Struys M M, De Smet T, Depoorter B, Versichelen L F, Mortier E P, Dumortier F J, Shafer S L, Rolly G
Department of Anesthesia, the University Hospital of Gent, Belgium.
Anesthesiology. 2000 Feb;92(2):399-406. doi: 10.1097/00000542-200002000-00021.
Target-controlled infusion (TCI) systems can control the concentration in the plasma or at the site of drug effect. A TCI system that targets the effect site should be able to accurately predict the time course of drug effect. The authors tested this by comparing the performance of three control algorithms: plasmacontrol TCI versus two algorithms for effect-site control TCI.
One-hundred twenty healthy women patients received propofol via TCI for 12-min at a target concentration of 5.4 microg/ml. In all three groups, the plasma concentrations were computed using pharmacokinetics previously reported. In group I, the TCI device controlled the plasma concentration. In groups II and III, the TCI device controlled the effect-site concentration. In group II, the effect site was computed using a half-life for plasma effect-site equilibration (t1/2k(eo)) of 3.5 min. In group III, plasma effect-site equilibration rate constant (k(eo)) was computed to yield a time to peak effect of 1.6 min after bolus injection, yielding a t1/2keo of 34 s. the time course of propofol was measured using the bispectral index. Blood pressure, ventilation, and time of loss of consciousness were measured.
The time course of propofol drug effect, as measured by the bispectral index, was best predicted in group III. Targeting the effect-site concentration shortened the time to loss of consciousness compared with the targeting plasma concentration without causing hypotension. The incidence of apnea was less in group III than in group II.
Effect compartment-controlled TCI can be safely applied in clinical practice. A biophase model combining the Marsh kinetics and a time to peak effect of 1.6 min accurately predicted the time course of propofol drug effect.
靶控输注（TCI）系统可控制血浆或药物作用部位的浓度。以作用部位为靶点的TCI系统应能够准确预测药物效应的时间进程。作者通过比较三种控制算法的性能对此进行了测试：血浆控制TCI与两种作用部位控制TCI算法。
120名健康女性患者通过TCI接受丙泊酚输注12分钟，目标浓度为5.4微克/毫升。在所有三组中，血浆浓度均使用先前报道的药代动力学进行计算。在第一组中，TCI设备控制血浆浓度。在第二组和第三组中，TCI设备控制作用部位浓度。在第二组中，使用血浆-作用部位平衡半衰期（t1/2k(eo)）为3.5分钟来计算作用部位。在第三组中，计算血浆-作用部位平衡速率常数（k(eo)），以使推注后达到峰值效应的时间为1.6分钟，从而得出t1/2keo为34秒。使用脑电双频指数测量丙泊酚的时间进程。测量血压、通气和意识消失时间。
用脑电双频指数测量，丙泊酚药物效应的时间进程在第三组中预测得最好。与以血浆浓度为靶点相比，以作用部位浓度为靶点缩短了意识消失时间，且未引起低血压。第三组呼吸暂停的发生率低于第二组。
效应室控制的TCI可安全应用于临床实践。结合Marsh药代动力学和1.6分钟峰值效应时间的生物相模型准确预测了丙泊酚药物效应的时间进程。
