Acute limb ischaemia and chronic limb-threatening ischaemia

• Acute limb ischaemia (ALI) is a sudden, usually very recent (less than two weeks) drop in blood supply to a limb that threatens its survival. Chronic limb-threatening ischaemia (CLTI) is the opposite end of the same disease: a chronic, progressive restriction of blood flow with rest pain, a non-healing ulcer or gangrene.
• ALI is recognised by the six Ps: pain, pallor, pulselessness, poikilothermia (coldness), paraesthesia and paralysis. It is classified by the Rutherford system into four classes, from viable to irreversible, and that class decides how fast you must act.
• Most ALI is either an embolus travelling from the heart or aorta, or thrombosis on top of diseased arteries. Most CLTI is atherosclerotic peripheral arterial disease (PAD) with long-standing narrowing in several levels.
• The first treatment for ALI, after assessment, is therapeutic intravenous unfractionated heparin, then urgent revascularisation by open thrombo-embolectomy or an endovascular technique. CLTI needs a vascular multidisciplinary team, best medical therapy, and revascularisation that matches patient risk, limb threat and anatomy.
• Amputation is a treatment, not a failure: a non-viable (Rutherford class III) limb should be amputated rather than reperfused, and primary amputation is appropriate for an unsalvageable limb, poor function or short life expectancy after shared decision-making.

By the end of this page you should be able to:

1. Recognise ALI from the six Ps, stage it with the Rutherford classification, and separate a viable from an irreversible limb.
2. Distinguish embolic from thrombotic ALI from the history, examination and imaging, and understand why the distinction changes treatment.
3. Explain the pathophysiology of reperfusion injury and compartment syndrome, and how to prevent or treat them.
4. Apply current guidance to the immediate, definitive and long-term management of ALI and CLTI, including the role of heparin, thrombolysis, surgery and fasciotomy.
5. Stage CLTI with WIfI, plan revascularisation on patient risk, limb threat and anatomy, and manage diabetic foot ulcers and amputation within a team.
6. Cite the guideline editions used and recognise where recommendations differ between US and European practice.

ALI and CLTI are not two diseases. They are the acute and chronic ends of arterial insufficiency in a limb. The distinction matters because the clock, the causes and the treatments differ: ALI is measured in hours, CLTI in weeks to months. CLTI has replaced the older terms "critical limb ischaemia" and "severe limb ischaemia" because those implied a single perfusion threshold, whereas in reality limb threat is a continuum of wound, ischaemia and infection components.

Limb ischaemia is common, morbid and frequently missed until it is advanced. Peripheral arterial disease itself affects roughly 113 to 236 million people worldwide, and a sizeable fraction of these patients never report typical claudication. Among patients with known PAD, roughly 11% to 20% develop CLTI, and historically one quarter to one third of patients presenting with CLTI die within a year, with major amputation in up to 30%. Against that background, ALI is less common: in a contemporary trial cohort of patients with symptomatic PAD followed for a mean of 30 months, the incidence of ALI was 1.7%, or 0.8 per 100 patient-years.^[1] The reason to be efficient with ALI is not that it is frequent, but that the limb becomes irreversibly damaged within hours, and the outcome after that is poor.

This topic focuses on the lower limb because that is where most cases occur and where the evidence is concentrated. Upper limb ischaemia behaves according to similar principles but is not covered in depth here.

• Global burden. PAD is common and under-recognised; many patients are asymptomatic or have atypical exertional symptoms rather than classic claudication.
• CLTI. It is the end stage of PAD. Between 11% and 20% of patients with known PAD develop CLTI, and it carries the majority of PAD-related major and minor amputations.^[1]
• Outcome of CLTI. Historically estimated one-year mortality of 25% to 35% and one-year amputation rates of up to 30% among patients presenting with CLTI have been reported; more recent revascularisation trials report lower figures. Looking at these numbers should make clear why CLTI is treated as a vascular emergency even when the limb is not acutely threatened.^[1]
• ALI. Previous lower limb revascularisation, atrial fibrillation and lower ankle-brachial index values (0.60 or below) are all associated with increased risk of ALI in patients with PAD. ALI usually occurs on top of existing disease: acute thrombosis at a stenosis, thrombosis of a previous bypass graft or stent, embolism, or an aneurysm.^[1]
• Sex and age. CLTI is more common in older adults and in those with diabetes, smoking, dyslipidaemia, hypertension and chronic kidney disease. Male sex predominates in most series of CLTI and ALI, though women are increasingly represented at older ages and may present later.

