Validation of the Eleveld propofol PKPD model

Target controlled infusion (TCI) of anaesthetic drugs such as propofol allows for more stable plasma concentrations or effect, and is a clinically applied technique for drug administration during general anaesthesia. TCI requires reliable pharmacokinetic (PK) or pharmacokinetic/pharmacodynamic (PKPD) models for the specific drug. For propofol, many PK(PD) models are available, but are developed from many different populations and from different study protocols. Extrapolation of such models may pose risks of under- and/or overdosing of patients. The Eleveld PKPD model was developed using available data from many of these studies. The population from which this model is derived, is therefore far broader than any existing models, and application of this model is theoretically also much broader. However, this model has yet to be validated in a separate study, which is the aim of this current study.

The Eleveld propofol PKPD model allows administration of propofol by use of target controlled infusion (TCI) in a broad population (children-adults-elderly-lean-obese).

close to 5, 10, 20, 30, 40 and 60 minutes after start of propofol TCI.

If operation takes longer than 60 minutes, samples will be taken at 30 minute intervals, with a maximum of 10 samples in total.

This is a validation study where patients from a broad population (age-range, lean and obese) receive TCI propofol using the Eleveld model. Blood samples will be taken to measure plasma concentrations of propofol and compared with predicted plasma concentrations. Bispectral index will be used as a surrogate measurement of propofol effect, and compared to predicted BIS and predicted effect-site concentrations.