Acute Limb Ischemia

Acute limb ischaemia is a sudden decrease in limb perfusion that threatens limb viability, with symptoms present for less than 2 weeks. Incidence is about 1 to 2 per 10,000 people per year. It carries a 30-day amputation rate of 10 to 30% and a mortality of 10 to 20%, largely from coexisting cardiovascular disease.

Causes

• Embolism (about 30 to 40%): from the heart in most cases. Sources are atrial fibrillation, left ventricular thrombus after myocardial infarction or in cardiomyopathy, prosthetic or diseased valves, infective endocarditis, and atrial myxoma. Others are proximal aortic atheroma or aneurysm, and paradoxical emboli through a patent foramen ovale. Emboli lodge at bifurcations, most often the common femoral bifurcation, then the popliteal and aortic bifurcations.
• In situ thrombosis (about 40%): on a pre-existing atherosclerotic stenosis, in bypass grafts or stents, or in a popliteal aneurysm.
• Other causes: aortic dissection, trauma (including iatrogenic injury from catheterisation and closure devices), compartment syndrome, vasculitis, hypercoagulable states (heparin-induced thrombocytopenia, antiphospholipid syndrome, malignancy, myeloproliferative disease), low flow states, and cocaine or vasopressor-induced vasospasm.

Pathophysiology and tissue tolerance

• Peripheral nerves and skeletal muscle tolerate ischaemia poorly. Nerve dysfunction appears within hours, and muscle necrosis becomes irreversible after about 4 to 6 hours of complete ischaemia. Collateral flow extends the window in chronic disease.
• Reperfusion releases potassium, myoglobin, lactate and free radicals, causing hyperkalaemia, acute kidney injury, metabolic acidosis, arrhythmia, and compartment syndrome.

Rutherford classification

• I (viable): no sensory loss or muscle weakness, audible arterial Doppler signal.
• IIa (marginally threatened): minimal sensory loss of toes, no weakness, often an inaudible arterial signal with an audible venous signal.
• IIb (immediately threatened): sensory loss beyond the toes with rest pain, mild to moderate weakness, inaudible arterial signal.
• III (irreversible): profound sensory loss and paralysis, rigor, no arterial or venous Doppler signals. Primary amputation is required.

The classical features are pain, pallor, pulselessness, paraesthesia, paralysis and perishing cold (poikilothermia). Paraesthesia and paralysis indicate threatened limbs and are the critical findings.

Distinguishing embolism from thrombosis

• Embolism: abrupt onset, often with a known source (atrial fibrillation, recent myocardial infarction), no history of claudication, normal pulses and well-perfused contralateral limb, and a clear demarcation level.
• Thrombosis: a history of claudication or rest pain, absent pulses in the contralateral limb, signs of chronic ischaemia (hair loss, atrophic skin), and a slower onset over hours to days.

Level of occlusion

• Aortic bifurcation: both legs, with back and buttock pain, and possible spinal cord ischaemia.
• Iliac and common femoral: cold, mottled limb up to the groin.
• Superficial femoral and popliteal: cold calf and foot with a palpable femoral pulse.
• Tibial: foot ischaemia with palpable popliteal pulse.

Examination priorities

• Motor and sensory function in the foot and toes (neurological deficit determines urgency), capillary refill, skin temperature and colour, and mottling that does not blanch.
• Pulse examination of all limbs, with handheld Doppler assessment of arterial and venous signals.
• Calf tenderness and a tense compartment that suggest compartment syndrome.
• Signs of a source: irregular pulse, murmurs, abdominal aortic aneurysm, and popliteal aneurysm.

Differential diagnosis: aortic dissection, phlegmasia cerulea dolens, compartment syndrome, cardiogenic shock with low flow, acute neurological deficit, and cellulitis with severe pain.

Red flags: fixed mottling, woody muscle, fixed paralysis, and absent venous Doppler signals, which indicate irreversible ischaemia.

Acute limb ischaemia is a clinical diagnosis. Diagnostic imaging must not delay revascularisation in an immediately threatened limb.

Bedside assessment

• Handheld Doppler for arterial and venous signals, with ankle brachial index if feasible. An index of zero with no signal in a threatened limb confirms severe ischaemia.
• 12-lead ECG for atrial fibrillation and myocardial infarction, and cardiac monitoring.

Imaging (in viable and marginally threatened limbs)

• CT angiography from the aorta to the feet is the usual first study, showing the level of occlusion, runoff vessels, aneurysm, and the likely source.
• Duplex ultrasound when CT is unavailable or in pregnancy.
• Catheter angiography is performed on the table before thrombolysis or endovascular therapy, and in the operating room.

Laboratory tests

• CBC with platelets (heparin-induced thrombocytopenia in patients on heparin), coagulation screen, creatinine and eGFR, electrolytes (potassium), lactate, creatine kinase, troponin, glucose, and group and screen.
• Urine for myoglobin.
• Later: thrombophilia screen (antiphospholipid antibodies), lipid profile and HbA1c in young patients or those with no clear source.

Source evaluation after stabilisation

• Transthoracic echocardiography, with transoesophageal echocardiography if embolism is suspected without atrial fibrillation or thrombus.
• Prolonged rhythm monitoring.
• Imaging of the aorta, and duplex of the contralateral popliteal artery for aneurysm.

