A threat to life and limb: acute lower limb ischaemia

Acute lower limb ischaemia (ALI) is defined by a sudden onset of reduced perfusion in one lower limb or both lower limbs, with a maximum duration of 14 days, which is usually a result of an arterial thromboembolic event1. The annual incidence of ALI is estimated to be 10–26 of 100 000 people, according to reports from the UK, the USA, and Sweden2–5. The aetiology, with historically a high proportion of embolic occlusions caused by valvular heart disease in otherwise young and healthy individuals, has shifted in developed countries to thrombotic disease caused by plaque rupture in atherosclerotic arteries (Fig. 1) and embolic disease mainly due to atrial fibrillation, in an older and often frail population6. A substantial portion of ALI is due to occlusions in a previous arterial reconstruction, be it a graft, a stentgraft, or a bare stent7. Another important aetiology, mainly affecting men, is thromboembolic occlusions caused by popliteal artery aneurysms, which can be challenging to treat8. However, ALI may also occur due to trauma, arterial dissection, severe deep-vein thrombosis, and iatrogenic injuries, but these factors will not be discussed further in this article. Atherosclerotic artery with plaque rupture and thrombus formation ©Emil Karonen. Risk factors for developing thrombotic ALI are similar to those for the development of peripheral artery disease (PAD), such as older age, smoking, hypertension, dyslipidaemia, and diabetes mellitus, as well as having previously undergone revascularization for PAD1,9. In the literature, the so-called ‘six Ps’ are used to describe the symptoms of ALI: pulselessness, pain, paraesthesia, poikilothermia (perishingly cold), pallor, and paralysis (Fig. 2)10. However, ALI is a dynamic disease, with signs arising at different time points and depending on severity. It is of essence for the clinician who is performing the initial evaluation to take a thorough medical history, especially with a focus on symptom duration, risk factors for ALI, and current medication. Patient examination should include manual examination of the pulses from the aorta to the pedal pulses, as well as measurment of the ankle-brachial index. Point-of-care duplex ultrasound examination of the arteries in the lower limb may also be performed, when adequate resources and expertise exist in the centre and when it does not delay management. An electrocardiogram may allow the diagnosis of an underlying atrial fibrillation. To be able to determine the severity of the symptoms, examination of sensory and motor functions is key, providing information that is used to categorize severity in accordance with the Rutherford criteria (Table 1)11. Key examinations and findings in acute lower limb ischaemia. Rutherford criteria11 Rutherford criteria11 When a patient presents with suspected ALI, urgent imaging should be performed, usually using computed tomography angiography; alternatively, when available in a timely manner, magnetic resonance imaging angiography can be used12. Imaging enables the vascular surgeon to localize the occlusion(s) and plan for best possible management. After ALI has been diagnosed, the patient should be administered an unfractionated heparin bolus intravenously, followed by continuous intravenous administration, to prevent further thrombus progression before open surgical or endovascular revascularization1. For the treatment of an embolism, a Fogarty embolectomy is often the preferred method. After exposure of the common femoral artery (Fig. 3) or the popliteal artery and clamping of the necessary arteries to accomplish proximal and distal control, arteriotomy is performed and a catheter with an expandable balloon at its tip is inserted into the arterial lumen to retrieve the thromboembolic clot (Fig. 4). This technique revolutionized and dominated the treatment of ALI for many decades, but, while still widely in use, there has been a shift towards minimally invasive endovascular procedures, starting with the introduction of catheter-directed thrombolysis (CDT) during the 1980s and 1990s13. Exposed right common femoral artery, superficial femoral artery, and deep femoral artery before clamping and arteriotomy ©Talha Butt. Sketch of an arterial thrombus being retrieved with a Fogarty catheter ©Emil Karonen. CDT is performed under local anaesthesia and, preferably after an ultrasound-guided puncture into the common femoral artery, an introducer is inserted percutaneously and a catheter is guided towards the occlusion using fluoroscopy, and placed into the occlusion, where a thrombolytic agent is continuously administered through small fenestrations in the distal segment of the catheter, dissolving the thrombus/embolus (Fig. 5a,b). CDT is usually administered for 24 h, but is sometimes continued for longer, when satisfying revascularization is not yet achieved. Three randomized controlled trials during the 1990s compared CDT with open vascular surgery, without any clear advantage to either modality14–16. CDT has long been considered not to be an alternative to surgery in patients with grade IIB ALI, but recent guidelines suggest where CDT can be started promptly it may be an alternative in select patients1. The risk of major