gms | German Medical Science

71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21.06. - 24.06.2020

Acute phase after experimental TB – influence of dabigatran overdose on contusion volume and diffuse axonal injury – an exploratory animal trial

Akutphase nach experimenteller traumatischer Hirnschädigung – Einfluss einer Überdosierung Dabigatranauf das Kontusionsvolumen unddie diffus axonale Hirnschädigung – ein explorativer Tierversuch

Meeting Abstract

  • presenting/speaker Benedikt Kremer - Universitätsklinikum RWTH Aachen, Klinik für Neurochirurgie, Aachen, Deutschland
  • Lisa Liebenstund - Universitätsklinikum RWTH Aachen, Klinik für Anästhesiologie, Aachen, Deutschland
  • Sarah Pinkernell - Universitätsklinikum RWTH Aachen, Klinik für Neurochirurgie, Aachen, Deutschland
  • Kay Nolte - Universitätsklinikum RWTH Aachen, Institut für Neuropathologie, Aachen, Deutschland
  • Oliver Grottke - Universitätsklinikum RWTH Aachen, Klinik für Anästhesiologie, Aachen, Deutschland
  • Mark Coburn - Universitätsklinikum RWTH Aachen, Klinik für Anästhesiologie, Aachen, Deutschland
  • Anke Höllig - Universitätsklinikum RWTH Aachen, Klinik für Neurochirurgie, Aachen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. sine loco [digital], 21.-24.06.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocV204

doi: 10.3205/20dgnc200, urn:nbn:de:0183-20dgnc2006

Published: June 26, 2020

© 2020 Kremer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Direct oral anticoagulants (DOAC) are widely used and indications expand. Various advantages compared to phenprocoumon have led to a widespread use. However, there are also disadvantages as the renal elimination of some DOACs (particularly dabigatran) which entails the risk that older patients - susceptible to renal failure - are overdosed. Still there is scarce data on the natural course of patients on supramaximal concentrations of DOACs suffering from traumatic brain injury (TBI). We present experimental data on the acute phase after TBI with regard to contusion volume and signs of diffuse axonal injury (DAI).

Methods: Sprague Dawley rats received TBI by controlled cortical impact (CCI), either as a control group (no anticoagulation; n=3) or after pretreatment with dabigatran etexilate (n=7; 120mg/kg;target plasma dose of dabigatran > 800ng/ml). Baseline dabigatran plasma levels were determined. Three hours after TBI the animals were euthanized, brain were harvested, formalin fixed and afterwards embedded in paraffin. Slices at 2µm thickness then were stained with H&E, GFAP and SNTF. Contusion volume was measured using H&E stained slices, GFAP and SNTF positive areas accounted for DAI (analyses via ImageJ). Data from the control group was compared to the dabigatran group using a Mann-Whitney U Test (SPSS 25.0); p value was set ≤0.05.

Results: Contusion volumes did not differ between the two groups (p=1.0; Mann Whitney U Test). A significantly higher GFAP expression for the dabigatran animals was seen in the corpus callosum (p=.006), the ipsilateral and contralateral hippocampus (p<.001 each) and the mean GFAP expression on the trauma side. Higher GFAP expression in the control group was detected for the contralateral internal capsule (p=.003). Using SNTF as a very specific marker for DAI only the ipsilateral expression in the cingulum was significantly higher in the dabigatran animal (p<.001) and the mean expression in the left hemisphere differed significantly from the right one (p=0.048).

Conclusion: Animals with supramaximal dabigatran concentrations did not show larger contusions following TBI. However, signs indicating a DAI (in terms of higher GFAP expression) were more frequently seen in the dabigatran treated group, whereas SNTF expression on the ipsilateral side was only slightly higher in the dabigatran group. In the very acute phase after TBI, supramaximal dabigatran levels are preliminary associated with broader axonal lesion pattern, but not with larger contusion volume.