Ginsberg B, Howell S, Glass P S, Margolis J O, Ross A K, Dear G L, Shafer S L
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Anesthesiology. 1996 Dec;85(6):1268-75. doi: 10.1097/00000542-199612000-00007.
This study determined the accuracy of previously defined adult fentanyl pharmacokinetics in children having surgery; from this population, the pharmacokinetics of fentanyl were characterized in children when administered via a computerized assisted continuous-infusion device.
Twenty children between the ages of 2.7 and 11 y scheduled to undergo elective noncardiac surgery were studied. After induction, anesthesia was maintained with 60% nitrous oxide in oxygen supplemented with fentanyl (n = 10) or fentanyl plus isoflurane (n = 10). Fentanyl was administered via computerized assisted continuous-infusion to target concentrations determined by clinical requirements. Plasma fentanyl concentrations were measured and used to evaluate the performance of the fentanyl pharmacokinetics and then to determine a new set of pharmacokinetic parameters and the variance in the context-sensitive half-times simulated for these patients.
The original adult fentanyl pharmacokinetics resulted in a positive bias (10.4%), indicating that measured concentrations were mostly greater than predicted. A two-compartment model with age and weight as covariates provided the optimal pharmacokinetic parameters. These resulted in a residual performance error of -1.1% and a median absolute performance error of 17.4%. The context-sensitive times determined from this pediatric population were considerably shorter than the context-sensitive times previously published for adults.
The pharmacokinetics of fentanyl administered by computerized assisted continuous-infusion differ between adults and children. The newly derived parameters are probably more suitable to determine infusion schemes of up to 4 h in children between the ages of 2 and 11 y.
本研究确定了先前定义的成人芬太尼药代动力学在接受手术儿童中的准确性；并在此人群中，对通过计算机辅助持续输注装置给药时儿童芬太尼的药代动力学进行了特征描述。
对20名年龄在2.7至11岁之间计划接受择期非心脏手术的儿童进行研究。诱导后，用60%氧化亚氮加氧气维持麻醉，其中10名儿童添加芬太尼，另10名儿童添加芬太尼加异氟烷。芬太尼通过计算机辅助持续输注给药，以达到临床要求的目标浓度。测量血浆芬太尼浓度，用于评估芬太尼药代动力学的性能，然后确定一组新的药代动力学参数以及为这些患者模拟的上下文敏感半衰期的方差。
最初的成人芬太尼药代动力学产生了正偏差（10.4%），表明测量浓度大多高于预测值。以年龄和体重作为协变量的二室模型提供了最佳药代动力学参数。这些参数导致残余性能误差为-1.1%，中位绝对性能误差为17.4%。从该儿科人群确定的上下文敏感时间明显短于先前发表的成人上下文敏感时间。
计算机辅助持续输注给药时，成人和儿童芬太尼的药代动力学不同。新推导的参数可能更适合确定2至11岁儿童长达4小时的输注方案。
