Comparison of predicted and real propofol and remifentanil concentrations in plasma and brain tissue during target‐controlled infusion: a prospective observational study

Abstract

Summary Target‐controlled infusion systems are increasingly used to administer intravenous anaesthetic drugs to achieve a user‐specified plasma or effect‐site target concentration. While several studies have investigated the ability of the underlying pharmacokinetic‐dynamic models to predict plasma concentrations, there are no data on their performance in predicting drug concentrations in the human brain. We assessed the predictive performance of the Marsh propofol model and Minto remifentanil model for plasma and brain tissue concentrations. Plasma samples were obtained during neurosurgery from 38 patients, and brain tissue samples from nine patients. Propofol and remifentanil concentrations were measured using gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry. Data were analysed from the nine patients in whom both plasma and brain samples were simultaneously obtained. For the Minto model (five patients), the median performance error was 72% for plasma and −14% for brain tissue concentration predictions. The model tended to underestimate plasma remifentanil concentrations, and to overestimate brain tissue remifentanil concentrations. For the Marsh model (five patients), the median prediction errors for plasma and brain tissue concentrations were 12% and 81%, respectively. However, when the data from all blood propofol assays (36 patients) were analysed, the median prediction error was 11%, with overprediction in 15 (42%) patients and underprediction in 21 (58%). These findings confirm earlier reports demonstrating inaccuracy for commonly used pharmacokinetic‐dynamic models for plasma concentrations and extend these findings to the prediction of effect‐site concentrations.

Efficacy and safety of remimazolam besylate versus propofol during hysteroscopy: single-centre randomized controlled trial

“…After remimazolam besylate or propofol induction, infusion of remifentanil (Yichang Humanwell Pharmaceutical Co., Ltd.) in both the groups was started with TCI pump (Guangxi VERYARK Technology Co., Ltd., China), and the effective effect-site concentration (Ce) (Minto pharmacokinetic model) was 1.5 ng/ml [16]. Remifentanil was increased by 0.5 ng/ml when analgesia was insufficient (facial grimace, movement, SBP > 140 mmHg, heart rate (HR) > 100 beats/min (bpm) or sudden increase of more than 30 bpm over baseline) and was decreased by 0.5 ng/ml with signs of excessive analgesia (respiratory depression, hypotension, or bradycardia) [17].…”

Measuring the effect‐site

“…Certain pharmacokinetic aspects of these models can be measured quite accurately, whereas with others we have had to make assumptions to fit the clinical experience. The study by Van Hese et al in this issue, challenges these assumptions on the effect‐site concentrations of propofol and remifentanil [1]. Theirs is the first human study to directly measure the effect‐site concentrations of propofol and remifentanil by sampling brain tissue from patients undergoing neurosurgery.…”

“…Certain pharmacokinetic aspects of these models can be measured quite accurately, whereas with others we have had to make assumptions to fit the clinical experience. The study by Van Hese et al in this issue, challenges these assumptions on the effect-site concentrations of propofol and remifentanil [1].…”

Brain concentrations of anaesthetic agents: the implications of epilepsy surgery

“…While there was a trend towards the Minto model overestimating brain concentrations of remifentanil, and the Marsh model under-estimating brain propofol concentration, there was considerable variation in error between patients [1].…”

“…We read with interest the paper by Van Hese et al. [1] and discussed it at our virtual journal club. This innovative study measured the concentrations of propofol and remifentanil in brain and blood samples taken from patients undergoing brain surgery for epilepsy control under total intravenous anaesthesia (TIVA), and compared these with the concentrations predicted by the Marsh and Minto pharmacokinetic models built into TIVA pumps in order to assess the accuracy of these modelling predictions.…”