Chronic Limb Threatening Ischaemia

Advanced peripheral artery disease with ischaemic rest pain, a non-healing ulcer or gangrene, present for more than 2 weeks and supported by objective evidence of severe ischaemia (ankle brachial pressure index less than 0.4, ankle pressure less than 50 mmHg, toe pressure less than 30 mmHg, or transcutaneous oxygen pressure less than 30 mmHg).

• It develops in about 1 to 3% of patients with peripheral artery disease per year, more in diabetes (about half or more of cases), chronic kidney disease, smokers, and older patients. In younger smokers, thromboangiitis obliterans (Buerger disease) should be considered.
• Outcome without revascularisation: about 20 to 30% major amputation and 20 to 25% death at 1 year. Five year mortality is about 50% or more, mostly from coronary and cerebrovascular disease. With successful revascularisation, limb salvage is about 80 to 85% at 1 year.
• Mechanism: multilevel atherosclerotic occlusion (femoropopliteal and tibial arteries, especially in diabetes and kidney disease) with failed collaterals, and small vessel disease and neuropathy in diabetes.

• Rest pain in the forefoot, worse at night and relieved by hanging the foot over the bed; non-healing ulcers on the toes, heel or lateral malleolus (punched out, pale, little bleeding, painful unless neuropathic); dry or wet gangrene.
• Signs: absent pedal pulses, cool and shiny skin, hair loss, atrophic nails, dependent rubor, pallor on elevation, delayed capillary refill, venous guttering, muscle wasting, infection (cellulitis, purulent discharge, probe-to-bone).
• Differential diagnosis: diabetic neuropathic ulcer, venous ulcer, pressure injury, vasculitis, thromboangiitis obliterans, cholesterol atheroembolism, calciphylaxis, pyoderma gangrenosum, peripheral neuropathy, spinal stenosis, osteomyelitis and Charcot foot.
• Complications: wound infection, osteomyelitis, sepsis, major amputation, myocardial infarction, stroke, and death.

• Ankle brachial pressure index (less than 0.4 severe); toe brachial index and toe pressure when vessels are calcified (ankle index greater than 1.3); transcutaneous oxygen pressure and pulse volume recordings.
• Duplex ultrasonography, then CT angiography or MR angiography to map disease before revascularisation; digital subtraction angiography at the time of treatment. Gadolinium and iodinated contrast need caution when eGFR is less than 30.
• Stage the wound, the ischaemia and the foot infection together to estimate amputation risk and benefit from revascularisation.
• Blood tests: HbA1c, lipids, full blood count, creatinine, CRP, ferritin; deep tissue culture (not superficial swab) and X-ray, with MRI for suspected osteomyelitis; ECG and echocardiography before surgery.
• In young patients: autoimmune screen, thrombophilia, and smoking history for thromboangiitis obliterans.

