Quantification of systemic o-toluidine after intrathecal administration of hyperbaric prilocaine in humans: a prospective cohort study

Archives of Toxicology volume 95, pages925–934(2021)Cite this article

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.

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Funding

This study received fundings from BARA, the Belgian association for Regional Anesthesia, BARA vzw, UZ Leuven – Departement Anesthesie, Herestraat 49, 3000 Leuven (BE), and Association Vésale, Maison des Infirmières – CHU St. Pierre – 322 Rue Haute – Bruxelles (BE).

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Author notes

  1. Emmanuel Guntz and Andrea Carini contributed equally to this work as first co-authors.

Affiliations

  1. Department of Anesthesiology, Hôpital de Braine L’Alleud Waterloo, CHIREC, Université Libre de Bruxelles (ULB), 35 rue Wayez, 1420, Braine l’Alleud, Belgium

    Emmanuel Guntz

  2. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute Ruhr University Bochum (IPA), Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Stephan Koslitz, Thomas Brüning & Tobias Weiss

  3. Department of Anesthesiology, CHU St. Pierre, Université Libre de Bruxelles (ULB), 322 rue Haute, 1000, Brussels, Belgium

    Andrea Carini & Panayota Kapessidou

Authors
  1. Emmanuel Guntz
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  2. Andrea Carini
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  3. Stephan Koslitz
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  4. Thomas Brüning
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  5. Panayota Kapessidou
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  6. Tobias Weiss
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Correspondence to Emmanuel Guntz.

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Ethical approval

Ethics committee registration number: EC 332, OM 157; B076201836443. This study was presented as a poster at the 38th annual ESRA Congress in Bilbao, Spain, 11–14 September 2019.

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Guntz, E., Carini, A., Koslitz, S. et al. Quantification of systemic o-toluidine after intrathecal administration of hyperbaric prilocaine in humans: a prospective cohort study. Arch Toxicol 95, 925–934 (2021). https://doi.org/10.1007/s00204-021-02973-w

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Keywords

  • Local anesthetic
  • Hyperbaric prilocaine
  • o-toluidine
  • Hemoglobin adducts
  • Spinal anesthesia