Acute arterial occlusion caused by ergotamine derivatives

Abstracts

Os derivados da ergotamina compõem diversas drogas amplamente utilizadas no tratamento de ataques agudos de migrânea. A intoxicação por estas substâncias resulta geralmente de sua administração crônica, promovendo sintomas secundários ao espasmo arterial e à consequente isquemia distal. Neste artigo, é relatado o caso de uma paciente de 47 anos com diagnóstico de oclusão arterial aguda em membros inferiores secundária ao uso de derivados da ergotamina. Após a suspensão da droga e a prescrição de anticoagulantes, vasodilatadores e antiagregante plaquetário, a paciente evoluiu com melhora da dor, da parestesia e com o retorno da coloração normal e dos pulsos distais em membros inferiores.

Ergotismo; ergotamina; isquemia; insuficiência arterial; oclusão arterial

CASE REPORT

Acute arterial occlusion caused by ergotamine derivatives

Edison Barreto de Souza^I; Márcia Marinho Gomes de Araújo^II

^ICirurgião vascular e chefe, Serviço de Cirurgia Vascular, Hospital Monsenhor Walfredo Gurgel, Natal, RN, Brazil

^IIMédica residente, Cirurgia Geral, Hospital Monsenhor Walfredo Gurgel, Natal, RN, Brazil

Correspondence

ABSTRACT

Ergotamine derivatives include several drugs widely used in the treatment of acute migraine attacks. Intoxication by these substances generally results from chronic administration, promoting symptoms secondary to arterial spasm and the consequent distal ischemia. The authors report the case of a 47-year old patient with acute arterial occlusion in lower limbs secondary to the use of ergotamine derivatives. After drugs were suspended and anticoagulants, vasodilators and antiplatelet drugs were prescribed, the patient progressed with improvement of pain, paresthesia and return of normal skin color and distal pulses in lower limbs.

Keywords: Ergotism, ergotamine, ischemia, arterial insufficiency, arterial occlusion.

Introduction

During the Middle Ages the first descriptions of intoxication caused by ergotamine derivatives were made. By that time, strange epidemics with the characteristic symptom of limb gangrene were reported.^1,2

Ergot is produced by a fungus Claviceps purpurea that grows on rye and other cereal plants. Its active components are alkaloids, all derived from lysergic acid.^3,4 Its side effects encompass three categories: neurological – headache, vertigo, psychosis, convulsion and agitation; gastrointestinal -- diarrhea, nausea, vomiting and abdominal pain; and vascular.^2,4-7

Despite the multiple symptoms of ergotism, peripheral ischemia secondary to vasospasm is the most frequent and it affects 0.01-0.02% of patients undergoing treatment with ergot alkaloids.^2,5

Ergotamine derivatives include several drugs widely used in the treatment of acute migraine attacks and post-partum hemorrhage.^1,3,8 Intoxication by these substances may be caused by chronic overdose, therapeutic doses in patients with hypersensitivity reactions and chronic intoxication may occur in cases of prolonged use of therapeutic doses.^1-3,9,10 However, the severity of ischemia is not always correlated with the serum concentration of ergotamine.⁸

About 90% of the metabolization of ergot compounds occurs in the liver, and there are several drugs metabolized in the liver that may enhance its vasoconstrictor action, such as macrolides, propranolol, sumatriptan, ampicillin, oral contraceptives and nicotine.^2,7,8

The fast absorption of the drug and the prolonged effects on the arterial network suggest that both the tight binding to its receptor and the presence of active metabolites in the blood circulation prolong its vasoconstrictor effect.⁸

The main pharmacological effects of ergotamine are: stimulating α-adrenergic, dopaminergic and serotonergic (5-HT) receptors and directly stimulating smooth muscle cells and central sympatholytic activity.^2-4,6,11,12

On the one hand, ergotamine derivatives may damage the vascular endothelium by inducing the proliferation of arterial muscle cells due to stimulation of the platelet-derived growth factor and, on the other hand, they cause thrombosis and necrosis of the tunica media; these are symptoms associated with poisoning by ergotamine.^2,4,9,11-13 Ergotism causes impaired perfusion of the arterial wall followed by parietal fibrosis, arterial stenosis and aneurysms in the site of these stenoses.^11-13

Arteriographic findings consist of arterial spasm, collateral network and in situ thrombosis.^2,8,12. Spasm is more frequently found in the peripheral arterial system, lower limbs are more affected than upper limbs and the induced vasospasm is usually bilateral, symmetrical. The most important arterial stenoses, including total arterial occlusions, are more common in small-diameter arteries of the limbs^2,8,12 (about 60-70%^2,3,5), although they may also occur in the visceral, coronary, carotid and ophthalmic arteries.^2-5

The objective of this study is to report a case of acute arterial occlusion of lower limbs as a consequence of the use of ergotamine tartrate, an infrequent condition, so that it can be diagnosed and treated as efficiently and early as possible.

Case report

A 47-year-old female patient was admitted with a sudden onset of paresthesia in upper and lower limbs with 4 days of evolution. At examination, she presented with loss of muscular strength on upper limbs, intense pain in lower limbs, below the knee, cyanosis of the toes and absence of distal pulses.

There was no previous history of smoking, heart disease or intermittent claudication, but the patient reported a history of migraine with chronic use of ergotamine tartrate. She underwent arteriography, which showed both lower limbs with: signs of severe spasm of the superficial femoral, deep femoral, popliteal arteries and of the tibial-fibular trunk (Figures 1 and 2); fibular and pedal arteries and plantar arch without opacification; and anterior and posterior tibial arteries with signs of spasm, with visualization of up to the distal third. Ergotamine was discontinued, as well as the use of heparin, cilostazol and buflomedil. The patient progressed with improvement of pain and upper and lower limb paresthesia, return of normal skin color and of distal pulses in the lower limbs; she was discharged on the sixth hospital day.