ALI is either an embolus arriving from upstream, or thrombus forming in situ. The distinction is the single most useful bedside question, because it changes the search for a source and the choice of revascularisation.

Embolism usually originates in the heart. The common sources are atrial fibrillation with left atrial or appendage thrombus; mural thrombus after myocardial infarction or in cardiomyopathy; infective endocarditis; valvular disease such as mitral stenosis; and paradoxical embolism across a patent foramen ovale. An embolus travels until it reaches a point where the vessel narrows, classically the common femoral artery bifurcation, the popliteal artery trifurcation, or the aortic saddle at the bifurcation, so it tends to lodge at branch points and to occlude a relatively normal artery suddenly, without warning symptoms.

In situ thrombosis occurs on diseased arteries. The underlying causes are listed in Table 20 of the 2024 AHA/ACC peripheral arterial disease guideline and include:^[1]

Two bedside clues help distinguish the two:

• Embolus: sudden onset in a patient with known atrial fibrillation or recent infarction; no previous claudication; often a normal contralateral pulse and palpable pulses elsewhere; the limb is viable until it is not.
• Thrombosis: gradually worsening claudication or rest pain over days; known PAD; bilateral disease; previous revascularisation; poor distal runoff.

Peripheral aneurysm, especially a popliteal aneurysm, deserves a deliberate search in every ALI, because it produces both thrombosis and distal embolisation and is commonly bilateral. If you find one aneurysm, look for the other.

CLTI arises where atherosclerotic narrowing, diabetes, neuropathy and poor wound healing coincide. The major amplifiers are smoking, diabetes, hypertension, dyslipidaemia, chronic kidney disease, age over 65 years, and atherosclerosis in another vascular bed. Among people with diabetes, poor glycaemic control is associated with more major amputation: in one cohort the odds ratio of major amputation was lower with a haemoglobin A1c below 6.5% than with values of 6.5% to 9.5% or above 9.5%, and a meta-analysis of diabetic foot ulcers found a lower risk of amputation with a haemoglobin A1c below 8%.^[1]

When flow stops, the tissue distal to the occlusion switches from aerobic to anaerobic metabolism. High-energy phosphate stores fall, cells swell, lysosomes leak, and membrane pumps fail. Muscle tolerates a few hours of warm ischaemia before necrosis becomes irreversible; nerve is even less forgiving, which is why paraesthesia and paralysis appear before skin necrosis. Limbs with pre-existing PAD tolerate a longer period of ischaemia better, because collaterals have already developed, and that is why the same Rutherford class in an embolic occlusion of a previously healthy artery is more dangerous than in a thrombotic occlusion of a chronically diseased one.

Collaterals explain why ALI sometimes presents late, or modestly, even with a complete occlusion. The speed of presentation depends on whether collaterals had time to develop.

Restoring flow is not the end of the problem. When oxygen returns to ischaemic tissue, xanthine oxidase generates superoxide and other reactive oxygen species, while ischaemic cell swelling and endothelial injury make capillaries leaky. The result is tissue oedema within tight fascial compartments, rising compartment pressure, and a self-perpetuating cycle of further ischaemia. This is the reperfusion syndrome. Oxygen free radicals are the central mechanism, and the clinical consequences include rhabdomyolysis, hyperkalaemia, myoglobinuria and acute kidney injury, acidosis and potentially cardiovascular collapse if a large muscle mass is reperfused suddenly. Shorter ischaemic times, systemic haemodynamic stability and cooling reduce the injury; prolonged ischaemia makes it more likely. Class III (irreversible) limbs are not reperfused at all, partly to avoid this metabolic hit.^[1]

