Acute Limb Ischemia: Clinical Guidelines

List of Abbreviations

BP – blood pressure

AC – anticoagulation

PAA – popliteal artery aneurysm

ASA – acetylsalicylic acid**

aPTT – activated partial thromboplastin time

CI – confidence interval

DSA – digital subtraction angiography

D-US – duplex ultrasonography

ЕОК – European Society of Cardiology

ESVS – European Society for Vascular Surgery

PTA – posterior tibial artery

MALE – major adverse limb events

PAD – peripheral arterial disease

VQI – Vascular Quality Initiative

RPBI – regional pressure branch index

CK – creatine kinase

CS – compartment syndrome

CTA – computed tomography angiography

CDT – catheter-directed thrombolysis (local endovascular transarterial thrombolysis)

UCDT – ultrasound-guided catheter-directed thrombolysis (local endovascular transarterial thrombolysis)

ABI – ankle-brachial index

PSV – peak systolic velocity

IU – international unit

CE-MRA – contrast-enhanced magnetic resonance angiography

LE – lower extremities

LMWH – low molecular weight heparin (ATC B01AB Heparin group)

NIS – National Inpatient Sample

UFH – unfractionated heparin (sodium heparin**)

CFA – common femoral artery

ALI – acute limb ischemia

RR – relative risk

OR – odds ratio

AAO – acute aortic occlusion

DOAC – direct oral anticoagulants (ATC B01AE Direct thrombin inhibitors, B01AF Direct factor Xa inhibitors)

SFA – superficial femoral artery

ATA – anterior tibial artery

RCT – randomized controlled trial

rt-PA – recombinant tissue plasminogen activator

IRI – ischemia-reperfusion injury

DSP – digital systolic pressure

CRP – C-reactive protein

TS – duplex scanning

CDU – color duplex ultrasonography

DUDS – duplex ultrasound angioscanning

PMT – pharmacomechanical thrombolysis

AF – atrial fibrillation

CSA – arterial angiography or digital subtraction angiography (DSA)

ECG – electrocardiography

ECMO – extracorporeal membrane oxygenation

Terms and Definitions

Embolism – acute occlusion of an artery by pathological particles (usually thrombi) circulating through the arterial or venous bed.

Stage embolism – multiple acute occlusions of an arterial vessel at different levels.

Fan (or scattering) embolism – simultaneous embolism into different vascular beds (e.g., left internal carotid + left brachial + superior mesenteric arteries).

Paradoxical embolism – acute occlusion of an artery by thrombus particles that have migrated from the venous bed in the presence of an atrial or ventricular septal defect.

Acute arterial thrombosis – sudden cessation of blood flow due to obstruction of the arterial lumen by a thrombus formed in an area of altered vessel wall (disease, trauma).

Arterial spasm – a functional state caused either by closed non-penetrating injury (contusion) or open penetrating trauma (puncture, catheterization).

Acute arterial (aortic) dissection – tear of the arterial (aortic) intima with blood penetrating between the layers of the vessel wall, often accompanied by complete occlusion of the vessel lumen and the development of acute limb ischemia.

Embolectomy, embólothrombectomy, thrombectomy – various options for removing emboli and/or thrombi from the lumen of the arterial bed.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Acute limb ischemia (ALI) or acute arterial insufficiency of the extremities (AAIE) – sudden cessation or reduction of arterial perfusion of a limb with a potential threat to its survival, requiring urgent diagnosis and treatment. Acute limb ischemia is considered when the duration of symptoms is less than two weeks.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

1.2.1 Etiology

The main causes of ALI are thrombosis, embolism, trauma, and vascular spasm. Among the causes of non-traumatic ALI, the most common is acute arterial thrombosis in the area of a previously performed bypass graft or stent, or the progression of atherosclerosis in the aorta and limb vessels [1–4]. There is an increase in the proportion of ALI associated with thrombosis of pathologically altered arteries or embolization into the atherosclerotic bed, which significantly affects the choice of treatment strategy [5].

Risk factors for ALI in patients with stable chronic limb ischemia associated with atherosclerotic disease include prior peripheral revascularization, atrial fibrillation (AF), a lower ankle-brachial index (ABI) [6], and a history of major amputation [7].

Quite rarely, ALI can be caused by thrombosis of arterial aneurysms (usually the popliteal artery) and aortic dissection.

In 90–96% of cases, the cause of arterial emboli is cardiac disease (coronary artery disease, myocardial infarction, AF, atherosclerotic cardiomyopathies, valvular heart disease). Over the past century, there has been an overall shift in the etiology of embolism from rheumatic or congenital valvular heart disease in relatively young patients to embolization due to cardiac pathology caused by atherosclerotic processes [8]. Iatrogenic causes include arterial injuries during endovascular procedures (balloon angioplasty, stenting, endografting).

About 10% of lower limb embolisms are caused by mural thrombi or the disruption of atherosclerotic plaques in the aorta and major arteries, including cases triggered by endovascular repair of an abdominal aortic aneurysm [9, 10].

The main causes of ALI are presented in Table 1.

Table 1. Main causes of acute limb ischemia.

Significantly less common causes include venous thrombosis with the development of paradoxical emboli (via cardiac shunt defects); vasculitis and vasoneuropathies (Raynaud's disease for the upper extremities, thromboangiitis obliterans for the lower extremities); hypercoagulable states (antiphospholipid syndrome, Factor V Leiden mutation, and protein C/S deficiency), among others [11–14] (Table 2).

Table 2. Rare causes of acute limb ischemia.

In patients with acute limb ischemia, the risk of major adverse cardiovascular events is 1.4 times higher, mortality is 3.3 times higher, and the risk of major amputation is 14.2 times higher compared to patients with intermittent claudication [15–19].

A sharp increase in the incidence of acute limb ischemia was noted during the COVID-19 (SARS-CoV-2) pandemic, more than 3-fold higher compared to patients who did not have coronavirus infection [20, 21].

1.2.2 Pathogenesis

Acute limb ischemia (ALI) is the result of a sudden decrease in arterial blood flow, rapidly leading to tissue necrosis due to insufficient time for collateral pathway development.

Main mechanisms:

– Rapid arterial occlusion (typically at a bifurcation site) with thrombus propagation in both directions, occlusion of collaterals, and exacerbation of ischemia.

– Secondary thrombosis, vascular spasm, and venous thrombosis worsen the condition.

– Against the background of atherosclerosis, the process may begin more slowly, but progresses just as rapidly once collateral pathways are blocked.

At the cellular level:

– Ion balance disruption → muscle edema, compression, hypoxia, metabolic acidosis.

– Cell membrane rupture, potassium release (hyperkalemia), phospholipase activation, accumulation of toxic products (free fatty acids, myoglobin), which enhances tissue damage.

Irreversible muscle necrosis develops within 4–6 hours in case of embolism or within 12–24 hours in case of thrombosis following arterial occlusion [22–29].

1.3 Epidemiology of the Disease or Condition

The incidence of acute limb ischemia (ALI) remains low: according to various sources, it ranges from 1 to 2 cases per 100,000 population per year [12, 30]. This rate is higher in the lower extremities at 9–16 per 100,000, whereas for the upper extremities it is only 1–3 cases per 100,000 [30, 31]. In the EUCLID study among patients with intermittent claudication, ALI occurred in 1.7% of patients, corresponding to an incidence of 0.8 cases per 100 patient-years [12, 30].

In Sweden, the incidence of ALI ranged from 3 to 14 cases per 100,000 person-years, predominantly in patients older than 80 years [33, 34]. In the USA, an analysis of data from 1988–2007 showed a decrease in hospital admission rates for ALI from 42.4 to 23.3 per 100,000 population, as well as a decrease in in-hospital mortality (from 8.3% to 6.3%) and amputation rates (from 8.1% to 6.4%) [35, 36]. Similar figures were reported in Sweden [37–39].

Despite earlier revascularization, the prognosis remains unfavorable: the amputation rate reaches 10–15% [12, 30]. The use of thrombolysis in 20.7% of patients is associated with improved outcomes [40], although data on the pattern of amputations are limited: 34% of them were performed above the knee within 30 days after admission [41].

1.4 Features of Coding the Disease or Condition

Arterial embolism and thrombosis (I74)

I74.0 Embolism and thrombosis of abdominal aorta;

I74.1 Embolism and thrombosis of other and unspecified parts of aorta;

I74.2 Embolism and thrombosis of arteries of upper extremities;

I74.3 Embolism and thrombosis of arteries of lower extremities;

I74.5 Embolism and thrombosis of iliac artery;

I74.8 Embolism and thrombosis of other arteries;

I74.9 Embolism and thrombosis of unspecified artery;

I77.0 Acquired arteriovenous fistula;

I77.8 Other specified disorders of arteries and arterioles;

S55.1 Injury of radial artery at forearm level.

1.5 Classification of the disease or condition

The classification of acute circulatory disorders has undergone numerous modifications. In Russia, the classification of acute limb ischemia proposed in 2002 by I.I. Zatevakhin et al. is adopted (Table 3) [22]

Table 3. Classification of acute limb ischemia.

The classification is based on clinical signs, which does not limit its applicability. As the degree of ischemia increases, new auxiliary signs appear while retaining the main features inherent to lower degrees of ischemia. The course of ischemia can be stable, progressive, or regressive (Table 4) [42].

Table 4. Clinical manifestations of acute ischemia.

The 2020 ESVS guidelines recommend using the Rutherford classification of acute limb ischemia (Table 5) [43, 44].

Table 5. Rutherford clinical categories of acute limb ischemia.

This is an identical copy of the table in the 1997 publication by Rutherford et al., with the exception of the asterisks (*)*. The original 1997 version stated that arterial Doppler signals are never detectable in stage IIA, and that rigor is always observed in stage III. According to the authors of the ESVS guidelines, there may be exceptions to these rules.

1.6 Clinical presentation of the disease or condition

The clinical presentation of ALI is variable and depends on multiple factors: the cause of arterial obstruction, underlying pathology, level of occlusion, degree of ischemia, and clinical course of ischemia [22, 26].

The classic clinical presentation of acute limb ischemia is characterized by the "6 Ps": pain, pulselessness, pallor, poikilothermia, paresthesia, and paralysis [45–49].

Signs of severe ischemia:

• Subfascial edema: very tense edema, typically extending from the foot to the knee joint or from the hand to the elbow joint (limb is in critical condition);

• Muscular and joint contracture: patient's inability to move the toes and perform plantar flexion of the foot, as well as absence of passive joint movements (limb is non-viable).

The typical clinical picture of ALI is characterized by rapidly progressive ischemia; a stable course of ischemia is observed much less frequently, and its regression or latent course is extremely rare.

2. Diagnostics, medical indications and contraindications for diagnostic methods

2.1 Complaints and Anamnesis

LoE 5; GoR C

Comment: Classically, the so-called "six Ps" are recognized as the primary clinical criteria for establishing the diagnosis [53]:

1. Pain (Sudden-onset, severe, distal, often not associated with exertion. May radiate proximally along the limb).

2. Pallor (The limb becomes pale, mottled, or cyanotic).

3. Pulselessness (Absence of pulses distal to the level of occlusion).

4. Paresthesia (Numbness, tingling sensation. A sign of neural involvement).

5. Paralysis or paresis (A sign of critical ischemia and impending necrosis).

6. Poikilothermia (Cold limb. A decrease in temperature of the affected limb is noted).

The main complaints in ALI include:

− Pain in the affected limb: in most cases, the first sign of acute arterial obstruction. Pain is particularly severe in cases of embolism.

− Numbness, coldness, paresthesias: pathognomonic symptoms of acute arterial obstruction.

When taking a history, it is important to pay attention to risk factors and comorbidities typical of ALI, prior arterial reconstructions, malignancies, and concurrent drug therapy, especially antiplatelet agents other than heparin and antithrombotic medications.

In all other respects, patient interview in acute limb ischemia follows the general principles of clinical medicine.

2.2 Physical Examination

Physical examination for suspected ALI should include assessment of all peripheral pulses and exclusion of visceral ischemia. It is critical to differentiate ALI from conditions with similar presentations (neurological disorders, deep vein thrombosis). Cardiac examination is performed considering a probable embolic source, without delaying treatment.

LoE 5; GoR C

Comment: There is a lack of high-quality scientific evidence in the literature regarding the methodology of general clinical examination of patients with ALI. Therefore, examination should be performed in accordance with the general principles of clinical medicine, paying attention to clinical signs of diseases and conditions that increase the risk of ALI (arrhythmias, acute myocardial infarction, history of limb arterial reconstructions), as well as potential signs of embolic occlusion of other aortic branches (brachiocephalic, visceral) (Appendix G1).

LoE 5; GoR C

Comment: Assessment of local status should include inspection and palpation of the limb. Inspection assesses skin color, signs of paresis/paralysis, trophic changes, and the nature of pain (Appendix G2-3). Palpation assesses limb temperature, arterial pulsations, signs of subfascial edema, muscle tenderness, and joint contractures.

LoE 5; GoR C

Detection of peripheral arterial pulses becomes more reliable when determining the ABI using a continuous-wave Doppler device [41]. In ALI, the ABI is also a prognostic indicator of outcome, and an index <0.7 is critical. Loss of sensory and motor function indicates an immediately threatened limb and requires prompt revascularization.

All features of clinical presentations are reflected in the ALI classification by I.I. Zatevakhin et al. (2002) (Table 6)

Table 6. Classification of acute limb ischemia (Zatevakhin I.I. et al., 2002) [23]

2.3 Laboratory Diagnostics

LoE 4; GoR C

Comment: Ensuring a comprehensive evaluation of the patient's general condition, identifying risk factors, metabolic abnormalities, and comorbidities, as well as preparing for potential emergency surgical or endovascular intervention to reduce the risk of complications and improve prognosis. Mandatory laboratory evaluation for patients with ALI includes a complete blood count (CBC) with hemoglobin, RBC, WBC, and platelet counts, differential WBC count, and hematocrit. Concurrently, a urinalysis is performed, as well as an erythrocyte sedimentation rate (ESR) when indicated. Coagulation profile: prothrombin (thromboplastin) time in blood or plasma, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen level, and D-dimer concentration in blood. Antithrombin III activity testing in blood is performed when indicated.

A general therapeutic routine blood biochemistry panel must cover renal function parameters (blood creatinine and blood urea tests), blood glucose testing, blood electrolyte composition (blood sodium, potassium, and chloride tests), liver enzymes (blood alanine aminotransferase (ALT) activity assay and blood aspartate aminotransferase (AST) activity assay), blood total bilirubin level test, blood serum C-reactive protein level test, blood lactic acid level test, as well as nonspecific markers of tissue ischemia and cytolysis: blood lactate dehydrogenase (LDH) activity assay and blood creatine kinase (CK) activity assay. If concomitant acute coronary syndrome or myocardial involvement in the ischemic process is suspected, blood troponin I and T testing is required.

All patients undergo primary AB0 blood group typing and Rhesus system D antigen (Rh factor) testing, as well as infection screening: HBsAg qualitative test (HBs antigen, hepatitis B virus surface antigen), Anti-HCV-total (antibodies to hepatitis B virus antigens), HIV 1 and 2 antibodies, and HIV 1 and 2 antigen (HIV Ag/Ab Combo). In the presence of epidemiological indications or in accordance with local sanitary and epidemiological regulations, COVID-19 screening is performed: detection of SARS-CoV-2 coronavirus RNA in nasopharyngeal and oropharyngeal swab samples by RT-PCR, and determination of IgM antibodies (qualitative, to S protein) and IgG antibodies (quantitative, to S protein).

Additionally, based on clinical necessity, acid-base balance and blood gas testing can be performed, especially in pronounced ischemia or signs of metabolic acidosis, with determination of pH, pCO₂, pO₂, HCO₃⁻, base excess, and lactate. In cases of thrombosis in young patients or with recurrent episodes in the anamnesis, it is advisable to test for antiphospholipid syndrome, including the determination of blood anticardiolipin antibodies, antiphospholipid antibodies, and anti-β₂-glycoprotein I antibodies. This allows for the identification of antiphospholipid syndrome, which is one of the causes of thrombotic complications, and the adjustment of further treatment and prevention tactics. If hemolysis is suspected, additional tests are performed: blood haptoglobin level test, blood reticulocyte level test, and blood lactate dehydrogenase (LDH) activity assay.

The primary laboratory panel must be completed within the first hour after patient admission. Follow-up tests are ordered dynamically — before initiating thrombolytic therapy, surgical intervention, and also in case of patient deterioration or the development of complications.

