研究氯胺酮在儿童中的药效学。
Investigating the pharmacodynamics of ketamine in children.
作者信息
Herd David W, Anderson Brian J, Keene Natalie A, Holford Nicholas H G
机构信息
Department of Paediatrics, Auckland Children's Hospital, Auckland, New Zealand.
出版信息
Paediatr Anaesth. 2008 Jan;18(1):36-42. doi: 10.1111/j.1460-9592.2007.02384.x.
BACKGROUND
The aim of this study was to describe ketamine pharmacodynamics (PD) in children. Adult ketamine concentrations during recovery are reported as 0.74 mg.l(-1) (sd 0.24 mg.l(-1)) with an EC(50) for anesthesia of 2 mg.l(-1) (sd 0.5 mg.l(-1)), but pediatric data are few.
METHODS
Children presenting for painful procedures in an Emergency Department were given ketamine 1-1.5 mg.kg(-1) i.v. Blood was assayed for ketamine on three to six occasions (median 3) over the subsequent 14-152 min (median 28.5). Procedures were videotaped. Level of sedation (0-5; unresponsive - spontaneously awake without stimulus) and a test of memory were recorded. PD was investigated using a variable slope E(max) model (sedation) or logistic regression (arousal time, memory) with nonlinear mixed effects models.
RESULTS
In total 60 children were enrolled. Pharmacokinetic data were collected in 54 of these children and there were 43 children available for PD study. The mean age was 8.15 years (sd 3.5 years) and weight was 34.9 kg (sd 15.8 kg). The half-time describing equilibration between the effect compartment and central compartment was 11 s (95% CI 0.07-20 s). The EC(50) for arousal was 0.52 (90% CI 0.22-1.17) mg.l(-1). The E(max) model with a baseline (E(0)) of five (spontaneously awake without stimulus) yielded a fractional E(max) 0.939 [coefficient of variability (CV) 24%], an EC(50) 0.56 (CV 136%) mg.l(-1) and a Hill coefficient 3.71. The EC(50) for recall memory was 0.44 (90% CI 0.09-1.70) mg.l(-1). The EC(50) for remembering was 0.38 (90% CI 0.12-1.75) mg.l(-1).
CONCLUSIONS
Concentrations associated with arousal in children are analogous to adults. The ability to recall and remember occurs at similar concentrations to those associated with arousal. A concentration of 1 mg.l(-1) was associated with a sedation level of three or less (arouses to consciousness with moderate tactile or loud verbal stimulus) in 95% of children while 1.5 mg.l(-1) was associated with a sedation level of two or less (rouses slowly to consciousness with sustained painful stimulus) in 95% of children. These concentrations can be attained for 3-4 min after 1 mg.kg(-1) and 1.5 mg.kg(-1) ketamine IV bolus, respectively. The mean arousal time can be anticipated at approximately 10 min (1 mg.kg(-1)) and 15 min (1.5 mg.kg(-1)).
背景
本研究旨在描述儿童氯胺酮的药效学（PD）。据报道，成人恢复期间氯胺酮浓度为0.74mg·l⁻¹（标准差0.24mg·l⁻¹），麻醉的半数有效浓度（EC₅₀）为2mg·l⁻¹（标准差0.5mg·l⁻¹），但儿科数据较少。
方法
在急诊科接受疼痛治疗的儿童静脉注射1 - 1.5mg·kg⁻¹氯胺酮。在随后的14 - 152分钟（中位数28.5分钟）内，对血液进行三至六次（中位数3次）氯胺酮检测。对治疗过程进行录像。记录镇静水平（0 - 5级；无反应 - 无刺激时自发清醒）和记忆测试情况。使用可变斜率E(max)模型（镇静）或逻辑回归（苏醒时间、记忆）及非线性混合效应模型研究药效学。
结果
共纳入60名儿童。其中54名儿童收集了药代动力学数据，43名儿童可用于药效学研究。平均年龄为8.15岁（标准差3.5岁），体重为34.9kg（标准差15.8kg）。效应室与中央室之间达到平衡的半衰期为11秒（95%置信区间0.07 - 20秒）。苏醒的EC₅₀为0.52（90%置信区间0.22 - 1.17）mg·l⁻¹。基线（E₀）为5（无刺激时自发清醒）的E(max)模型得出的最大效应分数为0.939[变异系数（CV）24%]，EC₅₀为0.56（CV 136%）mg·l⁻¹，希尔系数为3.71。回忆记忆的EC₅₀为0.44（90%置信区间0.09 - 1.70）mg·l⁻¹。记忆的EC₅₀为0.38（90%置信区间0.12 - 1.75）mg·l⁻¹。
结论
儿童中与苏醒相关的浓度与成人相似。回忆和记忆能力在与苏醒相关的相似浓度时出现。95%的儿童中，浓度为1mg·l⁻¹时镇静水平为三级或更低（中等触觉或大声言语刺激可唤醒至意识状态），而浓度为1.5mg·l⁻¹时95%的儿童镇静水平为二级或更低（持续疼痛刺激时缓慢唤醒至意识状态）。静脉注射1mg·kg⁻¹和1.5mg·kg⁻¹氯胺酮后，这些浓度分别可维持3 - 4分钟。平均苏醒时间预计约为10分钟（1mg·kg⁻¹）和15分钟（1.5mg·kg⁻¹）。
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