgements Not applicable. Funding This study was supported by grants from Guangxi Clinical Medical Research Center for Severe Treatment of Major Infectious Diseases（Contract No. Guike AD22035101). Guangxi Health Commission Key Laboratory of Diagnosis and Treatment of Acute espiratory Distress Syndrome (Contract No. ZZH2020013) Data availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of Guangxi Zhuang Autonomous Region People’s Hospital (No. KY-ZC-2025-001). Since this study was retrospective, the requirement for informed consent was waived, and the clinical trial number was not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Lorusso R, Shekar K, MacLaren G, et al. ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients. ASAIO J. 2021;67(8):827–44. PMID: 34339398. Jayaraman AL, Cormican D, Shah P et al. 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Acta Neurol Scand Suppl. 1977;64:452–3. PMID: 268870. Wong JK, Smith TN, Pitcher HT, et al. Cerebral and lower limb near-infrared spectroscopy in adults on extracorporeal membrane oxygenation. Artif Organs. 2012;36(8):659–67. PMID: 22817780. Patton-Rivera K, Beck J, Fung K, et al. Using near-infrared reflectance spectroscopy (NIRS) to assess distal-limb perfusion on venoarterial (V-A) extracorporeal membrane oxygenation (ECMO) patients with femoral cannulation. Perfusion. 2018;33(8):618–23. PMID: 29848162. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7417623","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":511030121,"identity":"6eedce7a-e600-4d18-8a8d-20fd9990d27f","order_by":0,"name":"Zhongzhi Xie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIie3RsQrCMBCA4TsO4lLUMYLQV4gIHX0Ox4OAz9DBQSi0Y1cfQxCcK4W6FPoALvEN2tFFjJtbbxTMvx3k4zgCEAr9ZOiA0/1mRnR1QkIGXNvYRaGsERN85ISnLkrmIhBvLfasFK1rSADSyzhZtTVpjpbTpIadg/YuIEXZAGtFntwM5hKSkQI2hOcMcy0i8STzhP35REpGTPS5pWqsrhUZltwSHy0Oz5f/yrIbXJ9KtlTfE48Dv+UgeRUKhUL/3RvkvDeCU2fMfgAAAABJRU5ErkJggg==","orcid":"","institution":"Guangxi Zhuang Autonomous Region People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zhongzhi","middleName":"","lastName":"Xie","suffix":""},{"id":511030122,"identity":"8a9c4f9d-d930-46f1-835a-87dd498e5a19","order_by":1,"name":"Shulin Xiang","email":"","orcid":"","institution":"Guangxi Zhuang Autonomous Region People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shulin","middleName":"","lastName":"Xiang","suffix":""},{"id":511030123,"identity":"1bfa3c0a-ff97-4fa7-8e04-579676cb8f68","order_by":2,"name":"Lin Han","email":"","orcid":"","institution":"Guangxi Zhuang Autonomous Region People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Han","suffix":""},{"id":511030124,"identity":"45e2586e-63f2-4a8d-92db-0151c773becd","order_by":3,"name":"Pang Jing","email":"","orcid":"","institution":"Guangxi Zhuang Autonomous Region People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pang","middleName":"","lastName":"Jing","suffix":""},{"id":511030125,"identity":"ce737dff-ff08-4c46-92bd-cfc3e33b3f14","order_by":4,"name":"Zhenjia Liu","email":"","orcid":"","institution":"Guangxi Zhuang Autonomous Region People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhenjia","middleName":"","lastName":"Liu","suffix":""},{"id":511030126,"identity":"43b9da6f-ddd4-4596-b0e4-ec3ea1d08553","order_by":5,"name":"Huirong Shi","email":"","orcid":"","institution":"Guangxi Zhuang Autonomous Region People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Huirong","middleName":"","lastName":"Shi","suffix":""},{"id":511030127,"identity":"3f424762-5806-4c00-a340-aa5092810961","order_by":6,"name":"Bin Xiong","email":"","orcid":"","institution":"Guangxi Zhuang Autonomous Region People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Xiong","suffix":""}],"badges":[],"createdAt":"2025-08-20 12:53:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7417623/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7417623/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91071672,"identity":"49f335e7-6789-4b6e-945b-f8820c76bbcd","added_by":"auto","created_at":"2025-09-11 10:53:18","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":132767,"visible":true,"origin":"","legend":"\u003cp\u003eROC Curves of Predictors for Lower Limb Ischemia Risk in VA-ECMO Patients with Arterial Cannulation\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7417623/v1/3ad502cdeefa3dae6c02592f.jpeg"},{"id":104880942,"identity":"242e4e08-b503-40fb-9347-732475a4dffb","added_by":"auto","created_at":"2026-03-18 09:14:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":745635,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7417623/v1/900d3872-bfb3-4782-8d09-3be64729944d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Role of regional tissue oxygen saturation (rSO₂) monitoring in lower limb ischemia during VA-ECMO: a retrospective case study","fulltext":[{"header":"Background","content":"\u003cp\u003eWith the continuous advancement of medical technology and improvements in critical patient care, extracorporeal life support technologies have undergone rapid development in recent years. The utilization rate of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has shown exponential growth, driven by its increasing role in managing life-threatening cardiopulmonary failures[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In VA-ECMO, arterial cannulation sites include the femoral artery and the axillary artery. The femoral artery is often the preferred choice due to its superficial anatomical location and ease of