Jardine L F, Ingram L C, Bleyer W A
Janeway Child Health Centre, Division of Haematology and Oncology, St. John's, Newfoundland.
J Pediatr Hematol Oncol. 1996 Aug;18(3):302-4. doi: 10.1097/00043426-199608000-00014.
Intrathecal methotrexate is a standard and important therapy in acute leukemia. Unfortunately, overdose is a well reported complication of this therapy. We report a fatal event secondary to intrathecal leucovorin.
PATIENTS, METHODS, AND RESULTS: An 11-year-old boy with a 6-month history of treatment of acute lymphocytic leukemia received an "overdose" of 20 mg of intrathecal methotrexate. He was treated with intrathecal leucovorin and subsequently experienced severe neurotoxicity and died. This was attributed to the use of intrathecal leucovorin, the first such case reported in the medical literature.
A review of the literature indicates that a careful definition of overdose needs to be applied in cases of intrathecal methotrexate: those <100 mg need less intervention, >500 mg will not respond to any intervention, and the middle group, 100-500 mg, can be treated with a variety of approaches, which are outlined. The standard treatment includes the use of ventriculolumbar washout, CSF exchange, or intravenous pharmacotherapy with leucovorin. Recently, the use of carboxypeptidase has been under investigation. All clinicians who administer intrathecal medications should be aware of these complications and the appropriate treatments of them (including rescue). Leucovorin should not be given intrathecally.
鞘内注射甲氨蝶呤是急性白血病的一种标准且重要的治疗方法。不幸的是，用药过量是该治疗方法一种报道较多的并发症。我们报告了一例鞘内注射亚叶酸钙继发的致命事件。
患者、方法及结果：一名11岁男孩，有6个月急性淋巴细胞白血病治疗史，接受了20毫克鞘内甲氨蝶呤的“过量”注射。他接受了鞘内亚叶酸钙治疗，随后出现严重神经毒性并死亡。这归因于鞘内使用亚叶酸钙，这是医学文献中报道的首例此类病例。
文献综述表明，在鞘内注射甲氨蝶呤的病例中需要对用药过量进行仔细界定：小于100毫克者所需干预较少，大于500毫克者对任何干预均无反应，而中间组，即100 - 500毫克者，可用多种方法治疗，本文对此进行了概述。标准治疗包括脑室 - 腰椎冲洗、脑脊液置换或静脉注射亚叶酸钙进行药物治疗。最近，羧肽酶的使用一直在研究中。所有进行鞘内给药的临床医生都应了解这些并发症及其适当的治疗方法（包括抢救）。不应进行鞘内注射亚叶酸钙。
