Anaphylactic Shock with Multiorgan Failure in a Cyclist after Intravenous Administration of Actovegin
Authors: Luis Maillo
Journal: Annals of Internal Medicine (2008)

Letters4 March 2008Anaphylactic Shock with Multiorgan Failure in a Cyclist after Intravenous Administration of ActoveginLuis Maillo, MDLuis Maillo, MDFrom Hospital Ramón y Cajal, 28039 Madrid, Spain.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-5-200803040-00022 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Actovegin (Nycomed Pharma, Zurich, Switzerland) is a calf-blood extract free of proteins and filtrated to remove prions. It is marketed in some countries for the treatment of cerebrovascular and metabolic disorders, peripheral flow disorders, burns, and wounds (1–4) and is used by some athletes to improve blood oxygenation without raising hematocrit, purportedly by promoting glucose and oxygen uptake by cells (5, 6). Actovegin has been banned by the International Olympics Committee since 2000.Objective: To report a case of anaphylaxis with use of Actovegin.Case Report: A 22-year-old man who was an amateur cyclist with no significant medical history self-injected intravenous Actovegin, 5 mL, over 5 minutes the night before a competition. He had administered the drug 1 year earlier with no consequences. Ten minutes later, the patient developed fever with rigors, abdominal pain, and vomiting. Three hours later, after taking anti-inflammatory medication with no effect, the patient presented to the emergency department. He was conscious and oriented, with a blood pressure of 100/60 mm Hg, heart rate of 87 beats/min, temperature of 37.9 °C, and normal oxygen saturation. His physical examination was normal except for epigastric and right upper quadrant pain with hepatomegaly on palpation. Initial blood analysis showed a blood urea nitrogen level of 19.3 mmol/L, creatinine level of 106.76 μmol/L (1.4 mg/dL), alanine aminotransferase (ALT) level of 566 U/L, aspartate aminotransferase (AST) level of 335 U/L, lactate dehydrogenase (LDH) level of 6.46 µkat/L, and bilirubin level of 15.74 μmol/L (0.92 mg/dL). Hemoglobin level was 138 g/L, leukocyte count was 2.1 × 109 cells/L, and platelet count was 133 × 109 cells/L. His electrocardiogram and chest radiograph were normal. During his stay in the emergency department, his blood pressure decreased to 77/50 mm Hg and liver test values increased to 824 U/L ALT, 564 U/L AST, and13.62 µkat/L LDH.The patient was transferred to the intensive care unit, where he was sleepy but still conscious. He remained hypotensive despite a fluid challenge and required dopamine, 10 μg per kg of body weight per minute, to maintain his blood pressure. He received nasal oxygen at 2 L/min. His arterial blood gas values were pH, 7.42; PCO2, 30 mm Hg; PO2, 164 mm Hg; and HCO3, 20 mmol/L. On arrival at the intensive care unit, his blood analysis showed a glucose level of 8.55 mmol/L (154 mg/dL), creatinine level of 109.8 µmol/L (1.44 mg/dL), ALT level of 796 U/L, AST level of 633 U/L, LDH level of 11.00 µkat/L, lactic acid level of 2.44 mmol/L, prothrombin activity of 47%, activated cephalin time of 62 seconds, international normalized ratio of 1.6, and fibrinogen level of 4.38 µmol/L. The rest of the blood analysis, including amylase, creatinine phosphokinase, and ammonia, were normal. A urine toxicology screening was negative.The patient was given an empirical antibiotic for a temperature of 38 °C. Thoracic–abdominal computed tomography showed enlargement of the inferior vena cava with increase of the suprahepatic veins. A follow-up abdominal ultrasonography showed hepatomegaly and moderate ascites but no Budd–Chiari syndrome. Indirect and direct antiglobulin testing (Coombs test) were normal.Over time, the patient's hepatic profile and coagulopathy normalized, and dopamine therapy was titrated downward and discontinued. After 2 days of supportive treatment, the patient was discharged from the intensive care unit to the general ward with a diagnosis of anaphylactic shock after intravenous administration of Actovegin, hypoxic hepatitis, and prerenal acute renal failure.Discussion: Although this case is no more than a hypersensitivity reaction type I (anaphylactic shock), it highlights the life-threatening adverse effects that may accompany administration of performance-enhancing ("doping") substances. The particular drug in this case was Actovegin, a substance with few indications that is marketed in a few countries. It was allegedly used by some cyclists in the 2000 Tour de France because it has properties similar to those of erythropoietin without raising hematocrit. Life-threatening anaphylaxis revealed that this individual had been doping, but most cases remain unknown. We think the medical community should be aware of the problem, especially because these substances are prescribed by physicians and very few articles describe these cases in the scientific literature (7, 8).Conclusion: Intravenous Actovegin can cause life-threatening anaphylaxis.Luis Maillo, MDHospital Ramón y Cajal28039 Madrid, SpainReferences1. Mychka VB, Chazova IE, Gornostaev VV, Sergienko VB. [Primary prophylaxis of cerebrovascular complications in patients with metabolic syndrome]. Ter Arkh. 2005;77:20-4. [PMID: 16320679] MedlineGoogle Scholar2. Boiarinov GA, Mukhina IV, Penknovich AA, Snopova LB, Zimin IuV, Balandina MV, et al. [Mechanisms of actovegin effect on the central nervous system during postischemic period]. Biull Eksp Biol Med. 1998;126:395-8. [PMID: 9825133] MedlineGoogle Scholar3. Kanowski S, Kinzler E, Lehmann E, Schweizer A, Kuntz G. 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A reappraisal in view of the Olympic Games of 2004. Hormones (Athens). 2003;2:35-42. [PMID: 17003000] CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Hospital Ramón y Cajal, 28039 Madrid, Spain.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByActovegin® reduces PMA-induced inflammation on human cellsThe Conservative Treatment of Muscle Injuries: General PrinciplesItalian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athleteUpdate on the Role of Actovegin in Musculoskeletal MedicineDoping Products and Their Demand 4 March 2008Volume 148, Issue 5Page: 407KeywordsAnaphylaxisBloodBlood pressureIntensive care unitsOxygenTemperature ePublished: 4 March 2008 Issue Published: 4 March 2008 CopyrightCopyright © 2008 by American College of Physicians. 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