• In adult patients with suspected ALI, it is recommended to determine blood creatine kinase and lactate dehydrogenase activity, blood myoglobin level, and detect myoglobin in urine to confirm the diagnosis. [58–60]

LoE 5; GoR C

Comment: There are no comparative studies in the literature regarding the algorithm for laboratory diagnosis of ALI. Characteristic laboratory signs of stage 2-3 acute limb ischemia include an elevation in plasma levels of creatine phosphokinase (CPK), myoglobin (Mb), and lactate dehydrogenase (LDH) [59, 60]. According to Currie et al., an elevated CPK concentration was the strongest predictor of early major limb amputation [59]. Laboratory signs of myoglobinuria and acute kidney injury may also be present [60].

Several clinical studies have confirmed the significance of markers of ALI and reperfusion syndrome [60]. Myoglobin and creatine kinase (CK) are well-known markers of skeletal muscle damage resulting from ischemia and rhabdomyolysis. CK is widely used as a marker of reperfusion syndrome and can assist in the decision-making process in ALI by assessing the risk of major amputation or limb salvage [59].

• For adult patients with signs of acute limb ischemia, it is recommended to use myoglobin and creatine kinase parameters upon hospitalization to decide on the feasibility of revascularization or primary amputation [58–60].

LoE 5; GoR C

Comment: there are no data in the literature linking lactate levels to the severity of ALI. European guidelines on mesenteric ischemia (ESVS 2017) do not recommend using serum lactate for the diagnosis of acute mesenteric ischemia, as it is a late sign of generalized hypoperfusion and is frequently within normal limits in the early acute phase [61].

2.4 Instrumental Diagnostics

• For patients with signs of acute limb ischemia, diagnostic imaging is recommended to determine the treatment plan, provided that its performance does not delay the initiation of treatment or the need for amputation is not obvious [62].

LoE 5; GoR C

Comment: in cases of suspected ALI, the time spent on imaging must be strictly limited so as not to delay emergency revascularization. The diagnostic phase should not exceed two hours from the moment of patient admission, especially in Rutherford grade IIa-IIb ischemia.

Most data on the accuracy of non-invasive imaging are based on studies in patients with chronic ischemia. Imaging of the distal runoff remains challenging due to insufficient collateral development in ALI.

2.4.1 Arterial Angiography or Digital Subtraction Angiography (DSA)

In the context of diagnostic accuracy, digital subtraction angiography (DSA) is still considered the gold standard examination in ALI [62]. This study must be performed within 20 minutes of admission to the hospital. DSA can establish the etiology and provides the advantage of unobstructed treatment; in modern practice, the possibility of its performance should be considered in combination with endovascular surgical intervention. A typical sign of embolic occlusion in this case is the presence of a horseshoe-shaped occlusion site or a "meniscus" sign combined with a normal appearance of other vessels. Thrombotic occlusion is characterized by the detection of atherosclerotic lesions in other areas of the vascular bed, with a developed collateral network. Arterial access during DSA should be chosen so as to evaluate both inflow and outflow. DSA in children with ALI is permissible and justified if performed in a specialized vascular/pediatric hospital setting with safety measures, minimal radiation exposure, and contrast load control.

2.4.2 Ultrasound Examinations in Acute Limb Ischemia

Ultrasound diagnostics for limb ischemia should be performed as quickly as possible after patient admission.

It includes:

1. Ultrasound Doppler examination (USDG) with evaluation of blood flow waveforms, segmental pressure, and regional systolic pressure indices, including the ankle-brachial index (ABI).

2. Duplex scanning, which allows for determining structural changes in arteries, the degree and extent of the lesion, the state of inflow and outflow, as well as collateral circulation.

The ABI is the ratio of systolic pressure in the artery at the ankle level to the pressure in the brachial artery. According to F. Fowkes et al. (2013), the sensitivity of ABI is 80%, and specificity is 95% [63].

Evaluation of the lesion should be performed only through a comprehensive analysis of parameters — Doppler waveform and RSPI, with mandatory consideration of central hemodynamics [64–66].

2.4.3 Computed tomography angiography of vessels

LoE 1; GoR B

Comment: despite the established link between the use of V08A — iodinated radiocontrast agents and acute kidney injury (AKI), the risk of their use becomes relative in life-threatening conditions. According to the guidelines of the European Society of Urogenital Radiology, the safe contrast agent administration threshold is lowered to a glomerular filtration rate of 30 mL/min/1.73 m² [67, 68].

The scanning zone usually extends from the head to the renal arteries and feet, with an average length of 120 cm. If visualization of distal vessels is insufficient (e.g., in femoropopliteal aneurysm or slow blood flow), a repeat study is required [69]. The advantage of CTA lies in the simultaneous evaluation of the thoracic and abdominal aorta, mesenteric vessels, and the detection of extravascular findings [52].

2.4.4 Contrast-enhanced magnetic resonance angiography (MRA)

LoE 1; GoR B

Comment: contrast-enhanced MR angiography visualizes arteries and veins similarly to conventional angiography, but requires precise timing of the scan due to contrast dynamics. The method has limited availability, long acquisition times, and is rarely used in acute limb ischemia (ALI). Venous return artifacts may occur, which are partially eliminated with four-dimensional imaging. In patients with chronic peripheral artery disease, the sensitivity of MR angiography for detecting stenosis >50% is 93%, and specificity is 94% [70].

2.4.5 Summary of imaging methods

According to current data, DSA, CTA, duplex ultrasound, and MR angiography can be used for the diagnosis of ALI, taking into account the experience of a particular institution, the availability of methods, and organizational conditions (Table 7).

Table 7. Summary of imaging modalities in acute limb ischemia [6].

∗ Availability largely depends on local conditions.

LoE 5; GoR C

Comment: There are no high-quality comparative studies in the literature regarding the instrumental diagnostic algorithm for ALI. Existing imaging methods for lower extremity arterial disease — duplex scanning of upper/lower extremity arteries, CTA, magnetic resonance angiography, arterial angiography, or digital subtraction angiography (DSA) — have sufficiently high sensitivity and specificity and are used in patients with ALI [5, 12, 16–18, 76, 83–90]. It is acceptable to omit vascular imaging in situations where the patient has unambiguous indications for primary high limb amputation [52, 64].

2.5 Other Procedures

2.5 Diagnosis of post-ischemic syndrome and reperfusion injury

• For patients who underwent revascularization for acute lower limb ischemia, clinical examination is recommended to diagnose post-ischemic compartment syndrome [87, 89].

LoE 5; GoR C

Comment: The diagnosis of compartment syndrome is largely based on clinical symptoms, but their sensitivity is insufficient, which may delay diagnosis [82]. Sensory impairment usually occurs early, but motor deficits eventually resolve completely in only 13% of patients [83]. Fascial compartment pressure exceeding 20–30 mmHg has high sensitivity and specificity (94%–98%) for compartment syndrome, but some authors believe the absolute value should be related to the mean arterial pressure at that moment [90, 91]. Compartment pressure is rarely measured routinely [91, 92]; indeed, routine measurement after reperfusion may even lead to over-treatment [92].

• Measurement of fascial compartment pressure is recommended for adults to diagnose post-ischemic syndrome when clinical diagnosis is difficult [91, 92].

LNC 5 LeC C

Comment: Several authors have attempted to identify risk factors for compartment syndrome, including ischemia duration >6 hours, young age, history of ALI, and hypotension [93]. Others found that elevated serum creatine kinase (CK), insufficient intraoperative retrograde blood flow, and a positive fluid balance were associated with compartment syndrome following ALI treatment [94]. However, based on years of experience from leading national clinics, only the severity of acute ischemia stage IIb (according to the classification by I.I. Zatevakhin et al.) serves as an indication for fasciotomy during revascularization.

According to the 2020 ESVS guidelines, fasciotomy should be performed within two hours after the onset of compartment syndrome.

2.6 Diagnosis of acute upper extremity ischemia

LeveL of Evidence (LoE) 4; Grade of Recommendation (GoR) C

LeveL of Evidence (LoE) 4; Grade of Recommendation (GoR) C

Comment: Clinical examination in acute upper limb ischemia (AULI) includes evaluation of complaints, medical history, and physical examination findings. Patients are more frequently female and older compared to those with lower limb ischemia [97]. Main symptoms: pain, paresthesia, paralysis. Objective findings include decreased or absent pulse (on the brachial, radial, ulnar arteries), skin color changes, and decreased skin temperature. Additionally, blood pressure measurement on both arms and auscultation of the subclavian arteries are performed.

In the absence of motor and sensory deficits, muscle tenderness, and preserved arterial Doppler signals (Rutherford class IIa), conservative treatment with anticoagulants is possible. However, even with preserved limb viability, dynamic circulatory disturbances can occur, causing exercise-induced pain and reduced quality of life [98].

LoE 4; GoR C

Comment: Arterial imaging in acute upper limb ischemia is not always necessary. It can be avoided in typical cardiac-origin embolism (atrial fibrillation, short-duration symptoms, preserved pulse). When atypical ischemia is suspected (compression syndrome, cervical rib, post-radiation therapy thrombosis, aneurysm, aortic dissection), imaging is mandatory. If the artery is patent, duplex ultrasound or DSA is recommended to confirm compression syndrome [99].

• Duplex ultrasound is recommended as an effective method for assessing the nature, location, extent, and severity of lesions in each segment of the limb arterial bed [99].

LoE 5; GoR C

Comment: Measurement of the wrist-brachial index (WBI) is equal to the ratio of systolic pressure in the forearm arteries to the systemic systolic pressure in the brachial artery of the contralateral limb [99].

• CT angiography of one anatomical region is recommended for adults as a diagnostic method to establish the localization of arterial lesions in ALI [99].

LoE 5; GoR C

Comment: CT angiography allows the detection of stenoses using intravenous contrast enhancement. The image is formed from a series of transverse slices and can be visualized in three planes. Modern multidetector CT angiography has advantages over X-ray contrast angiography: 3D reconstructions provide multiplanar vascular assessment [108, 109].

LoE 5; GoR C

Comment: As with duplex scanning, MRA allows determination of the localization and degree of arterial stenosis, and arterial visualization is similar to standard angiography. The evaluation of MRA accuracy depends on the technologies used, which currently allow 2D and 3D visualization, gadopentetate dimeglumine** contrast enhancement, subtraction, and cardiac gating.

• Digital subtraction angiography (DSA) is recommended for adults as a method providing the investigator with detailed information about arterial anatomy and for planning revascularization [100].

LoE 5; GoR C

Comment: Arterial angiography is an accessible and widely used method whose results are easily interpreted by specialists. Advances in X-ray equipment (digital subtraction angiography, reduced catheter diameter, selective catheterization) have improved visualization quality and procedural safety. Subtraction angiography provides sharper vascular images compared to traditional angiography.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Decision-making algorithm for acute limb ischemia

First aid

• For patients with acute limb ischemia awaiting revascularization, it is recommended to administer heparin sodium** in doses appropriate for their condition [102–104].

LOD 4; LoE C

Comment: First aid for acute limb ischemia includes adequate pain management and immediate intravenous administration of unfractionated heparin sodium** (UFH): a bolus of 5,000 IU or 70–100 IU/kg, followed by continuous infusion under aPTT monitoring. Target values are 1.5–2.5 times the control; monitoring is performed 6 hours after initiation or dose adjustment, and then daily.

Pediatric dosage: a bolus of 75–100 IU/kg over 10 min, followed by continuous infusion: 25–30 IU/kg/h in infants under one year of age, 18–20 IU/kg/h in children over one year (target aPTT level 60–85 s).

Antithrombotic therapy reduces the risk of recurrent embolism and thrombosis propagation, and exerts an anti-inflammatory effect [91, 92]. However, randomized trials confirming the efficacy of UFH in acute limb ischemia are lacking [106, 107, 108].

If thrombocytopenia, including heparin-induced thrombocytopenia, is suspected, replacement therapy is required [109]. Additionally, infusion therapy and oxygen therapy are administered [110].

Additionally, infusion therapy and oxygen therapy are administered [111]. Administration of UFH should be initiated immediately after diagnosis in the emergency department. Patients with thrombocytopenia require a hematology consultation.

In some cases, palliative treatment is indicated [104].

• For patients with acute limb ischemia awaiting revascularization, it is recommended to provide supplemental oxygen therapy [89, 111].

LoE 5; GoR C

• For patients with acute limb ischemia awaiting revascularization, it is recommended to administer appropriate pain management and infusion therapy [89, 106, 107].

LoE 5; GoR C

LoE 5; GoR C

3.2 Pharmacotherapy

3.2.1 General provisions

Medical treatment for acute ischemia as monotherapy has low efficacy, and there are no proven drugs to eliminate it. However, pharmacotherapy is important in the pre- and postoperative periods, as well as an alternative to surgery in the presence of contraindications and low-grade ischemia.

Goals of conservative treatment:

• prevention of thrombosis progression,

• thrombus lysis,

• improvement of blood flow in ischemic tissues,

• maintenance of vital organ functions.

Antithrombotic therapy is based on correcting disorders in all links of hemostasis: coagulation, fibrinolysis, and platelet aggregation.

3.2.2 Medications for medical therapy

The use of heparin sodium** and its derivatives is described in the recommendations section «3.1 First aid».

To reduce the risk of cardiovascular complications and prevent the progression of atherosclerosis in adult patients with acute limb ischemia resulting from arterial thrombosis, antithrombotic agents and HMG-CoA reductase inhibitors should be used [114, 124].

A meta-analysis performed by the Antithrombotic Trialists' Collaboration showed that in patients with symptomatic peripheral artery disease receiving antiplatelet therapy, the risk of cardiovascular complications (myocardial infarction, stroke, or vascular death) was reduced by 22% [112].

• Antiplatelet therapy is recommended for adults to reduce the risk of myocardial infarction (MI), stroke, or death [112, 113].

LOD 1; LoE B

Comment: Following infrainguinal reconstructions, antithrombotic therapy reduces the risk of graft thrombosis by 58% [115]. Modern guidelines assign a key role to monotherapy with antithrombotic agents in the prevention of systemic thrombotic complications [105, 116–119].

• As a safe and effective antiplatelet therapy for adults, it is recommended to administer antithrombotic agents to reduce the risk of MI, stroke, or death [106, 117–120].

LOD C; LoE 5

Comment: The efficacy of different doses of acetylsalicylic acid (ASA) was compared. The reduction in the risk of vascular events was 32% at a dose of 75–150 mg/day, 26% at 160–325 mg/day, and 19% at 500–1500 mg/day; and only 13% at a dose of <75 mg/day. High doses of ASA increased the risk of gastrointestinal complications and bleeding.

The ongoing incidence of atherothrombotic events in patients with peripheral artery disease has stimulated the search for more effective therapies. One approach has been the replacement or enhancement of ASA** monotherapy with other antithrombotic agents [120]. Clopidogrel** reduced the risk of the combined outcome (cardiovascular death, MI, ischemic stroke) by 8.7% (p = 0.043), but was not superior to ASA** in terms of mortality (p = 0.71), cardiovascular death (p = 0.29), and amputation rate (52 vs. 47 cases). Despite this, CAPRIE demonstrated that clopidogrel** can be used as an alternative to ASA** in patients intolerant to the latter.

• To reduce the risk of systemic ischemic complications (acute myocardial infarction, acute stroke, cardiovascular death), as well as to prevent arterial graft thrombosis and restenosis of reconstructed arteries in adult patients with peripheral artery disease, the use of HMG-CoA reductase inhibitors is recommended [121–123].

LOD 1; LoE B

Comment: There are no data in the literature demonstrating the efficacy of heparin sodium**, LMWH (heparin group), or anticoagulant therapy in preventing recurrent arterial thrombotic events. A comparative study on the efficacy of anticoagulant therapy in patients after femoropopliteal bypass concluded that anticoagulation was associated with a significant improvement in secondary patency in patients with synthetic grafts (Synthetic blood vessel graft***) (HR 0.77) [124]; therefore, long-term anticoagulant therapy may be the method of choice for conservative management after thrombectomy (or thrombolysis) from an occluded graft.

• In adult patients who have undergone revascularization for acute thrombosis of aortofemoral or femoropopliteal synthetic grafts, long-term anticoagulant therapy is recommended, and lifelong therapy if there is a high risk of recurrent thrombosis. The minimum duration of anticoagulation is at least 12 months [88].

LoE 5; GoR C

Comment: Since the main cause of arterial embolism is atrial fibrillation (AF) and intracardiac thrombosis, one of the key tasks in postoperative management is the prevention of recurrent embolism and identification of its source. The evaluation includes ECG, Holter monitoring, echocardiography, and, if the source is unidentified, aortic CTA [88].

