Pharmacokinetic-Pharmacodynamic Modeling of Propofol in Children

被引:54
作者
Rigouzzo, Agnes [1 ]
Servin, Frederique [2 ]
Constant, Isabelle [1 ]
机构
[1] Univ Paris 06, Dept Anesthesiol, Armand Trousseau Hosp, AP HP, F-75571 Paris 12, France
[2] Hop Xavier Bichat, Dept Anesthesiol, AP HP, Paris, France
关键词
EFFECT SITE EQUILIBRATION; BISPECTRAL INDEX; CONTROLLED INFUSION; ANESTHESIA; TIME; TARGET; SEVOFLURANE; SURGERY; PLASMA; BOLUS;
D O I
10.1097/ALN.0b013e3181e4f4ca
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: The aim of this study was to identify the best model to describe pharmacokinetics and pharmacodynamics in prepubertal children and therefore to calculate the corresponding pharmacodynamic parameters. In addition, and to confirm our method, a group of postpubertal subjects was also studied. Methods: Sixteen children (9.5 yr, range 6-12) and 13 adults (22 yr, range 13-35) were included. Induction was performed by plasma target-controlled infusion of propofol (6 mu g/ml) based on the Kataria model in children and on the Schnider model in adults. The relationship of bispectral index to predicted concentrations was studied during induction using the Kataria, pediatric Marsh, Schuttler, and Schnider models in children. Because the best performance was obtained, strangely enough, with the Schnider model, the two groups were pooled to investigate influence of puberty on pharmacodynamic parameters (kE(0) [plasma effect-site equilibration rate constant] and Ce-50 [effect-site concentration corresponding with 50% of the maximal effect]). The time-to-peak effect was calculated, and the kE(0) was determined for the Kataria model (nonlinear mixed-effects modeling; pkpdtools). Results: In children, the predicted concentration/effect relationship was best described using the Schnider model. When the whole population was considered, a significant improvement in this model was obtained using puberty as a covariate for kE(0) and Ce-50. The time to peak effect, T-peak (median, 0.71 [range, 0.37-1.64] and 1.73 [1.4-2.68] min), and the Ce-50 (3.71 [1.88-4.4] and 3.07 [2.95-5.21] mu g/ml) were shorter and higher, respectively, in children than in adults. The kE(0) linked to the Kataria model was 4.6 [1.4-11] min. Conclusions: In children, the predicted concentration/effect relationships were best described using the Schnider model described for adults compared with classic pediatric models. The study suggests that the Schnider model might be useful for propofol target-control infusion in children.
引用
收藏
页码:343 / 352
页数:10
相关论文
共 35 条
  • [1] Accuracy of the 'Paedfusor' in children undergoing cardiac surgery or catheterization
    Absalom, A
    Amutike, D
    Lal, A
    White, M
    Kenny, GNC
    [J]. BRITISH JOURNAL OF ANAESTHESIA, 2003, 91 (04) : 507 - 513
  • [2] Maturational pharmacokinetics of single intravenous bolus of propofol
    Allegaert, Karel
    De Hoon, Jan
    Verbesselt, Rene
    Naulaers, Gunnar
    Murat, Isabelle
    [J]. PEDIATRIC ANESTHESIA, 2007, 17 (11) : 1028 - 1034
  • [3] Scaling for size: some implications for paediatric anaesthesia dosing
    Anderson, BJ
    Meakin, GH
    [J]. PAEDIATRIC ANAESTHESIA, 2002, 12 (03): : 205 - 219
  • [4] Non-steady state analysis of the pharmacokinetic interaction between propofol and remifentanil
    Bouillon, T
    Bruhn, J
    Radu-Radulescu, L
    Bertaccini, E
    Park, S
    Shafer, S
    [J]. ANESTHESIOLOGY, 2002, 97 (06) : 1350 - 1362
  • [5] An initial investigation of bispectral monitoring as an adjunct to nurse-administered propofol sedation for colonoscopy
    Chen, SC
    Rex, DK
    [J]. AMERICAN JOURNAL OF GASTROENTEROLOGY, 2004, 99 (06) : 1081 - 1086
  • [6] Rapid emergence does not explain agitation following sevoflurane anaesthesia in infants and children: a comparison with propofol
    Cohen, IT
    Finkel, JC
    Hannallah, RS
    Hummer, KA
    Patel, KM
    [J]. PAEDIATRIC ANAESTHESIA, 2003, 13 (01): : 63 - 67
  • [7] Development of a WHO growth reference for school-aged children and adolescents
    de Onis, Mercedes
    Onyango, Adelheid W.
    Borghi, Elaine
    Siyam, Amani
    Nishida, Chizuru
    Siekmann, Jonathan
    [J]. BULLETIN OF THE WORLD HEALTH ORGANIZATION, 2007, 85 (09) : 660 - 667
  • [8] Propofol-nitrous oxide versus sevoflurane-nitrous oxide for strabismus surgery in children
    Gürkan, Y
    Kiliçkan, L
    Toker, K
    [J]. PAEDIATRIC ANAESTHESIA, 1999, 9 (06): : 495 - 499
  • [9] Determination of the median effective concentration (EC50) of propofol during oesophagogastroduodenoscopy in children
    Hammer, GB
    Litalien, C
    Wellis, V
    Drover, DR
    [J]. PAEDIATRIC ANAESTHESIA, 2001, 11 (05): : 549 - 553
  • [10] Variability of target-controlted infusion is less than the variability after bolus injection
    Hu, CP
    Horstman, DJ
    Shafer, SL
    [J]. ANESTHESIOLOGY, 2005, 102 (03) : 639 - 645