access, making it a pragmatic option for rapid deployment in critical scenarios[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, femoral artery cannulation in VA-ECMO may lead to acute limb ischemia in the ipsilateral extremity and even tissue necrosis.This has become a major complication of VA-ECMO technology, significantly and adversely affecting patient prognosis[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The current research focus is on preventing lower limb ischemia and optimizing distal blood perfusion in the lower extremities of VA-ECMO patients. Placing a distal perfusion catheter (DPC) in the limb ipsilateral to the arterial cannula is the primary method for preventing and mitigating ischemia in VA-ECMO patients[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, this does not provide complete prevention. An ideal monitoring method should enable early detection of lower limb ischemia.The '6 Ps' are commonly used clinical indicators for observation, including pain, pallor, pulselessness, paresthesia, paralysis, and poikilothermia. These constitute the classic presentation of lower limb ischemia[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, there are certain limitations. Alternatively, methods such as lower limb vascular color Doppler ultrasonography and biomarker tests\u0026mdash;including hemoglobin, platelets, troponin, and myocardial enzymes\u0026mdash;may be employed for prediction. However, these approaches fail to deliver accuracy, objectivity, and real-time capability, substantially compromising the clinical outcomes of patients with lower limb ischemia. There is an urgent clinical need for a convenient, rapid, non-invasive, and effective monitoring method to provide early warning for lower limb hemorrhage and ischemic adverse events in VA-ECMO patients.Near-infrared spectroscopy (NIRS) is a non-invasive and convenient technique that can effectively and rapidly monitor regional oxygen saturation (rSO₂). This mature technology has been routinely applied to monitor cerebral perfusion during cardiopulmonary bypass in cardiac surgery[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Studies have reported that when rSO₂ falls below 50% or decreases by more than 20% from baseline values, interventions to ensure adequate cerebral blood and oxygen supply should be initiated. Conversely, rSO₂ levels above 50% may indicate adequate limb perfusion[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Based on a retrospective summary and analysis of lower limb rSO₂ levels monitored by NIRS technology in VA-ECMO patients and related data, this study provides relevant clinical evidence for the association between rSO₂ levels and lower limb ischemia.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003ePatients and study design\u003c/p\u003e\u003cp\u003e This study enrolled 40 patients who received VA-ECMO treatment in the Intensive Care Unit of Guangxi Zhuang Autonomous Region People's Hospital between May 2024 and May 2025. Based on the diagnostic criteria for acute lower limb ischemia[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], patients were categorized into the ischemia group and the non-ischemia group.\u003c/p\u003e\u003cp\u003eThis study enrolled 40 patients who received VA-ECMO treatment. Inclusion criteria: (1) Patients receiving VA-ECMO support, aged 23\u0026ndash;71 years; (2) SOFA score between 2 and 8 points; (3) Absence of lower extremity vascular diseases or traumatic injuries. Exclusion criteria: (1) Patients with pre-existing lower extremity fractures or vascular pathologies; (2) Patients who withdrew from ECMO therapy or died during the study period.\u003c/p\u003e\u003cp\u003e This study received approval from the Ethics Committee of Guangxi Zhuang Autonomous Region People's Hospital (No. : KY-ZC-2025-001), and informed consent was waived due to the retrospective nature of the research.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003erSO₂Monitoring\u003c/h2\u003e\u003cp\u003eAfter cleansing the dorsal foot skin of the patients, NIRS monitoring probes (Cerebral and Regional Tissue Oxygen Saturation Monitor, Model: 01-06-X100, Jiangxi EluDeli Medical Technology Co., Ltd.) were placed. The rSO₂ value was recorded after 2 minutes of signal stabilization. For all patients undergoing VA-ECMO, dynamic monitoring was conducted over 24 hours, with values recorded every 6 hours. The lowest value was selected as the target value, and the bilateral rSO₂ difference was calculated (ΔrSO₂).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eData regarding age, sex, smoking history, the ratio of arterial catheter diameter to femoral artery diameter (d/D), cannulated-side arterial rSO₂ (rSO₂), bilateral rSO₂ difference (ΔrSO₂), and the results of the first laboratory tests were obtained after the patient was admitted to the Intensive Care Unit (ICU) for treatment: white blood cell count (WBC), red blood cell count (RBC), hematocrit (HCT), hemoglobin (Hb), platelet count (PLT), blood lactate (Lac), creatine kinase (CK), myoglobin (Mb), D-dimer, interleukin-6 (IL-6), antithrombin III (AT-III), and fibrinogen (Fib).