The efficacy of anticoagulant therapy in AF has been confirmed by numerous studies [126, 127]. A large comparative study showed that the use of warfarin** after embolectomy reduces the risk of early limb loss [127]. According to an audit by the Vascular Society of Great Britain and Ireland, the recurrence of acute limb ischemia was less frequent in patients who started warfarin** therapy from the first day and continued it through one year [128].

Warfarin** has long been the standard of care; however, a 2013 meta-analysis showed that direct oral anticoagulants (DOACs) are non-inferior in efficacy for preventing systemic embolisms, including stroke, and cause fewer intracranial hemorrhages [129]. A subsequent meta-analysis (2016) demonstrated that in patients with AF, DOACs further reduce the risk of acute limb ischemia compared with warfarin** [114–119].

As noted in section «3.1 First aid», early administration of heparin sodium** following surgical treatment of acute limb ischemia remains justified, although data on its long-term efficacy in acute thromboembolic occlusion are lacking in the literature [94, 120].

• Following revascularization in adults due to acute limb ischemia caused by embolism resulting from atrial fibrillation or intracardiac thrombus, direct factor Xa inhibitors are recommended over vitamin K antagonists [132].

LOD 2; LoE B

Comment: COMPASS and VOYAGER confirmed the benefits of combination therapy with low-dose rivaroxaban** and ASA** in patients with chronic peripheral artery disease, and the expected benefits are maintained in acute limb ischemia due to thrombosis [133].

• To reduce the risk of systemic ischemic complications (acute myocardial infarction, acute stroke, cardiovascular death), as well as to prevent arterial graft thrombosis and restenosis of reconstructed arteries in adult patients with acute limb ischemia resulting from thrombosis, combination therapy with rivaroxaban** 2.5 mg twice daily and ASA** 100 mg once daily is recommended for a minimum duration of 12 months; lifelong therapy is recommended if high vascular risk and concomitant atherothrombotic diseases persist [134].

LOD 2; LoE B

3.3 Open revascularization

3.3.1 Goals of surgical treatment, indications for surgical treatment of acute limb ischemia

Patients with acute limb ischemia (ALI) must be treated in specialized vascular surgery departments. If transfer is not possible, the management strategy is determined by a mobile vascular surgery team [135]. The urgency of the intervention depends on the degree of ischemia (Zatevakhin I.I. et al. classification, Table 3, Section 1.5).

Algorithm: 1) establish the diagnosis; 2) determine the nature of occlusion (embolism, thrombosis, embolism on the background of chronic limb ischemia); 3) assess the degree of ischemia.

• Patients diagnosed with ALI are recommended to be urgently transferred from a non-specialized hospital to a vascular center that offers a full range of open and endovascular interventions [135–137].

LOD 4; LoE C

Comment: the optimal treatment method for acute occlusion is rapid and complete restoration of blood flow, which allows limb salvage and function preservation. In cases of embolism in intact arteries, the method of choice is Fogarty catheter embolectomy under local anesthesia, which is acceptable even in severely ill somatic patients.

In cases of occlusion on the background of chronic arterial insufficiency, reconstructive surgery remains the definitive option, the scope of which is determined by imaging data. If performing a full-scale intervention is impossible, palliative methods are used for limb salvage, even with partial loss of its function.

Absolute contraindications: agonal state, severe decompensation in grade I ischemia.

Relative contraindications: acute myocardial infarction, stroke, inoperable tumors, and other severe diseases in mild ischemia without progression. In total ischemic contracture (grade IIIB), reconstructive surgeries are contraindicated due to the high risk of reperfusion syndrome; in such cases, emergency primary amputation is performed.

• In adult patients with severe ischemic contracture of the knee or ankle joint due to ALI, it is recommended to refrain from revascularization and consider limb amputation [138].

LOD 2; LoE B

Comment: According to the Swedish National Registry, the proportion of open interventions was 59.9%, and endovascular interventions accounted for 40.1% [54]. According to the US Medicare insurance claims database, the proportion of open revascularizations for ALI in 2009 was 51.6% [136]. In retrospective cohort studies, endovascular interventions were statistically associated with lower early mortality and major amputation rates, as well as higher primary patency compared to open revascularizations [54, 153–155]. At the same time, a meta-analysis of randomized trials did not reveal statistically significant differences between these techniques in terms of early mortality and major amputation rates [138]. Regarding hybrid revascularization techniques for ALI, no quality comparative studies can be found in the literature.

• In patients with ALI, it is recommended to determine the indications for surgical intervention (revascularization or major amputation) based on the degree and etiology of ALI, individual assessment of operative risk, prospects for preserving a functional and load-bearing limb, mid-term survival, and the technical feasibility of the intervention taking into account the principles of informed consent [129, 132, 307].

LoE 3; GoR B

• Arterial reconstruction in patients with ALI is recommended to be performed in a hybrid operating room or an operating room equipped with a mobile C-arm digital X-ray diagnostic system, with the participation of a clinical team capable of performing the full range of open or endovascular interventions [135].

LOD 4; LoE C

Comment: The choice of strategy depends on the experience and equipment of the personnel, the duration and severity of ALI, the localization and cause of occlusion, concomitant diseases, and treatment risks.

Delay in initiating therapy during transfer to a specialized hospital or insufficient surgical experience at the admission site creates a dilemma. All such patients require an initial examination by a vascular surgeon to decide on transfer or performing surgery on-site.

3.3.2 Methods of open revascularization

3.3.2.1 Thromboembolectomy

• For adult patients requiring surgical thromboembolectomy for ALI, it is recommended to perform either regional or local anesthesia, but mandatory in the presence of an anesthesiologist-resuscitator [149].

LOD 4; LoE C

• For adult patients requiring surgical thromboembolectomy for ALI, it is recommended to perform embolectomy using catheters with metallic guidewires under fluoroscopic control [146, 147, 152].

LOD 4; LoE C

Comment: The operative field for thromboembolectomy covers the entire limb. Direct and indirect embolectomy are standardized thanks to Fogarty catheters [143]. Balloon embolectomy remains the standard for embolism of normal arteries, most commonly performed via a femoral approach [144]. For popliteal artery occlusion, a tibiomedial approach is required [147]. For the upper extremity, an approach through the cubital fossa is used. Transverse arteriotomy is preferable, while longitudinal arteriotomy requires venous patch angioplasty [148].

Embolectomy is generally performed under local anesthesia, and spinal or epidural anesthesia is also used. An anesthesiologist-resuscitator must always be present in the operating room to administer analgesics, hypnotics, and sedatives to correct any heart rhythm disturbances or cardiac abnormalities during reperfusion [151].

3.3.2.2 Other methods of open revascularization

Surgeries for acute arterial thrombosis are characterized by the need to combine thrombectomy with arterial reconstruction. The basic principle is "sufficient efficacy with minimal intervention," given the limited preparation time. Limb and life salvage depend on the chosen scope of surgery.

LOD 4; LoE C

Comment: there are no randomized clinical trials comparing autogenous veins and synthetic blood vessel grafts*** during emergency interventions, but two retrospective studies reported higher patency rates when using autogenous veins [146, 147]. The preferred use of a synthetic blood vessel graft*** is possible in patients with severe ischemia and high operative risk.

• In adult patients requiring infrainguinal bypass surgery due to ALI, the use of an autogenous vein is recommended [157, 158].

LOD 4; LoE C

Comment: In acute aortic or iliac artery thrombosis, various types of bypass procedures are performed. Depending on the patient's clinical status and the extent of occlusive-stenotic lesions, these may include orthotopic procedures—aortofemoral or iliofemoral bypass, or extra-anatomic bypass (cross-over iliofemoral, femorofemoral, or axillofemoral bypass).

In acute thrombosis of the femoropopliteal segment, possible procedures include femoropopliteal bypass to the proximal or distal popliteal artery, femorotibial bypass, and various types of profundaplasty (profunda femoris plasty). Autogenous vein is the preferred bypass material, however, in the absence of an autogenous vein, a synthetic blood vessel graft*** can be used via an autogenous vein cuff.

3.3.2.3 Treatment of acute limb ischemia caused by popliteal artery aneurysm

• For adult patients with acute limb ischemia secondary to popliteal artery aneurysm thrombosis, it is recommended to use the great saphenous vein as a bypass graft [159–161].

LOD 2; LoE B

Comment: Popliteal artery aneurysm (PAA) can cause acute limb ischemia (ALI) due to thrombosis or distal embolism affecting up to three crural arteries. Popliteal artery thrombosis more frequently leads to severe ischemia due to rapid occlusion of distal vessels. In a study of 55 patients with ALI caused by PAA, it was difficult to differentiate between grade II and III ischemia [157], and according to a systematic review, the amputation risk is 14.1% [158].

PAA is often diagnosed clinically (as a palpable pulsatile mass), and is bilateral in 50% of cases. Duplex scanning or CTA is used to confirm the diagnosis. Patency of the crural arteries is critical for choosing the treatment method as it determines bypass success.

Autogenous vein bypass remains the standard and outperforms synthetic options in one-year patency [159], although endovascular stenting using a peripheral vascular endovascular stent-graft*** has become a viable alternative.

The popliteal artery is exposed via a medial or posterior approach. According to a meta-analysis of seven studies, the posterior approach demonstrated better outcomes in primary and secondary patency, exclusion of the aneurysm from circulation, and reduction of the need for reinterventions [161], although it was more frequently used for short lesions. These data cannot be extrapolated to patients with acute ischemia.

3.3.2.4 Additional imaging after surgery or embolectomy

• Adults undergoing open and endovascular surgery for ALI are recommended to undergo control intraoperative angiography [135].

LOD 4; LoE C

Commentary: There is a consensus on the necessity of control angiography for an objective assessment of thrombembolectomy efficacy, as residual thrombi are quite common, and additional imaging reduces the need for reintervention and limb loss [136, 148].

If technical performance of intraoperative angiography is impossible, ultrasound duplex scanning or CT angiography is indicated within the first few hours after surgery.

3.4 Hybrid treatment

• Following open revascularization for ALI in adults, simultaneous endovascular intervention addressing stenotic lesions of the proximal and distal arterial bed should be considered [165, 166, 170].

LOD 2; LoE B

Commentary: despite the crucial role of thrombembolectomy and bypass surgery in the treatment of ALI, many patients present with multilevel arterial lesions. A combined approach involving open surgery and endovascular interventions is considered the most effective strategy [141, 164, 165]. In cases of incomplete thrombembolectomy, intra-arterial thrombolysis, thrombus aspiration, or mechanical thrombectomy can be used. When concomitant stenosis is identified, balloon angioplasty or stenting is performed. If necessary, endovascular procedures are supplemented by open surgery (thromboendarterectomy, fasciotomy).

It is optimal to perform such interventions in a hybrid operating room with a team capable of providing the full scope of both open and endovascular care in a single procedure. However, in some cases, surgeries are performed in standard operating rooms or angiographic suites due to patient condition limitations or facility equipment constraints.

Data on the benefits of a hybrid approach in ALI are limited. In a study of 1,480 patients, endovascular treatment was associated with a lower rate of amputations, but with no difference in 30-day mortality and reinterventions [140]. In another study, intraoperative angiography after embolectomy increased the rate of additional interventions due to residual stenosis, but reduced the risk of re-occlusion at 24 months [162].

3.5 Endovascular treatment methods

3.5.1 Thrombolysis

3.5.1.1 Evaluation prior to catheter-directed thrombolysis (Evaluation prior to local endovascular transarterial thrombolysis (LTT))

• Local endovascular transarterial thrombolysis is not recommended in patients with acute onset of intermittent claudication symptoms (Rutherford category I) in the absence of limb-threatening ischemia [179].

LoE 5; GoR C

• For the treatment of patients with Rutherford category IIa acute limb ischemia, local endovascular transarterial thrombolysis is recommended as an alternative to open surgery [183, 184].

LOD 4; LoE C

• For the treatment of adult patients with Rutherford category IIb acute limb ischemia, the use of local endovascular transarterial thrombolysis is recommended, provided it is initiated promptly—no later than 90 minutes from the patient's admission and within 6 hours of the onset of ischemic symptoms. Local endovascular transarterial thrombolysis can be used either as a standalone method or in combination with endovascular thrombus aspiration or mechanical thrombectomy [178].

Level of Evidence (LoE) 2; Grade of Recommendation (GoR) C

Commentary: Intra-arterial catheter-directed thrombolysis (CDT) in ALI demonstrates efficacy comparable to open surgery [161, 169, 170]. Initially recommended for patients without limb-threatening ischemia, studies have shown its applicability in Rutherford category IIb ischemia with outcomes similar to surgical interventions [168–170]. At the same time, amputation-free survival is lower in patients with category IIb ischemia compared to IIa, which is typical for both CDT and surgery [171–173]. In class I ischemia, CDT is associated with an increase in complications and mortality [174], and the long-term effect is minimal [175]; conservative therapy is indicated for such patients. Modern data indicate a high technical success rate of CDT (80–90%) [137, 181]. The method is used for native artery thrombosis, bypass grafts, stents, embolic occlusions, and thromboembolism in the area of popliteal aneurysms [128, 174]. Amputation-free survival reaches 84% at 30 days [25] and ~75% at one year [173, 180]. The main complications are bleeding (13–30%) and rare (0.4–2.3%) fatal intracranial hemorrhages [128, 181]. Current guidelines outline absolute and relative contraindications to CDT [179]. Oncology and advanced age are no longer considered absolute limitations, which expands the indications for therapy.

3.5.1.2 Access and technique for local endovascular transarterial thrombolysis

Vascular access-related complications are the most common issue during CDT.

Groin hematomas frequently occur following percutaneous puncture of the common femoral artery (CFA). To prevent this complication, through-and-through puncture of the common femoral artery should be avoided.

LoE 5; GoR C

Commentary: An analysis of five RCTs showed that ultrasound-guided arterial puncture reduces the complication rate compared to anatomical landmark-guided puncture [180]. Ultrasound use reduced the number of puncture attempts (OR 0.24), the risk of venous puncture (OR 0.18), and bleeding (OR 0.41). There are no comparative data on the efficacy of antegrade versus retrograde access during thrombolysis. Antegrade access through the CFA simplifies the recanalization of distal arterial thromboses, while upper extremity access facilitates crossing a thrombosed aortic bifurcation. Retrograde contralateral access via the CFA is the most common, provides a stable catheter position, and reduces the risk of displacement and bleeding [181]. This access also avoids the need to compress the CFA of the ischemic lower extremity during hemostasis after removing the vascular access sheath from the puncture site.

CDT is preferably performed using specialized infusion catheters, but their supply in the Russian Federation is limited; makeshift 5–6 F catheters with side holes spaced every 1–1.5 cm are acceptable.

• When performing endovascular intervention in patients with acute limb ischemia, it is recommended to perform the access arterial puncture under ultrasound guidance [181].

LoE 5; GoR C

Commentary: Contraindications to local endovascular transarterial thrombolysis in acute limb ischemia:

Absolute:

1. Confirmed cerebrovascular accident (including transient ischemic attack) within the last two months.

2. Enhanced tissue bleeding tendency.

3. Recent gastrointestinal bleeding (<10 days).

4. Neurosurgical procedures (intracranial, spinal) within the last three months.

5. Intracranial trauma within the last three months.

Relatively major:

1. Cardiopulmonary resuscitation performed within the last 10 days.

2. Major surgery (other than vascular interventions) or trauma within the last 10 days.

3. Uncontrolled arterial hypertension (systolic BP >180 mmHg or diastolic BP >110 mmHg).

4. Arterial puncture with anticipated difficult hemostasis (e.g., in severe obesity or severe arterial calcification).

5. Brain tumor.

6. Recent ophthalmic surgery.

Relatively minor:

1. Liver failure, especially accompanied by coagulopathy.

2. Bacterial endocarditis.

3. Pregnancy.

4. Diabetic hemorrhagic retinopathy.

3.5.1.3 Monitoring fibrinogen levels during local endovascular transarterial thrombolysis

• When performing local endovascular transarterial thrombolysis in adult patients with acute limb ischemia, routine blood fibrinogen testing is not recommended [182].

LoE 3; GoR B

Comment: Fibrinogen levels decrease during thrombolysis, and its measurement can be used to predict bleeding complications or to adjust antithrombotic dosages. Although some evidence indicates that very plasma low fibrinogen levels (<1.0 g/L or <1.5 g/L) affect the incidence of bleeding during catheter-directed thrombolysis (CDT), a systematic review concluded that the prognostic value of plasma fibrinogen measurement has not been proven, and therefore routine monitoring is not recommended [182].

