Catheter-directed prostaglandins effective in the treatment of critical limb ischaemia

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By Marcelo Pataro, Marcelo Dándolo, Juan Chica and Oscar Ojeda

 

Prostaglandins are unsaturated fatty acids that are produced by the metabolism of phospholipids of the cellular membrane and are synthesised by the action of enzymes such as cyclo-oxygenase. Prostaglandin E1 (PGE1) has several effects:  vasodilation, antiplatelet action, modifier leukocyte activation and endothelial damage and has been found also in the microcirculatory with thrombolytic and increased erythrocyte flexibility effects.

Today its use has spread to other peripheral vascular diseases such as Raynaud’s Syndrome vessel occlusion with trophic lesions, peripheral atheroembolism, and vasculitic ulcers. The purpose of this drug is related to limb salvage, wound healing and relieve of pain at rest.

 

A Cochrane review of 20 well-designed studies concluded that prostanoids appear to be effective in relieving pain and healing ischaemic ulcers, but there has been no conclusive evidence from meta-analysis on long-term effectiveness and safety of these acids. The drawback with this review is that it was based on only two studies that applied intra-arterial PGE1 in the affected limb. So this collection of studies is based on application of intravenous prostaglandins. It is important to note that it is in the pulmonary circuit that the most of the active ingredient alprostadil is metabolised.

 

In our hospital we have more than 10 years of experience in the use of alprostadil in patients with peripheral arterial disease of lower limbs. We [Oscar Ojeda] presented our experience in the VEITHsymposium 2012, in New York, USA.

Our team, led by Marcelo Pataro, performed intra-arterial PGE1 infusion in 48 patients with chronic atherosclerotic obliterative arteriopathy of lower limb Fontaine grade 3 and 4 (38 patients), vasculitic ulcers (five patients), Raynaud syndrome (four patients) and cholesterol embolism (one patient).

All patients were evaluated clinically by Doppler fluxometry and selective angiography. The route of administration was intra-arterial and it was used in inpatients and outpatients. The use in hospitalisation patients (inpatients) with selective catheterisation requires intraoperative infusion of alprostadil at high doses (300ug) requiring epidural or neuroleptic sedation. In ambulatory patients, it is performed through a direct puncture of the femoral artery at low doses (20ug = one ampoule) in weekly cycles.

Chronic atherosclerotic obliterative arteriopathy of lower limb

The indication for the use of this drug was in patients with critical limb ischaemia (Fontaine 3 and 4), with no possibility of endovascular and surgical revascularisation where a direct flow to the foot could not be establish and with subsequent poor outcome of trophic lesions. The 38 patients were divided into two groups:

Patients without possibility of revascularisation: In the 21 patients in whom angiography showed the absence of distal beds, we decided for hospitalisation and administration of the drug at high doses (200 or 300ug) with previous epidural or neuroleptic sedation.

Patients with combined treatment: In this group the drug was administered during the revascularisation procedure and then continued on an outpatient fashion by direct puncture of femoral artery with needle 50/8 at low dose (20ug) with a weekly cycle. The total dose ranged between 200 to 400ug.

The first group had no complications with the administration of the drug. The major amputation rate was 34%. In three (14%) patients follow-up could not be completed, three (14%) patients died within a year of treatment, eight (38%) patients with viable lower limb (including decreased pain, ulcer healing or tissue loss and improved quality of life) continue on treatment.

The second group had two patients who required intramuscular analgesia post-administration of prostaglandin and one patient had respiratory failure relieving in few minutes. Five patients needed minor procedures (minor amputations). The major amputation rate was 5% (one patient) and two patients died within the first year of follow-up, 14 (68%) patients remain with their lower limb viable (including decreased pain, ulcer healing or tissue loss and improved quality of life).

To conclude, in the two groups, the average dose of PGE1 was 200ug, and 45% of the patients needed more than one cycle. The major amputation rate was 19%, and the mortality rate was 12% at one year. There were no deaths at 30 days. Fifty three per cent of patients remain with viable lower limbs and three of them remain under outpatient treatment.

Based on these results, we believe that this procedure in indicated for patients who are in  Fontaine stage 3 and have no possibility of revascularisation or Fontaine 4 with localised necrosis on toes or ischaemic ulcers with an ABI.

 

 

Conclusion

The use of intra-arterial alprostadil as a limb salvage method in patients without possibility of revascularisation is feasible. If a revascularization procedure, preferably endovascular, is associated with the administration of intra-arterial, catheter-directed PGE1, the chances of limb salvage increase considerably. Although the mortality rate could not vary, it is clear that in this combined therapy group, the salvage rate of the lower limb is greater than those with no possibility of revascularisation.

We believe that this therapy should be offered to all patients who have lost all possibility of revascularisation or those in which despite of endovascular treatment or bypass, failure to obtain direct flow to the foot. Unfortunately due to the economic situation of the country and the cost of the drug, this salvage therapy of lower limb is only available to a small group of the population.

 

Marcelo Pataro, Marcelo Dándolo, Juan Chica and Oscar Ojeda are with the Department of Vascular and Endovascular Surgery, Itoiz Professor Hospital, Buenos Aires, Argentina

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