BJA Advance Access published online on March 27, 2007
British Journal of Anaesthesia, doi:10.1093/bja/aem063
Predictive performance of the Domino, Hijazi, and Clements models during low-dose target-controlled ketamine infusions in healthy volunteers
1 University Division of Anaesthesia, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
2 Department of Anesthesiology, Harborview Medical Centre, Seattle, WA, USA
3 Bvba Demed, Hollebeek 145, B-9140 Temse, Belgium
4 University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2SP
5 Brain Mapping Unit, School of Clinical Medicine, Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
* Corresponding author. E-mail: ara30{at}wbic.cam.ac.uk
Background: Healthy volunteers received low-dose target-controlled infusions (TCI) of ketamine controlled by the Domino model while cognitive function tests and functional neuroimaging were performed. The aim of the current study was to assess the predictive performance of the Domino model during these studies, and compare it with that of three other ketamine models.
Methods: Fifty-eight volunteers received ketamine administered by a TCI device on one or more occasions at target concentrations of either 50, 100, or 200 ng ml–1. At each target concentration, two or three venous blood samples were withdrawn during infusion, with a further sample after the infusion ended. Ketamine assays were performed by gas chromatography. The plasma concentration time courses predicted by the Hijazi, Clements 125, and Clements 250 models were calculated retrospectively, and the predictive performance of each of the models was assessed using Varvel methodology.
Results: For the Domino model, bias, inaccuracy, wobble, and divergence were –2.7%, 33.9%, 24.2%, and 0.1463 % h–1, respectively. There was a systematic increase in performance error over time. The Clements 250 model performed best by all criteria, whereas the Hijazi model performed least well by all criteria except for bias.
Conclusions: Performance of the Domino model during control of low-dose ketamine infusions was sub-optimal. The Clements 250 model may be a better model for controlling low-dose TCI ketamine administration
Keywords: anaesthetics, i.v., ketamine; pharmacokinetics