Chronic limb-threatening ischaemia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Chronic limb-threatening ischaemia is the advanced clinical expression of PAD in which perfusion is inadequate to relieve ischaemic rest pain or sustain tissue viability. The Global Vascular Guidelines define CLTI by objectively documented PAD plus ischaemic rest pain present for more than two weeks with abnormal haemodynamics, gangrene, or non-healing lower-limb ulceration present for at least two weeks with objective ischaemia. Pure venous or traumatic wounds, acute limb ischaemia, embolic disease and non-atherosclerotic causes are outside that definition. The time qualifier is descriptive, not a waiting rule: an ischaemic ulcer, gangrene or infection may require same-day action before two weeks have elapsed.

Rest pain is usually distal, worse when the foot is elevated at night and partly relieved by dependency, but neuropathy, arthritis, infection and pressure injury can alter or mimic this pattern. Tissue loss includes ulcers and gangrene, often with diabetes, renal disease, neuropathy and infection. Palpable pulses can be misleading in oedema; ABPI can be falsely normal or high when tibial arteries are calcified and incompressible. Objective testing therefore begins with ankle pressure and ABPI, then uses toe pressure and toe-brachial index in tissue loss; pulse-volume recording, transcutaneous oxygen or skin-perfusion pressure can help when standard pressures cannot be obtained.

WIfI grades three distinct drivers of limb threat: wound extent, degree of objective ischaemia and foot infection. The combined clinical stage estimates amputation risk and potential benefit from revascularisation, but it is not simply an anatomical score. PLAN orders revascularisation reasoning as Patient risk, Limb severity and ANatomic complexity. GLASS then describes a preferred target arterial path and expected anatomic complexity. This order prevents a dramatic angiogram from eclipsing frailty, infection, functional goals or the actual severity of perfusion failure.

Care is simultaneous. Refer urgently to vascular specialists; involve multidisciplinary diabetic-foot services when relevant; provide analgesia; control systemic risk; protect and offload the foot; assess nutrition; remove non-viable or infected tissue through a coordinated plan; and restore perfusion when benefit is plausible. Deep-space infection or wet gangrene requires immediate drainage and debridement, including minor amputation if needed, plus antibiotics; restage after source control before the next reconstruction decision. Most patients should be considered for limb salvage, but primary amputation or palliation may best achieve comfort or function for an unsalvageable limb, very poor function or limited life expectancy after shared decision-making.

Key points

CLTI is a clinical syndrome: objectively documented PAD with ischaemic rest pain lasting more than two weeks, gangrene, or non-healing ulceration lasting more than two weeks.
The two-week definition identifies chronicity; never wait two weeks when an ischaemic or infected foot already needs urgent care.
Refer every patient with suspected CLTI urgently to a vascular specialist unless medically urgent major amputation takes precedence.
Confirm and quantify ischaemia objectively; ankle pressure and ABPI start assessment, while toe pressure is preferred with tissue loss or incompressible vessels.
Use WIfI to grade wound, ischaemia and foot infection and to communicate limb threat, not to replace clinical judgement.
For deep-space infection or wet gangrene, drain and debride urgently, commence antibiotics and restage the limb afterwards.
Choose revascularisation through PLAN: Patient risk, Limb severity and ANatomic complexity, with vein availability and patient goals.
Do not declare a limb unreconstructible without adequate imaging and review by a qualified vascular specialist.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Atherosclerotic PAD

Multilevel aorto-iliac, femoropopliteal or infrapopliteal atherosclerosis limits distal perfusion; smoking, diabetes, kidney disease, dyslipidaemia and hypertension increase risk.

Diabetes and renal disease

Medial calcification, distal arterial disease, neuropathy, immune dysfunction and impaired healing combine to increase ulceration, infection and amputation risk.

Acute-on-chronic thrombosis

Thrombosis of severe native disease or a previous reconstruction can abruptly worsen a chronically threatened limb and create an emergency.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Perfusion-demand mismatch
Chronically reduced pressure and flow become insufficient for resting tissue metabolism, producing distal rest pain and failure of minor trauma to heal.
2
Tissue breakdown cycle
Ischaemia impairs repair and immune delivery; ulceration permits infection, while oedema, inflammation and necrosis further increase metabolic demand.
3
Neuropathy and loading
Loss of protective sensation permits repetitive pressure injury and delays presentation, while motor changes redistribute plantar load and perpetuate wounds.
4
Systemic atherosclerosis
The threatened limb is one manifestation of widespread vascular disease, so myocardial infarction, stroke, renal decline and death remain major competing outcomes.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Ischaemic rest painRed flag

Persistent distal forefoot pain is often worse with elevation or at night and relieved by dependency, with objective evidence of poor perfusion.