Compartment syndrome in ALI is a consequence of reperfusion, not of the initial occlusion. Pressure rises inside the fascial compartments of the lower leg (the lower leg is by far the commonest site, although the thigh can also be involved), venous outflow is impeded, arterial inflow falls, and tissue necrosis follows. The diagnosis is clinical: pain out of proportion, a tense compartment, pain on passive stretch, sensory change and, late, pulselessness and pallor. Compartment pressures can be measured where there is doubt, and serum creatine kinase serves as a marker of muscle injury. Because delayed fasciotomy is associated with a higher risk of major amputation, a high index of suspicion and early surgical decompression are essential.^[1]

ALI is described by six clinical features, all consequences of sudden arterial occlusion:^[1]

1. Pain. Usually sudden, severe, distal, and out of proportion to any injury. Rest pain in a previously asymptomatic limb is typical of embolism.
2. Pallor. The limb is pale and waxy, sometimes with a sharp line of colour change at the level of occlusion.
3. Pulselessness. No palpable pulses distal to the occlusion; compare with the other limb.
4. Poikilothermia. The limb takes on the temperature of the environment and feels cold. The older term "polar" is sometimes used; "poikilothermia" is preferred.
5. Paraesthesia. Numbness or tingling is an early sign of nerve ischaemia and precedes loss of motor function.
6. Paralysis. Weakness or inability to move toes, ankle or foot. This marks advanced ischaemia.

Paralysis and complete sensory loss mean the limb is probably class III and not salvageable. Paraesthesia is the warning sign that there are hours left. Document motor and sensory findings carefully and repeatedly, because they change and they determine management.

• Ischaemic rest pain classically affects the forefoot, is worse with the limb elevated (for example in bed) and is relieved by dependency. Patients may sleep with the foot hanging over the edge of the bed or in a chair.
• Tissue loss. A non-healing ulcer or gangrene present for more than two weeks, often on the toes or plantar aspect of the foot.
• Chronic findings. Hair loss, thin atrophic skin, dystrophic nails, dependent rubor, elevation pallor, muscle wasting and absent pulses are the background changes of long-standing PAD.
• Infection. A diabetic foot ulcer that is not healing, or any ulcer with surrounding cellulitis, should be examined for deep infection and osteomyelitis. Probe-to-bone testing is a simple bedside test for osteomyelitis in the diabetic foot.

The sudden cold painful leg has several mimics, and the most dangerous mistake is to treat a compartment syndrome or an acute venous thrombosis as arterial ischaemia.

For CLTI, the main task is to distinguish arterial ulceration from venous, neuropathic and pressure ulcers, and to recognise when a diabetic foot wound is driven by infection rather than by ischaemia alone.

• Clinical first. ALI is diagnosed clinically. Do not wait for imaging before giving heparin.
• Bedside. Palpate all pulses in both limbs, compare skin temperature and colour, test capillary refill, and document motor and sensory findings. Hand-held Doppler distinguishes audible from inaudible arterial and venous signals and is what the Rutherford classes are built on.
• Baseline bloods. Full blood count, renal function, electrolytes, glucose, coagulation screen, creatine kinase, troponin when appropriate, and a group and save. An electrocardiogram looks for atrial fibrillation or recent infarction.
• Imaging for planning. Duplex ultrasound can confirm occlusion and localise it at the bedside. Computed tomography angiography (CTA) from the aorta to the feet is the preferred study when revascularisation is planned because it shows the whole arterial tree and the run-off; the 2022 ESVS update emphasises complete imaging in patients with COVID-19 because of more extensive disease.^[3] Magnetic resonance angiography is an alternative where CTA is contraindicated.

The 2024 AHA/ACC guideline sets out a clear ladder of physiological testing:^[1]

• Resting ankle-brachial index (ABI). Abnormal at 0.90 or below, borderline 0.91 to 0.99, normal 1.00 to 1.40, non-compressible above 1.40. ^[1]
• Toe pressure and toe-brachial index. Preferred in CLTI and always performed when the ABI is above 1.40 (non-compressible, common in diabetes and chronic kidney disease) or when tissue loss is present.
• Duplex ultrasound. First-line arterial imaging in many pathways.
• CTA or magnetic resonance angiography when non-invasive imaging is needed before revascularisation; catheter angiography is reserved for when it is required for treatment planning.
• Objective ulcer assessment. Probe-to-bone testing, deep tissue sampling for microbiology, and plain radiographs for osteomyelitis. Vascular imaging is complemented by assessment of wound depth, infection and perfusion.

