Emergency Treatment of Life-Threatening Intrathecal Methotrexate Overdose

Abstract

A male 34-year-old patient with aggressive diffuse malignant lymphoma was hospitalized for treatment. Because of high likelihood of CNS involvement, intrathecal methotrexate (MTX) 15 mg was administered with hydrocortisone 100 mg. Shortly after the intrathecal injection the patient became agitated, and complained of severe low back pain and 2 h later he became confused and developed generalized seizures. At this stage, it was realized that the dose contained 1200 mg of MTX (80-fold overdose). The patient developed ARDS and was comatose; he was intubated and transferred to ICU. The patient was immediately treated with intravenous leucovorin 1200 mg, and 15 mg every 6 h, thereafter, for 72 h. In addition, CSF exchange with warm normal saline was initiated via intrathecal catheter, and a total of 200 ml of CSF were replaced during 48 h. Finally, at the end of the exchange 2 mg of leucovorin with 2 mg of dexamethasone were administered intrathecally. MTX levels in CSF 7 h post-injection were 770 μM, and increased to 1250 μM 2 h later. Thereafter, the levels in CSF declined, and 48 h post-injection were 47 μM. The plasma levels of MTX 7 h post-injection were 10 μM, and declined to 0.7 μM at 68 h. The patient regained consciousness and underwent successful weaning from ventilator after tracheostomy. The highest reported intrathecal dose after which the patient survived was 625 mg. Due to the rarity of reported cases, there are no clear guidelines for treatment of massive intrathecal overdose. There is a controversy regarding the toxicity of intrathecal injection of leucovorin. We propose CSF exchange and intravenous leucovorin as the mainstay of treatment.