\u003c/p\u003e\n\u003ch3\u003eStatistical methods\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS 26.0 software. For continuous variables, the t-test was used if the data followed a normal distribution and were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x̄ \u0026plusmn; SD); otherwise, the rank-sum test was used, and the data were expressed as median and quartiles [Q (P25, P75)]. For categorical variables, the chi-square test was used and results were expressed as n (%). To identify independent risk factors, multivariable logistic regression analysis was performed using all variables that showed significant differences. The Receiver Operating Characteristic (ROC) curve was used to analyze the diagnostic performance of clinical indicators for lower limb ischemia after VA-ECMO, where an Area Under the Curve (AUC) of 0.5 indicated no predictive value, and an AUC closer to 1 indicated higher accuracy. Statistical significance was defined as P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eGeneral information of the two patient groups\u003c/h2\u003e\u003cp\u003eA cohort of 40 VA-ECMO patients was included, among whom 12 developed lower limb ischemia (with outcomes: 10 resolved after intervention, 1 required amputation, and 1 discontinued treatment), resulting in an ischemia incidence rate of 30%. Comparison between the ischemic and non-ischemic groups revealed no significant differences in gender, age, smoking history, WBC, RBC, HCT, Hb, PLT, Lac, CK, Mb, D-dimer, IL-6, and Fib (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, rSO₂, ΔrSO₂, d/D, and AT-III in the ischemic group were significantly lower than those of patients in the non-ischemic group (P See Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for details.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIndependent risk factors associated with lower limb ischemia in VA-ECMO patients.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUnivariate binary logistic regression analysis was performed with significantly different indicators as independent variables and ischemia occurrence as the dichotomous dependent variable, and the results showed that d/D (adjusted OR 1.060; 95% CI, 1.009\u0026ndash;1.113; P\u0026thinsp;=\u0026thinsp;0.019), rSO₂ (adjusted OR 0.644; 95% CI, 0.496\u0026ndash;0.864; P\u0026thinsp;=\u0026thinsp;0.003), ΔrSO₂ (adjusted OR 1.983; 95% CI, 1.324\u0026ndash;2.971; P\u0026thinsp;=\u0026thinsp;0.001), and AT-III (adjusted OR 0.943; 95% CI, 0.895\u0026ndash;0.995; P\u0026thinsp;=\u0026thinsp;0.031) were all statistically significant. These independent variables were subsequently analyzed using multivariate binary logistic regression, revealing that ΔrSO₂ (adjusted OR 1.692; 95% CI, 1.033\u0026ndash;2.772; P\u0026thinsp;=\u0026thinsp;0.037) is an independent influencing factor for VA-ECMO-associated lower limb ischemia. See Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e for details. The ROC curve demonstrates that the area under the curve for rSO₂ was 0.952 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 95% CI, 0.893\u0026ndash;1.000), indicating high predictive value, and the four-marker panel demonstrated superior diagnostic accuracy, with an area under the curve of 0.982 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 95% CI, 0.951\u0026ndash;1.000). See Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e for details and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGeneral information of the two patient groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNon ischemic(n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIschemic(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52.97\u0026thinsp;\u0026plusmn;\u0026thinsp;13.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47.41\u0026thinsp;\u0026plusmn;\u0026thinsp;17.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.283\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale,gender (n,%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20(71.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(66.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.763\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking History\u003c/p\u003e\u003cp\u003e(n,%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(28.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(16.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.426\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ed/D(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68.71\u0026thinsp;\u0026plusmn;\u0026thinsp;16.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erSO2(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.00\u0026thinsp;\u0026plusmn;\u0026thinsp;7.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.58\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔrSO2(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(6.0,9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.5(16.0,17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC(x10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.53(10.12,17.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.35(7.51,27.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.555\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRBC(x10\u003csup\u003e12\u003c/sup\u003e/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.979\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCT(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.17\u0026thinsp;\u0026plusmn;\u0026thinsp;8.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.52\u0026thinsp;\u0026plusmn;\u0026thinsp;10.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.913\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb(g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e93.96\u0026thinsp;\u0026plusmn;\u0026thinsp;27.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e94.50\u0026thinsp;\u0026plusmn;\u0026thinsp;35.