3.5.1.4 Heparinization during local endovascular transarterial thrombolysis

Some authors recommend concomitant administration of unfractionated sodium heparin** (UFH) during CDT. However, the TOPAS trial showed that combined intravenous UFH (sodium heparin**) administration during CDT resulting in activated partial thromboplastin time (aPTT) exceeding 1.5–2 times baseline was associated with a high risk of major bleeding (RR 2.19, 95% CI 1.13–4.24). A small RCT evaluated intra-arterial UFH (sodium heparin**) administration during CDT at a dose of 250 IU/h [183], but no benefits were observed.

• Continuous systemic heparinization is not recommended in adult patients with acute limb ischemia undergoing local endovascular transarterial thrombolysis [171].

LOD 4; LoE C

3.5.1.5 Complications of local endovascular transarterial thrombolysis

Patients receiving local endovascular transarterial thrombolysis (CDT) for ALI are at risk for limb- and life-threatening complications. The procedure must be performed by experienced personnel with mandatory monitoring of vital signs and limb status [184].

Main complications:

– Bleeding is the most frequent and significant complication; major bleeding occurs in 8–10% of patients [159, 201, 202], most commonly at the access site. Prevention: fixation of the introducer sheath, restriction of hip movement. Minor bleeding allows continuation of CDT, whereas massive bleeding warrants discontinuation of therapy [188].

– Distal embolization occurs during guidewire passage or fibrinolytic infusion (B01AD) and can exacerbate ischemia. Management: increasing the fibrinolytic dose or proceeding to thrombectomy/open surgery [189].

– Progressing ischemia develops when local endovascular transarterial thrombolysis is ineffective. Regular monitoring is required; if no improvement is seen within 6–12 hours, the treatment strategy should be changed.

– Compartment syndrome is a potential complication requiring timely diagnosis.

• Monitoring of vital signs, potential access-site complications, and limb status is recommended during local endovascular transarterial thrombolysis in adult patients with acute limb ischemia [160].

LOD 4; LoE C

• In adult patients with acute limb ischemia, it is recommended to discontinue local endovascular transarterial thrombolysis if severe bleeding develops during treatment [189].

LOD 4; LoE C

• If minor bleeding is observed during local endovascular transarterial thrombolysis in adult patients with acute limb ischemia, continuation of treatment should be considered after weighing the potential risks and benefits of stopping versus continuing thrombolysis [188].

LOD 4; LoE C

3.5.1.6 Clinical significance of thrombolytic therapy in acute limb ischemia

In the Rochester study [190], regardless of whether ALI was caused by embolic or thrombotic occlusion, surgical intervention and thrombolysis were equally effective in limb salvage. However, one-year survival was found to be higher in patients with embolism who underwent thrombolysis (100% vs. 51%). The advantage for patients with thrombotic occlusion was less significant.

In the TOPAS trial, subgroup analysis demonstrated that surgery and local endovascular transarterial thrombolysis had similar outcomes in patients with native artery occlusion as well as in patients with vascular graft thrombosis [191].

In the STILE trial, patients with acute graft occlusion (<14 days) derived greater benefit from local endovascular transarterial thrombolysis [184, 189]. In a recent Swedish Vascular Registry study, primary amputation-free survival was higher after primary endovascular intervention, regardless of whether ALI was caused by embolism or thrombosis [192].

Taken together, these studies suggest that local endovascular transarterial thrombolysis may have an advantage in treating acute vascular graft occlusion, with primary outcomes being better for synthetic grafts compared to venous bypass grafts.

3.5.1.7 Significance of occlusion length in local endovascular transarterial thrombolysis

Data from the TOPAS trial were analyzed using a Cox proportional hazards model to determine whether baseline data could be used to guide the decision between surgery and local endovascular transarterial thrombolysis; occlusion length proved to be the only significant parameter [167].

3.5.1.8 The role of local endovascular transarterial thrombolysis in popliteal artery aneurysm presenting with acute limb ischemia

• Preoperative or intraoperative local endovascular transarterial thrombolysis is recommended for adult patients with acute limb ischemia secondary to popliteal artery aneurysm thrombosis to improve outflow [193, 199, 200].

LE 3; GR C

Comment: Adjuvant intra-arterial thrombolysis may be beneficial in patients with ALI caused by PAA thrombosis. Unlike native vessel thrombosis, the goal of peripheral artery local endovascular transarterial thrombolysis is not to recanalize the entire vessel lumen, as this carries a risk of catastrophic distal embolization [189]. Preoperative and/or intraoperative thrombolysis improved one-year primary graft patency but did not reduce the risk of amputation compared to surgery alone (thromboembolectomy and bypass) [158]. According to registry data, thrombolysis for PAA was associated with higher doses of rTPA, more hemorrhagic complications requiring blood transfusion, an increased rate of fasciotomies, a higher 30-day major amputation rate, and lower amputation-free survival compared to local endovascular transarterial thrombolysis for ALI caused by native vessel or graft occlusion. The authors concluded this was due to a higher incidence of severe ischemia with motor deficits at presentation [193].

Unlike native vessel thrombosis, the goal of peripheral artery local endovascular thrombolysis is not complete luminal recanalization (which increases the risk of distal embolization [189]), but rather the restoration of patency in the tibial arteries to enable potential bypass surgery [194]. Following partial lysis, treatment can be continued with endovascular therapy and stent-graft placement; however, if distal run-off is preserved, bypass grafting is preferred when suitable veins are available.

Intraoperative administration of fibrinolytics (B01AD Enzyme preparations) following popliteal artery exploration can facilitate the clearance of fresh thrombi from the tibial vessels. This approach has been shown to increase the likelihood of limb salvage compared to preoperative thrombolysis and delayed intervention [195].

3.5.2 Thrombectomy aspiration

LOD 4; LoE C

Comment: Currently, a number of catheters are available that allow aspiration through an end-hole. In addition, the Penumbra aspiration pump for thrombus removal with accessories is available (registration certificate FSZ 2012/12358). The pump creates a vacuum in the system, resulting in aspiration. Additional treatments (thrombolysis, angioplasty with possible stenting) should be anticipated. The mismatch between the catheter size and the artery diameter is the main reason for the failure to completely remove the thrombus. Complete thrombus removal is much more frequently unsuccessful in the femoropopliteal segment than in the crural arteries. Aspiration techniques are considered to work better when an acute thrombus is present (thrombosis duration of less than 14 days) and when the lumen of the catheters used is larger. In addition, aspiration may be effective after failed thrombolysis. According to C. H. Ricky, Kwok et al., the use of endovascular aspiration thrombectomy as a first-line method can reduce the need for local endovascular transarterial thrombolysis without increasing costs [197].

3.5.3 Endovascular mechanical thrombectomy

According to a study comparing CDT with pharmacomechanical thrombolysis (PMT), the use of PMT increases the rate of technical success of the intervention. A comparative analysis showed no differences in limb salvage, patency, and mortality between the groups [169]. A limitation of PMT is the risk of hemolysis, which can lead to hyperglycemia, hemoglobinuria, and renal injury.

• In adult patients with acute limb ischemia, it is recommended to consider performing endovascular aspiration thrombectomy and mechanical thrombectomy [196, 197].

LOD 2; LoE B

Comment: In patients with acute limb ischemia, the revascularization method is determined by the degree of ischemia, the duration of thrombosis, and the time of treatment initiation. Diagnosis and tactics should be established within 90 minutes, active treatment initiated no later than 2 hours, and complete revascularization performed within 6 hours of symptom onset.

For ischemia grade I–IIa, aspiration thrombectomy is the method of choice, especially when the duration of thrombosis is <14 days; if ineffective within 15–20 minutes, mechanical thrombectomy is performed. For grade IIb, urgent revascularization is required—aspiration, mechanical, or open surgery if the endovascular option is unavailable. For grade III with signs of necrosis, primary amputation or palliative intervention is indicated.

Aspiration thrombectomy is most effective for fresh crural artery thromboses; in case of residual thrombosis, local thrombolysis is performed, and if it fails, balloon angioplasty with stenting. According to non-randomized studies, aspiration and mechanical thrombectomy are recognized as effective and safe.

3.5.4 Ultrasound-Accelerated Catheter-Directed Thrombolysis (Ultrasound-Assisted Thrombolysis)

• In adult patients with acute limb ischemia, it is recommended to consider performing ultrasound-accelerated catheter-directed thrombolysis [198].

LOD 2; LoE B

Comment: In the randomized DUET trial, the efficacy and safety of standard catheter-directed thrombolysis (CDT) and ultrasound-accelerated catheter-directed thrombolysis (US-CDT) were compared in 60 patients with acute lower limb ischemia caused by thrombotic occlusion of native arteries or bypass grafts below the inguinal ligament. In the US-CDT group, the thrombus dissolution time (17.7 h vs. 29.5 h; p = 0.009) was significantly lower than with standard CDT. There were no statistically significant differences in the rate of technically successful revascularization (75% vs. 84%; p = 0.52), the combined rate of deaths and severe adverse events (29% vs. 19%; p = 0.54), and 30-day primary patency (71% vs. 82%; p = 0.035).

3.5.5 Endovascular treatment methods for acute bypass graft occlusion

Identification and elimination of the cause of thrombosis are of key importance. Thromboembolectomy alone rarely restores circulation in a venous bypass graft [155, 156]. If an anatomical cause is identified (anastomotic stenosis, outflow tract disease), treatment results are significantly better [157, 158]. Early graft thrombosis (<30 days) is usually associated with technical problems (poor vein quality, stenosis, kinking), while late thrombosis (>30 days) is associated with atherosclerosis progression, fibrous stenosis, or intimal hyperplasia [155, 156].

There are no randomized trials determining the optimal management strategy for bypass graft thrombosis. In the absence of critical ischemia, a watchful waiting strategy is possible, but with pronounced symptoms, blood flow restoration with revision of anastomoses is indicated.

CDT is effective for acute graft thrombosis: angiographic patency is 82% for prosthetic grafts and 61% for autologous vein bypass grafts [185]. In a Swedish study, the mean duration of thrombolysis was 19 h, and amputation-free survival was 89% at 1 month and 75% at 1 year [203]. The method allows identification of the cause of occlusion and planning of re-intervention [165].

• For all patients with ALI caused by graft (conduit) thrombosis, it is recommended to use endovascular revascularization approaches to identify and eliminate the cause of acute graft (bypass) occlusion, optimally within no more than 6 hours from the patient's admission [132, 136, 147, 149, 154, 155].

LoE 5; GoR C

Comment: The main surgery for this pathology is graft thrombectomy with simultaneous correction of the cause that led to thrombosis. Most frequently, this is correction of a stenotic anastomosis, straightening of a graft branch in case of excessive length or angulation, etc. In case of "outflow tract" disease (stenosis or occlusion of the distal bed), endovascular intervention can be used, including recanalization, catheter aspiration or mechanical thrombectomy (including catheter-directed thrombolysis), balloon angioplasty, and stenting. Intimal hyperplasia may develop in the area of the synthetic blood vessel graft anastomosis; this zone is less favorable for balloon angioplasty than a typical eccentric atherosclerotic plaque, in these cases the effect of angioplasty is short-lived, and full restoration of the stenosis zone lumen is not always achieved. Many surgeons believe that the method of choice should be exposure of the distal anastomosis, graft thrombectomy, and patch plasty of the narrowed anastomosis or graft replacement. In some cases, when the above surgical technique is impossible, repeated bypass grafting to the distal segments without exposing the graft and the distal anastomosis zone is advisable.

3.6 Management features of acute aortic occlusion with bilateral lower limb ischemia

Acute aortic occlusion (AAO) is an acute pathological condition characterized by a sudden disruption of blood flow in the aorta with the development of acute ischemia of both lower limbs, which poses a real threat to the viability not only of the limbs, but of the body as a whole.

The most important clinical symptoms are pronounced pain syndrome (in almost 100% of cases) and lower limb paresis/paralysis (up to 80% of observations). Diagnosis of AAO can be difficult in a number of cases, especially when the patient presents with bilateral lower limb paralysis, and delay in active management is directly associated with an unfavorable prognosis [204–206].

The main complications of AAO are associated with existing soft tissue ischemia, severe electrolyte disturbances, as well as the entry into the body of a large amount of under-oxidized products and toxins from muscle masses in the event of performed revascularization, with the development of myoglobinuric tubular nephrosis and acidosis, which ultimately leads to the development of cardiovascular failure. Most such publications are based on the study of relatively small patient groups, where it is difficult to perform qualitative statistical data processing. Several publications conclude that despite the use of modern diagnostic and treatment methods, the treatment outcomes of AAO do not improve over time [207].

• For adult patients with acute limb ischemia secondary to acute aortic occlusion, it is recommended to perform emergency revascularization [207].

LOD 4; LoE C

• Adult patients after revascularization for acute limb ischemia secondary to acute aortic occlusion require full-scale measures to reduce complications of the ischemia-reperfusion syndrome [208].

LOD 4; LoE C

3.6.1 Results of endovascular interventions on the aorta

The more frequent use of endovascular aneurysm repair (EVAR) has increased the risk of stent-graft thrombosis [209]. Newer endovascular systems possess greater flexibility and kinking resistance, which reduces the risk of occlusion [210].

There is an increase in the proportion of endovascular interventions for acute lower limb ischemia — 43.8% in 2008–2014 versus 15.6% in 1994–2000 [211].

The experience of their use in acute lower limb ischemia associated with aneurysm and atherosclerosis is published [226, 227]. A hybrid approach combines open revascularization with thrombectomy from visceral or distal arteries [214].

When making decisions regarding surgical tactics for acute lower limb ischemia, the etiology of occlusion, comorbidities, material equipment, and practical experience should be taken into account, guided by standard principles of vascular surgery.

3.6.2 Management and treatment of post-ischemic syndrome and reperfusion injury

Post-ischemic syndrome (PIS) occurs after blood flow restoration in ischemic tissues. Damage is initiated in the ischemic phase and exacerbated during reperfusion due to the release of free radicals and neutrophil infiltration [215], which causes vasodilation, increased capillary permeability, and edema. Potential biomarkers of PIS include metalloproteinases, lipocalin, and cytokines [216].

The severity of PIS correlates with the degree of ischemia and depends on the completeness of revascularization and the body's compensatory mechanisms. Local manifestations include firm, painful edema of the calf muscles with preserved subcutaneous tissue. Systemic disturbances are caused by the release of unoxidized metabolites, acidosis, myoglobinuria, and the development of cardiovascular failure [217].

PIS occurs after embolectomy, thrombolysis, and bypass surgery, most frequently in cases of prolonged ischemia. The incidence reaches 25-30% [275, 276]. The main consequences are amputation (up to 50%) [249] and mortality up to 23% [234]. Delayed fasciotomy increases the risk of major amputation (50% vs. 5.9%; p=0.002).

3.6.3 Fasciotomy as a method of treatment and prevention of post-ischemic syndrome

Fasciotomy is performed both for the prevention of post-ischemic syndrome and as treatment for already developed PIS. The lower leg is the most frequent source of PIS. The only therapeutic method for severe PIS is fasciotomy, a procedure involving an incision along the fascia to relieve pressure, allowing the muscle to expand. If PIS is only anticipated (stage IIB ischemia), a prophylactic fasciotomy is performed. If PIS has already developed, a therapeutic fasciotomy must be performed.

Previously, it was recommended to make a single incision of the anterior compartment [219], but this is risky because the posterior compartment does not receive adequate treatment and remains ischemic. Complete four-compartment fasciotomy is the current standard of care, which is usually achieved with two incisions.

• Emergency fasciotomy of at least two, and whenever possible four, compartments of the lower leg is recommended for the treatment of post-ischemic compartment syndrome [90, 210, 211].

LoE 5; GoR C

Comment: Compartment decompression must be complete, which requires skin incisions at least 15 cm in length. The incision should be left open; early closure of fasciotomy incisions is associated with PIS recurrence. Various wound closure techniques after fasciotomy have been described, including vacuum-assisted wound closure, shoelace suturing, skin stretching, and skin grafting. Fasciotomy is less frequently required in the upper extremity.

The timing of fasciotomy is critical for patients who have developed PIS. If left untreated, PIS increases ischemic muscle damage and the risk of myoglobinuria followed by renal failure. In this situation, fasciotomy is an emergency procedure and should take precedence over other urgent surgical conditions. Fasciotomy can be performed in the intensive care unit or critical care unit to avoid delay.

• When post-ischemic compartment syndrome is diagnosed, fasciotomy is recommended to be performed as soon as possible and within no more than 2 hours [220].

