Acute Limb Ischaemia

Overview

Acute limb ischaemia refers to any sudden decrease in limb perfusion that causes a potential threat to viability. It is associated with pain, motor and sensory loss, and cold sensation. It affects one in about 6000 of the population1 and is more common in the lower limb, with less than 17% of cases affecting the upper limb4. If left untreated, it can lead to limb loss or even death3.

Definition

Acute limb ischaemia is defined by a rapid drop in arterial blood flow resulting in cessation of nutrient and oxygen delivery to the tissues.
Compartment syndrome is a complication that occurs when there is an increase in pressure in a closed muscle compartment leading to compression of blood vessels and nerves, causing swelling, tightness and pain.

Aetiology and Risk Factors

Acute thrombosis in a vessel with preexisting atherosclerosis (60% of cases):

  • May arise from plaque rupture, hypovolemia, increased blood coagulability, or myocardial infarction5

Emboli (30% of cases)

  • More than 70% of emboli are attributed to atrial fibrillation5

Less common

  • Aortic dissection
  • Trauma
  • Iatrogenic injury
  • Peripheral aneurysm (particularly popliteal)
  • Intra-arterial drug use

Sudden onset limb ischaemia  in a previously normal limb suggests embolism (often cardiac source, e.g. AF) where as gradual onset, collaterals present → more likely thrombosis on pre-existing PAD.

Virchow’s triad: hypercoagulability, blood flow stasis, endothelial injury – leads to increased risk of thrombosis.

Side note

Atrial fibrillation is an atrial arrhythmia that causes impaired contraction of atria leading to blood stasis in the atrium. A clot can form and travel to an artery in the limbs, obstructing blood flow and causing ischaemia.

Risk Factors

  • Metabolic: ischaemic heart disease, CKD, hypertension, hyperlipidaemia, diabetes 
  • Active malignancy or other comorbidities promoting thrombosis
  • Atrial fibrillation
  • Smoking: current or previous
  • Elderly male
  • Previous arterial intervention

Pathophysiology

Arterial occlusion causes sudden cessation in blood flow and nutrient and oxygen delivery to tissues. This leads to the tissue relying on anaerobic instead of aerobic metabolism. Anaerobic metabolism produces lactate, which increases the acidity in affected tissue, causing muscle injury. This eventually leads to depletion of ATP and leakage of free calcium, which causes skeletal muscle fiber necrosis.4

Virchow’s triad – set of 3 factors that contribute to thrombosis, presence of any of the elements increases the risk of acute limb ischaemia:

  • Hypercoagulability
    • Factor V Leiden mutation
    • Antithrombin deficiency
    • Protein S deficiency
    • Protein C deficiency
    • Malignancy
    • Oral contraceptive pill
  • Blood flow stasis
    • Immobility
    • Obesity
    • Pregnancy
  • Endothelial injury
    • Smoking
    • Hypertension
    • Atherosclerosis

Classification

Divided into 3 classes based on Rutherford criteria:

Clinical Manifestations

The most common symptoms are the 6 Ps:

  • Pain
  • Pallor
  • Pulselessness
  • Perishingly cold
  • Paraesthesia
  • Paralysis

Clinical examination

General inspection: findings change as damage to tissue becomes more prominent, from least to most severe: 

  • ‘Marble’ white
  • Blanching light blue or purple mottling
  • Non blanching mottling darker in colour
  • Blistering and liquefication

Pain on squeezing muscle indicates infarction and irreversible ischaemia

Arterial pulse can be weak or absent

Acute limb ischaemia of right leg on general inspection

Diagnosis

  • Chronic limb ischaemia
  • Compartment syndrome
  • Sepsis (eg. diabetic foot, septic arthritis)
  • DVT
  • Infection (eg. cellulitis, infected venous ulcer, bites)
  • Necrotising fasciitis
  • Myocardial infarction (referred to upper limb pain)
  • Central or peripheral neuropathy (eg. stroke, Guillain-Barre)

Acute limb ischaemia can have a vague presentation, such as mild pain, making the list of potential diagnosis very broad.

Diagnosis

Investigations are performed only if they do not delay urgent vascularisation.

Bedside:

  • ECG – to evaluate for arrhythmia (eg. atrial fibrillation)

Bloods:

  • Routine bloods
  • Lactate: assess ischaemia 
  • Creatine kinase – to assess extent of muscle damage

Imaging:

  • Doppler US – elevated peak systolic velocities suggest vascular stenosis
  • MRI/CT angiography – gold standard imaging to detail site and extent of occlusion

Remember

Don’t delay revascularisation for imaging if the limb is immediately threatened.

Creatine kinase (CK) is an enzyme found in the heart, brain and skeletal muscles. It helps produce energy and is released when the tissue is damaged. Higher levels of CK in the blood indicate a higher degree of injury.