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.959\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT(x10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e125.50(63.50,195.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e148.00(79.50,212.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.745\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLac(mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.50(3.80, ,11.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.40(3.10,16.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.712\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMb(ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e457.50(102.95, 1206.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1027.40(221.00,3000.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eck(u/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e336.50(106.00,4852.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e492.50(114.00,2737.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eD-Dimer(mg/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.34(2.95,18.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.32(8.35,19.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.364\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAL-6(pg/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e210.00(85.27,1034.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e604.50(108.88,4171.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.281\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAT-III(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.82\u0026thinsp;\u0026plusmn;\u0026thinsp;17.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.75\u0026thinsp;\u0026plusmn;\u0026thinsp;11.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFib\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.48(2.67,5.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.74(1.76,4.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.488\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: d/D(Ratio of arterial catheter diameter to femoral artery diameter),\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003erSO₂(Cannulated-Side Arterial rSO₂),ΔrSO₂(Bilateral rSO₂difference), WBC (White blood cell count), RBC (Red blood cell count), HCT (Hematocrit), Hb (Hemoglobin), PLT (Platelet count), Lac (Lac blood lactate), CK (Creatine kinase), MB (Myoglobin), IL-6 (Interleukin-6 ), AT-III (Antithrombin III), Fib (fibrinogen)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and multivariable analysis of ischemic complications in VA-ECMO patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u003cp\u003eMultivariable analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95%\u003cem\u003eCl\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95%\u003cem\u003eCl\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ed/D(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.060\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.009\u0026ndash;1.113\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.039\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.952\u0026ndash;1.134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.390\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erSO\u003csub\u003e2\u003c/sub\u003e(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.644\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.497\u0026ndash;0.864\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.709\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.454\u0026ndash;1.109\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.132\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔrSO\u003csub\u003e2\u003c/sub\u003e(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.983\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.324\u0026ndash;2.971\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.692\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.033\u0026ndash;2.772\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAT-III(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.943\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.895\u0026ndash;0.995\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.966\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.851\u0026ndash;1.096\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.598\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eNote: d/D(Ratio of arterial catheter diameter to femoral artery diameter),\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003erSO₂(Cannulated-Side Arterial rSO₂),ΔrSO₂(Bilateral rSO₂difference), AT-III (Antithrombin III)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eROC Curve analysis results demonstrating diagnostic performance for lower limb ischemia in VA-ECMO patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAUC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95%CL\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ed/D(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.757\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.080\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.601\u0026ndash;0.914\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erSO\u003csub\u003e2\u003c/sub\u003e(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.952\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.893\u0026minus;1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔrSO\u003csub\u003e2\u003c/sub\u003e(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.940\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.058\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.827\u0026minus;1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAT-III(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.722\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.082\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.561\u0026ndash;0.883\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efour-marker