LoE 5; GoR C

In stage IIA acute limb ischemia, it is advisable to omit prophylactic fasciotomy, especially when arterial reconstruction was performed against the background of chronic limb-threatening ischemia (CLTI), which features well-developed collateral circulation.

• In acute stage IIB ischemia, performing a prophylactic fasciotomy during revascularization is recommended [220].

LoE 5; GoR C

Comment: Certainly, this is the simplest option for patients who have undergone surgery, but its feasibility should be considered only after all urgent revascularizing procedures. The decision should be made individually for each patient, taking into account the risk factors listed above [221]. However, this comparison had numerous confounding factors, including the timing of the necessary fasciotomy, making it difficult to clearly formulate the results of analyzing these data.

3.6.4 Closure of fasciotomy skin defects

• In adult patients undergoing revascularization for acute lower limb ischemia, routine prophylactic fasciotomy of the lower leg in low grades of ischemia (I-IIB) is not recommended, as it is associated with increased hospital stay, local infection, and subsequent development of venous insufficiency [252].

LoE 5; GoR C

Comment: At low risk of post-ischemic syndrome (PIS), the fascia can be left open, while the skin is closed with interrupted sutures or staples for staged revisions and necrectomies. This method reduces pain and allows rapid decompression. With marked muscle bulging, both skin and fascia are left open, preferably using vacuum dressings. Negative pressure therapy (40-125 mmHg) reduces edema, prevents skin edge retraction, and accelerates primary wound closure; without it, healing is prolonged up to two months, the risk of infection increases, and skin grafting is required.

Fasciotomy is not a safe procedure: it increases the risk of infections and can lead to chronic venous insufficiency in about half of the patients [222]. The decision to perform it must be strictly weighed.

3.7 Treatment of acute upper extremity ischemia

• As with lower limb ischemia, it is recommended to consider all options and individualize the risks and benefits for each patient [99, 228].

LoE 5; GoR C

Comment: Factors to take into account include whether the affected arm is dominant, the patient's age and condition, the patient's occupation, and the severity of ischemia.

• If the decision is made to treat upper limb ischemia conservatively using anticoagulation alone, it is recommended to examine the arm every 6 hours for the subsequent 3 days to ensure there is no deterioration in its condition [224].

LoE 4; GoR C

Comment: It has been proposed to use anticoagulation as monotherapy in initial treatment, but a review of 23 studies suggested that conservative treatment most frequently led to unfavorable outcomes [225, 226].

3.7.1 Open surgical intervention

• In adult patients with subclavian artery stenosis/occlusion, revascularization is recommended [231, 232].

LoE 4; GoR C

• To perform embolectomy in adults from upper extremity arteries, it is recommended to use an approach from the antecubital fossa with exposure of the brachial artery bifurcation [231, 232].

LoE 4; GoR C

Comment: Most patients with upper extremity ischemia are treated by embolectomy; surgical bypass is rarely required on an emergency basis. Surgery under local anesthesia should be considered standard; the presence of an anesthesiologist-resuscitologist is required, with the capability for intravenous sedation and resuscitation if necessary [96, 231, 232].

3.7.2 Endovascular surgical intervention

• In adult patients with subclavian artery stenosis/occlusion, both revascularization options (stenting or open surgery) are recommended on a case-by-case basis according to lesion characteristics and patient risk [228].

LeveL of Evidence (LoE) 4; Grade of Recommendation (GoR) C

Comment: Endovascular interventions, such as percutaneous thrombectomy, aspiration endovascular thrombectomy, or local endovascular transarterial thrombolysis, have been used previously in acute upper extremity ischemia, but descriptions of their benefits and complications exist only as case reports [229, 230]. Local endovascular transarterial thrombolysis with a femoral approach and catheter insertion into the aortic arch is associated with a risk of intracranial vessel embolism, but it can also be performed via a brachial approach to minimize this risk. Thrombi can also detach and migrate toward intracranial vessels from the proximal end of the occlusion, a phenomenon known as vortex embolism.

3.7.3 Compartment syndrome and fasciotomy

Compartment syndrome is a symptom complex characterized by increased subfascial pressure, leading to ischemia and necrosis of the contents of the fascial compartment.

• In adults, performing a fasciotomy is recommended for limb ischemia lasting more than 6 hours combined with marked edema, pain on passive motion, sensory or motor deficit, and intracompartmental pressure greater than 30 mmHg [230].

LoE 4; GoR C

Comment: Compartment syndrome is a rare complication of successful upper limb revascularization. However, if it develops, it can still lead to long-term impairment through contracture formation or even limb loss. Palmar fasciotomy is suggested, but some authors recommend performing a dorsal hand fasciotomy simultaneously. Consultation and assistance from orthopedic trauma surgeons, hand surgeons, or plastic surgeons may be required.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

The procedure for developing and implementing an individual rehabilitation and habilitation program for a person with a disability is approved and carried out in accordance with Order of the Ministry of Labor and Social Protection of the Russian Federation No. 466n dated September 18, 2024, "On approval of the procedure for developing and implementing an individual rehabilitation and habilitation program for a person with a disability, an individual rehabilitation and habilitation program for a disabled child and their forms, as well as the procedure for involving rehabilitation organizations in the development of the individual rehabilitation and habilitation program for a person with a disability and the individual rehabilitation and habilitation program for a disabled child, and the procedure for coordinating the implementation of the individual rehabilitation and habilitation program for a person with a disability and the individual rehabilitation and habilitation program for a disabled child, including monitoring such implementation and submitting information on monitoring results to the highest executive body of a subject of the Russian Federation." The scope and range of rehabilitation measures can, of course, vary. Nevertheless, it is necessary to outline the general principles of rehabilitation for patients with the consequences of acute limb ischemia, which should be adhered to in all cases.

The essence of the rehabilitation program is a set of measures aimed at compensating for lost (impaired) functions and activity limitations. The goal of the program is to improve the patient's quality of life. In acute limb ischemia, these tasks are implemented through behavioral and lifestyle modification, along with an additional set of therapeutic and prophylactic medical measures.

LoE 5; GoR C

Comment: Observing hygiene is a crucial principle. It is important to monitor the skin in the area of the surgical incision and inspect it daily for any changes. It is recommended to take contrast showers and use baby soap for washing, and to dry the wound thoroughly with a soft towel. If necessary, special creams prescribed by the attending physician should be used.

Blood pressure control. According to the Framingham Heart Study, hypertension increases the risk of intermittent claudication by 2.7 times [231].

LoE 5; GoR C

Comment: Blood glucose testing. Impaired glucose tolerance increases the risk of arterial disease threefold in men and eightfold in women [234]. Therefore, it is necessary to properly organize one's diet and avoid large amounts of fast carbohydrates (sweets, baked goods). Whenever possible, all sucrose-containing products should be replaced with fruit.

In the postoperative period, it is important to properly care for the suture, follow the rules for stump formation, strive to maintain the mobility of all joints, and strengthen the muscular corset—after the amputation of one leg, considerable physical effort will be required to learn to walk again, correctly distributing the load across the entire body and maintaining balance [235–238].

To reduce edema in the first days after surgery, it is important to position the stump above the level of the patient's heart. Subsequently, elastic medical compression bandages, medical compression knitwear (including compression stockings, socks, tights, sleeves, gloves, and underwear), and massage are used to reduce edema. Bandaging should preferably not be too tight. Bandaging above the level of the stump helps prevent blood circulation problems in the body [235–238].

The main principle of contracture prevention is that the stump must not be kept in a flexed position for long periods, as this will lead to muscle shortening. For rapid recovery, therapeutic exercises must be performed. Initially, exercises are carried out under medical supervision. The better and faster the patient's muscles are prepared for the intended load, the sooner the prosthetic phase will begin [235–238].

• For the purpose of rehabilitating patients who have undergone lower extremity arterial surgery, it is recommended to engage in therapeutic physical training for peripheral vascular disease [151, 269].

LNC 4 LeC C

Comment: To reduce the likelihood of phantom limb pain, stump bandaging, massage, physiotherapy, and phantom-impulse exercises are required. Emotional support from loved ones, as well as the work of medical psychologists, can help alleviate this pain [235–238].

Evidence confirming the effectiveness of medically supervised therapeutic exercise for major blood vessel diseases as initial therapy for dynamic circulatory disorders continues to emerge and remains very convincing, based on numerous previously conducted RCTs [240–246]. Moreover, medically supervised therapeutic exercise for major blood vessel diseases is more effective than unsupervised exercise [252, 253]. The CLEVER study included patients with aortoiliac atherosclerotic lesions and intermittent claudication; a comparison of supervised exercise and endovascular revascularization was performed at 6 and 18 months. Good results were obtained in both patient groups over this follow-up period [250, 251].

• For patients after lower extremity amputations, therapeutic exercise for major blood vessel diseases is recommended to prevent postoperative complications, prepare for prosthetics, and learn to use a prosthesis [251].

LoE 5; GoR C

Comment: The objectives of therapeutic exercise for major blood vessel diseases in the early postoperative period are: 1) prevention of postoperative complications (congestive pneumonia, intestinal atonia, thrombosis, embolism); 2) improvement of blood circulation in the stump; 3) prevention of stump muscle atrophy; 4) stimulation of regeneration processes [240–242, 256, 257].

During the preparation period for prosthetics, mobility in the remaining joints of the amputated limb is restored first. Great attention is paid during this period to exercises aimed at increasing the strength and endurance of the shoulder girdle muscles, as well as general conditioning exercises. 3-4 weeks after surgery, standing and walking training on a training prosthesis begins, which facilitates the transition to walking on permanent prostheses [240–242, 256, 257].

At the final stage of rehabilitative treatment after limb amputation (the period of mastering the prosthesis), the patient is taught how to use the prosthesis [240–242, 256, 257].

• Following limb artery surgery, the use of physiotherapeutic methods is recommended in patient rehabilitation [235, 236, 256, 257].

LoE 5; GoR C

Comment: Hypolipidemic methods used in patients with peripheral arterial disease: electrosleep, liver galvanization, drug-based methods; transcranial ultra-high-frequency therapy, infrared radiation, therapeutic mud application for peripheral vascular diseases; ozone therapy.

Immunocorrective methods used in patients with peripheral arterial disease: electrophoresis for major blood vessel diseases, therapeutic radon baths [258, 260–262].

Hypocoagulant methods used in patients with peripheral arterial disease: medicinal electrophoresis with heparin group drugs and antiplatelet agents other than heparin, low-frequency magnetotherapy of the heart region, iodine-bromine baths, laser blood irradiation [258, 260–262].

Antihypoxic and antioxidant methods used in patients with peripheral arterial disease: medicinal electrophoresis; hyperbaric oxygen therapy, normobaric hypoxic therapy, red laser therapy, oxygen baths, ozone baths, air baths, long-term low-flow oxygen therapy, round-the-clock air therapy [258, 260–262].

Vasodilator methods used in patients with peripheral arterial disease: galvanization, medicinal electrophoresis with peripheral vasodilators, sauna [258, 260–262].

5. Prevention and Dispensary Observation

• Following revascularization for acute limb ischemia of embolic origin, it is recommended to conduct a diagnostic search for the source of embolism to prevent recurrence [89, 259, 263, 264].

LoE 5; GoR C

Comment: In accordance with Order No. 168n of the Ministry of Health of the Russian Federation dated March 15, 2022, routine health check-ups (dispensary observation) are aimed at detecting chronic non-communicable diseases and risk factors for their development [259]. In patients with chronic venous diseases, prevention must include the prevention of recurrent embolism, thrombosis of native vessels, and occlusion of bypass grafts or stents.

Since the main cause of arterial embolism is atrial fibrillation (AF) and intracardiac thrombosis, a key objective of postoperative management is the prevention of recurrence. To this end, the source of embolism is identified using ECG, echocardiography, 24-hour monitoring, and aortic CTA.

The efficacy of anticoagulation (AC) in AF has been confirmed [261, 262]. In a large study, the use of warfarin** after embolectomy reduced the risk of early limb loss [8, 262]. According to meta-analyses, direct oral factor Xa inhibitors are comparable in efficacy to warfarin**, but are less frequently associated with intracranial hemorrhages [263]; antiplatelet therapy also reduces the risk of acute limb ischemia in patients with AF [130].

• Following revascularization for acute limb ischemia, subsequent follow-up is recommended, including assessment of the patient's cardiovascular status and the functional status of the limb [264].

LoE 5; GoR C

Comment. A review of 50 patients who sought medical care due to acute limb ischemia showed that patients without AF or intracardiac thrombus may not carry the same risk of recurrence as patients with these risk factors [265]. Long-term AC may not be necessary in this group of patients, as there is insufficient data to support this approach [268, 272]. It may include both an evaluation of the patient's cardiovascular status and an assessment of the functional status of the limb (Appendix G4).

• Adult patients with popliteal artery aneurysms are at an increased risk of developing a new aneurysm in the contralateral popliteal region, aorta, and other locations, and it is recommended that they undergo examination of healthy arterial segments every three years [267].

LOD 4; LoE C

Comment: Patients with popliteal artery aneurysms have an increased risk of developing a new aneurysm in the contralateral popliteal region, aorta, and other locations [268]. Therefore, these patients should be monitored, and if a new aneurysm develops, vascular reconstruction may be necessary to protect the patient's life and limb viability. Upon re-examination of 190 patients who had 108 aneurysms at the time of surgery, 131 new aneurysms were detected after an average of seven years [268].

• Adult patients who have undergone open or endovascular treatment for a thrombosed popliteal artery aneurysm are recommended to undergo regular dynamic follow-up using duplex ultrasound of the lower extremity arteries. For adults, follow-up duplex ultrasound of the lower extremity arteries is performed 1 month after treatment, then every 3 months during the first year, once every 6 months in the second year, and annually starting from the 3rd year in the absence of negative dynamics. In children, the first check-up is carried out 2–4 weeks after treatment, then once every 2 months during the first half-year, and subsequently once every 3 months until the completion of the first year of follow-up. In a stable condition and with no signs of recurrent thrombosis, the frequency of examinations is reduced to once every 6 months [268–270].

LOD 4; LoE C

Comment: If duplex ultrasound scanning reveals restenosis, repeat intervention or open surgery is recommended. In patients who have undergone endovascular intervention for a popliteal artery aneurysm or open surgical intervention via a midline approach, exclusion of the aneurysm sac from the blood flow should also be thoroughly evaluated, as late expansion is common (in 33% of cases after an average follow-up of seven years) [268].

• Adult patients following thrombectomy or endovascular therapy for bypass graft occlusion (synthetic blood vessel prosthesis***) are recommended to undergo long-term anticoagulant therapy for at least 12 months, with the possibility of extension to lifelong treatment if there is a high risk of re-occlusion, under the control of clinical and laboratory parameters (INR for warfarin**, platelet and creatinine levels) and duplex ultrasound scanning of the upper extremity arteries (vascular access) every 3 months during the first year, and subsequently every 6 months [271].

LOD 4; LoE C

Comment: There are no data demonstrating any efficacy of heparin sodium**, low-molecular-weight heparins (LMWHs) (ATX heparin group), or anticoagulant (AC) therapy in preventing the recurrence of arterial thrombotic events. A registry-based study concluded that AC was associated with a significant improvement in secondary patency in patients with synthetic grafts (RR 0.77) [271]. In the COMPASS trial, adult patients with stable peripheral artery disease (PAD) demonstrated positive effects of rivaroxaban** 2 × 2.5 mg combined with 100 mg ASA** [272]. In a small subgroup of patients with ALI within this study, a significant reduction in amputation rates and mortality was observed [7].

• Following surgical or endovascular revascularization for ALI caused by arterial thrombosis, regular follow-up is recommended for adults, including clinical and functional status assessment (palpation of peripheral pulses in the femoral, popliteal, and distal arteries, and bilateral ABI measurement). As part of dynamic monitoring, the patient should be evaluated by a cardiovascular surgeon or general surgeon every 3 months during the first year, then every 6 months, and annually thereafter if stable [48, 279].

LNC 5 LeC C

Comment: Following surgical or endovascular revascularization for ALI caused by arterial thrombosis, regular follow-up may be beneficial, including clinical and functional status assessment [48, 279]. However, this issue has not been studied in detail. Pulse examination and ABI measurement are performed during follow-up visits. If clinical symptoms worsen or a significant decrease in ABI is noted, vascular imaging is required (via duplex ultrasound, contrast-enhanced MR angiography, or CTA).

5.1 Follow-up after arterial embolism

Since the main causes of arterial embolism are atrial fibrillation and intracardiac thrombosis, the key objective of postoperative management is the prevention of recurrence. The source of embolism must be verified. Diagnostics include ECG, 24-hour Holter monitoring if necessary, myocardial infarction marker assays, echocardiography, and contrast-enhanced CT angiography of major arteries [88].