Note that the ABI can be falsely reassuring in diabetes because medial calcification makes the vessels non-compressible; a normal or raised ABI never excludes PAD in a person with diabetes.^[4]

The Rutherford system for ALI separates four clinical situations, and the treatment flows from them:^[1]

Classes I and IIa/IIb are treated by revascularisation. Class III is treated by amputation of non-viable tissue as the index procedure: the risks of reperfusion, including multi-organ failure and cardiovascular collapse from circulating ischaemic metabolites, outweigh any benefit once the limb is insensate and paralysed.^[1] Note that an "audible" Doppler signal is a haemodynamic finding, not a clinical one; the decisions are made at the bedside by motor and sensory examination and the Doppler is used to confirm.

Two staging tools are used together:

• WIfI (Wound, Ischaemia, foot Infection) grades the wound, the degree of ischaemia and the severity of foot infection, each from 0 to 3, and estimates amputation risk. Higher WIfI stage means higher limb threat. The 2019 Global Vascular Guidelines (ESVS, SVS and WFVS) endorse WIfI as the preferred staging system for CLTI.^[2]
• Rutherford and Fontaine are used for the chronic severity of PAD. Most vascular specialists are familiar with both, but WIfI is the one that drives the treatment algorithm because it combines the three elements that actually determine amputation: the wound, the ischaemia and the infection.
• ABI, toe pressure and TBI provide the haemodynamic numbers that feed the ischaemia grade.

1. Resuscitate and assess. Airway, breathing, circulation, pain score and an electrocardiogram.
2. Give analgesia appropriate to the severity.
3. Give intravenous fluids and oxygen as needed; keep the leg warm and slightly dependent to promote perfusion, not elevated.
4. Anticoagulate. Therapeutic intravenous unfractionated heparin (a bolus followed by a continuous infusion) should be given as soon as ALI is diagnosed, unless there are significant contraindications such as active bleeding in the previous 24 to 48 hours or recent surgery. The unfractionated drug is preferred at this stage because of its short half-life and titratability while revascularisation is being planned. This practice is widely accepted even though no randomised trial has compared it with no anticoagulation or with other agents. For patients with a history of heparin-induced thrombocytopenia, a direct thrombin inhibitor is used instead. Unfractionated heparin also limits propagation of thrombus and distal embolisation and may lessen ischaemia through an anti-inflammatory effect. Anticoagulation for ALI should always be weighed against bleeding risk, and it should not be delayed while arranging other tests.^[1][3]
5. Stage the limb with Rutherford class I to III and decide the pathway in parallel with arranging imaging.
6. Avoid unnecessary delay: for a viable but threatened limb the clock determines whether the limb survives.

Revascularisation is indicated in ALI with a salvageable limb in order to prevent irreversible damage and major amputation.^[1]

• Surgical thrombo-embolectomy, usually through a cutdown and a Fogarty balloon catheter, was historically the primary mode of revascularisation and remains so in many centres. It is rapid and effective for an embolus in a relatively healthy artery.
• Endovascular options include catheter-directed thrombolysis, ultrasound-accelerated thrombolysis, and pharmacomechanical or vacuum-assisted percutaneous mechanical thrombectomy. These have expanded the armamentarium considerably, and run-off, thrombus burden and local expertise all influence the choice.
• Patient-specific and anatomic factors and local resource availability are important in selecting the strategy; many cases also need definitive treatment of the underlying lesion (for example angioplasty or stenting, or aneurysm repair) once the acute thrombus has been cleared, to prevent recurrence. Vascular centres that can offer the full range of open and endovascular treatment are preferred.
• Class III limbs are not revascularised; amputation is the index procedure.
• Post-revascularisation medical therapy. After initial revascularisation to clear thrombus, definitive treatment of any underlying culprit lesion optimises success and prevents recurrence. Long-term antiplatelet therapy and risk-factor control follow.

