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Toluidine blue for the intraoperative staining of the ureters. Studies on the safe administration in rats

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Abstract

Purpose

Acute cardiovascular events have repeatedly been reported to occur during the intraoperative presentation of the urinary tract with toluidine blue (TB). We here assessed the minimum TB dose required, and its safest and most suitable form of intravenous administration for the intraoperative staining of the ureters in rats.

Methods

TB (0.13, 0.4, 1.3, or 4.0 mg/kg) was administered to anesthetized rats either by intravenous injection within 1 min or by infusion within 10 min. During the experiments, biomonitoring parameters such as electrocardiograms (ECGs) and mean arterial blood pressure (MAP) were recorded, blood gas analysis was performed, and methemoglobin measured. Tissue injury was assessed from released plasma enzyme activities and histopathologically. The intraoperative staining of the ureters was documented photographically, and total urinary excretion and final urine/plasma TB concentrations were determined.

Results

Parameters of blood gas analysis, methemoglobin concentrations, and markers of tissue injury were slightly affected by the two highest TB doses but not at all by the lower ones. At doses of ≥0.4 mg/kg, ureters were stained sufficiently. Staining was more intense, and urine excretion of TB higher on average when the dye was injected. The 1-min injection of ≥1.3 mg TB/kg strongly and temporarily decreased the MAP, while the infusions caused lesser effects. Mean ECG parameters were not affected by any TB administration, but one animal developed a temporary bundle branch block after the 1-min injection of 4.0 mg/kg.

Conclusions

In rats, intravenous injection of 0.4 mg TB/kg was sufficient for the intraoperative staining of the urinary tract without the risk of severe cardiovascular and hemodynamic side effects. Provided our results are transferable to humans, the administration of low TB doses could allow its safer clinical use for the intraoperative visualization of the ureters.

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Abbreviations

TB:

Toluidine blue

ECG:

Electrocardiogram

MAP:

Mean arterial blood pressure

MB:

Methylene blue

PO2 :

Arterial oxygen partial pressure

metHb:

Methemoglobin

Hb:

Hemoglobin

SO2 :

Oxygen saturation

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Acknowledgments

We would like to thank Mr. Falk Kaehler, who excellently performed the experiments and respective tests, and Mr. Manfred Schmidtmann (Institut für Physiologie, Universität Duisburg-Essen) for his technical assistance regarding the ECG measurements. This work was supported by Dr. F. Köhler Chemie (Bensheim, Germany).

Conflicts of interest

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Authors and Affiliations

  1. Institut für Physiologische Chemie, Universitätsklinikum, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Frank Petrat, Tim Hamburger & Herbert de Groot

  2. Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Hufelandstr. 55, 45122, Essen, Germany

    Matthias Hartmann

  3. Dr. Franz Köhler Chemie, Werner-von-Siemens-Str. 22, 64625, Bensheim, Germany

    Ernst Schmidt

  4. Institut für Pathologie und Neuropathologie, Universitätsklinikum Essen, Hufelandstr. 55, 45122, Essen, Germany

    Florian Grabellus

Authors
  1. Frank Petrat
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  2. Matthias Hartmann
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  3. Ernst Schmidt
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  4. Florian Grabellus
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  5. Tim Hamburger
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  6. Herbert de Groot
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Correspondence to Frank Petrat.

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Petrat, F., Hartmann, M., Schmidt, E. et al. Toluidine blue for the intraoperative staining of the ureters. Studies on the safe administration in rats. Langenbecks Arch Surg 397, 983–993 (2012). https://doi.org/10.1007/s00423-012-0907-y

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  • DOI: https://doi.org/10.1007/s00423-012-0907-y

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