Direct factor Xa inhibitors are prescribed only with clear indications: atrial fibrillation with heart failure, hypertension, age ≥75 years (2 points), diabetes mellitus, stroke/TIA (2 points), vascular disease, age 65–74 years, female sex, CHA₂DS₂-VASc ≥2, mechanical heart valve, recurrent deep vein thrombosis, or pulmonary embolism. PAD adds 1 point to the score and may alter the indication.

The ROCKET-AF trial demonstrated an increased risk of bleeding in patients with PAD receiving rivaroxaban or warfarin (HR 1.40; 95% CI 1.06–1.86) compared to those without PAD (HR 1.03; 95% CI 0.95–1.11; p=0.037). Further studies are needed to confirm this [274].

• Following revascularization in adult patients for acute limb ischemia, it is recommended to consider follow-up, including cardiovascular assessment and functional evaluation of the limb [129, 272].

LOD 4; LoE C

• For adult patients following revascularization for acute limb ischemia of embolic origin, it is recommended to identify the source of embolism [268, 270, 272].

LoE 5; GoR C

5.2 Follow-up after native arterial thrombosis or arterial occlusion treated by endovascular or open surgical methods

• Following surgical or endovascular revascularization for acute limb ischemia caused by arterial thrombosis, regular follow-up with assessment of the clinical status and functional state of the limb is recommended, although no specific studies addressing this issue have been conducted [273].

LoE 5; GoR C

• Following surgical or endovascular revascularization for acute limb ischemia caused by arterial thrombosis, regular follow-up with assessment of the clinical status and functional state of the limb is recommended for adult patients [106, 279].

LoE 5; GoR C

Comment: Patients with acute limb ischemia (ALI) are prone to recurrent major adverse cardiovascular events, frequently leading to repeat hospitalization and the need for surgical intervention. In patients with symptomatic peripheral artery disease (PAD), ALI is most commonly caused by thrombosis of a diseased native vessel, acute bypass graft occlusion, or occlusion of a previous endovascular intervention site. Follow-up visits include pulse palpation and ankle-brachial index (ABI) measurement. If clinical symptoms worsen or there is a significant decrease in ABI, vascular imaging is required (ultrasound, CT angiography, MR angiography, digital subtraction angiography).

5.3 Smoking cessation

• Smoking cessation is recommended for adult smoking patients with acute lower limb ischemia [275].

LoE 3; GoR B

Comment: Smoking is a major risk factor for the development and progression of PAD [7, 282]. Several studies indicate that smoking cessation is associated with a lower incidence of cardiovascular ischemic and limb-related events, amputation, and death [300, 301]. Therefore, smoking patients should be advised to quit smoking at each subsequent visit [273].

5.4 Antithrombotic drugs and statins (ATC HMG-CoA reductase inhibitors)

• Following revascularization in adult patients performed for arterial thrombosis, antiplatelet therapy and HMG-CoA reductase inhibitors are recommended to reduce cardiac complications and prevent the progression of atherosclerotic disease [111].

LoE 5; GoR C

Comment: Antiplatelet therapy (APT) in PAD is insufficiently studied [278]. Individual studies have compared clopidogrel** and ASA** [120], their combination [303, 304], as well as dual therapy with rivaroxaban** (COMPASS), which demonstrated a convincing advantage over monotherapy [278]. However, no pronounced reduction in complications was noted, except for the risk of stroke (RR 0.64).

In the CAPRIE meta-analysis (n=6,452), clopidogrel** was superior to ASA** in patients with PAD in reducing cardiovascular mortality (OR 0.76) and cardiovascular events (OR 0.78), especially in the presence of concomitant diabetes [120]. In the EUCLID trial (n=13,885), no differences were found between ticagrelor** and clopidogrel** [281].

The efficacy of DAPT remains controversial: CHARISMA showed a reduction in the risk of MI (OR 0.63), but an increase in bleeding (OR 1.99) [286]; CASPAR (n=851) showed no advantages of the ASA** + clopidogrel combination, except in cases of bypass grafting (OR 0.65), alongside an increased risk of bleeding (OR 2.65) [64].

In the Dutch BOA study (2-year follow-up), no differences were found between ASA** and vitamin K antagonists (VKAs) regarding graft patency, mortality, and amputations, but the risk of bleeding doubled at INR >3.0 [282]. Warfarin** combined with ASA** increased the bleeding risk without improving graft patency [283]. The VKA** + clopidogrel regimen improved anastomotic patency, but was accompanied by an increase in bleeding and no effect on cardiovascular events [284].

Independently, it has been shown that HMG-CoA reductase inhibitors improve prognosis in patients with PAD, increase pain-free walking distance, and reduce the risk of complications [124, 291].

5.5 Imaging during the follow-up period

Ultrasound is the preferred imaging modality during follow-up. It is non-invasive and the most appropriate method for assessing the degree of stenosis after various surgical treatment methods. CT angiography and MR angiography are alternative non-invasive tools for follow-up. MR angiography can provide useful information on the remodeling process after endovascular interventions and can also determine the patency and restenosis of reconstruction zones [286].

Ultrasound evaluation of autogenous vein grafts (in general, rather than specifically after ALI treatment) has been preferred for over 20 years, but the evidence for this practice remains conflicting [312, 313]. A recent meta-analysis showed that ultrasound compared to clinical examination and ABI measurement was not associated with a significant change in autogenous vein graft patency, amputation rate, or mortality [289]. Although data on optimal treatment timing are lacking, many cardiovascular surgeons suggest performing imaging studies at four to six weeks, three and six months, and at one and two years after bypass surgery [290].

• Ultrasound is recommended as the preferred imaging modality in adult patients during follow-up [286].

LOD 4; LoE C

5.6 Follow-up after popliteal artery aneurysm thrombosis

Patients with popliteal artery aneurysm often present with aneurysms of the contralateral popliteal artery, aorta, and other vessels, which requires long-term dynamic monitoring [268].

A similar interval can be applied after endovascular treatment of a thrombosed popliteal artery aneurysm, although data on improved outcomes with ultrasound monitoring are lacking. When a hemodynamically significant restenosis is detected, repeat endovascular intervention or open surgery is indicated [268]. Ultrasound monitoring helps detect arterial enlargement, but CT angiography remains a more reliable method.

No specific studies have been conducted on the use of antiplatelet agents and HMG-CoA reductase inhibitors after surgery for thrombosed popliteal artery aneurysms, but based on general data, their use may be beneficial.

• For adult patients receiving treatment for thrombosed popliteal artery aneurysm, following open or endovascular intervention, routine duplex scanning of lower extremity arteries is recommended [270].

LOD 4; LoE C

• For adult patients who have undergone open or endovascular intervention for a thrombosed popliteal artery aneurysm, duplex scanning of the lower extremity arteries is recommended on both the ipsilateral and contralateral limbs, as well as the aorta, iliac, and femoral arteries every three years [161].

LOD 2; LoE B

6. Organization of Medical Care

Medical care for patients with acute lower limb ischemia is provided in accordance with Order No. 918n of the Russian Ministry of Health dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to Patients with Cardiovascular Diseases" [291] and Order No. 514n of the Ministry of Health of the Russian Federation dated August 10, 2017, "On Approval of the Procedure for Dispensary Observation of Children", and may be delivered in the following settings:

- out-patiently (in settings not requiring round-the-clock medical observation and treatment);

- in a day hospital (in settings providing medical observation and treatment during daytime hours, not requiring round-the-clock medical observation and treatment);

- inpatiently (in settings providing round-the-clock medical observation and treatment).

- outside a medical organization (at the location of the emergency, including specialized emergency medical team dispatch, as well as in a vehicle during medical evacuation).

- primary health care;

Medical care includes a complex of medical measures: diagnostic procedures for the purpose of diagnosis; therapeutic measures, including surgical ones (according to indications); preventive measures; rehabilitation measures.

Medical care for patients with acute lower limb ischemia is provided in the form of:

- emergency, including specialized, medical care;

- specialized medical care, including high-tech medical care.

Primary health care for patients with acute lower limb ischemia includes:

1) primary pre-medical health care;

2) primary medical health care;

3) primary specialized health care.

Patients with acute lower limb ischemia receive emergency, including specialized, care both outside medical organizations and in outpatient and inpatient settings. It is provided by paramedic, physician, and specialized emergency teams in accordance with Order of the Russian Ministry of Health No. 179 of 01.11.2004 [292] as amended [293].

Patients are transported as quickly as possible to regional vascular centers or the nearest facilities equipped with departments of vascular surgery, endovascular diagnostic and treatment imaging, and anesthesiology-resuscitation. In the absence of such centers, transportation or air medical evacuation is carried out to an organization with the necessary specialists and intensive care units. When indicated, the patient is transferred to a center where urgent endovascular interventions are performed. Medical organizations operate in accordance with Appendices No. 1–29 to Order No. 918n [291].

Treatment of patients with acute lower limb ischemia is carried out by vascular and endovascular specialists in fully equipped centers [54]. The urgency of transfer is determined by the severity of ischemia (grade 2A and higher according to the I.I. Zatevakhin classification [22]).

The need to initiate emergency measures depends on the severity of ischemia and is assessed according to the clinical classifications of V.S. Saveliev, I.I. Zatevakhin [22], and Rutherford [294]. In the presence of neurological deficit (grade 2B/IIb), immediate revascularization is indicated. Consensus documents [48, 254, 255] indicate that 24/7 availability of open and endovascular surgeries improves survival [40, 50]. In settings with limited resources, the strategy should be coordinated with a vascular surgeon prior to deciding on transfer. Small hospitals, especially in remote areas, should be integrated into a rapid patient routing network.

• Patients diagnosed with acute limb ischemia are recommended to be transferred to a vascular center that offers a full range of open and endovascular interventions necessary depending on the severity of ischemia [297].

LoE 5; GoR C

LoE 5; GoR C

7. Additional Information

7.1 Acute limb ischemia in children

7.1.1 Epidemiology

Acute limb ischemia (ALI) in children is rare but represents a potentially catastrophic event associated with mortality, limb loss, or permanent long-term disability. This nosological entity is observed in every 26–85 out of 100,000 pediatric hospitalizations [347, 348] and in <1% of pediatric injuries [349, 350]. In most cases, ischemia is iatrogenic in nature and results from secondary thrombosis following umbilical or femoral artery catheterization, particularly in newborns and infants [298]. Other causes of ALI are associated with penetrating or blunt trauma, cardiac embolism in infants with congenital heart or great vessel malformations, inherited coagulation disorders, or intrauterine external compression.

7.1.2 Diagnosis

• For infants and children undergoing femoral artery catheterization, it is recommended to perform vessel puncture under ultrasound guidance and carry out ultrasound monitoring after the procedure [303].

LOD 4; LoE C

Comment: Clinical manifestations of ALI in newborns and infants may be less obvious than in adults. Therefore, a high index of clinical suspicion is required, especially during arterial catheterization. This can be explained by the limited ability to express complaints verbally, as well as the smaller size of the limb and less developed muscles, which tolerate hypoxia better. Moreover, collateralization can improve and develop rapidly at an early age [349, 351]. The most frequent manifestations are cyanosis and delayed capillary refill. Necrotic changes are less common [298]. Several publications have suggested that duplex scanning of upper extremity arteries is a useful tool for monitoring vessel puncture, having reduced the incidence of catheter-related arterial thromboses [302–304].

7.1.3 Treatment options and outcomes

Conservative management with systemic heparinization has been the cornerstone of ALI treatment in children, predominantly based on expert opinion and small patient cohort analyses due to the scarcity of literature. Heparin monotherapy is evidently a relatively safe early strategy in most cases, allowing partial or complete thrombus dissolution, collateral development, and restoration of limb perfusion [351, 355–358] with a low risk of hemorrhagic complications (3% in one study) [223]. For UFH (#sodium heparin**) in patients >1 year of age, a bolus of 75 IU/kg is used followed by continuous infusion at 28 IU/kg/h, and for infants <1 year of age, 20 IU/kg/h for older children, titrated to an aPTT of 55–85 seconds [102]. Successful treatment with systemic thrombolysis has also been reported; however, its use carries a risk of intracranial hemorrhage, particularly in premature infants. The long-term outcomes of conservative management have also been evaluated, suggesting that 15% of affected children will develop either intermittent claudication or limb length discrepancies resulting from impaired subsequent growth [355, 360, 361].

• For infants and children under 2 years of age with acute limb ischemia, it is recommended to initiate primary conservative management using #sodium heparin** [103, 309–311].

Level of Evidence (LoE) 3; Grade of Recommendation (GoR) B

Comment: The use of unfractionated #sodium heparin** in children involves an initial intravenous bolus dose of 75 IU/kg over 10 minutes, followed by maintenance infusion: for children under 1 year of age – 28 IU/kg/h, for children over 1 year of age – 20 IU/kg/h. The maintenance dose is adjusted based on activated partial thromboplastin time (aPTT) values, the target range of which is 55–85 seconds. If the aPTT value is less than 50 seconds, administration of an additional bolus of #sodium heparin** is recommended; at 50 to 95 seconds, the infusion is continued at the previous rate; at 96 to 120 seconds, the infusion is suspended for 30 minutes; if it exceeds 120 seconds – for 60 minutes. Monitoring of aPTT is performed 4 hours after the initial bolus, and subsequently 4 hours after each infusion rate adjustment. Once the target therapeutic aPTT range is achieved, monitoring is carried out once daily.

Nearly 17% of children with ALI underwent revascularization in a population-based study; they were older than children who received conservative treatment, and the etiology was more frequently traumatic [308]. Infants and young children pose significant technical challenges for revascularization, and their surgical outcomes are worse than those of older children [144, 315]. Specifically, outcomes in infants do not improve following surgical intervention compared to conservative management [308].

Endovascular therapy appears to be a safe strategy and can be selectively used in the most severe cases with threatened limb viability [300]. A recent systematic review, including all management strategies, suggested that the limb salvage rate is 88% (95% CI 1%–31%) and overall mortality is 7% (95% CI 2%–14%) [310].

• For infants and children with acute limb ischemia and no clinical improvement within 4–6 hours after initiating conservative therapy with unfractionated #sodium heparin**, it is recommended to perform local endovascular transarterial thrombolysis or open surgical revascularization [310].

LoE 3; GoR B

Comment: An analysis of 25 children under 12 months of age with iatrogenic ALI showed that 88% had lower extremity involvement, the diagnosis was most frequently established via ultrasound duplex scanning (64%) or cyanosis (60%). The main treatment was anticoagulant therapy, with thrombolysis used in selected cases; amputation was required in one child. Long-term outcomes were satisfactory, confirming the efficacy of anticoagulants [307].

Ischemia occurs upon injury to the brachial artery and is usually resolved following closed reduction and fracture stabilization. In cases of pronounced ALI symptoms, arterial exploration is indicated. In most cases, an expectant management strategy is recommended: pulses typically recover within a week. Surgical intervention is indicated if ischemia progresses or shows no improvement within 7 days [311]. Preferred methods include exploration with release of the entrapped artery, primary repair, angioplasty with a vein patch, or vein graft interposition [312].

• In adolescents with supracondylar humerus fractures and absent radial pulse in the presence of preserved perfusion, as an alternative to immediate surgical exploration, an expectant management strategy is recommended [312].

LOD 4; LoE C

Comment: Perfusion monitoring is carried out using: regular assessment of capillary refill (<2 seconds), skin temperature, color (pink, pale, cyanotic), distal oxygen saturation levels (pulse oximetry),

upper extremity arterial Doppler ultrasound (presence of retrograde/weakened blood flow), and evaluation of finger sensation and motor function.

Frequency of monitoring: every hour for the first 6–12 hours, then every 2–4 hours until stabilization of the condition.

Objective methods for assessing limb viability: upper extremity arterial Doppler ultrasound, infrared capillaroscopy (if available), radioisotope aortoarterioscintigraphy (rarely, in case of doubt), and compartment pressure measurement if deterioration occurs.

Indications for urgent surgical exploration: deterioration of clinical perfusion (increased pallor, coldness, absence of capillary refill), onset or progression of pain, paresthesias, motor deficits, lack of improvement within 4–6 hours, and increasing edema with suspicion of compartment syndrome.

Criteria for Evaluating the Quality of Medical Care

Quality criteria for specialized medical care for adults and children with acute limb ischemia (ICD-10 codes: I74.0, I74.1, I74.2, I74.3, I74.5, I74.8, I74.9, S55.1, I77.0, I77.8).