Discussion

The diagnosis of ischemia induced by ergotamine derivatives is based on the patient's clinical history, physical examination and on angiographic aspects. When arterial spasm is observed, especially if it is bilateral and symmetrical, intoxication by ergotamine should be suspected.⁴ Greater is the suspicion if the patient has no history of hypercoagulability, heart disease, hepatic and/or renal dysfunction, thyreotoxicosis, atherosclerotic disease or any type of vasculitis.²

Differential diagnosis is necessary, since occlusive atherosclerotic disease, thromboembolic disease, arteritides, fibromuscular dysplasia and the Raynaud's phenomenon all have vasospastic symptoms similar to those of ergotism.²

Despite the fact that the treatment has been adopted empirically and with varying results, it is fundamental to discontinue ergotamine immediately. Treatment options include anticoagulants such as heparin, oral vasodilators, platelet antiaggregants, anesthetic blocks, calcium channel blockers, hyperbaric oxygen, as well as intravascular volume expansion.^2-6,8,10

Despite nitroprusside being considered an antidote for ergotism due to its efficient action over the vascular smooth muscle, it is used only for severe cases because of problems with dosage, need for an infusion pump and multiple side effects.^3,6-8,14 More recently, intravenous nitroglycerin has been reported as preferable due to its vasodilatory action and low toxicity.⁶

In recent publications, percutaneous angioplasty has been reported as an adjuvant treatment for arterial spasm; however, due to the risk of injury to the intimal layer of the vessels, consequently causing thrombosis, it should be avoided whenever possible.^2,5,6

Treatment duration depends on individual progress of each patient and, in case of persistent vasospasm, the possibility that the patient is still using ergotamine derivatives for migraine attacks should be investigated.⁸

Conclusion

Ergotism is caused, in most cases, by the prolonged abuse of ergotamine derivatives in the treatment of acute migraine attacks. Despite the fact that acute arterial occlusion caused by ergotamine derivative is a rare clinical condition, it should be considered in the differential diagnosis of ischemic syndromes, especially in young patients without cardiovascular risk factor, or of severe arterial embolism.

The first and most important step in the treatment is to discontinue the causing agent; however, vasodilating therapy is fundamental for the improvement of the patient's clinical status.

Early diagnosis and treatment are fundamental in order to avoid severe and potentially fatal complications.

References

• 1. Vega ME, Ortega CV, Mendoza RC, Ibargüen GM, Rosas HB, Castillo EC. Ergotismo: ¿iatrogenia o idiossincrasia? Rev Mex Angiol. 1998;26:72-5.
• 2. Ruano-Calderón LA, Zermeño-Pohls F. Ergotismo. Presentación de un caso y revisión de la bibliografia. Rev Neurol. 2005;40:412-6.
• 3. Cairols MA, Gimenéz A, Sieyro F, Miralles M. Intoxicación ergotamínica. Dos casos de isquemia periférica. Angiologia. 1991;43:148-52.
• 4. Sandri JL, Sandri GA. Oclusão arterial aguda bilateral em mulher jovem sem fonte embolígena. J Vasc Bras. 2003;2:83-4.
• 5. Pérez Burkhardt JL. Isquemia aguda secundária a ergotismo. An Med Interna. 2004;21:101-2.
• 6. Amaral LT, Carvalho JG, Marks SG, Branco PP, Mulinari AS, Laffitte A. Insuficiência arterial periférica e isquemia miocárdica no ergotismo. Relato de caso e revisão da terapêutica. Arq Bras Cardiol. 1984;43:255-8.
• 7. Aizen B. Intoxicación por ergotamina: presentación de un caso clínico, consideraciones diagnósticas y terapeuticas. Rev Med Urug. 1987;3:171-4.
• 8. Dilmé-Muñoz JF, Barreiro-Veiguela J, Yeste-Campos M, et al. Ergotismo: revisión de la bibliografia y presentación de casos. Angiologia. 2003;55:311-21.
• 9. Pajewski M, Modai D, Wisgarten J, Freund E, Manor A, Starinski R. Iatrogenic arterial aneurysm associated with ergotamine therapy. Lancet. 1981;2:934-5.
• 10. Jeong SY, Lim ES, Shin BS, et al. Ergotism with ischemia in all four extremities: a case report. J Clin Neurol. 2006;2:279-82.
• 11. Cunningham M, de Torrenté A, Ekoé JM, Ackermann JP, Humair L. Vascular spasm and gangrene during heparin-dihydro-ergotamine prophylaxis. Br J Surg. 1984;71:829-31.
• 12. Enriquez E, Rangel A, Velasco CE, Basave MN, López Rodriguez R. Ergotismo por automedicacion. Arch Inst Cardiol Mex. 2000;70:603-8.
• 13. Goodman GA, Rall TW. Prostaglandins, ergot, alkaloids and other drugs. Toxolytic agents. In the pharmacological basis of therapeutics. 8th ed. New York: McGraw Hill; 1992. p. 933-51.
• 14. Musikatavorn K, Suteparuk S. Ergotism unresponsive to multiple therapeutic modalities, including sodium nitroprusside, resulting in limb loss. Clin Toxicol (Phila). 2008;46:157-8.

Publication Dates

• Publication in this collection
  05 Jan 2010
• Date of issue
  Sept 2009

History

• Received
  22 Mar 2009
• Accepted
  04 June 2009