Feenstra, N. (Nienke) (2014) Evaluatie van een online geïndividualiseerd farmacokinetisch model voor propofol infusie. thesis, Medicine.
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Abstract
Background: Target controlled infusion (TCI) systems programmed with Pharmacokinetic (PK) models can be used to titrate propofol towards a predicted plasma concentration. These PK-models are population based and therefore cannot be exactly accurate for individuals because of inter-individual differences in PK. It has been accepted that these predictions may have an error of about 20-30% compared to the measured propofol concentrations. Objective: This study was conducted to see whether adaptation of a population based PK-model of propofol could decrease the residual error between predicted and measured plasma concentrations compared to a classical, population based PK-model. Furthermore we were interested in bias, change in residual errors in time and concentration stabilizing performances of the adapted model. Methods: 45 patients undergoing off-pump coronary artery bypass graft surgery (CABG) and receiving propofol administered via TCI were randomized into an intervention and a control group. In the intervention group, propofol concentrations in blood samples obtained prior to 60 minutes after the start of propofol infusion were measured using a ‘Pelorus 1500 analyser’. Concentrations were entered into the TCI system to be the input for the Beyesian adaptation of the population based FK-model (Eleveld model). After adaptation several blood samples were taken to evaluate the online adaptation. In the control group, blood samples were taken at concurrent sample times and propofol concentrations were measured likewise, however no adaptation of the Eleveld model took place. Performance characteristics of the adapted model and the Eleveld model were compared by calculating the median absolute performance error (MDAPE), median performance error (MDPE), divergence and wobble from predicted and measured propofol concentrations. Results: Compared to the Eleveld model, no significant change in MDAPE was observed in the adapted model and no significant difference was found in divergence or wobble. The adapted model did show a significant smaller MDPE (median 0,6%[-4,7-7,7]) compared to the Eleveld model (median 6,4%[1,0-25,3]). Data without significant results lack statistical power, because of the shortage in sample size. Conclusion: In this group of patients undergoing CABG surgery, the online adapted model did not decrease the residual errors between measured and predicted concentrations compared to a classical non-adaptive population. However, it did show a decrease in positive bias. No improvement in divergence and wobble was seen. Continuation of the study is necessary to include a required sample size of 120 patients, 60 in each arm.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Struys, Prof. Dr. M.M.R.F. and Berg, Drs. J.P. van den |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:01 |
| Last Modified: | 25 Jun 2020 11:01 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2101 |
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