Reperfusion Syndrome and Critical Limb Ischemia

Written by
Michael Cumming, MD, MBA

Reperfusion syndrome occurs when blood flow is restored to tissue after a period of ischemia.  Reperfusion syndrome in the setting of acute limb ischemia is a well-defined entity.  However, in the setting of critical limb ischemia, reperfusion syndrome has not been well described.


The restoration of blood flow to ischemic tissue can result in a phenomena called reperfusion injury.  Reperfusion injury is a complex inflammatory response and may cause further injury to the tissues.  In part this occurs due to microvascular dysfunction and increased capillary and arteriolar permeability.


In patients with critical limb ischemia, restoration of blood flow to the foot may result in increased pain and swelling which is attributed to reperfusion.  The incidence and significance of reperfusion injury after revascularization in patients with critical limb ischemia is unknown.  In my experience the syndrome occurs in less than 10% of patients and is self-limited, often resolving 1 week after revascularization.  In the calf, severe reperfusion injury may result in compartment syndrome.  Compartment syndrome involving the foot has not been described but in theory could happen.


The diagnosis of reperfusion syndrome is one of exclusion. Patients with increasing pain and swelling after a revascularization procedure need to be seen and a complication related to the procedure such as acute arterial thrombosis, embolization, and DVT need to considered.  Treatment is generally supportive.  Pain is usually managed using non-steroidal anti-inflammatories and edema can be controlled with compression stockings (if there is adequate skln perfusion).  Medical management of reperfusion injury in the setting of critical limb ischemia has not been investigated.  We have used allopurinol in some patients with significant pain and swelling.  Anecdotally, this seems to beneficial.

The images below are from an 82 year old female with right great toe ischemic ulcers and rest pain at night. On the center image, 2 days after revascularization, note the increased swelling of the toes and forefoot. The patient was having severe pain. Clinical and physiologic evaluation showed adequate perfusion and the pain was managed using acetomenphen (patients choice). On the right hand images, 5 days later (7 days post revascularisation) the swelling has resolved. The eschar and ulcers have been debrided.

Right foot prior to and after revascularization showing marked increase in swelling 2 days after. Reperfusion injury has revolved at 7 days.

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