bleeding, especially the rare, but not insignificant, occurrence of often fatal intracranial haemorrhage, begs for careful consideration of whether the patient has contraindications to CDT. Treatment of a peripheral thrombotic occlusion with catheter directed thrombolysis and stenting a Sketch of a fenestrated thrombolysis catheter introduced into a thrombus. ©Emil Karonen. b Sketch of a fenestrated thrombolysis catheter administering thrombolytic agents locally into a thrombus with clot dissolution. © Emil Karonen. c Sketch of the same arterial segment after thrombus dissolution and placement of a bare stent. ©Emil Karonen. Endovascular pharmacomechanical thrombolysis may be used as an alternative to CDT, where a bolus dose of thrombolytic agent is administered into an arterial thromboembolic occlusion through a catheter, which fragments the clot, followed by expulsion of high-pressure saline jets to further fragment the clot, creating a vacuum effect that allows the clot fragments to be drawn into the catheter. This can reduce the amount of thrombolytic agent needed, potentially reducing the risk of major bleeding and enabling shorter treatment times, with satisfactory results17. However, pharmacomechanical thrombolysis may cause haemolysis and acute kidney injury, especially with extended use18. Thromboaspiration, where a catheter with strong suction is used to retrieve the embolus/thrombus, has shown promising results for treating patients with ALI without the use of thrombolytic agents, but may result in significant blood loss19. Independent of the chosen revascularization approach, it is often necessary to perform additional procedures to address underlying PAD, usually using percutaneous angioplasty, with or without stenting, to improve the chances of retaining long-term patency (Fig. 5c). Upon revascularization, swelling of the muscles, which are constrained by the semi-rigid muscle fascia (Fig. 6), may increase intracompartmental pressure. This may ultimately compromise perfusion and cause ischaemia, resulting in acute compartment syndrome20. The development of acute compartment syndrome is usually quite insidious, with non-specific early symptoms; more specific symptoms present later, with a high risk of a limb already having established muscle necrosis and permanent nerve damage at the time of diagnosis and treatment21. Acute compartment syndrome is most commonly seen in the calf and must be treated using a full four-compartment fasciotomy (Fig. 7). In some high-risk patients, the surgeon may opt for a prophylactic fasciotomy before the development of acute compartment syndrome, but with the risk of overtreatment. Axial view of the four compartments of the left lower leg ©Talha Butt. View of the medial fasciotomies of a young patient treated with bilateral four-compartment fasciotomy due to acute compartment syndrome after emergency open surgical revascularization for an aortic occlusion ©Stefan Acosta. Although there have been advances in surgical treatment, with the development of new endovascular techniques and with more aggressive medical therapy, improvements in outcomes have been lagging behind22. For patients undergoing revascularization, the 30-day and 1-year mortality rates have been reported to be 4.5–8.9%23–26 and 14.2–24.4%23–26 respectively and 30-day and 1-year major amputation rates have been reported to be 7.6–11.0%24,26 and 14.3–19.2%24–26 respectively. However, these rates do not reflect total major amputation and mortality rates for all patients with ALI, as these studies were conducted on patients undergoing revascularization for ALI, whereas patients treated using primary amputation, conservative medical treatment, or palliative care were excluded. Two epidemiological studies have been conducted that investigated total major amputation and mortality rates for all patients who developed ALI in a single area during 1 year, reporting 30-day mortality and major amputation rates of 26.2% and 7.1% respectively5 and 1-year mortality and major amputation rates of 32.3% and 22.4% respectively4. Another study, of all US Medicare patients aged 65 years and older who were admitted to hospital with a diagnosis of ALI, reported 30-day and 1-year mortality rates of 19.2% and 42.5% respectively and 30-day and 1-year amputation rates of 8.1% and 11.0% respectively2. However, it is necessary to remember that mortality is a competing risk to major amputation and, especially in cohorts including patients not undergoing revascularization, a high mortality rate probably masks a higher major amputation rate than what is reported. Even with advancements including development of high resolution imaging, increased access to imaging, and a modern arsenal of minimally invasive revascularization techniques, survival and limb salvage rates for patients with ALI remain rather stagnant. The authors have no funding to declare. Emil Karonen (Conceptualization, Methodology, Resources, Visualization, Writing—original draft), Talha Butt (Resources, Software, Supervision, Visualization, Writing—review & editing), Frida Eek (Supervision, Writing—review & editing), and Stefan Acosta (Conceptualization, Project administration, Supervision, Visualization, Writing—review & editing) The authors declare no conflict of interest.