panel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.982\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.951\u0026minus;1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: d/D(Ratio of arterial catheter diameter to femoral artery diameter),\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003erSO₂(Cannulated-Side Arterial rSO₂),ΔrSO₂(Bilateral rSO₂difference), AT-III (Antithrombin III)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eVA-ECMO technology involves withdrawing venous blood from the patient, oxygenating it via an artificial membrane lung, and returning the oxygenated blood to the arterial circulation. This system provides partial circulatory support for patients with refractory circulatory failure, sustaining vital perfusion for periods ranging from days to months[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This technology is also indicated for extracorporeal cardiopulmonary resuscitation (ECPR) in patients with cardiac arrest of varied etiologies[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. With continuous technological advancements, the clinical applications of VA-ECMO are expanding rapidly across diverse medical scenarios[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Complications, including hemolysis, hemorrhage, infection, renal impairment, and lower limb ischemia, have been frequently reported in patients on VA-ECMO support. VA-ECMO cannulation approaches are categorized into central and peripheral techniques based on anatomical insertion sites. Central cannulation is typically indicated for transitioning from cardiopulmonary bypass to VA-ECMO support following open-heart surgery.Peripheral cannulation is more widely applied in clinical practice. The femoral vessels provide superficial anatomical positioning and ample operative space, allowing rapid bedside cannulation under color Doppler guidance with high procedural success rates\u0026mdash;establishing this approach as the predominant cannulation strategy for adult VA-ECMO. However, patients on VA-ECMO support often present with circulatory failure and hemodynamic instability, necessitating vasoactive agents to maintain hemodynamic stability. Vasoactive agents induce potent vasoconstriction, reducing arterial lumen diameter and slowing intravascular flow. This hemodynamic alteration, when compounded by arterial cannulation, further impairs perfusion\u0026mdash;potentially culminating in flow cessation\u0026mdash;which predisposes patients to the development or exacerbation of lower limb ischemia[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Several studies have reported [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] that lower limb ischemia occurs in 10\u0026ndash;70% of patients undergoing VA-ECMO support via peripheral cannulation, with 1.9\u0026ndash;4.7% of these cases progressing to limb amputation. During VA-ECMO support, non-pulsatile blood flow, vascular endothelial injury, and thrombogenesis collectively contribute to distal hypoperfusion in the lower extremities.These pathophysiological alterations precipitate the development of limb ischemia, which not only severely compromise patients' quality of life but are also associated with elevated mortality rates[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Consequently, early identification, timely detection, and prompt intervention for lower limb ischemia are critical strategies to halt progression to irreversible ischemic damage in VA-ECMO patients. Early and effective surveillance methods are imperative for preventing irreversible complications. Although the \"6P\" syndrome (Pain, Pallor, Pulselessness, Paresthesia, Paralysis, Poikilothermia) remains a valuable clinical assessment tool, its utility is limited in patients with confounding factors such as edema, jaundice, or hypothermia\u0026mdash;conditions that impede accurate evaluation of skin color and temperature. Pain assessment is not applicable in sedated and analgesized patients. Furthermore, the diagnostic latency inherent in clinical symptoms and physical signs (typically 6\u0026ndash;24 hours post-ischemia onset) renders conventional monitoring modalities suboptimal for early detection of lower limb ischemia in VA-ECMO patients.These pathophysiological alterations precipitate the development of limb ischemia. While color Doppler ultrasonography enables anatomical vascular patency assessment, its diagnostic reliability is significantly compromised during VA-ECMO support due to the prevalent non-pulsatile flow characteristic of extracorporeal circulation.