© 2005 Oxford University Press
CORRESPONDENCE |
Re: Treatment of Accidental Intrathecal Methotrexate Overdose
Affiliation of authors: Department of Pharmacology and Clinical Toxicology, Newcastle Mater Misericordiae Hospital, Newcastle, New South Wales, Australia
Correspondence to: Dr. Sophie Gosselin, Department of Clinical Pharmacology and Toxicology, Newcastle Mater Misericordiae Hospital, Level 5 Clinical Sciences Building, Waratah, NSW 2298, Australia (e-mail: sophie.gosselin{at}mcgill.ca).
Widemann et al. (1) presented data on the use of cerebrospinal fluid (CSF) exchange to remove methotrexate before carboxypeptidase G2 (CPDG2) administration among patients who had an accidental intrathecal methotrexate overdose. They reported that CSF drainage removed 32%–58% of the methotrexate dose. Although they showed the percent decreases in CSF methotrexate concentration before and after CPDG2 administration, they did not show the CSF methotrexate concentrations before CSF exchange. The absence of this information raises questions about the effectiveness of CSF drainage compared with CPDG2 administration and about whether the combination of procedures removes more methotrexate than either procedure alone. We are also curious about what method was used to determine the total amount of drug removed with CSF exchange. Calculating the amount extracted by using the difference in CSF methotrexate concentrations is complicated by ongoing movement of methotrexate out of the CSF. The most accurate method would be to measure the total amount of methotrexate in the CSF collected from the exchange.
In another recent report (2) that described the use of CSF exchange for accidental intrathecal methotrexate overdose, CSF exchange was performed over a 48-hour period. The graph of CSF methotrexate concentration versus time did not show a rapid drop in CSF methotrexate concentration, suggesting that the exchange had minimal effect on CSF methotrexate elimination. It is unclear how the exchange was done in the Widemann et al. study because the method used was not described in detail.
We conducted an informal survey among medical oncology and hematology units in New South Wales and the Australian Capital Territory (Australia) to find out whether any had protocols to treat accidental intrathecal methotrexate overdose (Table 1). It proved difficult to reach a consultant on call at the different hospitals; nevertheless, the health care provider responsible for administering the drug in most institutions (a nurse, pharmacist, or advanced trainee) was not aware of any protocols to that effect. Only eight individuals were aware that CPDG2 is a potential rescue therapy, and only one individual had heard of CSF exchange. None of the individuals interviewed said they would consider using CSF exchange as a treatment.
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Many consultants interviewed expressed concerns about how such an overdose might occur. They noted that their institutions had introduced numerous steps to check methotrexate dosages. They also noted that the volume limitation inherent to intrathecal administration would limit the amount of methotrexate inadvertently given via this route. Widemann et al. (1) do not discuss how these unfortunate incidents occurred, but such knowledge would also be useful in understanding the steps that might need to be implemented to prevent their occurrence.
Our survey results suggest that more information on these treatment modalities is required so that chemotherapy units can design protocols for rescue treatment of patients who receive an accidental overdose and to provide information for clinical toxicologists or pharmacologists who might be required to give advice if faced with this unfortunate situation. Specifically, what is the maximum amount of CSF that can be withdrawn at one time? How much fluid can be infused back into the thecal space?
REFERENCES
(1) Widemann BC, Balis FM, Shalabi A, Boron M, O'Brien M, Cole DE, et al. Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2. J Natl Cancer Inst 2004;96:1557–9.
(2) Finkelstein Y, Zevin S, Heyd J, Bentur Y, Zigelman Y, Hersch M. Emergency treatment of life-threatening intrathecal methotrexate overdose. Neurotoxicology 2004;25:407–10.[CrossRef][Medline]
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J Natl Cancer Inst 2005 97: 610-611.
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