Influence of an “electroencephalogram (EEG) based” monitor choice on the delay between the predicted propofol effect site concentration and the measured drug effect.

Marko Sahinovic, Pieter Colin, E. Weber Jensen, Pedro L Gambus, I. Sanjore, Michel Struys

Research output: Contribution to journalMeeting AbstractAcademic


Background and Goal of the Study: Clinicians can optimise propofol titration
by using two sources of pharmacodynamic (PD) information: the predicted effect
site concentration (Ceprop) and the electroencephalographically (EEG) measured
drug effect. Relation between these sources should be time-independent, i.e.
perfectly synchronized. In reality, various issues corrupt time-independency leading to asynchrony caused by hysteresis. This can result in conflicting information making drug dosing difficult. In this study we first tried to quantify and minimize the hysteresis between the Ceprop (Schnider model) and EEG measured drug effect using nonlinear mixed effects modelling (NONMEM).Further we measured the influence of EEG based monitor choice, namely Bispectral index (BIS) vs qCON monitor, on propofol PD hysteresis.
Material and Methods: We analysed the PD data from 165 patients undergoing
propofol-remifentanil anaesthesia for outpatient surgery. Drugs were administered using target controlled infusion pumps (TCI). Pumps were programmed with Schnider model for propofol and Minto model for remifentanil. We constructed 2 PD models (direct models) relating the Schnider Ceprop to the measured BIS and Neuroanaesthesiology 143 qCON monitor values. We quantified the models’ misspecification due to hysteresis, on an individual level, using the root mean square of errors (RMSE). Subsequently we attempted to minimize the RMSE, i.e. optimize the PD models’ predictions, by adding a lag factor to both models. (lag PD models)
Results and Discussion: There is a counter clockwise hysteresis between Ceprop
and BIS/qCON values. Not accounting for this it resulted in a direct PD model with
a Ce50 of 6.24 and 8.62 µg/ml and RSME (median and interquartile range (IQR))
of 9.38 (7.92-11.23) and 8.41(7.04-10.2) for BIS and qCON, respectively. Adding a modelled lag factor of 49 seconds to the BIS model and 53 seconds to the qCON model improved both models’ prediction significantly, resulting in similar Ce50 (3.66 and 3.62 µg/ml for BIS and qCON) and lower RMSE (median (IQR) of 7.87 (6.49- 9.90) and 6.56 (5.28-8.57) for BIS and qCON
Conclusion: There is a significant, monitor dependent, “Ceprop vs EEG measured
drug effect” hysteresis. Not accounting for it leads to conflicting PD information and false high, monitor-dependent, Ce50s for propofol. Adding a lag term improved the PD model performance, “pump-monitor” synchronyand and made the estimates of Ce50 for propofol realistic and monitor-independent.
Original languageEnglish
Article number06AP03-9
Pages (from-to)143-144
Number of pages1
JournalEuropean Journal of Anaesthesiology
Issue numbere-Supplement 57
Publication statusPublished - Jun-2019
EventEuroanesthesia 2019: ESA congress 2019 Vienna Austria - Vienna, Austria
Duration: 1-Jun-20193-Jun-2019

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