Ischaemic tissue lossRed flag

A non-healing ulcer, black dry gangrene or wet infected necrosis with PAD indicates threatened tissue rather than stable claudication.

Infected threatened footRed flag

Purulence, spreading erythema, deep tenderness, crepitus, systemic illness or wet gangrene requires immediate infection and vascular escalation.

Calcified vessel phenotype

Diabetes, chronic kidney disease and advanced age increase medial calcification, making ankle pressure or ABPI falsely reassuring despite tissue threat.

Acute on chronic changeRed flag

Sudden severe pain, cold mottling, sensory loss or weakness indicates superimposed acute limb ischaemia and an immediate emergency.

Red flags requiring action

New motor weakness, sensory loss, cold mottling or rapidly worsening pain indicates acute or acutely worsened ischaemia and demands immediate vascular review.
Ulceration with fever or sepsis, limb ischaemia, suspected deep soft-tissue or bone infection, or gangrene is an immediate diabetic-foot referral under NICE NG19.
Wet gangrene, crepitus, bullae, purulent tracking or systemic instability requires urgent operative source control alongside antimicrobials.
Rapid tissue loss, uncontrolled rest pain, heel necrosis or failure of a wound to progress despite care requires urgent reassessment of perfusion and salvageability.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Ankle pressure, ABPI and Doppler waveformsFirst stepFirst line
Why
Provide first-line objective evidence and quantify haemodynamic impairment in suspected CLTI.
Interpretation and limitations
Low pressure and abnormal waveforms support ischaemia, but normal or high ABPI cannot exclude disease in calcified vessels; reconcile every result with the threatened foot.
02
Toe pressure and toe-brachial index
Why
Measure distal perfusion in tissue loss and when ankle vessels are incompressible.
Interpretation and limitations
The Global Vascular Guidelines prefer toe pressure for CLTI assessment. Use the value within WIfI and laboratory context; oedema, technique and local tissue condition still affect interpretation.
03
Wound and infection assessment
Why
Define tissue depth, necrosis, infection severity and urgent source-control requirements.
Interpretation and limitations
Measure and photograph with consent, probe an open ulcer to bone where appropriate, assess systemic toxicity and grade WIfI components. Normal inflammatory markers do not exclude osteomyelitis.
04
Foot radiograph and MRI when indicated
Why
Assess gas, foreign body, bone destruction and suspected osteomyelitis around tissue loss.
Interpretation and limitations
Plain films may show gas or established bone change but can be normal early. NICE recommends considering MRI when osteomyelitis remains suspected after initial radiography.
05
Duplex, CTA, MRA or catheter angiography
Why
Map inflow, target arterial path, runoff and ankle-foot vessels for potential revascularisation.
Interpretation and limitations
Use non-invasive imaging where possible before catheter angiography, but obtain adequate-quality views through the foot. No-revascularisation decisions require specialist review of adequate imaging.
06
Blood tests, cultures and physiological assessment
Why
Identify sepsis, anaemia, renal risk, glycaemic disturbance and procedural hazards.
Interpretation and limitations
FBC, renal profile, CRP, glucose and lactate support severity assessment but do not rule CLTI in or out. In infection, obtain deep tissue or bone samples after debridement when feasible without delaying antibiotics.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Acute limb ischaemia

Symptoms developing within two weeks, especially sudden pain, coldness, sensory loss or weakness, require the immediate acute-ischaemia pathway.

Neuropathic pain or ulcer

Burning symmetrical pain, sensory loss and pressure-site ulceration may predominate, but neuropathy and CLTI commonly coexist and still require perfusion assessment.

Venous ulceration

Gaiter-region shallow ulcers, oedema, pigmentation and venous disease suggest a venous driver, although mixed arterial disease alters compression safety.

Pressure injury or trauma

A clear pressure point or injury mechanism may explain tissue loss, but absent pulses or failed healing still justifies arterial assessment.

Inflammatory or malignant ulcer

Atypical edge, rapid progression, disproportionate inflammation or unusual distribution may indicate vasculitis, pyoderma or cancer and require targeted specialist evaluation.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Worked caseAssess an ulcer with a misleading ABPIFirst stepA person with diabetes has a painful toe ulcer for three weeks, absent pulses and an apparently normal ABPI.

1Inputs: record duration, rest pain, wound depth, gangrene, infection, neuropathy, pulses, Doppler signals, diabetes, renal disease, mobility and current systemic observations.
2Reasoning: the ulcer duration and PAD signs fit suspected CLTI, while diabetes makes calcific incompressibility and a falsely reassuring ABPI plausible.
3Action: refer urgently to vascular and foot services, obtain toe pressure or another validated perfusion measure, grade WIfI and arrange complete arterial imaging if salvage is feasible.
4DefinitiveVerification: name the team owning the referral, document wound and perfusion baselines, and review infection, pain and tissue progression while definitive treatment is arranged.

