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A Large Case Series of Acute Pediatric Methotrexate Ingestions: Significant Clinical Effects Are Rare
Matthew D Hensley1, Vikhyat S Bebarta, Douglas J Borys
1From the *San Antonio Military Medical Center, San Antonio, TX; †Medical Toxicology, Department of Emergency Medicine, University of Colorado School of Medicine; ‡140 MDG, Colorado Air National Guard, Aurora, CO; and §School of Pharmacy, Concordia University, Mequon, WI.
Objective:
Significant adverse effects after acute pediatric methotrexate (MTX) exposures have been limited to parenteral exposures. Treatment recommendations for pediatric MTX exposures do not differentiate between routes of exposure. We report the incidence of significant clinical effects and drug-specific treatments reported in a large series of acute, pediatric MTX ingestions.
Methods:
Poison center records of all MTX ingestions by patients younger than 17 years during 2000 to 2005 were collected from 6 poison centers. The cases included all MTX ingestions including those with additional substances. One trained reviewer, blinded to the study purpose, used a standardized data collection form to extract study data. Missing or conflicting data were reconciled with predetermined process.
Results:
Forty-seven cases were documented for 6 years, 42 (89%) of which were unintentional. Thirty-six percent (17/47) were male. The mean age for the unintentional ingestions was 3.7 years (range, 20 days-17 y; median, 2 y). Five cases (11%) were intentional suicidal ingestions in teenagers. The mean dose in acute, unintentional ingestions (AUIs) in all children and in children younger than 6 years was the same, 8 mg (range, 2.5-17.5 mg). Eleven patients (23%) had follow-up greater than 12 hours. No patient with an AUI developed MTX-induced sedation, hepatotoxicity, renal insufficiency, seizures, or bone marrow suppression. Three patients with an AUI received folinic acid, but no patients in this group received sodium bicarbonate or hemodialysis. One patient with an intentional suicidal exposure developed hepatotoxicity, but the patient also ingested a toxic dose of acetaminophen and valproate. Hemodialysis was performed once on this patient. No patient died.
Conclusions:
Acute pediatric MTX ingestion is uncommon. Methotrexate-induced seizure, renal failure, hepatic injury, and sedation were not documented in our series. Supportive care and observation only should be considered the mainstay of treatment of pediatric AUIs. Prospective verification of our findings is warranted.
Insights
Acute pediatric methotrexate (MTX) ingestion is rare and typically does not cause severe adverse effects. Supportive care and observation are recommended for unintentional ingestions, as serious toxicity was not observed.
Area of Science:
- Pediatric Toxicology
- Clinical Pharmacology
- Emergency Medicine
Background:
- Parenteral methotrexate (MTX) exposure is associated with significant adverse effects in children.
- Current treatment guidelines for pediatric MTX exposure do not differentiate by route of administration.
- The safety profile of acute pediatric MTX ingestion requires further investigation.
Purpose of the Study:
- To determine the incidence of significant clinical effects and treatments in pediatric patients following acute MTX ingestions.
- To evaluate the outcomes of unintentional versus intentional MTX ingestions in children.
- To inform treatment recommendations for acute pediatric MTX exposures.
Main Methods:
- A retrospective review of poison center records from 2000-2005.
- Inclusion of all MTX ingestions in patients under 17 years old, including co-ingestions.
- Data extraction by a blinded reviewer using a standardized form.
Main Results:
- Forty-seven cases of MTX ingestion were identified, with 89% being unintentional.
- No patients with unintentional MTX ingestions developed MTX-induced sedation, hepatotoxicity, renal insufficiency, seizures, or bone marrow suppression.
- One patient with intentional ingestion and co-ingestions developed hepatotoxicity; no fatalities occurred.
Conclusions:
- Acute pediatric MTX ingestion is uncommon and generally associated with a benign clinical course.
- Supportive care and observation appear to be sufficient for acute unintentional pediatric MTX ingestions.
- Further prospective studies are needed to validate these findings.
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