All patients should be monitored for compartment syndrome and reperfusion injury after revascularisation, whether it was surgical or endovascular, including after catheter-directed thrombolysis.^[1]

• Clinical compartment syndrome: immediate fasciotomy of all involved compartments.
• Prophylactic fasciotomy: reasonable in threatened but salvageable limbs (Rutherford IIa and IIb), because early decompression avoids the delayed diagnosis and devastating consequences of untreated compartment syndrome (tissue necrosis, infection, amputation, systemic metabolic toxicity). Observational studies associate early fasciotomy with lower amputation rates and shorter hospitalisation. The benefit must be balanced against nerve injury, incisional complications and infection; where delayed primary closure is not possible, negative pressure wound therapy is effective.^[1]
• Amputation at the same time: in patients with prolonged ischaemia, poor premorbid function or frailty, partial or complete revascularisation followed by concurrent major amputation, leaving the amputation site open for delayed closure, can be clinically appropriate.
• Reperfusion injury is mitigated by shortening ischaemic time, monitoring and correcting electrolytes and renal function, and avoiding sudden reperfusion of a large muscle mass without preparation.

CLTI requires a different mindset: there is time to stage, to optimise and to decide, but the mortality is high and the limb is at risk.

Best medical therapy applies to every patient with CLTI, regardless of whether revascularisation is performed:^[2]

• Antiplatelet therapy: treat all patients with CLTI with an antiplatelet agent; clopidogrel may be considered the single antiplatelet agent of choice. ^[2]
• Moderate or high-intensity statin therapy to reduce all-cause and cardiovascular mortality.
• Blood pressure control to a target below 140 mmHg systolic and below 90 mmHg diastolic. ^[2]
• Metformin as the primary hypoglycaemic agent in type 2 diabetes, with control aiming for a haemoglobin A1c below 7% (53 mmol/mol), and withholding metformin for 24 to 48 hours around iodinated contrast when renal function is reduced. ^[2]
• Low-dose aspirin plus rivaroxaban 2.5 mg twice daily may be considered to reduce cardiovascular and limb ischaemic events. ^[2]
• Smoking cessation interventions for all patients who use tobacco.
• Analgesia for ischaemic rest pain (paracetamol with opioids, escalated to strong opioids when needed) until pain resolves after revascularisation.
• Pressure offloading, wound care and footwear advice for patients with foot wounds.

Revascularisation should only follow staging and team review. The Global Vascular Guidelines frame decisions on three independent axes, in order of priority: patient risk, limb severity and anatomic pattern of disease.^[2] In Europe this is the basis of the 2019 guidelines; in the United States the same principles are restated in the 2024 AHA/ACC guideline, which also covers ALI explicitly. UK practice follows NICE CG147, which requires that all people with critical limb ischaemia be assessed by a vascular multidisciplinary team before treatment decisions are made, and offers angioplasty or bypass surgery to those requiring revascularisation, taking comorbidities, pattern of disease, availability of a vein and patient preference into account.^[4]

Key practical points that recur across all three frameworks are:

• Refer all patients with suspected CLTI to a vascular specialist for consideration of limb salvage, unless major amputation is medically urgent.^[2]
• An average-risk surgical patient is one with anticipated periprocedural mortality of 5% or less and estimated two-year survival of 50% or more; high-risk patients have the opposite thresholds. This classification is a reasonable guide, even though it is based on observational data.^[2]
• Revascularisation is indicated for advanced limb threat (for example WIfI stage 4) with significant perfusion deficit in average-risk patients; it is considered, and often delayed or avoided, for lower limb threat or for patients with adequate perfusion.
• The preferred target artery path is defined from high-quality ankle and foot imaging; the Global Limb Anatomic Staging System (GLASS) grades femoropopliteal and infrapopliteal disease and stratifies anatomical complexity for endovascular intervention.
• Autologous vein is the preferred conduit for infrainguinal bypass; avoid non-autologous conduit unless no endovascular option and no adequate vein exists.
• Correct inflow disease first when both inflow and outflow disease are present; restage the limb after inflow correction before the next decision.
• Endovascular approaches are often preferred for high-risk patients and for less complex anatomy; vein bypass may be preferred for average-risk patients with advanced limb threat and high-complexity disease. Modern algorithms also favour endovascular therapy when technically feasible, with open surgery reserved for appropriate cases.
• Do not perform revascularisation in the absence of significant ischaemia (WIfI ischaemia grade 0), with limited exceptions for progressive wounds despite good wound care.