Immediate measures (all patients)

• Unfractionated heparin 5,000 units IV bolus (or 70 to 100 units/kg), then infusion at about 18 units/kg/h to an aPTT of 1.5 to 2.5 times control. Use argatroban 0.5 to 2 micrograms/kg/min if heparin-induced thrombocytopenia is suspected.
• Analgesia with IV morphine 2.5 to 5 mg titrated, with an antiemetic such as ondansetron 4 mg.
• Oxygen to maintain saturation at or above 94%, IV fluids if volume depleted, and keep the patient nil by mouth.
• Keep the limb in a neutral or slightly dependent position, loosely wrapped in cotton wool. Avoid direct heat or cold.
• Urgent vascular surgical review and notify the operating room.
• Treat contributing conditions such as heart failure, arrhythmia and sepsis.

Revascularisation by category

• Category I (viable): urgent imaging and revascularisation, usually within 6 to 24 hours.
• Category IIa (marginally threatened): revascularisation urgently, within 6 to 12 hours.
• Category IIb (immediately threatened): emergency revascularisation, within 6 hours.
• Category III (irreversible): primary amputation, with resuscitation and management of metabolic complications first.

Endovascular therapy

• Catheter-directed thrombolysis: best for viable and marginally threatened limbs, thrombosed grafts and stents, and distal occlusions. Alteplase 0.5 to 1 mg/h (some units use 0.5 to 2 mg/h) through a multi-sidehole catheter within the thrombus, with a low-dose heparin infusion of 300 to 500 units/h via the sheath. Check fibrinogen every 4 to 6 hours, and reduce or stop infusion if it falls below 100 mg/dL. Repeat angiography at 12 to 24 hours, with treatment for 24 to 48 hours at most. An alternative is tenecteplase 0.25 to 0.5 mg/h.
• Absolute contraindications: haemorrhagic stroke or any intracranial haemorrhage, ischaemic stroke within 2 months, active bleeding, recent intracranial surgery or trauma within 3 months.
• Relative contraindications: major surgery within 10 days, gastrointestinal bleeding within 10 days, uncontrolled hypertension (above 180/110 mmHg), and pregnancy.
• Mechanical or pharmacomechanical thrombectomy, with aspiration devices, shortens lysis time and reduces bleeding.
• Angioplasty and stenting of an underlying lesion once flow is restored.

Surgical therapy

• Embolectomy: Fogarty balloon catheter embolectomy via femoral cutdown under local anaesthesia, for embolic occlusions of the femoropopliteal segment and for immediately threatened limbs. Passage of catheters into tibial vessels should be gentle to avoid injury.
• Bypass: for thrombosis on chronic disease where thrombectomy fails. Autologous vein is preferred, and polytetrafluoroethylene is an alternative.
• Endarterectomy with patch angioplasty for focal common femoral disease.
• Completion angiography to verify clearance of the runoff vessels. On-table thrombolysis with alteplase 5 to 10 mg directly into the distal vessels is an adjunct.
• Fasciotomy: four-compartment fasciotomy of the leg, either as prophylaxis in limbs with prolonged ischaemia (over 4 to 6 hours) and after reperfusion of Rutherford IIb limbs, or when compartment syndrome develops. Compartment syndrome can occur hours after reperfusion.

Management of reperfusion injury

• Monitor potassium, creatinine, CK and urine output frequently for 48 hours.
• Hyperkalaemia: calcium gluconate 10% 10 to 20 mL IV over 5 to 10 minutes for ECG changes, insulin 10 units IV with 25 g glucose, and salbutamol 10 to 20 mg nebulised. Dialysis when refractory.
• Rhabdomyolysis: isotonic crystalloid to maintain urine output at 200 to 300 mL/h until CK falls below 5,000 units/L, with avoidance of nephrotoxins. Sodium bicarbonate is not routine.
• Metabolic acidosis: treat the cause, and use renal replacement therapy for refractory acidosis or hyperkalaemia.
• Cardiac arrhythmia monitoring.

Postoperative and long term care

• Continue therapeutic anticoagulation postoperatively, then individualise.
• Atrial fibrillation: long-term anticoagulation with a direct oral anticoagulant such as apixaban 5 mg twice daily (2.5 mg twice daily when two of age 80 or above, weight 60 kg or below, creatinine 1.5 mg/dL or above are present). Switch from heparin once the patient is stable.
• Left ventricular thrombus: warfarin (target INR 2 to 3) or a DOAC for at least 3 to 6 months.
• Atherosclerotic thrombosis: aspirin 75 to 100 mg daily, atorvastatin 40 to 80 mg daily, and consider low-dose rivaroxaban 2.5 mg twice daily with aspirin.
• Heparin-induced thrombocytopenia: non-heparin anticoagulation, with platelet recovery before warfarin.
• Surveillance duplex of grafts and stents at 1, 3, 6 and 12 months.
• Treat the source: surgery or endovascular repair of aneurysm, ablation or anticoagulation for atrial fibrillation, and valve surgery for endocarditis with antibiotics.
• Smoking cessation, blood pressure and glycaemic control, and cardiac rehabilitation.
• Amputation, when needed, is performed at the lowest viable level, with early rehabilitation and prosthetic fitting.
• Upper limb ischaemia is managed by the same principles, usually with brachial embolectomy and a lower threshold for early endovascular therapy.