Consider PGE₁ Injections in Severe Microembolization

CHICAGO -- Intra-arterial injection of prostaglandins appears to be an effective treatment of severe microembolization when all other treatments have failed.

Dr. Juan Parodi reported on a series of 16 patients with atheroembolism who were treated over the last 4 years at Jackson Memorial Hospital in Miami and Barnes-Jewish Hospital in St. Louis with intra-arterial prostaglandin E1 at a dose of 200-1,500 mcg per session. Seven patients had only one session, seven needed two sessions, and two needed four sessions.

Eight of the patients had compromise of the upper extremities, and eight of the lower extremities. Causes of the atheroemboli were abdominal aortic aneurysms, iliac artery ulcer, common femoral artery stenosis, patent foramen ovale, tympanic stenosis ulcer, threatened myocardial infarction with gangrene of the hand, instrumentation of the superficial femoral artery, and nonestablished cause in two patients.

No complications were seen and all patients experienced significant pain relief after their first injection, said Dr. Parodi, chief of vascular and endovascular surgery at the University of Miami. Amputation considered in three patients was not performed because of the treatment's success.

"We not only achieved dilation, but we have also reversed the aggregation of platelets, leukocytes, and small vessels, and we reversed inflammation," he said at a symposium on vascular surgery sponsored by Northwestern University.

Side effects were pain during injection and shortly afterward, hypotension during injection, and edema of the limb after repeated injections. Death occurred in two patients after massive atheroembolism following endograft placement. Two minor amputations resulted from the series. The results were durable, with all patients followed for more than 1 year, he said.

The main risk factor for atheroembolism is established atherosclerosis, but it is becoming more common with the popularity of endovascular procedures, which can induce atheroembolism by instrumentation inside the artery, he said.

It is thought that treatment with prostaglandins, which are naturally occurring lipid components derived from unsaturated 20-carbon fatty acids, might be a form of replacement therapy, as atherosclerotic vessels are known to have impaired prostaglandin synthesis.

He began using intra-arterial PGE1 in 1985 because of encouraging results with PGE1 therapy in Buerger's disease and the failure of standard medical treatment of atheroembolism with heparin, high-dose corticosteroids, local urokinase, papaverine, nitroglycerin, and sympathectomy. From 1985 to 1995, he treated 16 patients with atheroembolism with PGE1, of which 14 recovered completely and 2 died after massive microembolism.

"Unfortunately, the lack of control series cannot make a level one evidence [recommendation] that this is useful," Dr. Parodi said. "We don't have enough patients to randomize, and the results are so impressive for us that we hesitate to put patients in the control group."

Dr. Parodi reserves PGE1 therapy for patients with persistent pain resistant to medication, severe ischemia with risk of tissue loss, presence of distal pulses, or positive Doppler signals. Of the prostaglandins in clinical use, he prefers PGE1 to iloprost, and said PGE1 is best used intra-arterially because one passage through the lungs inactivates almost 90% of the drug.

The recent TASC II Inter-Society Consensus for the Management of Peripheral Arterial Disease report suggests that therapy with prostanoids, which include prostaglandins, might be of value in chronic limb ischemia, but that only a limited proportion of patients will respond. The evidence did not support using prostaglandins for claudication (J. Vasc. Surg. 2007;45[suppl. 1]:S5-67).

When asked to comment, Dr. Brian G. Rubin, professor of surgery, Washington University, St. Louis, stated: "As one of Dr. Parodi's former partners who has used intra-arterial infusion of PGE1 for patients with microvascular disorders such as blue toe syndrome, I support his contention that it works best in patients with a modest atheroembolic burden and preserved large and medium size arteries. The benefits persist long after all of the infused drug has been metabolized, with an initial infusion often resulting in relief that may last for weeks or be permanent. We have nothing other than palliative therapy to offer these patients, so broader application of this approach is encouraged. We need to accrue larger numbers of treated patients to elucidate the appropriate role for this technique in future." Dr. Rubin is an associate editor of Vascular Specialist.