Wound care and limb preservation. Continue optimal wound care until the wound is completely healed or the patient undergoes amputation. Pressure offloading is essential for diabetic foot ulcers; non-removable devices are superior to removable ones for wound healing. Hyperbaric oxygen may be considered as an adjunct after revascularisation in selected non-healing diabetic foot ulcers. The effectiveness of non-revascularisation therapies (spinal cord stimulation, intermittent pneumatic compression, prostanoids) has not been established outside carefully selected patients.^[1][2]

Amputation is not a marker of defeat; it is part of limb care. The 2019 Global Vascular Guidelines set out the principles:^[2]

• Primary amputation or palliation for limited life expectancy, poor functional status or an unsalvageable limb, after shared decision-making.
• Transmetatarsal amputation of the forefoot when more than two digital ray amputations would be needed to resolve distal necrosis, especially with hallux involvement. ^[2]
• Secondary (major) amputation when reconstruction has failed, no further revascularisation is possible, and there is incapacitating pain, non-healing wounds or uncontrolled sepsis.
• Revascularisation to allow healing at a more distal, more functional amputation level (for example above-knee to below-knee) where the patient is likely to rehabilitate and continue to walk.
• Involvement of a multidisciplinary rehabilitation team from the time the decision to amputate is made until rehabilitation is complete.

NICE adds an important rule for UK practice: major amputation is not offered to people with critical limb ischaemia unless all options for revascularisation have been considered by a vascular multidisciplinary team.^[4] The wider point, true everywhere, is that the level and timing of amputation should be chosen after the whole team has considered revascularisation, the wound, the infection, and what the patient values.

People with diabetes and PAD are the largest single group presenting with CLTI, and their care differs enough to deserve its own heading.

• Screening. The International Working Group on the Diabetic Foot, as cited in the 2024 AHA/ACC guideline, proposes foot inspection according to risk: annual screening at low risk, every 3 to 6 months at moderate risk, and every 1 to 3 months at high risk. Simple actions that materially reduce risk include removing shoes and socks to inspect the bare feet at every visit, and referral to a podiatrist for deformity.^[1]
• Diagnosis in diabetes. Do not exclude PAD on a normal or high ABI alone, and do not use pulse oximetry to diagnose PAD in diabetes. Measure toe pressures.^[1][4]
• Glycaemic control. Aim for a haemoglobin A1c below 7% (53 mmol/mol) in CLTI with diabetes, and use metformin as the first hypoglycaemic agent. There is also evidence that amputation risk rises as A1c rises.^{[1] [2]}
• Offloading. Patients with CLTI and diabetic foot ulcers should receive pressure offloading whenever possible to promote tissue growth and wound healing. Podiatrists or other foot-trained professionals are best placed to assess and provide it.^[1]
• Preventive foot care runs through the 2024 AHA/ACC guidance: at every office visit remove shoes and socks and inspect the feet; refer deformities; use therapeutic footwear to reduce plantar pressure; consider home foot temperature monitoring in high-risk patients. Engagement of a multidisciplinary team that includes a foot specialist is associated with lower amputation rates in Medicare data.^[1]
• Screening for microvascular disease. Check for peripheral neuropathy as part of every vascular assessment in diabetes.
• Hyperbaric oxygen may be considered to assist wound healing in non-healing diabetic foot ulcers after revascularisation.^[1]

Amputation in the diabetic foot follows the same principles as above, with particular attention to the fact that the level of amputation and the prospect of rehabilitation are what determine whether the patient will walk again.

• Compartment syndrome and reperfusion injury, described above, are the two serious early complications of ALI treatment.
• Re-thrombosis and restenosis after revascularisation, particularly in COVID-19 and in poor runoff, demand close follow-up.
• Renal impairment from rhabdomyolysis and contrast, worsening in chronic kidney disease.
• Wound infection after fasciotomy or amputation.
• Major amputation and its sequelae, including phantom pain, deconditioning and depression.
• Cardiovascular and cerebrovascular events, because ALI and CLTI are manifestations of systemic atherosclerosis.
• Bleeding from anticoagulation and surgery.

