Influence of a modified propofol equilibration rate constant (k_e0) on the effect‐site concentration at loss and recovery of consciousness with the Marsh model

Abstract

SummaryThis study compared the predicted effect-site concentration of propofol at loss and recovery of consciousness when using target-controlled infusion devices with the same pharmacokinetic model (Marsh) but a different plasma effect-site equilibration rate constant (k e0 ), the Diprifusor TM (k e0 0.26 min À1) and Base Primea TM (k e0 1.21 min À1). We studied 60 female patients undergoing minor gynaecological surgery under general anaesthesia. Although the total dose of propofol and time until loss of consciousness were comparable, the effect-site concentration at loss of consciousness was significantly lower with the Diprifusor than with the Base Primea (1.2 (0.3) lg.ml À1 vs 4.5 (0.9) lg.ml À1, respectively, p < 0.001). The effect-site concentration at recovery of consciousness was significantly higher with the Diprifusor than with the Base Primea (1.8 (0.4) lg.ml À1 vs 1.5 (0.2) lg.ml À1, respectively, p = 0.01). In conclusion, the effect-site concentration of propofol differs depending on the k e0 , despite the use of the same pharmacokinetic model. Therefore, the k e0 should be considered when predicting loss and recovery of consciousness based on the effect-site concentration of propofol. Target-controlled infusion (TCI) systems control the infusion rate of intravenous drugs according to predetermined pharmacokinetic profiles targeting plasma or effect-site concentration of the drug. After intravenous administration, the plasma concentration of a drug gradually equilibrates with its effect-site concentration. The rate of equilibration between plasma and effect-site concentration depends on the rate of transfer of the drug from the plasma to the effect-site [1]. The time course of equilibration between plasma and effect-site concentrations can be mathematically described by a first-order rate constant, known as the plasma effect-site equilibration rate constant (k e0 ), which can be used to estimate effect-site concentration [2].There are currently several commercial TCI devices designed for the infusion of propofol, such as the Diprifusor TM (AstraZeneca, Macclesfield, UK) and Base Primea TM (Fresenius-Vial, Br ezins, France). The 1232

A comparison of the predictive performance of three pharmacokinetic models for propofol using measured values obtained during target‐controlled infusion

“…A similar pattern of change in bias with the Schnider model was seen in a previous study in which propofol was given by continuous infusion [13]. This observation has important implications in the interpretation of studies that have attempted to compare predicted effect-site concentrations (Ce CALC ) at induction and recovery [14][15][16]. These studies derive Ce CALC as a convolution of Cb CALC with the disposition function of the effect site with a particular k e0 value and make the assumption that any bias in a particular model is similar at times of induction and recovery.…”

The influence of target concentration, equilibration rate constant (ke0) and pharmacokinetic model on the initial propofol dose delivered in effect-site target-controlled infusion

“…They found that, with fast k e0 s of 0.45 min À1 with the Schnider model and 1.21 min À1 with the Marsh model, Ce CALC values after a rapid infusion were greater than those observed after a slow infusion, whereas the opposite was seen with the slower k e0 of 0.26 min À1 using the original Marsh model. Similar results were obtained in another study with the Marsh model and a k e0 of 0.26 min À1 [19] and a marked difference in predicted effect site concentrations at loss of consciousness was seen with the Marsh model and k e0 s of 0.26 min À1 or 1.2 min À1 [20]. The results of our simulations of the two infusion rates used (Table 4) replicate the results with the model/k e0 combinations studied in the original study of Sepulveda.…”

Calling the patient's own name facilitates recovery from general anaesthesia: a randomised double‐blind trial

“…Return of consciousness from general anaesthesia is achieved when the effect‐site concentration of the anaesthetic agent decreases below its therapeutic range . During this process, providing additional stimulation can facilitate return of consciousness , so anaesthetists routinely call the patient loudly or use physical stimulation during emergence from anaesthesia.…”

“…Eye opening is commonly used to assess a patient's responsiveness and return of consciousness during emergence from general anaesthesia . However, although patients first open their eyes when responding to a verbal command, they may be in a transitional state between consciousness and unconsciousness rather than in a fully awake state , so they commonly become unresponsive and unconscious again after first opening their eyes.…”