Pharmacokinetics and pharmacodynamics of propofol: Changes in patients with frontal brain tumours

Abstract

Background: Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour influences propofol pharmacokinetics and pharmacodynamics and existing PK-PD model performance. Methods: Twenty patients with a frontal brain tumour and 20 control patients received a propofol infusion to achieve an induction-emergence-induction anaesthetic sequence. Propofol plasma concentration was measured every 4 min and at each transition of the conscious state. Bispectral index (BIS) values were continuously recorded. We used non-linear mixed-effects modelling to analyse the effects of the presence of a brain tumour on the pharmacokinetics and pharmacodynamics of propofol. Subsequently we calculated the predictive performance of Marsh, Schnider, and Eleveld models in terms of median prediction error (MdPE) and median absolute prediction error (MdAPE). Results: Patients with brain tumours showed 40% higher propofol clearance than control patients. Performance of the Schnider model (MdPEpk-20.0%, MdAPEpk 23.4%) and Eleveld volunteer model (MdPEpk-8.58%, MdAPEpk 21.6%) were good. The Marsh model performed less well (MdPEpk-14.3%, MdAPEpk 41.4%), as did the Eleveld patient model (MdPEpk-30.8%, MdAPEpk 32.1%). The first-order rate constant (k e0; 0.108 min-1), the concentration in the effects compartment associated with 50% of the maximum effect (Ce 50; 2.77 ml litre-1) and γ (1.49) did not significantly differ between groups. Lower baseline BIS values were found in patients with brain tumours (90 vs 95). Conclusions: Brain tumours might alter the pharmacokinetics of propofol. Caution should be exerted when using propofol TCI in patients with frontal brain tumours due to higher clearance. Trial registry number: NCT01060631.