References

Appendix A1. Working Group Composition

Members of the Expert Panel (in alphabetical order):

1. Abugov SA, Professor, MD, PhD, Head of the Department of X-ray Endovascular Diagnostic and Treatment Methods, Petrovsky National Research Centre of Surgery of the Russian Ministry of Health; First Deputy Chairman of the Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists; Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS); Board Member of the Moscow Cardiological Society (MCS); Member of The Society for Cardiovascular Angiography and Interventions (SCAI);

2. Akchurin RS, Academician of the Russian Academy of Sciences, Head of the Department of Cardiovascular Surgery, Deputy General Director for Surgery at the National Medical Research Center for Cardiology of the Russian Ministry of Health, President of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

3. Aleyan BG, Academician of the Russian Academy of Sciences, MD, PhD, Professor, Deputy Director for Science and Innovation Technologies at the Vishnevsky National Medical Research Center of Surgery of the Russian Ministry of Health, Chairman of the Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists;

4. Arakelyan VS, MD, PhD, Professor, Head of the Department of Arterial Pathology Surgery at the Bakulev National Medical Research Center for Cardiovascular Surgery of the Russian Ministry of Health, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Member of the Association of Cardiovascular Surgeons of Russia (ACSR), European Society for Vascular Surgery (ESVS);

5. Belov YV, Academician of the Russian Academy of Sciences, Director of the Institute of Cardio-Aortic Surgery at the Petrovsky National Research Centre of Surgery of the Russian Ministry of Health, Vice-President of the Angiology Society of Russia, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Member of the Association of Cardiovascular Surgeons of Russia (ACSR), European Society for Vascular Surgery (ESVS), American Association for Thoracic Surgery (AATS);

6. Bredikhin RA, MD, PhD, Professor, Head of the Vascular Surgery Department at the Interregional Clinical and Diagnostic Center, Kazan, Member of the Executive Council of the Association of Phlebologists of Russia (APR), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

7. Bondarchuk DV, Radiologist at the Department of Expertise and Quality of the Moscow Center for Diagnostics and Telemedicine "Moscow Radiology", Highest Qualification Category Physician, Radiologist at the Department of Diagnostic Radiology of the Pirogov National Medical and Surgical Center;

8. Burleva EP, MD, PhD, Professor at the Department of General Surgery, Ural State Medical University, Member of the Executive Council of the Association of Phlebologists of Russia (APR), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

9. Vachev AN, Professor, MD, PhD, Head of the Department of Faculty Surgery, Samara State Medical University;

10. Gavrilenko AV, Academician of the Russian Academy of Sciences, MD, PhD, Professor, Head of the Vascular Surgery Department at the Petrovsky National Research Centre of Surgery of the Russian Ministry of Health, Member of the Russian Society of Surgeons (RSS), Member of the Association of Cardiovascular Surgeons of Russia (ACSR), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Member of the Executive Council of the Association of Phlebologists of Russia (APR), European Society for Vascular Surgery (ESVS);

11. Zholkovsky AV, Head of the Vascular Surgery Department at the Rostov Clinical Hospital of the Southern District Medical Center of the Federal Medical-Biological Agency of Russia, Member of the Russian Scientific Society of Interventional Cardioangiology (RSSIC);

12. Eroshkin IA, MD, PhD, Head of the Department of X-ray Endovascular Diagnostic and Treatment Methods at the Odintsovo Military Hospital (25th Central Military Clinical Hospital of the Strategic Missile Forces);

13. Eroshenko AV, PhD, Interventional Radiologist, Vascular Surgeon, Head of Peripheral Interventions at the K+31 Clinic, Moscow, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

14. Zatevakhin II, Academician of the Russian Academy of Sciences, Head of the Department of Faculty Surgery, Pediatric Faculty, Pirogov Russian National Research Medical University, President of the RSS;

15. Zavatsky VV, Head of the Vascular Surgery Department at the Dzhanelidze Research Institute of Emergency Medicine, Member of the RSAVS, RSS, ESVS;

16. Zolkin VN, Professor, MD, PhD, Deputy Chief Medical Officer for Surgery at the Pletnev City Clinical Hospital of the Moscow Healthcare Department, Member of the Association of Cardiovascular Surgeons of Russia (ACSR), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

17. Imaev TE, MD, PhD, Head of the Laboratory of Hybrid Methods for Treating Cardiovascular Diseases, Department of Cardiovascular Surgery, Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology of the Russian Ministry of Health;

18. Kavteladze ZA, Professor, MD, PhD, Head of the Department of Emergency Vascular and X-ray Endovascular Surgery, Zhadkevich City Clinical Hospital;

19. Kalinin RE, MD, PhD, Professor, Member of the Executive Council of the Association of Phlebologists of Russia (APR), Member of the Russian Society of Surgeons (RSS), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Member of the Association of Cardiovascular Surgeons of Russia (ACSR), European Society for Vascular Surgery (ESVS);

20. Kazakov YI, Professor, MD, PhD, Head of the Cardiosurgery Department No. 2, Tyumen Regional Clinical Hospital, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Chairman of the Regional Branch of the Association of Phlebologists of Russia (APR);

21. Karpenko AA, Professor, MD, PhD, Head of the Research Department of Vascular and Hybrid Surgery, Institute of Circulation Pathology, Meshalkin National Medical Research Center of the Russian Ministry of Health, Member of the Association of Phlebologists of Russia (APR), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Member of the Association of Cardiovascular Surgeons of Russia (ACSR);

22. Kuryanov PS, Head of the City Center for Diabetic Foot and Surgical Infection, St. George City Hospital (Saint Petersburg), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

23. Lobastov KV, PhD, Associate Professor at the Department of General Surgery and Radiology, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Member of various Russian and international phlebological societies (EVF, IUA, ESVS, APR, SPVF);

24. Maksimov A.V., Professor, D.Sc. (Medicine), Head of the Department of Cardiovascular Surgery, Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

25. Matyushkin A.V., Professor, D.Sc. (Medicine), Head of the Department of Vascular Surgery at the University Clinic, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Member of the Association of Cardiovascular Surgeons of Russia (ACSR), European Society for Vascular Surgery (ESVS);

26. Pankov A.S., Ph.D. (Medicine), Associate Professor, X-ray and Endovascular Surgeon at the Department of X-ray Endovascular Diagnostic and Treatment Methods, Clinical Hospital No. 1 of the Office of the President of the Russian Federation, Member of the Russian Society of Angiography and Interventional Radiology (RSAIR) and CIRSE;

27. Petrosyan K.V., D.Sc. (Medicine), Head of the Department of X-ray Endovascular Research and Treatment Methods for Heart and Blood Vessels, Head of the Department of X-ray Endovascular Diagnostic and Treatment Methods at the Institute of Advanced Training and Professional Education, A.N. Bakulev National Medical Research Center for Cardiovascular Surgery;

28. Platonov S.A., Ph.D. (Medicine), Head of the Department of Endovascular Surgery, I.I. Janelidze St. Petersburg Research Institute of Emergency Medicine, St. Petersburg, Russia.

29. Sapelkin S.V., Professor, D.Sc. (Medicine), Leading Researcher at the Department of Vascular Surgery, A.V. Vishnevsky National Medical Research Center of Surgery of the Russian Ministry of Health, Member of the Russian Society of Surgeons (RSS), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

30. Svetlikov A.V., D.Sc. (Medicine), Head of the Center for Vascular Surgery, Clinical Hospital No. 122, St. Petersburg, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

31. Sokurenko G.Ю., Professor, D.Sc. (Medicine), Chief Physician of Clinic No. 2, A.M. Nikiforov All-Russian Center for Emergency and Radiation Medicine of the EMERCOM of Russia, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

32. Soroka V.V., D.Sc. (Medicine), Professor, Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

33. Suchkov I.A., Professor, D.Sc. (Medicine), President of the Association of Phlebologists of Russia (APR), Member of the Russian Society of Surgeons (RSS), Russian Society of Angiologists and Vascular Surgeons (RSAVS), Member of the Association of Cardiovascular Surgeons of Russia (ACSR), European Society for Vascular Surgery (ESVS);

34. Troitsky A.V., Professor, D.Sc. (Medicine), General Director of the Federal Research and Clinical Center of the Federal Medical-Biological Agency of Russia, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS), Member of the European Association for Cardio-Thoracic Surgery (EACTS);

35. Fokin A.A., Professor, D.Sc. (Medicine), Head of the Department of Surgery, Institute of Continuing Professional Education, South Ural State Medical University of the Russian Ministry of Health, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

36. Fomin K.N., Ph.D. (Medicine), Cardiovascular Surgeon, Researcher at the I.I. Janelidze St. Petersburg Research Institute of Emergency Medicine, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

37. Khubulava G.G., Academician of the Russian Academy of Sciences, Head of the Department of Faculty Surgery with Courses in Laparoscopic and Cardiovascular Surgery with Clinic; Chief Cardiac Surgeon of St. Petersburg and the Northwestern Federal District of the Russian Federation, Member of the Russian Society of Surgeons (RSS), Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

38. Charchyan E.R., Professor of the RAS, Corresponding Member of the RAS, Head of the Department of Reconstructive and Plastic Cardiovascular Surgery, B.V. Petrovsky National Research Center of Surgery of the Russian Ministry of Health, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

39. Chernyavsky A.M., Professor, D.Sc. (Medicine), General Director of the Academician E.N. Meshalkin National Medical Research Center, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

40. Chernykh N.A., Cardiovascular Surgeon, Deputy Head of the Medical and Simulation Center at the A.N. Bakulev National Medical Research Center for Cardiovascular Surgery of the Russian Ministry of Health, Member of the Association of Cardiovascular Surgeons of Russia (ACSR), Russian Society of Angiologists and Vascular Surgeons (RSAVS);

41. Chupin A.V., D.Sc. (Medicine), Head of the Department of Vascular Surgery, A.V. Vishnevsky National Medical Research Center of Surgery of the Russian Ministry of Health, Board Member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

42. Shipovsky V.N., Professor, D.Sc. (Medicine), Head of the X-ray Endovascular Department, D.D. Pletnev City Clinical Hospital;

43. Shumilina M.V., Professor, D.Sc. (Medicine), Head of the Ultrasound Diagnostics Group for Cardiovascular and Organ Pathology, A.N. Bakulev National Medical Research Center for Cardiovascular Surgery of the Russian Ministry of Health, Professor at the Department of Cardiology and Functional Diagnostics, Institute of Advanced Training and Professional Education, A.N. Bakulev National Medical Research Center for Cardiovascular Surgery of the Russian Ministry of Health, Moscow.

Author group (in alphabetical order):

• Arakelyan V.S.

• Burleva E.P.

• Zolkin V.N.

• Kalinin R.E., Suchkov I.A.

• Kuryanov P.S.

• Matyushkin A.V.

• Pankov A.S.

• Panov I.O.

• Platonov S.A.

• Sapelkin S.V.

• Chernykh N.A.

• Shumilina M.V.

Corresponding Author: Valery S. Arakelyan (Moscow, A.N. Bakulev National Medical Research Center for Cardiovascular Surgery of the Russian Ministry of Health)

Executive Secretary: Nikolay A. Chernykh (Moscow, A.N. Bakulev National Medical Research Center for Cardiovascular Surgery of the Russian Ministry of Health)

All members of the Working Group confirmed the absence of financial support or other conflicts of interest in the preparation of these guidelines.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the clinical guidelines:

1. Cardiovascular surgeon;

2. X-ray and Endovascular Surgeon;

3. Surgeon;

4. Ultrasound diagnostics physician;

5. Medical students, residents, postgraduate students.

The recommendations are based on a cumulative analysis of evidence presented in global literature and obtained through the clinical application of modern principles and methods for diagnosing and treating lower extremity varicose veins. The main provisions of the Recommendations are ranked in accordance with Order No. 103n of the Ministry of Health of the Russian Federation dated February 28, 2019, "On approval of the procedure and timelines for the development of clinical guidelines, their revision, the standard form of clinical guidelines and requirements for their structure, composition, and scientific validity of the information included in clinical guidelines." The recommendations were prepared in accordance with the Methodological Recommendations for Assessing the Scientific Validity of Information Included in Clinical Guidelines, Center for Expertise and Quality of Medical Care of the Ministry of Health of the Russian Federation, 2019.

Table 8. Levels of Evidence (LoE) rating scale for diagnostic methods (diagnostic interventions)

Table 9. Levels of Evidence (LoE) rating scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Table 10. Grades of Recommendation (GoR) rating scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Appendix A3. Reference Materials

1. On the Basics of Protecting the Health of Citizens in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011);

2. Procedure for Providing Medical Care to Patients with Cardiovascular Diseases (Order of the Ministry of Health of Russia No. 918n of November 15, 2012);

3. On Classification and Criteria Used in Disability Determination and Medical and Social Expertise of Citizens by Federal State Institutions of Medical and Social Expertise (Order of the Ministry of Health of Russia No. 1024n of December 17, 2015);

4. Order of the Ministry of Health of Russia No. 103n dated February 28, 2019 "On Approval of the Procedure and Timelines for the Development of Clinical Practice Guidelines, Their Revision, Standard Template of Clinical Practice Guidelines, and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Practice Guidelines" (Registered with the Ministry of Justice of Russia on May 8, 2019, No. 54588);

5. Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017, "On approval of criteria for assessing the quality of medical care";

6. Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017 "On approval of the nomenclature of medical services";

7. Order of the Ministry of Health of the Russian Federation No. 700n of October 7, 2015, "On Nomenclature of Specialties of Specialists with Higher Medical and Pharmaceutical Education"; Order of the Ministry of Health of Russia No. 1183n of December 20, 2012 (as amended on August 1, 2014) "On Approval of the Nomenclature of Positions of Medical and Pharmaceutical Workers";

8. Order of the Ministry of Health of Russia No. 4n of June 6, 2012 (as amended on September 25, 2014) "On Approval of the Nomenclature Classification of Medical Devices".

9. Ultrasound diagnostic methods and regional systolic pressure index in occlusive arterial diseases of the extremities.

The main quantitative indicator of the adequacy of blood supply in various segments of the extremity is the regional systolic pressure index (RSPI). To measure regional systolic pressure, cuffs are applied at 4 levels of the lower extremity, the layout of which is shown in Fig. 1. The first cuff (12 cm for adults) is applied to the highest possible upper third of the thigh. The second cuff (12 cm for adults) is applied to the lower third of the thigh, without involving the knee joint. The third cuff (10 cm) is applied at the border of the proximal and middle thirds of the lower leg, since a high position (closer to the fibular head) yields a false regional pressure value and, consequently, a false-positive index. The fourth cuff (10 cm) is applied to the lower part of the lower leg just above the ankle joint.

Fig. 1. Cuff placement scheme and arterial localization points during Doppler ultrasound (USDG).[66]

The RSPI is calculated as the ratio of the regional systolic blood pressure in an extremity segment to the systemic systolic blood pressure, which is the higher of the two pressures measured at the brachial arteries. Normally, the blood pressure gradient between the upper extremities is no more than 5 mm Hg when measured with a standard manometer, and no more than 10 mm Hg when measured with a mechanical sphygmomanometer.

During the localization of iliac artery occlusions, no systolic murmur is auscultated. The RSPI value in this case depends on the extent of the occlusion. Higher pressure indices are possible with focal occlusion. A bilaterally low (approximately 0.6) RSPI value indirectly suggests an occlusion of the abdominal aorta.

In iliac artery occlusion and SFA disease, blood pressure on the 2nd cuff decreases by 5–10 mmHg, and the PI in the popliteal artery increases. If iliac artery occlusion is accompanied by SFA occlusion, a blood pressure decrease of more than 5 mmHg is recorded on the 2nd cuff, along with a decrease in PI in the popliteal artery. In popliteal artery occlusion, the blood pressure gradient between the 2nd and 3rd cuffs may exceed 20 mmHg.

To assess the distal segments of the SFA and the popliteal artery, pressures measured by the 2nd and 3rd cuffs are compared. The higher of the two pressures from the 3rd cuff is taken (ankle-brachial index based on the posterior tibial or anterior tibial artery).

If the difference in blood pressure measured by the 3rd cuff between the posterior and anterior tibial arteries is greater than 5 mmHg, there is an arterial lesion with the lowest blood pressure in the proximal third of the leg.

To determine the systolic digital pressure (SDP), a digital cuff is placed on the proximal phalanges. It should be noted that this parameter correlates with the cuff size—cuffs that are too narrow lead to an overestimation of the SDP [313, 314]. According to Carter S.A. et al. (1971), normal SDP is on average 13% lower than the brachial systolic blood pressure, and the mean resting gradient between ankle and digital systolic pressures is normally 38±15 mmHg (ranging from 34 to 46 mmHg) [315]. According to Conrad M.C. et al. (1964), these parameters do not differ in most healthy individuals, and there is no gradient between brachial and digital pressures [316]. According to Shumilina M.V. et al., under normal conditions in clinostasis, toe blood pressure in the patient's horizontal position is 5–10 mmHg lower than the ankle pressure [64–66].

