Toluidine blue for the intraoperative staining of the ureters. Studies on the safe administration in rats.
OBJECTIVE
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.
Institut für Physiologische Chemie, Universitätsklinikum, Universität Duisburg-Essen, Hufelandstrasse 55, Essen, Germany. frank.petrat@uni-duisburg-essen.de
Frank
F
Petrat
Matthias
M
Hartmann
Ernst
E
Schmidt
Florian
F
Grabellus
Tim
T
Hamburger
Herbert
H
de Groot
D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001774:Blood Chemical Analysis; D001784:Blood Gas Analysis; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000175:diagnosis; D004396:Coloring Agents / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007430:Intraoperative Care / Q000379:methods; D007677:Kidney Function Tests; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D017751:Safety Management; D014048:Tolonium Chloride / Q000009:adverse effects*; D014513:Ureter / Q000601:surgery*
D004396:Coloring Agents; D014048:Tolonium Chloride