Treatment

Start with an A-E assessment to determine if patient is stable or unstable 

Resuscitate if necessary:

  • Administer 100% O2
  • Get IV access and consider up to 1L of crystalloid fluid
  • Give opiate analgesia, usually morphine
  • Request appropriate tests – blood, ECG and imaging
  • Keep patient Nil by Mouth in case surgery is needed

1. Give unfractionated heparin to all patients if there are no contraindications (eg. aortic dissection, multiple traumas, head injury) (1)

2. Early vascular consult and confirmatory imaging

  • Digital Subtraction Angiography (DSA)
  • Computed Tomography Angiography (CTA)
  • Magnetic Resonance Angiography (MRA)

Unfractionated heparin is an anticoagulant that is commonly used in patients with venous thromboembolism and cardiovascular disease. Mechanism of action: binds to antithrombin III enhancing its activity, which in turn deactivates factors IIa (thrombin) and Xa. Side effects: the most common is bleeding. Unfractionated heparin can be reversed with protamine sulfate.

3. Perform a limb vitality assessment using examination and urgent Doppler (1,4):

Examination and dopplerSuggestsDefinitive treatment
Normal examination
Doppler – arterial and venous flow both audible
ViableConservative management, usually with anticoagulation
Sensory loss in toes, intact motor
Doppler – arterial flow may be absent
Marginally threatenedSalvageable with revascularisation
Sensory + motor loss
Doppler – absent arterial flow
Immediately threatenedRequires urgent revascularisation
Fasciotomy (if compartment syndrome suspected)
Fixed mottling, hard muscles
Doppler – absent arterial and venous flow
Irreversible ischaemiaAmputation likely

Remember

Consider fasciotomy if delayed revascularisation → compartment syndrome risk.

Diagram showing approach to management2

Fasciotomy is a surgical procedure where the fascia (connective tissue covering various organs, including muscles) is cut open to relieve pressure.

Thrombolysis is the use of medication to break down clots. It is used in ischaemia, pulmonary embolism and myocardial infarction. Common medications are urokinase and drugs ending with the suffix -plase (eg. alteplase). Mechanism of action: convert plasminogen to plasmin, which initiates breakdown of fibrin.

Angioplasty is a procedure used to dilate narrow arteries. A catheter is placed in the vessel and a balloon is inflated at the point of narrowing causing the vessel lumen to dilate. A stent is often left in place to prevent recurrent narrowing.

Embolectomy is a surgical procedure used to remove an embolus (blood clot) from an artery. A balloon catheter is inserted inside the artery and the balloon is inflated distal to the embolus, the balloon is then retrieved out of the artery together with the embolus.

Complications and Prognosis

Complications

  • Limb loss or death
  • Reperfusion injury
  • Compartment syndrome
  • Neurological injury
  • Arterial ulcers

Reperfusion injury can occur when blood supply is restored in tissue that has been deprived of oxygen, which causes release of free radicals, oxidative stress and inflammation. This can lead to swelling and cell death.

Prognosis

The mortality and amputation rates depend on the type of treatment received, presence of comorbidities and stage of ischaemia. 7

The in-hospital mortality ranges between 10-20%.5

References

  1. Peripheral vascular disease. In: McLatchie G, Borley N, Agarwal A, Jeyarajah S, Harries R, Weerakkody R, et al., editors. Oxford Handbook of Clinical Surgery: Oxford University Press; 2022. p. 0. https://doi.org/10.1093/med/9780198799481.003.0019 
  2. Lacey HMMAM. Vascular surgery. In: Lacey HMMAM, editor. Crash Course Surgery2025. p. 171-205. https://www.clinicalkey.com/student/content/book/3-s2.0-B9780443115714000065 
  3. Coșarcă MC, Lazăr NA, Șincaru SV, Bandici BC, Argatu EC, Carașca C, et al. Treatment Strategies and Prognostic Outcomes in Acute Limb ischaemia: A Systematic Review and Meta-Analysis Comparing Thrombolytic Therapy and Open Surgical Interventions. Medicina. 2025;61(5):828. https://doi.org/10.3390/medicina61050828 
  4. Arnold J, Koyfman A, Long B. High risk and low prevalence diseases: Acute limb ischaemia. The American Journal of Emergency Medicine. 2023;74:152-8. https://doi.org/10.1016/j.ajem.2023.09.052 
  5. Tambyraja AL. Vascular and endovascular surgery. In: Garden OJCBEBMBCMDDFFFFFFFFFF, Parks RWMBBBAOMDFFF, Wigmore SJBMMDFFF, editors. Principles and Practice of Surgery2023. p. 368-401. https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702082511000224 
  6. Cai PL, Forsyth JM. Acute limb ischaemia. Surgery (Oxford). 2025;43(5):319-28. https://doi.org/10.1016/j.mpsur.2025.03.005 
  7. Genovese EA, Chaer RA, Taha AG, Marone LK, Avgerinos E, Makaroun MS, et al. Risk Factors for Long-Term Mortality and Amputation after Open and Endovascular Treatment of Acute Limb ischaemia. Annals of Vascular Surgery. 2016;30:82-92. https://doi.org/10.1016/j.avsg.2015.10.004 

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