British journal of anaesthesia
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The recently introduced open-target-controlled infusion (TCI) systems can be programmed with any pharmacokinetic model, and allow either plasma- or effect-site targeting. With effect-site targeting the goal is to achieve a user-defined target effect-site concentration as rapidly as possible, by manipulating the plasma concentration around the target. Currently systems are pre-programmed with the Marsh and Schnider pharmacokinetic models for propofol. ⋯ The Schnider model should thus always be used in effect-site targeting mode, in which larger initial doses are administered, albeit still smaller than for the Marsh model. Users of the Schnider model should be aware that in the morbidly obese the LBM equation can generate paradoxical values resulting in excessive increases in maintenance infusion rates. Finally, the two currently available open TCI systems implement different methods of effect-site targeting for the Schnider model, and in a small subset of patients the induction doses generated by the two methods can differ significantly.
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Recent studies of mechanisms of anaesthesia have been mainly 'target orientated', investigating the activity of both volatile and i.v. agents at putative sites of action. An alternative approach is one that is 'ligand orientated', focusing on the properties of molecules that define their immobilizing ability and secondly define their potency. ⋯ The same approach can also be used to model other properties of anaesthetic agents, such as cardiovascular depression. The present data suggest that, for the i.v. agents, it may be difficult to separate immobilizing (anaesthetic) activity and cardiovascular depression within a single molecule.