Clot busting drugs are effective at restoring blood flow in blocked leg arteries. Intravenous infusion (injection into veins) causes more haemorrhagic complications (risk of serious bleeding) than injection into arteries (arterial infusion). Acute reduction in blood flow to a limb (peripheral arterial ischaemia) is usually caused by a blood clot blocking an artery. The condition can be life threatening if not treated promptly. Infusion of clot-busting drugs (thrombolysis) can restore blood flow by dispersing the clot. This review found evidence suggesting that arterial infusion is more effective than intravenous infusion. The risk of haemorrhage with intravenous infusion is high. However, none of the different arterial infusion techniques studied have been shown to be more effective in preventing limb loss, amputation or death. More research is needed to confirm these findings.
Implications for practice
Thrombolysis should be reserved for patients with limb threatening ischaemia, due to the high risk of haemorrhage or death.
Greater benefit is seen when the thrombolytic agent is delivered into the thrombus. Systemic intravenous thrombolysis is less effective than intra-arterial thrombolysis and is associated with an increase in bleeding complications.
'High dose' and 'forced infusion' techniques, or adjunctive agents such as platelet glycoprotein IIb/IIIa inhibitors may speed up thrombolysis, but these are not accompanied by lower amputation rates or a decreased need for adjunctive endovascular or surgical procedures.
'Low dose continuous infusion', following initial lacing of the thrombus with a high dose of the thrombolytic agent, is the least labour intensive technique.
Implications for research
Only large multicentre trials with carefully controlled inclusion criteria will be sufficiently powerful to demonstrate genuine benefit for a particular thrombolytic regime.
Thrombolytic therapy is a useful tool in the management of acute peripheral arterial ischaemia. Fibrinolytic drugs are used to disperse blood clot to clear arterial occlusion. A variety of techniques are used to deliver these agents.
To determine the optimal technique for infusion of fibrinolytic drugs in peripheral arterial ischaemia.
The Cochrane Peripheral Vascular Diseases Group searched for randomised controlled trials (RCTs) in their Specialised Register (February 6, 2006) and CENTRAL in The Cochrane Library (Issue 1, 2006). We searched Vascular Surgical and Radiological Societies' meetings proceedings. Reference lists of identified studies were also searched for relevant trials. Major pharmaceutical firms and trialists were asked about unpublished trials.
Two authors independently selected RCTs comparing infusion techniques of fibrinolytic agents in the treatment of acute peripheral arterial ischaemia. Trials with poor quality methodology were excluded.
We included the following data: limb salvage, amputation, death, vessel patency, time to achieve thrombolysis, and reduction in the need for surgical intervention. We compared complication rates for major haemorrhage, cerebrovascular accident and distal embolization.
Intra-arterial delivery of thrombolytic agents appeared to be more effective than intravenous administration. Thrombolysis was more effective when the angiographic catheter was placed within the thrombus. Although 'high dose' and 'forced infusion' techniques achieved vessel patency in less time than 'low dose infusion', there were more bleeding complications, and no increase in patency rates or improvement in limb salvage at 30 days.