Prognosis is driven by the underlying disease burden, the severity of the presenting episode and the speed of treatment. In ALI, immediate mortality has historically been high, and limb loss is common when presentation is late. The Rutherford class at presentation is the single best bedside predictor of limb salvage. In CLTI, one-year mortality of 25% to 35% and amputation in up to 30% of those presenting have been historically reported. Achieving complete wound healing after successful revascularisation is associated with very high limb salvage rates.^[1][2]

• Find PAD early. Assess people for PAD if they have symptoms, diabetes, non-healing leg or foot wounds, unexplained leg pain, or if interventions or compression hosiery are being considered. Measure the ABI.^[4]
• Screen those at risk. An ABI is reasonable in patients at increased risk of PAD (age 65 years or older; age 50 to 64 with atherosclerotic risk factors or chronic kidney disease; symptomatic atherosclerosis in another bed) and not recommended in those at low risk without suggestive findings.^[1]
• Secondary prevention. Every patient with ALI or CLTI is a cardiovascular patient: treat blood pressure, lipids, diabetes and smoking as above, and remember that limb events and cardiovascular events share the same risk factors and the same medicines.^[4]

• Diabetes is covered in its own section above; poor glycaemic control and neuropathy are the drivers of foot complications and amputation. Tight control and foot surveillance are the interventions with the clearest evidence.
• Older adults and the frail. CLTI is a disease of older, multimorbid patients. Functional status, cognitive ability and support at home determine whether a patient will benefit from major revascularisation or from a palliative and amputative pathway, and that judgement should be made by a multidisciplinary team with the patient and family.
• Renal impairment. Chronic kidney disease amplifies both PAD and the risks of contrast and major surgery. Use toe pressures and alternative perfusion measures when the ABI is unreliable, and avoid nephrotoxic drugs and unnecessary contrast. Adjust metformin around imaging as above.
• Women. Women tend to present later and may have smaller vessels, which affects both diagnosis and surgical planning. Surgery is not contraindicated, but conduit size and runoff matter.
• Immunocompromise and sepsis. Bedside judgement and early source control dominate; major surgery on a patient with active sepsis and an irreversible limb is hazardous.
• Younger patients with ALI raise the possibility of a popliteal aneurysm, an embolic source or a hypercoagulable state, including cancer-associated thrombosis; investigate accordingly.

• ALI can be diagnosed at the bedside with examination, hand-held Doppler and a clinical Rutherford class; do not wait for CTA before giving heparin. A clinical diagnosis and a borrowed Doppler save more limbs than a scanner.
• Heparin, fluids, analgesia and oxygen are the treatments available in most settings and are the ones that buy time.
• Revascularisation by balloon catheter thrombo-embolectomy needs only basic equipment and an experienced operator; thrombolysis needs drugs and a monitored bed.
• Where revascularisation is not available, stabilise, anticoagulate, keep the leg dependent and warm, control pain and infection, and refer early to a centre that can offer surgery. If the limb is class III, amputation without reperfusion avoids the metabolic catastrophe of reperfusion.
• Fasciotomy for suspected compartment syndrome is a surgical emergency that can be performed with basic instruments.
• CLTI and diabetic foot. Daily foot inspection, pressure offloading with felt pads or inexpensive footwear, debridement of necrotic tissue, and glycaemic control prevent most amputations; training primary-care and diabetes-clinic staff to inspect feet is a high-value, low-cost intervention. Amputation level should be chosen with rehabilitation in mind.
• System-level. Delays in presentation, referral and imaging kill more limbs than lack of technology. Clear referral pathways and same-day vascular review matter most.

• Cardiology: peripheral arterial disease (the cardiology counterpart that covers the same condition from the medical cardiology side).
• Cardiology: atrial fibrillation and flutter (the commonest embolic source).
• Diabetic foot and neuropathy (as it becomes a topic), wound care and pressure offloading.
• Vascular surgery: popliteal artery aneurysm, graft surveillance, bypass and endovascular revascularisation.
• Renal medicine: chronic kidney disease and vascular calcification.
• Infectious diseases: infective endocarditis and COVID-19 associated thrombosis.
• Anaesthesia and critical care: fasciotomy, reperfusion syndrome and regional anaesthesia.
• Rehabilitation medicine and prosthetics: amputation level and recovery.
• Pharmacology: antiplatelet, anticoagulant and lipid-lowering drugs.