Multimodal rescue strategy after a ten-fold intrathecal methotrexate overdose in pediatric acute lymphoblastic leukemia: a case report
This case report demonstrates that a multimodal rescue strategy involving early cerebrospinal fluid exchange, continuous lumbar drainage, and concentration-guided leucovorin administration successfully prevented neurological sequelae and enabled full recovery in an 11-year-old boy who received a ten-fold intrathecal methotrexate overdose.
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In the treatment of childhood leukemia, doctors often use a powerful drug called methotrexate to stop cancer cells from hiding in the brain and spinal cord. To reach these hidden cells, the medicine is injected directly into the fluid that surrounds the brain and spinal cord, a process known as an intrathecal injection. This method is a standard and vital part of saving lives, but it walks a very fine line. The amount of medicine needed to kill the cancer is only slightly higher than the amount that can cause severe damage to the nervous system. Because the margin for error is so small, even a tiny mistake in preparing the dose can turn a life-saving treatment into a life-threatening emergency. When too much of this drug enters the central nervous system, it can cause seizures, confusion, and permanent brain injury, making the management of such errors one of the most critical challenges in pediatric oncology.
A recent case report from Guangzhou describes how a team of doctors successfully managed a catastrophic medication error involving an eleven-year-old boy. The child, who was being treated for a specific type of leukemia, was supposed to receive a standard dose of twelve milligrams of methotrexate into his spinal fluid. Due to a mix-up in the pharmacy, a vial containing one thousand milligrams was used instead of the correct one, resulting in the boy receiving one hundred and twenty milligrams—a tenfold overdose. Within two hours of the injection, the boy suffered a severe seizure, losing consciousness and becoming rigid. His pupils, which control how much light enters the eye, became fixed and dilated, signaling that his brain was under extreme stress. While the seizure was stopped with medication, the danger remained high because the toxic drug was still circulating in his spinal fluid.
The medical team immediately launched a multi-step rescue plan designed to physically remove the poison from the boy's system. First, they performed a spinal fluid exchange, drawing out forty milliliters of the contaminated fluid and replacing it with warm saline. This single step reduced the concentration of the drug in his spinal fluid by about two-thirds. However, the team knew that the drug could slowly seep back from deeper parts of the brain into the spinal fluid, so they did not stop there. They placed a small tube, known as a lumbar drain, into the lower back to continuously drain the fluid over the next several days. Over a period of three days, they removed nearly seven hundred milliliters of fluid, constantly monitoring the levels of the drug to ensure it was being cleared effectively.
Alongside the physical removal of the fluid, the doctors administered a large amount of leucovorin, a substance that acts as an antidote to methotrexate, through an intravenous line. They carefully adjusted the dose of this antidote based on how much of the original drug was still present in the boy's blood, ensuring he received enough protection without giving too much. They also gave him fluids to help his kidneys flush out the drug and a steroid to reduce inflammation. Throughout this process, the team tracked the levels of the drug in both the spinal fluid and the blood. The data showed a steady and dramatic decline: the drug level in the spinal fluid dropped from a dangerously high 416 units at the start to less than one unit after three days, a reduction of nearly ninety-nine percent.
The boy made a full recovery. He experienced no lasting neurological damage, his memory and thinking skills remained normal, and he was able to resume his cancer treatment just one week after the incident. By the time he was discharged, he had no detectable deficits, and at a three-month checkup, he remained in remission with a healthy nervous system. This outcome is significant because it demonstrates that even a massive overdose of this potent drug can be reversed if the response is fast, systematic, and guided by real-time measurements of the drug levels. The case also highlights that while a specific enzyme treatment exists to break down the drug, it is not available in all hospitals. This report suggests that a combination of draining the fluid and using the antidote can achieve similar results when that enzyme is not an option.
The authors of the report emphasize that while the medical team's actions saved the child, the incident itself was entirely preventable. The error occurred because a pharmacist used a vial that was ten times too strong, a mistake that underscores the need for strict safety checks, such as having two people verify the medication and keeping different types of drugs physically separated to avoid confusion. The report concludes that while such errors are rare, they are potentially reversible if hospitals have a clear, coordinated plan to act immediately. The success of this rescue offers a practical framework for other medical centers to follow, proving that with the right combination of mechanical removal and chemical antidotes, a child can survive a tenfold overdose and continue on the path to recovery.
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