Tranexamic Acid(Grassin-Delyle) validation

The anti-fibrinolytic drug tranexamine acid(TA) is a useful drug for limiting bloodloss in major surgical operations like cardiac surgery. Grassin-Delyle and co-authors promote the use of a relative high dose, aiming at a concentration of 150 µg/ml. This concentration should be maintained during the whole surgical procedure.  They developed a two compartment pharmacokinetic model with allometric scaling to weight that  very accurately describes the bloodconcentrations of TA.

Grassin-Delyle, S. et al. Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Br J Anaesth 111, 916–924 (2013).

Two infusions are advised for the high concentration. The first hour 46 mg/kg and thereafter an infusion rate dependent on the weight of the patient. An adaptation for bypass was not necessary. As TA is fully cleared by the kidney, this infusion scheme is not valid for patients with kidney problems such as a reduced glomerular filtration rate. Disadvantage of the scheme is the relative slow increase of the plasma concentration during the first hour.

With Tivatrainer IVassist it is possible to obtain and maintain the required concentration more swiftly. Adaptation to the weight is done by the Tivatrainer software. Validation of the implementation here is done by graphically comparing the predicted blood concentrations from Tivatrainer with the graphs published in the article. This is done for a  50, 100 and 125 kg patient. Both the graphical representation as the pharmacokinetic data are identical. The model for tranexamine acid as described by Grassin-Delyle is correctly implemented in Tivatrainer.

fig 1: Using Tivatrainer simulation graph to filter 125kg simulation in publication(pict C)
fig 2: Using Tivatrainer simulation graph to filter 100kg simulation in publication(pict B)
fig 3: Transparancy overlay from Tivatrainer graph over published pict A

.In fig 1 and fig 2 the line graph from the Tivatrainer simulation is used to allow the correct line in the published pictures B and C to show through. In fig 3 a simple transparancy overlay from Tivatrainer on the published graph is used.

You may find a video on the use of IVassist in Tivatrainer for tranexamin acid in the on line manual of Tivatrainer.