Localization of the digital arteries is performed using an 8 MHz (10 MHz) probe at the most distal surface. In vascular bed disease with the development of trophic disorders or hyperkeratosis, localization of terminal arteries is difficult. In such cases, the digital arteries are localized at the base of the fingers along their lateral surfaces.

For reconstructive surgery, it is extremely important to know the patency of the arcuate artery, dorsal metatarsal arteries (from the anterior tibial system), and the plantar arch (from the posterior tibial system), their interconnections, and the antegrade or retrograde filling of each arterial bed. To determine this, when localizing the artery of interest (taking into account its anatomical location), sequential compression of the proximal (and, if necessary, distal) segments of the inflow arteries is performed with the investigator's fingers.

Duplex scanning of upper/lower extremity arteries

When determining the surgical treatment strategy, the structure of the thrombosis, which correlates with its chronicity, is very important. The lesion structure is assessed in B-mode. Fresh arterial thromboses are visualized as hypoechoic masses (Fig. 2), which may form on echopositive parietal atherosclerotic plaques.

Fig. 2. Relatively fresh thromboses. A – femoropopliteal bypass thrombosis (homogeneous, hypoechoic thrombus structure). B – hypoechoic, homogeneous SFA stent thrombosis.

One study demonstrated that in patients with acute limb ischemia (ALI), an arterial expansion of 0.5 mm in the segment proximal to the occlusion level compared to the contralateral limb suggests an embolic occlusion, whereas a 0.5 mm decrease in lumen diameter corresponds to thrombotic occlusion [44].

When addressing reconstruction, it is crucial to evaluate the extent of occlusion, as well as the presence and diameter of proximal/distal collaterals. For visualizing collaterals in crural artery disease, triplex scanning is inferior to radiological diagnostic methods.

The sensitivity of duplex ultrasound angiography (DUSA) in ALI is 88% (95% confidence interval [CI] 80%–98%), and its specificity is 96% (95% CI 89%–99%) for detecting >50% stenosis or occlusion in patients with chronic lower extremity PAD [317]. DUSA can provide necessary information in 90% of cases when revascularization is considered for ALI patients and is the optimal imaging method for determining complete or incomplete obstruction in the common femoral, superficial femoral, and popliteal arteries, as well as vascular bypass grafts [318]. Diagnostic accuracy in identifying tibial artery stenosis or occlusion is lower, but ALI is rarely caused by such distally located lesions.

In a retrospective analysis of 181 patients with acute ischemia of the lower extremities (AILE), 90 patients treated based on duplex ultrasound data as the sole imaging modality showed results comparable to those who underwent preoperative intra-arterial digital subtraction angiography (IADSA) and computed tomography angiography (CTA) [73].

Appendix B. Physician Action Algorithms

The action algorithm consistently consists of solving the main tasks: 1) establishing the diagnosis of AILE; 2) determining the nature of the occlusion—embolism, acute thrombosis, or embolism on the background of chronic arterial obstruction (CAO); 3) assessing the degree of ischemic tissue damage in the limb.

The required treatment must be initiated promptly, depending on the severity of ischemia, which is assessed using the clinical classification by Zatevakhin I.I. et al. (Table 11) [319].

Table 11. Clinical classification of AILE (Zatevakhin I.I. et al., 2002)

Course: regressive, stable, progressive

In grade 1 ischemia with absolute certainty of the diagnosis of embolism and a stable patient condition, emergency revascularization must be performed. In case of acute thrombosis or an uncertain diagnosis with stable ischemia, there is no need for emergency surgery. There is an opportunity to examine the patient, conduct trial conservative treatment, and select the definitive treatment method, whether simple embolectomy, complex arterial reconstruction, intrathrombal thrombolysis, or endovascular intervention (see Table 12).

Table 12. Treatment tactics according to the classification by I.I. Zatevakhin et al. (2002) [319].

The algorithm of actions for acute lower limb ischemia is presented as a flowchart in Fig. 3.

Below is the treatment algorithm for acute limb ischemia according to the Rutherford strategy and classification (Fig. 4), including indications for angiography, endovascular, and surgical treatment.

Figure 4. Treatment algorithm for acute limb ischemia according to the Rutherford classification [320].

Class I ischemia does not threaten limb loss, and treatment can be conservative, especially in sedentary patients—sometimes symptoms disappear after anticoagulation. Management tactics are similar to class IIA: rapid revascularization after urgent angiography, predominantly using endovascular methods (thrombolysis, mechanical thrombectomy). If these are ineffective, open surgery is possible.

In class IIB ischemia, the only way to save the limb is emergency revascularization. The most preferred method is open embolectomy performed via access to the femoral arteries, which allows passage of a balloon catheter into both the aorta and vessels below the knee. In embolic occlusions, isolated embolectomy is possible, while thrombosis may require bypass surgery. If blood flow in the pedal arteries is not restored, control angiography is required [321]. Distal thrombi are removed via access to the popliteal artery or using catheter-directed thrombolysis.

Class III ischemia is considered irreversible. Ultrasound shows no arterial or venous signals; muscle rigidity, purplish-cyanotic spots, profound anesthesia, and paralysis are observed. Emergency embolectomy within the first 2 hours can save the limb, but with later revascularization, the chances are low: there is a high risk of acute kidney injury due to rhabdomyolysis and the development of permanent contracture followed by amputation. Even with successful restoration of blood flow, compartment syndrome often develops, requiring prophylactic fasciotomy [322].

Appendix C. Patient Information

Below is a patient information leaflet for individuals requiring surgical treatment for acute limb ischemia.

"Dear patient, you have been diagnosed with acute limb ischemia requiring urgent surgical treatment due to the high risk of limb loss and potential life-threatening complications. Before the surgery, your attending physician will explain its nature and risks in detail. The decision to undergo surgery is voluntary. This information will help you prepare for the discussion with your doctor."

What is acute limb ischemia?

This is a sudden disruption of blood flow in the arteries of an upper or lower extremity caused by their occlusion with a thrombus or embolus. This condition leads to a sharp decrease in the supply of blood and oxygen to tissues, which threatens their viability and can lead to serious complications.

Acute limb ischemia most frequently develops against the background of atherosclerosis, a disease in which plaques form in the arteries, narrowing the vessel lumen. The rupture of such a plaque can trigger the formation of a blood clot and complete occlusion of the artery, leading to acute ischemia.

What can happen without treatment?

Without treatment, acute limb ischemia progresses rapidly, causing tissue destruction, pronounced intoxication, and severe pain syndrome, which can lead to severe complications affecting the cardiovascular and other body systems. The longer treatment is delayed, the more severe the degree of ischemia and the higher the risk of adverse consequences.

Emergency surgery is the only effective method to eliminate ischemia and restore the patient to normal life.

How is the surgery performed?

The surgery is performed under general anesthesia or regional block anesthesia; the anesthesiologist will inform you about the risks of anesthesia.

There are several types of interventions, the main goal of which is to restore blood flow through the arteries or venous system. The choice of method depends on the severity and duration of ischemia, the location and cause of occlusion, concomitant diseases, as well as the resources and expertise of the specialists.

One treatment method is thrombolysis—the dissolution of a blood clot using special medications. Antithrombotic agents effectively relieve vessels by destroying the fibrin strands that make up the thrombus. If a thrombus completely blocks an artery, it is important to start treatment within a few hours to preserve limb function.

These drugs are administered directly into the vessel and differ from agents used for the prevention of cardiovascular diseases.

Enzymatic thrombolytics are used to dissolve large blood clots, especially in debilitated or elderly patients. Thrombosis causes ischemia—a disruption of blood supply and oxygen starvation of tissues; a dislodged thrombus can lead to embolism of vital vessels.

Thrombolytic therapy (TLT) is a method aimed at restoring blood flow by dissolving a blood clot. The main contraindication is a high risk of bleeding within the preceding 6 months, as TLT can provoke internal bleeding (gastrointestinal, pulmonary, uterine, hematuria, etc.).

Endovascular surgery is a modern method of treating vascular diseases in which the procedure is performed from inside the vessel. The procedure is performed under local anesthesia through a small puncture, most commonly in the femoral artery. A guidewire is inserted through it, over which catheters and other instruments are delivered to treat the vascular wall. Following the intervention, the patient is hospitalized for several days, spending the first hours or day in the intensive care unit.

Which treatment techniques are most commonly used in endovascular surgery?

Balloon dilation (angioplasty)—expansion of a narrowed artery using a special balloon. The method is effective in certain vascular zones (for example, the iliac arteries), but the effect is often short-lived.

Stenting—placement of a metal stent into the vessel, which supports its lumen and restores blood flow. The method is minimally invasive and well tolerated, but suitable for localized, short-segment stenoses.

Endoprosthetics—insertion of a synthetic tube with a self-expanding framework into the artery, most commonly used for aneurysms, such as of the abdominal aorta.

Combined angioplasty includes balloon expansion followed by stent placement to prevent restenosis.

Endovascular methods are characterized by a low risk of complications and a short hospital stay, whereas open surgeries provide a more lasting result but require prolonged recovery. The choice of treatment method is individual and depends on the patient's characteristics and the physician's experience.

In modern vascular surgery, "hybrid operations" combining two approaches are widely used:

• Open surgery—radical and reliable,

• Endovascular methods—minimally invasive and fast.

This combination achieves high efficacy and minimal invasiveness. Additional advantages include:

1. The ability to perform several therapeutic stages within a single operation.

2. Monitoring results at each stage using angiography.

The hybrid approach is most frequently used for multilevel lesions of the femoral and tibial arteries: bypass surgery is performed first, followed by endovascular angioplasty of the tibial arteries.

The physician discusses the stages of the surgical intervention (whether open, endovascular, or hybrid) with you; however, during the surgery, the need for additional unplanned stages may arise.

What complications can occur?

In certain cases, complex surgeries may be associated with complications.

• Bleeding and hematomas.

• Infectious complications—suppuration, prolonged healing, risk of keloid scar formation.

• Deep vein thrombosis with the risk of pulmonary embolism; prevention involves prescribing anticoagulants (carrying a bleeding risk).

• Compression of nerves and soft tissues due to prolonged immobility—usually resolves within a week.

• Need for blood transfusion—an extremely rare risk of infection.

• Allergic reactions to medications or contrast agent—ranging from itching to rare severe manifestations.

• Keloid scars in case of predisposition.

What are the treatment outlooks?

In most cases, surgery leads to an improvement in condition, relief of complaints, and preservation of the weight-bearing function of the limb. To maintain the result, your active participation is important: complete smoking cessation, adherence to the recommended diet, and correction of risk factors in agreement with your attending physician.

What should be paid attention to after surgery?

Regular follow-up with a local vascular surgeon is mandatory: it is necessary to compare the condition before and after surgery, undergo follow-up ultrasound scans, and follow all recommendations. The frequency of visits and examinations is determined individually with your attending physician.

Immediate medical attention is required in case of:

• Return or onset of severe pain in the limb.

• Impaired sensation or movement, coldness, numbness, or pallor of the skin.

• Sharp decrease in pain-free walking distance.

• Signs of inflammation or heavy discharge from the wound.

• Disappearance of a pulse in a peripheral artery if it was previously palpable

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1.

Risk assessment scale for thromboembolic complications in patients with atrial fibrillation/flutter

Original name: CHA2DS2-VASc (Revised Venous Clinical Severity Score, rVCSS)

Source (official developer website, validation publication): Olesen, Jonas Bjerring, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. Bmj 342 (2011): d124.

Type: rating scale

Purpose: stratification of the risk of stroke and systemic thromboembolic complications to determine the need for antithrombotic therapy in patients with atrial fibrillation/flutter.

Content (template):

Key (interpretation):

Explanation: none

Appendix G2.

DN4 questionnaire for pain type diagnosis

Original name: Douleur Neuropathique 4 questions – DN4

Source (official developer website, validation publication): Bouhassira D., et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005;

Type: questionnaire

Purpose: diagnosis of neuropathic pain and determination of the presence of a neuropathic component in mixed pain syndromes.

Content (template):

Key (interpretation): a total score of 4 or more points indicates that the patient's pain is neuropathic, or that a neuropathic pain component is present (in mixed nociceptive-neuropathic pain syndromes).

Explanation: The DN4 questionnaire is designed for rapid differentiation between neuropathic and nociceptive pain. It consists of 10 items based on patient complaints and examination findings. It is used for screening neuropathic pain syndromes, assessing therapy dynamics and efficacy. A result of ≥4 points indicates the presence of neuropathic pain.

Appendix G3.

Critical-Care Pain Observation Tool

Original title: Critical-Care Pain Observation Tool (CPOT)

Source (official developer website, validation publication): Zhai Y, Cai S, Zhang Y. The Diagnostic Accuracy of Critical Care Pain Observation Tool (CPOT) in ICU Patients: A Systematic Review and Meta-Analysis. J Pain Symptom Manage. 2020 Oct;60(4):847-856.e13. doi: 10.1016/j.jpainsymman.2020.06.006. Epub 2020 Jun 13.

Type: rating scale

Purpose: objective assessment of pain level in intensive care unit patients, including intubated patients, to determine the need for analgesia and sedation adjustment.

Content (template):

Key (interpretation): for patients with a CPOT score >2: an unacceptable level of pain is present. Consider further or alternative analgesia and sedation.

Explanation: The CPOT scale is used for the objective assessment of pain in patients who cannot speak (e.g., due to intubation or deep sedation). It is based on observing facial expressions, body movements, and physiological responses. It is used in intensive care units for patient monitoring, selecting analgesia, and evaluating its efficacy, including during invasive procedures.

Appendix G4.

Quality of Life Questionnaire (Modified Russian Version)

Original title: The Short Form-36 (SF-36)

Source (official developer website, validation publication): Quality of Life Questionnaire [Belova A.N., Shchepetova O.N., 2002]

Type: questionnaire

Purpose: comprehensive assessment of the patient's physical and psychological status, functional capacity, and social functioning to determine the impact of disease and treatment on quality of life.

Content (template):

1. In general, would you rate your health as (circle one number):

A) Excellent – 1;

B) Very good – 2;

C) Good – 3;

D) Fair – 4;

E) Poor – 5.

2. How would you rate your health now compared to one year ago? (circle one number):

A) Much better than one year ago – 1;

B) Somewhat better than one year ago – 2;

C) About the same as one year ago – 3;

D) Somewhat worse than one year ago – 4;

E) Much worse than one year ago – 5.

3. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities as a result of your physical health? (circle one number on each line):

4. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities as a result of any emotional problems (such as feeling depressed or anxious)? (circle one number on each line):

5. During the past 4 weeks, to what extent has your physical health or emotional problems interfered with your normal social activities with family, friends, neighbors, or groups? (circle one number):

A) Not at all – 1;

B) Slightly – 2;

C) Moderately – 3;

D) Quite a bit – 4;

E) Extremely – 5.

6. How much bodily pain have you had during the past 4 weeks? (circle one number)

A) None – 1;

B) Very mild – 2;

C) Mild – 3;

D) Moderate – 4;

E) Severe – 5;

F) Very severe – 6.

7. During the past 4 weeks, to what extent has your physical health or emotional problems interfered with your normal social activities with family, friends, neighbors, or groups? (circle one number)

A) Not at all – 1;

B) Slightly – 2;

C) Moderately – 3;

D) Quite a bit – 4;

E) Extremely – 5.

8. These questions are about how you feel and how things have been with you during the past 4 weeks. For each question, please give the one answer that comes closest to the way you have been feeling. How much of the time during the past 4 weeks (circle one number on each line):

8. During the past 4 weeks, how much of the time has your physical health or emotional problems interfered with your social activities (like visiting with friends, relatives, etc.)? (circle one number):

A) All of the time – 1;

B) Most of the time – 2;

C) Some of the time – 3;

D) A little of the time – 4;

E) None of the time – 5.

9. How TRUE or FALSE is each of the following statements for you? (circle one number on each line)

Key (interpretation): The 36 items of the questionnaire are grouped into eight scales. The scales are aggregated into two summary measures: the physical component summary and the mental component summary.

Explanation: The SF-36 questionnaire is a universal instrument for the quantitative assessment of patients' quality of life regardless of nosology. It is used in clinical trials, treatment efficacy monitoring, and dynamic patient condition assessment.