\u003c/p\u003e\u003cp\u003eNIRS technology operates on the Lambert-Beer Law principle, quantifying rSO₂ by measuring differential light absorption between deoxygenated and oxygenated hemoglobin in the near-infrared spectrum (700\u0026ndash;900 nm), where the attenuation of incident versus diffusely reflected light intensities correlates directly with tissue oxygenation states. Jobsis pioneered the application of near-infrared spectroscopy (NIRS) for regional tissue oxygen saturation (rSO₂) monitoring in 1977, as documented in his seminal Science publication [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Patton-Rivera et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] demonstrated that NIRS-measured lower limb rSO₂ at 4 minutes predicted VA-ECMO-associated limb ischemia with 100% sensitivity and 95% specificity. Crucially, they established that an rSO₂ decline of \u0026ge;\u0026thinsp;25% from baseline necessitates immediate clinical intervention.Consistent with our findings, the mean rSO₂ in the ischemic cohort of this study was 43.58% \u0026plusmn; 4.21% (SD), representing a critical hypoperfusion threshold validated by current literature. Simultaneous bilateral near-infrared spectroscopy (NIRS) monitoring provides critical etiological differentiation for lower limb ischemia during ECMO support. An absolute rSO₂ difference\u0026thinsp;\u0026gt;\u0026thinsp;15% between limbs strongly suggests cannulation-induced ischemia (sensitivity 92%, specificity 88%), whereas differences\u0026thinsp;\u0026le;\u0026thinsp;15% indicate systemic hypoperfusion or microcirculatory failure, requiring distinct management strategies[19]. This study shows that rSO₂ has high value in predicting the risk of lower extremity ischemia (AUC\u0026thinsp;=\u0026thinsp;0.952), and indicates that rSO₂, ΔrSO₂, d/D, and AT-III are all significant in predicting lower extremity ischemia. Combined detection has the highest predictive value, with a maximum AUC of 0.982.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIIn summary, this study included 40 patients treated with VA-ECMO, with the incidence of lower extremity ischemia being 30%. Lower extremity ischemia is caused by multiple factors, among which rSO₂ has a high predictive value for lower extremity ischemia. Monitoring rSO₂ can help identify patients with lower extremity ischemia at an early stage during VA-ECMO treatment, providing a basis for medical staff to formulate early treatment plans, reduce or halt the progression of lower extremity ischemic events, and improve the quality of treatment and patient satisfaction. Due to the small number of cases in this study, the research results need to be further verified.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from Guangxi Clinical Medical Research Center for Severe Treatment of Major Infectious Diseases（Contract No. Guike AD22035101). Guangxi Health Commission Key Laboratory of Diagnosis and Treatment of Acute espiratory Distress Syndrome (Contract No. ZZH2020013)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Medical Ethics Committee of Guangxi Zhuang\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAutonomous Region People\u0026rsquo;s Hospital (No.\u0026nbsp;KY-ZC-2025-001). Since this study was retrospective, the requirement for informed consent was waived, and the clinical trial number was not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLorusso R, Shekar K, MacLaren G, et al. ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients. ASAIO J. 2021;67(8):827\u0026ndash;44. PMID: 34339398.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJayaraman AL, Cormican D, Shah P et al. Cannulation strategies in adult veno-arterial and veno-venous extracorporeal membrane oxygenation: Techniques, limitations, and special considerations. Ann Card Anaesth, 2017, 20(supplement): S11-S18. PMID: 28074818.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHu S, Lu A, Pan C, et al. Limb Ischemia Complications of Veno-Arterial Extracorporeal Membrane Oxygenation. Front Med (Lausanne). 2022;9:938634. PMID: 35911410.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarbach JA, Faugno AJ, Pacifici S, et al. Strategies to reduce limb ischemia in peripheral venoarterial extracorporeal membrane oxygenation: a systematic review and Meta-analysis. Int J Cardiol. 2022;361:77\u0026ndash;84. PMID: 35523371.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuglin M, Zucker MJ, Bazan VM, et al. Venoarterial ECMO for adults: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019;73(6):98\u0026ndash;716. PMID: 30765037.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLaflam A, Joshi B, Brady K, et al. Shoulder surgery in the beach chair position is associated with diminished cerebral autoregulation but no differences in postoperative cognition or brain injury biomarker levels compared with supine positioning: the anesthesia patient safety foundation beach chair study. Anesth Analg. 2015;120(1):176\u0026ndash;85. PMID: 25268397.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGerhard-Herman MD, Gornik HL, Barrett C et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol, 2017, 69(11): e71-e126. PMID: 27851992.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKayama T, Sano M, Inuzuka K, et al. A Pilot Study Investigating the Use of Regional Oxygen Saturation as a Predictor of Ischemic Wound Healing Outcome after Endovascular Treatment in Patients with Chronic Limb-Threatening Ischemia. Ann Vasc Dis. 2021;14(1):23\u0026ndash;30. PMID: 33786096.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJongkind V, Earnshaw JJ, Bastos Gon\u0026ccedil;alves F, et al. editors. 's Choice - Update of the European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia in Light of the COVID-19 Pandemic, Based on a Scoping Review of the Literature. Eur J Vasc Endovasc Surg, 2021, 63(1): 80\u0026ndash;89. PMID: 34686452.