Adaptive pharmacokinetic and pharmacodynamic modelling to predict propofol effect using BIS-guided anesthesia.

BACKGROUND AND OBJECTIVE: Propofol is widely used for hypnosis induction and maintenance of general anesthesia. Its effect can be assessed using the bispectral index (BIS). Many automatic infusion systems are based in pharmacokinetics (PK) and pharmacodynamics (PD) models to predict the response of the patient to the drug. However, all these models do not take into account intra and inter-patient variability. An adjusted intraoperative drug administration allows faster recovery and provides post-operative side-effect mitigation METHODS: BIS evolution and surgery-recorded propofol infusion data of a group of 60 adult patients (30 males/30 females) with ASA I/II physical status were used to test a real time PK/PD compartmental model. This new algorithm tunes three model parameters (ce50, γ and ke0), minimizing a performance function online. RESULTS: The error in the BIS signal predicted by the real time PK/PD model was smaller than the error measured with fixed parameter equations. This model shows that ce50, γ and ke0 change with time and patients, given a mean (95% confidence interval) of 3.89 (3.52-4.26)mg/l, 4.63 (4.13-5.13) and 0.36 (0.31-0.4)min(-1), respectively. CONCLUSIONS: The real time PK/PD model proposed provides a closer description of the patient real state at each sample time. This allows for greater control of the drug infusion, and thus the quantity of drug administered can be titrated to achieve the desired effect for the desired duration, and reduce unnecessary waste or post-operative effects.

Modelling propofol pharmacodynamics using BIS-guided anaesthesia.

Using Schnider's pharmacokinetic model, propofol pharmacodynamics were modelled during total intravenous anaesthesia. The method involved adjusting a pharmacokinetic/pharmacodynamic model according to data obtained from 42 patients having operative procedures with remifentanil analgesia. Parameters Ce50 and γ were estimated for induction and maintenance by analysing patients' bispectral index. The pharmacodynamic models were different for induction and maintenance. The mean (95% CI) Ce50 for induction and maintenance was Ce50 = 3.35 (2.79-3.91) mg.l(-1) and 2.23 (1.95-2.51) mg.l(-1) , respectively, with a higher concentration required to achieve the same effect during induction, even during remifentanil co-administration. During induction and maintenance, γ was 1.24 (1.44-2.00) and 1.58 (1.32-1.84), respectively. As γ is related to the concentration-effect slope, patient response is accentuated during maintenance compared with induction. The influence of sex and age on the model was analysed. Sex had no significant influence on the model, although a linear relation was found between age and Ce50 .