• Refer urgently to a vascular service (assessment within days). The plan combines revascularisation, wound care, infection control, pain control and risk factor modification.
• Pain control:
  • Paracetamol 1 g four times daily, morphine 5 to 10 mg orally every 4 hours as needed (reduce in renal impairment), gabapentin 100 to 300 mg at night titrated to 300 to 600 mg three times daily for neuropathic pain. Avoid NSAIDs because of cardiovascular and renal risk.
  • Lumbar sympathectomy, epidural or spinal cord stimulation for refractory rest pain in patients with no revascularisation option (evidence is limited).
• Infection:
  • Mild (local cellulitis less than 2 cm): cefalexin 500 mg four times daily or flucloxacillin 500 mg four times daily for 7 to 10 days; clindamycin 300 to 450 mg three times daily if penicillin allergic.
  • Moderate to severe (spreading cellulitis, abscess, sepsis, deep infection): IV piperacillin tazobactam 4.5 g every 6 to 8 hours, with vancomycin 15 to 20 mg/kg every 8 to 12 hours when methicillin resistant Staphylococcus aureus is likely; adjust to culture and renal function.
  • Duration: 1 to 2 weeks for soft tissue infection; about 6 weeks for osteomyelitis without resection; a few days after complete resection with clear margins.
  • Drain abscesses, debride devitalised tissue promptly, and amputate toes or a ray for infection that threatens the foot.
• Wound care: sharp debridement, moist dressings, and strict offloading (offloading shoe, total contact cast only when perfusion allows).
• Revascularisation (achieve inline flow to the foot within days to 2 weeks of diagnosis):
  • Endovascular: balloon angioplasty with or without drug coated balloons or stents in the iliac, femoropopliteal and tibial arteries; technical success about 85 to 95%; patency is lower in tibial disease and diabetes.
  • Surgical bypass with great saphenous vein (femoropopliteal or femoro distal) for long occlusions or after failed endovascular treatment, in patients with adequate life expectancy and vein; 5-year patency about 50 to 70% for vein grafts; perioperative mortality about 2 to 4%.
  • Hybrid procedures (endarterectomy with endovascular treatment). Choose by anatomy, comorbidity, available vein and life expectancy.
  • During endovascular treatment give unfractionated heparin 70 to 100 units/kg IV; after treatment give aspirin 75 to 100 mg daily and clopidogrel 75 mg daily for 1 to 3 months, then single antiplatelet therapy; for patients at low bleeding risk add rivaroxaban 2.5 mg twice daily to aspirin 100 mg.
  • Prostanoids such as iloprost 0.5 to 2 nanograms/kg/min IV for 6 hours daily for 2 to 4 weeks may relieve rest pain in patients with no revascularisation option, with limited evidence.
• Amputation:
  • Major amputation (at transtibial level when possible) for unreconstructable ischaemia, uncontrolled sepsis, extensive necrosis, uncontrollable pain, or a patient unfit for revascularisation; primary amputation in non-ambulatory patients with extensive disease.
  • Rehabilitation, prosthetic fitting and psychological support.
• Medical therapy for every patient:
  • Aspirin 75 to 100 mg daily or clopidogrel 75 mg daily.
  • Atorvastatin 40 to 80 mg daily (target LDL cholesterol less than 1.4 mmol/L), with ezetimibe 10 mg daily if not reached.
  • Ramipril 2.5 to 10 mg daily; blood pressure target less than 140/90 mmHg (less than 130/80 mmHg when tolerated and in diabetes).
  • Glycaemic control with HbA1c about 53 mmol/mol (7%), SGLT2 inhibitors or GLP-1 receptor agonists in diabetes as indicated.
  • Smoking cessation: nicotine patch 21 mg/24 h (14 mg for 10 or fewer cigarettes a day), varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks. Complete tobacco cessation is essential in thromboangiitis obliterans.
  • Foot care education, daily foot inspection, protective footwear and podiatry every 4 to 8 weeks.
• Special groups:
  • Diabetes: early referral to a multidisciplinary foot team; tight infection control and offloading.
  • Chronic kidney disease and dialysis: higher amputation and mortality risk; avoid contrast when possible, and use toe pressures and tissue oxygen measures because vessels are calcified.
  • Elderly and frail: palliative approach, pain control and wound care when revascularisation risk exceeds benefit.
  • Thromboangiitis obliterans: absolute tobacco cessation (the only treatment that alters course), iloprost infusion, and sympathectomy or spinal stimulation for refractory pain.
  • Pregnancy: very rare; avoid statins and ACE inhibitors.
  • HIV: control infection and use antiretroviral therapy.
• Red flags: wet gangrene, spreading cellulitis, fever or sepsis, sudden worsening with a cold foot (acute-on-chronic occlusion), uncontrolled pain, new weakness.
• Follow up: review at 2 weeks, then monthly until the wound heals; duplex surveillance of bypass grafts at 1, 3, 6 and 12 months then yearly; ankle brachial pressure index every 3 to 6 months; lifelong podiatry and vascular risk factor clinic.