Model-based drug administration: current status of target-controlled infusion and closed-loop control

Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the ongoing research in the field.

TCI is becoming mature technology clinically used in many countries nowadays with proven safety. Nevertheless, changing populations might require adapting the established PK/PD models. As TCI requires accurate PK/PD models, new models have been developed which should now be incorporated into the pumps to allow more general use of this technology. Closed-loop administration of hypnotic drugs using an electro-encephalographic-derived-controlled variable has been well studied and has been shown to outperform manual administration. Computer administration for other drugs and fluids have been studied recently. Feasibility has been shown for systems controlling multiple components of anaesthesia, but more work is required to show clinical safety and efficiency.

Evidence in the literature is increasing that TCI and closed-loop technology could assist the anaesthetists to optimize drug administration during anaesthesia.