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Abstract CASE DESCRIPTION:
A 49-year-old woman underwent an outpatient surgical procedure with planned intrathecal anesthesia when she developed tachycardia, altered mental status, and myoclonus. The providers were concerned about bupivacaine toxicity and administered midazolam, labetalol, and intralipid emulsion with minimal clinical improvement. They subsequently suspected inadvertent intrathecal tranexamic acid (TXA) administration and transferred the patient to the emergency department (ED). In the ED, the patient was obtunded with generalized myoclonus. She was intubated for airway protection and sedated with high dose propofol and midazolam, along with bolus doses of fentanyl. Despite a high level of sedation, she continued to have significant muscle rigidity and frequent spontaneous myoclonic jerking. The Regional Poison Center was consulted and recommended CSF lavage in addition to ongoing sedation. A lumbar drain was placed and the intensivist completed four total CSF aliquot lavages that were submitted to the toxicology laboratory for analysis.
BACKGROUND:
TXA, a synthetic lysine analog commonly used in the perioperative setting for hemostasis, often has similar packaging and appearance to Bupivicaine. Inadvertent intrathecal injection of TXA is an uncommon but often fatal medication error (40% mortality) characterized by profound neurotoxicity and refractory seizures. Death can precipitate secondary to complications from refractory status epilepticus or cardiac arrest. When drugs are administered erroneously into the CSF, drainage or lavage may be warranted to enhance drug removal. Although the effectiveness and safety profile of the technique are not well established, pursuing the intervention in addition to symptomatic management may be preferable to symptomatic management alone. Laboratory detection of TXA in cerebrospinal fluid (CSF) may assist clinical management and toxicologic consultation; however, validated CSF assays are not routinely available. We report the rapid identification of TXA in CSF using a new mass spectrometry platform and broad-spectrum screening library.
MS METHOD AND RESULTS:
Four CSF aliquots collected during the lavage procedure were submitted for toxicologic analysis. A 50 µL sample of each aliquot was diluted with 10 µL internal standard (proadifen) in 1 mL water and analyzed using a newly acquired mass spectrometer with a broad-spectrum drug screening library (Thermo Scientific Orbitrap Exploris) not previously validated for CSF TXA detection. Chromatographic retention time and mass spectral library match scores were assessed. To confirm compound identity, pharmacy-obtained TXA reference material was prepared at five concentrations (1,000–250,000 ng/mL) and analyzed using the same method for comparative evaluation. TXA was detected in all four CSF specimens. Patient sample retention times clustered tightly between 0.72–0.74 minutes, with mass spectral library match scores of approximately 90%. Reference TXA dilutions demonstrated consistent library match scores (~90%) and retention times of 0.73–0.75 minutes. All patient and reference samples eluted within a 0.03-minute window, providing strong chromatographic concordance.
DISCUSSION AND CONCLUSION:
The near-identical retention times and reproducible spectral match scores observed in the patient sample and pharmacy-sourced reference standard supported confident compound identification despite the absence of prior method validation for this matrix-analyte combination. This case demonstrates how adaptable, high-resolution mass spectrometry provides the timely, actionable data essential for managing rare but life-threatening medication errors in acute care. A formal report was issued to the regional Poison Center and results were communicated to the referring institution’s Laboratory Medical Director. After the lavage procedure, the patient continued to have intermittent epileptic activity confirmed on EEG through hospital day (HD) 2 and received additional phenobarbital and Keppra. Her myoclonus resolved by HD3. She was found to have an occipital lobe infarct and a trace subdural hematoma on her MRI on HD3. Her creatinine kinase (CK) peaked at >19,000 units/L on HD6. She was extubated on HD5 to room air and discharged on HD14 neurologically intact.
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= Discovery stage. (57.21%, 2026)
= Translation stage. (23.38%, 2026)
= Clinically available. (19.40%, 2026)
