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Four-Limb Acute Ischemia Induced by Ergotamine in an AIDS Patient Treated With Protease Inhibitors

2011; Lippincott Williams & Wilkins; Volume: 124; Issue: 12 Linguagem: Inglês

10.1161/circulationaha.111.020586

1524-4539

Leopoldo Mariné, Pablo Castro, Andrés Enríquez, Douglas Greig, Luís Sanhueza, Renato Mertens, Michel Bergoeing, Albrecht Krämer, F Valdés, Michel Serri,

Lipoproteins and Cardiovascular Health

HomeCirculationVol. 124, No. 12Four-Limb Acute Ischemia Induced by Ergotamine in an AIDS Patient Treated With Protease Inhibitors Free AccessBrief ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessBrief ReportPDF/EPUBFour-Limb Acute Ischemia Induced by Ergotamine in an AIDS Patient Treated With Protease Inhibitors Leopoldo Marine, MD, Pablo Castro, MD, Andres Enriquez, MD, Douglas Greig, MD, Luis Manuel Sanhueza, MD, Renato Mertens, MD, Michel Bergoeing, MD, Albrecht Kramer, MD, Francisco Valdes, MSCCh, FACS and Michel Serri, MD Leopoldo MarineLeopoldo Marine From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Pablo CastroPablo Castro From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Andres EnriquezAndres Enriquez From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Douglas GreigDouglas Greig From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Luis Manuel SanhuezaLuis Manuel Sanhueza From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Renato MertensRenato Mertens From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Michel BergoeingMichel Bergoeing From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Albrecht KramerAlbrecht Kramer From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. , Francisco ValdesFrancisco Valdes From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. and Michel SerriMichel Serri From the Departments of Vascular Surgery (L.M., R.M., M.B., A.K., F.V.), Cardiovascular Diseases (P.C., A.E., D.G., L.M.S.), and Infectious Diseases (M.S.), Pontificia Universidad Catolica de Chile, Santiago, Chile. Originally published20 Sep 2011https://doi.org/10.1161/CIRCULATIONAHA.111.020586Circulation. 2011;124:1395–1397A 32-year-old man infected with HIV presented to the emergency department of our hospital reporting pain, coldness, paresthesias, and cyanosis in both feet and hands. The symptoms had started 3 days before, with lower extremities claudication at 200 m, which progressed to rest pain the day of admission; it was worse on the right foot. He was on chronic antiretroviral therapy with 300 mg QID tenofovir (Viread), 300 mg BID abacavir (Ziagen), and two 200/50 mg BID lopinavir/ritonavir (Kaletra). His CD4 cell count was 245 cells/mm and his HIV viral load was 45 copies/mL. When directly interviewed, the patient remembered that he had taken a single dose of ergotamine (1 mg) for migraine 24 hours before the onset of symptoms. He denied any recent drug intake. On examination, his 4 extremities were cold, cyanotic, and pulseless (Figure 1A). Only femoral pulses were weakly palpable. Plethysmography revealed bilateral multilevel ischemia, with severe proximal disease and flat curves at popliteal and distal levels (Figure 2A). Lower limb computed tomographic angiography showed diffuse arterial narrowing from the external iliac arteries to the distal, consistent with severe and diffuse spasm (Figure 3A). A similar pattern was seen in the upper extremities.Download figureDownload PowerPointFigure 1. Right foot perfusion. A, Severe forefoot ischemia on admission. B, Improvement of perfusion after treatment, residual mild ischemia on first toe that recovered later.Download figureDownload PowerPointFigure 2. Upper and lower extremities plethysmography. A, On admission, bilateral multilevel upper and lower extremities ischemia with flat curves at distal levels. B, Normal perfusion in upper and lower extremities after treatment.Download figureDownload PowerPointFigure 3. Lower extremities computed tomographic arteriogram before (CTA pre) and after (CTA post) treatment. On CTA pre (leftA and B), maximum intensity projection images show diffuse narrowing of the right external iliac (leftA, arrow 1), superficial femoral (A2), and popliteal (B3) arteries. Arrow B4 shows absence of right leg arteries. Similar findings are seen on the left side. On CTA post (rightA and B): normal CTA with complete resolution of vasospasm in both lower extremities arteries (rightB, arrow 5).Antiretroviral drugs were withdrawn, and the patient was started on therapeutic intravenous administration of heparin, morphine, and sodium nitroprusside infusion, with no evident response. An arteriography was then performed, confirming the presence of diffuse arterial spasm, with no images of thrombosis (Figure 4). A selective intra-arterial prostaglandin E1 (Prostin) injection was done, with partial improvement of the right-leg plethysmography curves and foot perfusion. Therefore, treatment with intravenously administered iloprost (up to 2.0 ng · kg−1 · min−1), a synthetic prostaglandin I2 analog, was started in association with orally administered sildenafil (25 mg TID). The patient's condition improved dramatically, with progressive restoration of pulses