Quantification of systemic o-toluidine after intrathecal administration of hyperbaric prilocaine in humans: a prospective cohort study
- 21 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Archives of Toxicology
- Vol. 95 (3), 925-934
- https://doi.org/10.1007/s00204-021-02973-w
Abstract
Hyperbaric 2% prilocaine is increasingly used for spinal anesthesia. It is the only local anesthetic metabolized to o-toluidine, a human bladder carcinogen. Increase of o-toluidine hemoglobin adducts, a marker of o-toluidine ability to modify the DNA structure, was described following subcutaneous injection. In this prospective cohort study we aimed to assess and quantify o-toluidine hemoglobin adducts and urinary o-toluidine after a single intrathecal dose of hyperbaric prilocaine. 10 patients undergoing surgery received 50 mg of hyperbaric prilocaine intrathecally. Blood and urine samples were collected before injection and up to 24 h later (Hospital Braine l’Alleud-Waterloo, Braine l'Alleud, Belgium). Urinary o-toluidine and o-toluidine hemoglobin adducts were measured by tandem mass-spectrometry after gas-chromatographic separation (Institute of the Ruhr-Universität, Bochum Germany). The trial was registered to ClinicalTrials.gov (NCT03642301; 22-08-2018) Intrathecal administration of 50 mg of hyperbaric prilocaine leads to a significant increase of o-toluidine hemoglobin adducts (0.1 ± 0.02–11.9 ± 1.9 ng/g Hb after 24 h, p = 0.001). Peak of urinary o-toluidine was observed after 8 h (0.1 ± 0.1–460.5 ± 352.8 µg/L, p = 0.001) and declined to 98 ± 66.8 µg/L after 24 h (mean ± SD) Single intrathecal administration of hyperbaric prilocaine leads to a systemic burden with o-toluidine and o-toluidine hemoglobin adducts. O-toluidine-induced modifications of DNA should be examined and intrathecal hyperbaric prilocaine should not be proposed to patients chronically exposed to o-toluidine. Clinical trial number and registry URL NCT03642301.Keywords
Funding Information
- Fondation vesale CHU Saint Pierre and BARA
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