Year: 2005
Type: article
Abstract: We thank Drs. Gosselin and Isbister for their letter and welcome the opportunity to provide additional information. The causes of the accidental intrathecal methotrexate overdoses in our report are similar to those previously reported ( 1 , 2 ) . There were two main causes of the accidental intrathecal methotrexate overdoses reported in our study. Three of the patients in our study were scheduled to receive methotrexate intravenously as a bolus dose and as an intrathecal injection on the same day. Accidental intrathecal administration of the higher intravenous dose, which was prepared in a small volume, resulted in the overdose. The other four overdoses were due to preparation errors; for three overdoses, the wrong-sized vial of methotrexate (1 g instead of 20 mg) was reconstituted. For one patient no details regarding the preparation error were available. We calculated the amount of methotrexate that was removed by lumbar drainage by multiplying the volume of cerebrospinal fluid (CSF) removed by the concentration of methotrexate measured in an aliquot of the CSF drainage. Table 1 shows the sequence of rescue interventions undertaken for each patient in our study. Six of seven patients underwent ventriculolumbar perfusion or ventricular or lumbar exchange. However, we had an aliquot from the entire volume exchanged for only one of those patients (patient 4), in whom 20% of the administered methotrexate dose was removed by lumbar exchange. Sequence of rescue procedures for accidental intrathecal methotrexate overdoses and details regarding the duration of and the volume of cerebrospinal drainage, exchange, or perfusion * VL = ventriculolumbar; CPDG 2 = carboxypeptidase G 2 . No data available on the volume of drainage. Sequence of rescue procedures for accidental intrathecal methotrexate overdoses and details regarding the duration of and the volume of cerebrospinal drainage, exchange, or perfusion * VL = ventriculolumbar; CPDG 2 = carboxypeptidase G 2 . No data available on the volume of drainage. The survey performed by Drs. Gosselin and Isbister showed a surprising lack of awareness of treatment options, such as CSF exchange and carboxypeptidase G 2 (CPDG 2 ), for accidental intrathecal metho-trexate overdoses considering the fact that recommendations on potential treatment options for such overdoses based on the pharmacokinetics of methotrexate in CSF have been previously published ( 3 – 6 ) . Within 1 hour of lumbar injection of a radiolabeled tracer, radioactivity can be detected in the basal cisterns ( 7 ) , implying that removal of an intrathecally injected drug such as methotrexate via lumbar drainage can only be successful if it occurs within a short time period after intrathecal injection. In 1981, Addiego et al. ( 3 ) developed a pharmacokinetic model that predicted the amount of methotrexate that can be removed by lumbar puncture and drainage by gravity at various time points after intrathecal methotrexate overdoses. They concluded that lumbar CSF drainage alone is unlikely to rescue patients who receive more than 10-fold the intended dose of methotrexate unless large volumes of CSF are removed within 15 minutes of the overdose, and they recommended emergency ventriculostomy placement and ventriculolumbar perfusion as a cornerstone of treatment. The availability of CPDG 2 allows us to modify these recommendations. In cases of accidental intrathecal methotrexate overdose, we recommend immediate lumbar drainage to remove CSF followed by intrathecal administration of CPDG 2 . Preparation for ventriculolumbar perfusion should be made in case the patient's clinical condition deteriorates. Meanwhile, systemic corticosteroids and leucovorin should be administered to minimize chemical meningitis and the risks of systemic toxicity, respectively. The rapid action of CPDG 2 may improve the outcome of patients and, in some cases, might obviate the need for the more invasive and less readily available procedure of ventriculolumbar perfusion. Although procedures to prevent the inadvertent administration of an overdose of intrathecal methotrexate are critical, institutions should have a plan to treat an intrathecal methotrexate overdose should it occur.
DOI: 10.1093/jnci/dji109
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2108677809