in the following 24 hours (Figure 1B). The results of a repeat computed tomographic angiography after 3 days of therapy were normal (Figure 3B), and the patient was discharged in good condition 5 days after admission.Download figureDownload PowerPointFigure 4. Lower extremities angiography. A, Distal abdominal aorta, common iliac, and hypogastric arteries are normal; both external iliac arteries are hardly seen, with diffuse narrowing of their lumen (1). B, Spasm is also present in right femoral territory, especially on distal superficial femoral artery.2C, Popliteal narrowing is worse at the level of its bifurcation (3); no distal leg arteries are seen. D, A 4F Glide Catheter is placed on the proximal posterior tibial artery for selective prostaglandin injection. Completion angiogram shows contrast in distal posterior tibial artery not seen before.4Vasospasm is a rare but well recognized complication of ergot alkaloid agents. The term St. Anthony′s fire was used in the Middle Ages for referring to ergotamine intoxication due to the consumption of grain infected with the fungus Claviceps purpurea, with limb necrosis and burning pain. Ergotism mostly affects the lower extremities, but involvement of the carotid, coronary, mesenteric, and renal arteries has also been reported.1 Toxicity may occur with ergotamine overdose or with low doses in association with drugs that inhibit its hepatic metabolism. Protease inhibitors used for HIV treatment, such as ritonavir and lopinavir, are potent inhibitors of cytochrome P-450 isoenzymes, mainly CYP3A4, which is responsible for the metabolism of ergot.2 Severe ergotism has been described in patients taking ritonavir, even after a single dose of ergotamine.3 The optimum therapy has not been established. Pharmacological interventions include nitroprusside, nitroglycerin, prazosin, calcium channel blockers, heparin, intravenously administered iloprost, and intra-arterial infusion of prostaglandin E1. In severe forms refractory to pharmacological treatment, intra-arterial balloon dilatation or surgical sympathectomy can be effective.4 Early and aggressive treatment of arterial spasm prevents limb amputations.DisclosuresNone.FootnotesCorrespondence to Pablo Castro, MD, Department of Cardiology and Cardiovascular Diseases, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile. E-mail [email protected]esReferences1. Voyvodic F, Hayward M. Case report: upper extremity ischaemia secondary to ergotamine poisoning. Clin Radiol. 1996; 51:589–591.CrossrefMedlineGoogle Scholar2. Caballero-Granado FJ, Viciana P, Cordero E, Gómez-Vera MJ, del Nozal M, López-Cortés LF. Ergotism related to concurrent administration of ergotamine tartrate and ritonavir in an AIDS patient. Antimicrob Agents Chemother. 1997; 41:1207.CrossrefMedlineGoogle Scholar3. Blanche P, Rigolet A, Gombert B, Ginsburg C, Salmon D, Sicard D. Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir. Postgrad Med J. 1999; 75:546–547.CrossrefMedlineGoogle Scholar4. Ausband SC, Goodman PE. An unusual case of clarithromycin associated ergotism. J Emerg Med. 2001; 21:411–413.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Wu C, Wu C, Tsai S and Liao W (2022) A rare complication of coronary vasospasm associated with concomitant use of ergotamine, cobicistat, and darunavir, Antiviral Therapy, 10.1177/13596535211068957, 27:2, (135965352110689), Online publication date: 1-Apr-2022. Mohamedi N, Mirault T, Durivage A, Di Primio M, Khider L, Detriche G, El Batti S, Sapoval M, Messas E and Goudot G (2021) Ergotism with acute limb ischemia, provoked by HIV protease inhibitors interaction with ergotamine, rescued by multisite transluminal balloon angioplasty, JMV-Journal de Médecine Vasculaire, 10.1016/j.jdmv.2020.12.002, 46:1, (13-21), Online publication date: 1-Feb-2021. Fermo O and Rosenberg J (2016) Headache in HIV Chronic Pain and HIV, 10.1002/9781118777374.ch5, (38-50) Alves M, Janneau-Magrino L, Legendre N, Pateron D, Guidet B and Yordanov Y (2015) Human Immunodeficiency Virus Post-exposure Prophylaxis: Primum Non Nocere, The American Journal of Medicine, 10.1016/j.amjmed.2014.10.060, 128:4, (e3-e4), Online publication date: 1-Apr-2015. Ferry F, Da Silva G, Motta R, Carvalho R and De Sá C (2014) USE OF LOPINAVIR/RITONAVIR ASSOCIATED WITH ERGOTAMINE RESULTING IN FOOT AMPUTATION: BRIEF COMMUNICATION, Revista do Instituto de Medicina Tropical de São Paulo, 10.1590/S0036-46652014000300013, 56:3, (265-266), Online publication date: 1-Jun-2014. Ayarragaray J (2014) Ergotism: A Change of Persepective, Annals of Vascular Surgery, 10.1016/j.avsg.2013.02.005, 28:1, (265-268), Online publication date: 1-Jan-2014. Mintz B and Jaff M (2013) Severe Limb Ischemia Related to Systemic Vasopressor Use Atlas of Clinical Vascular Medicine, 10.1002/9781118618189.ch4, (8-9) Sobieszczyk P (2013) Acute Arterial Occlusion Vascular Medicine: A Companion to Braunwald's Heart Disease, 10.1016/B978-1-4377-2930-6.00046-X, (557-571), . September 20, 2011Vol 124, Issue 12 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.111.020586PMID: 21931103 Originally publishedSeptember 20, 2011 PDF download Advertisement SubjectsAngiographyCardiovascular SurgeryComputerized Tomography (CT)