Wintermeeting 2024: Frank Engbers

With a Hammer everything looks like a Nail

How to use Tivatrainer

Frank Engbers

Friday 19 January 9:00-9:30

Initially, pharmacokinetic models were developed in pharmacological research to elucidate and forecast the temporal profile of drug concentrations upon administration to the body. The utilization of these models in Target Controlled Infusion pumps involves reverse engineering them to eliminate the time component in dosing. Throughout the evolution of Target Controlled Infusion techniques, I believe that the significance of the virtual blood or effect site concentration has been somewhat overestimated, leading to chaotic and uncontrolled implementation in commercial infusion pumps. This is evident through various implementations of the same drug model, different models for the same drug, extrapolation of patient data to inexplicable extremes, the ongoing challenge of determining the correct blood brain equilibration delay and its impact on induction dosage, as well as references to publications that cannot be traced. Tivatrainer was developed several years ago to educate healthcare professionals on IV drug dosing and facilitate comparisons between models, thereby bringing attention to deviations and issues associated with this technology.

In brief, Tivatrainer can be used to

  • Explain the principles of intravenous drug administration
  • Illuminate the fundamental tenets of Target Controlled Infusion (TCI) for achieving desired effects.
  • Compare different models for TCI
  • by letting one model recalculate the concentrations based on the other models dose data
  • reveal the difference in dose data for the same target
  • Compare the influence of different patient data
  • Determine an optimised manual dosing regimen that achieves a desired blood or effect target with adjustable precision.
  • Assess the potential outcomes of medication dosage mistakes and the legal ramifications associated with them.
  • Export data to spreadsheet software for the purpose of publication.
  • Verify data and conclusions in publications.
  • Check performance of commercial and experimental TCI pumps.

Tivatrainer has recently undergone reprogramming to be compatible with iOs, macOs, Android, and Windows operating systems. The updated version of Tivatrainer has garnered over 2000 downloads and has facilitated more than 6000 simulations since mid-2023. Its widespread usage is evident from the chart below, which displays the locations where Tivatrainer simulations have been conducted in the past 30 days.

Geographical locations of Tivatrainer simulations of 30 days. Lighter green spots indicate more simulations at the same spot. Note North America missing TCI
Drugs used for simulation in 30 days. Top rank is propofol-Marsh because it is the first listed drug and therefore used by many to get an impression of the software.

To illustrate how Tivatrainer has contributed to the identification of yet another anomaly in the implementation of drug models in Target Controlled Infusion (TCI) pumps, we will discuss the case of the Gepts model for Sufentanil. Due to an incorrect application of the Time To Peak effect principle, two different blood brain equilibration half-lives are mistakenly utilised for the integration of the Gepts model in the different brands of TCI pumps. For more detailed information, please refer to


‘To err is human’

Despite thorough checks and revisions, typographical errors can still occur. Nonetheless, many publications tend to retain graphs generated from the published model, particularly when the model is based on population data. In the case of newly implemented models, each implementation is typically accompanied by a blog post that validates the Tivatrainer implementation. This validation often involves comparing the graphical output using an overlay. If any unexplainable differences arise, the authors of the original article are contacted to provide clarification.

Future developments

There are still some features that were present in the original Tivatrainer for PC and TivatrainerX that have to be implemented in the current version:

  • Graphical dynamic representation of the state of the model
  • Display of more effect compartments and related effects e.g. Dexmedetomidine
  • Interactions e.g. between propofol and opioids
  • Adjustment of the pk parameters by the user.
  • Context sensitive decrement time
  • Real time display

And some new features

  • load dosing data from user spreadsheets and use it for simulations
  • supply more links and data in the drugs files so that it also becomes a reference for IV drug properties
  • store user files in the Tivatrainer cloud with ability to exchange data between users.

The development of new features and implementation of other drugs will be dependent on the feedback of the user.