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePonikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891\u0026ndash;975. PMID: 27207191.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSwol J, Belohl\u0026aacute;vek J, Brodie D, et al. Extracorporeal life support in the emergency department: a narrative review for the emergency physician. Resuscitation. 2018;133:108\u0026ndash;17. PMID: 30336233.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBonicolini E, Martucci G, Simons J et al. Limb ischemia in peripheral veno-arterial extracorporeal membrane oxygenation: a narrative review of incidence, prevention, monitoring, and treatment. Crit Care, 2019, 23(1): 266. PMID: 31362770.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePozzi M, Koffel C, Djaref C, et al. High rate of arterial complications in patients supported with extracorporeal life support for drug\u0026emsp; intoxication-induced refractory cardiogenic shock or cardiac arrest. J Thorac Dis. 2017;9(7):1988\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYau P, Xia Y, Shariff S, et al. Factors Associated with Ipsilateral Limb Ischemia in Patients Undergoing Femoral Cannulation Extracorporeal Membrane Oxygenation. Ann Vasc Surg. 2018;54:60\u0026ndash;5. PMID: 30217709.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen KH, Chen YT, Yeh SL, et al. Changes in quality of life and health status in patients with extracorporeal life support: a prospective longitudinal study. PLoS ONE. 2018;13(5):e0196778. PMID: 29746522.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJ\u0026ouml;bsis FF. Non-invasive, infra-red monitoring of cerebral O2 sufficiency, bloodvolume, HbO2-Hb shifts and bloodflow. Acta Neurol Scand Suppl. 1977;64:452\u0026ndash;3. PMID: 268870.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWong JK, Smith TN, Pitcher HT, et al. Cerebral and lower limb near-infrared spectroscopy in adults on extracorporeal membrane oxygenation. Artif Organs. 2012;36(8):659\u0026ndash;67. PMID: 22817780.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatton-Rivera K, Beck J, Fung K, et al. Using near-infrared reflectance spectroscopy (NIRS) to assess distal-limb perfusion on venoarterial (V-A) extracorporeal membrane oxygenation (ECMO) patients with femoral cannulation. Perfusion. 2018;33(8):618\u0026ndash;23. PMID: 29848162.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Near-infrared spectroscopy, Regional oxygen saturation, Veno-arterial extracorporeal membrane oxygenation, Acute lower limb ischemia","lastPublishedDoi":"10.21203/rs.3.rs-7417623/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7417623/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and objectives\u003c/h2\u003e\u003cp\u003eVA-ECMO can provide circulatory support for critically ill patients with cardiogenic failure for periods ranging from several days to months; however, it may result in lower limb ischemia. This study aims to analyze and investigate the risk factors contributing to lower limb ischemia in VA-ECMO patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e This study included 40 consecutive patients who received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support therapy and were admitted to the Intensive Care Unit (ICU) of the People's Hospital of Guangxi Zhuang Autonomous Region from May 2024 to May 2025. By analyzing and comparing differences in baseline characteristics, multivariate logistic regression analysis was applied to identify independent risk factors for lower extremity ischemia in patients treated with VA-ECMO.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong 40 VA-ECMO patients, 12 (30%) developed lower limb ischemia. Compared to the non-ischemia group, the ischemia group showed significantly lower values in regional oxygen saturation (rSO₂), bilateral lower limb rSO₂ difference, femoral catheter-to-artery diameter ratio (d/D), and antithrombin III (AT-III) levels (p Logistic regression analysis demonstrated that rSO₂ more accurately reflects the status of lower limb ischemia, with rSO₂, bilateral rSO₂ difference, d/D ratio, and AT-III all showing statistical significance. Multifactorial binary logistic regression analysis identified bilateral rSO₂ difference as an independent predictor of lower limb ischemia (OR\u0026thinsp;=\u0026thinsp;1.692, p ROC curve analysis demonstrated that rSO₂ had a high predictive value for lower limb ischemia risk, with the highest predictive performance (AUC\u0026thinsp;=\u0026thinsp;0.982) achieved through combined biomarker assessment.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003erSO₂ monitoring enables early prediction of lower limb ischemia in VA-ECMO patients, demonstrating significant clinical value. When combined with complementary biomarkers, it further enhances predictive accuracy, offering high utility in clinical practice.\u003c/p\u003e","manuscriptTitle":"Role of regional tissue oxygen saturation (rSO₂) monitoring in lower limb ischemia during VA-ECMO: a retrospective case study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 10:53:12","doi":"10.21203/rs.3.rs-7417623/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b8b97f81-015d-492e-9349-754697a79091","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T09:12:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 10:53:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7417623","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7417623","identity":"rs-7417623","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}