02Emergency source controlTreat wet gangrene and deep infectionSuspected CLTI presents with wet gangrene, deep-space infection, systemic toxicity or sepsis.

1Use ABCDE, obtain senior vascular, surgical and diabetic-foot help immediately, and treat shock or sepsis without awaiting elective tests.
2Obtain appropriate cultures close to treatment, start empirical antibiotics through the current severe diabetic-foot or sepsis protocol, and give analgesia.
3Drain and debride infected spaces urgently, performing minor or major amputation when source control and viability require it.
4Restage wound, objective ischaemia and infection after source control, then decide the next revascularisation or amputation step.

03Limb salvageSelect evidence-based revascularisationCLTI is confirmed and reconstruction could achieve healing, pain relief or useful limb function.

1Estimate procedural risk, life expectancy, frailty, functional potential and the patient’s goals before choosing an anatomical strategy.
2PreferredStage limb threat with WIfI, define a preferred target arterial path with GLASS and map autologous vein if bypass is possible.
3Choose endovascular, open or hybrid treatment through vascular multidisciplinary review, matching complexity and durability to urgency and patient risk.
4Verify haemodynamic improvement, infection control, pain relief and progressive wound healing rather than relying on technical patency alone.

04No-option or non-beneficial reconstructionPrioritise comfort and functionAdequate specialist imaging finds no useful target, or treatment burden outweighs plausible limb benefit.

1Confirm that a qualified vascular specialist reviewed complete imaging and that correctable infection, inflow disease and functional goals were considered.
2Discuss wound care, analgesia, palliation, minor or major amputation and rehabilitation openly with the patient and support network.
3Use shared decision-making to select the route most likely to control pain and sepsis while preserving achievable independence.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Major limb loss

Progressive necrosis, uncontrolled infection or failed reconstruction may require major amputation to relieve pain, remove sepsis and achieve healing.

Sepsis and osteomyelitis

Ischaemic ulcers can progress to deep soft-tissue infection, bone infection, bacteraemia, shock and death without rapid source control.

Revascularisation failure

Thrombosis, restenosis, embolisation or inadequate distal perfusion can leave pain and wounds unresolved and consume future reconstruction options.

Functional decline

Pain, prolonged non-weight-bearing care, repeated admissions and deconditioning reduce independence even when the limb is anatomically preserved.

Cardiovascular events

CLTI marks advanced systemic atherosclerosis and carries high risks of myocardial infarction, stroke, renal deterioration and premature death.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Reassess pain, sensory and motor function, skin temperature, Doppler signals and systemic observations while urgent review is pending.
Record wound dimensions, depth, necrosis, exudate and infection at planned intervals using the same method and photograph with consent.
Repeat WIfI and haemodynamic assessment after drainage, debridement, minor amputation or inflow correction before the next major decision.
After revascularisation, track perfusion, patency, pain and wound trajectory; failure to progress prompts review of flow, infection, offloading and nutrition.
Continue cardiovascular secondary prevention, diabetes and kidney care, smoking treatment and contralateral-foot protection through named follow-up.
Ensure every discharge plan includes who to contact immediately for new pain, colour change, fever, discharge, odour or spreading erythema.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Two weeks is not permission

The ulcer-duration criterion distinguishes chronic disease in the guideline definition; urgent infection or ischaemia must never wait for that clock.

Objective ischaemia is essential

Ulceration plus an arterial stenosis is insufficient without physiological context because venous, pressure, neuropathic and inflammatory wounds can coexist.

Toe pressure often clarifies

Digital arteries are less often incompressible than tibial vessels, making toe pressure particularly useful in diabetes, renal disease and tissue loss.

WIfI separates mechanisms

A large wound, severe perfusion deficit and deep infection each add limb risk differently and may need simultaneous but distinct treatments.

Infection changes sequence

Wet gangrene or deep-space sepsis demands immediate drainage, debridement and antibiotics; definitive reconstruction planning follows stabilisation and restaging.

Salvage means function

A perfused but painful, unstable or non-functional foot may not represent successful limb salvage from the patient’s perspective.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every chronic leg ulcer CLTI without objective PAD and haemodynamic evidence.
02
Excluding CLTI because ABPI is normal or high in diabetes, renal disease or suspected arterial calcification.
03
Using WIfI as an automatic treatment order without patient risk, anatomy, goals or centre capability.
04
Waiting for outpatient imaging when sepsis, wet gangrene, deep infection or acute neurological change is present.
05
Giving antibiotics without drainage or debridement when deep-space infection needs urgent source control.
06
Declaring a limb unreconstructible from incomplete imaging that omits ankle and foot vessels.
07
Focusing on patency while neglecting wound care, offloading, nutrition, infection, analgesia and cardiovascular prevention.

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