Cortejoso Lucía, García-Lledó Javier, Giménez-Manzorro Alvaro, Salcedo-Plaza Magdalena, Matilla-Peña Ana, Sanjurjo-Sáez María
1Pharmacy Department; and 2Gastroenterology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Am J Ther. 2014 Sep-Oct;21(5):e163-5. doi: 10.1097/MJT.0b013e31826a94fc.
A 56-year-old man attended the emergency room with respiratory failure, deteriorated general status, fatigue, and diarrhea. His clinical history included a liver transplant because of alcoholic cirrhosis, which developed to hepatocellular carcinoma. Initial immunosuppression consisted of corticosteroids, tacrolimus, and mycophenolate mofetil. Examination of the explant revealed vascular invasion, and tacrolimus was replaced with everolimus. The patient presented recurrence of the carcinoma with peritoneal implants, and treatment with sorafenib was started. He was admitted to the gastroenterology department and, after withdrawal of sorafenib, the patient improved clinically. However, 6 days later, he was admitted to the intensive care unit with acute respiratory failure and metabolic acidosis. The final diagnosis was cardiogenic shock. Although cardiogenic shock is not mentioned in the summaries of product characteristics of sorafenib or everolimus, there are reports of a relationship between cardiotoxicity and antiangiogenic therapy that inhibits the proliferation of vascular smooth muscle cells, as is the case with these drugs. We believe that there is a relationship between sorafenib (especially when combined with everolimus) and cardiogenic shock. Application of the Karch and Lasagna algorithm to assess the causality of the reaction induced by the combination of sorafenib and everolimus revealed the relationship to be probable.
一名56岁男性因呼吸衰竭、全身状况恶化、疲劳和腹泻就诊于急诊室。他的临床病史包括因酒精性肝硬化进行肝移植，后发展为肝细胞癌。初始免疫抑制方案包括皮质类固醇、他克莫司和霉酚酸酯。对移植肝的检查发现有血管侵犯，他克莫司被依维莫司替代。患者出现癌复发并伴有腹膜种植转移，开始使用索拉非尼治疗。他被收入胃肠病科，停用索拉非尼后，患者临床症状改善。然而，6天后，他因急性呼吸衰竭和代谢性酸中毒被收入重症监护病房。最终诊断为心源性休克。尽管索拉非尼或依维莫司的产品说明书摘要中未提及心源性休克，但有报道称心脏毒性与抑制血管平滑肌细胞增殖的抗血管生成治疗之间存在关联，这些药物就是如此。我们认为索拉非尼（尤其是与依维莫司联合使用时）与心源性休克之间存在关联。应用Karch和Lasagna算法评估索拉非尼和依维莫司联合使用引起的反应的因果关系，发现这种关联很可能存在。
