门诊儿科患者通过鼻腔给予右美托咪定的药代动力学及镇静作用研究
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Pharmacokinetics and Sedative Effects of Intranasal Dexmedetomidine in Ambulatory Pediatric Patients
背景与目的
我们的目的是研究通过鼻腔内给予右美托咪定作为小儿磁共振检查镇静剂的药代动力学和镇静作用。
方 法
这是一项开放性单周期研究，没有随机分组。本临床试验包括5个月至11岁的儿童患者，他们计划进行MRI检查，并接受右美托咪定作为术前治疗。在MRI前约1小时内单次滴鼻2-3ug·kg右美托咪定。在4小时内采集5或6个静脉血样本进行右美托咪定浓度分析。用Comfort-B 评分监测镇静，并记录生命体征。采用非室模型拟合药代动力学参数计算变量，并比较3个年龄组（1-24个月，24-6岁，6-11岁以上）的药代动力学变量。
结 果
我们评估了187例连续患者的可行性，其中132例被排除。纳入其余55例患者，其中5例在分析前被排除。平均（标准偏差[SD]）剂量校正峰值血浆浓度（Cmax）为0.011升（0.0051），达到峰值浓度（tmax）的中位数（四分位距[IQR]）时间为37分钟（30-45）分钟）。Cmax与年龄呈负相关（r = -0.58; 95％置信区间[CI]，-0.74至-0.37; P <.001），但与tmax无关（r = -0.14; 95％CI，0.14- 0.39; P = .35）。浓度 - 时间曲线下的剂量校正面积与年龄呈负相关（r = -0.53; 95％CI，0.70至-0.29; P <.001）。Comfort-B镇静评分的中位数（IQR）最大降低为8（6-9），在给药后45分钟（40-48分钟）达到。心率中位数（IQR）比基础值降低15％（9％-23％）。
结 论
右美托咪定在给药后吸收相对较快，对小儿患者具有临床意义，但其镇静作用持续时间较短。
原始文献摘要
Panu Uusalo, MD, Samuel Guillaume,et al；Pharmacokinetics and Sedative Effects of Intranasal Dexmedetomidine in Ambulatory Pediatric Patients.[J] Anesth Analg.2019; 126:186–91
BACKGROUND:
Our aim was to characterize the pharmacokinetics and sedative effects of intranasally (IN) administered dexmedetomidine used as an adjuvant in pediatric patients scheduled for magnetic resonance imaging (MRI) requiring sedation.
Methed:
This was an open-label, single-period study without randomization. Pediatric patients from 5 months to 11 years of age scheduled for MRI and receiving IN dexmedetomidine for premedication as part of their care were included in this clinical trial. Single doses of 2-3 µg·kg of dexmedetomidine were applied IN approximately 1 hour before MRI. Five or 6 venous blood samples were collected over 4 hours for dexmedetomidine concentration analysis. Sedation was monitored with Comfort-B scores, and vital signs were recorded. Pharmacokinetic variables were calculated with noncompartmental methods and compared between 3 age groups (between 1 and 24 months, from 24 months to 6 years, and over 6-11 years).
Results：
We evaluated 187 consecutive patients for suitability, of which 132 were excluded. Remaining 55 patients were recruited, of which 5 were excluded before the analysis. Data from 50 patients were analyzed. The average (standard deviation [SD]) dose-corrected peak plasma concentration (Cmax) was 0.011 liter (0.0051), and the median (interquartile range [IQR]) time to reach peak concentration (tmax) was 37 minutes (30-45 minutes). There was negative correlation with Cmax versus age (r = -0.58; 95% confidence interval [CI], -0.74 to -0.37; P < .001), but not with tmax (r = -0.14; 95% CI, 0.14-0.39; P = .35). Dose-corrected areas under the concentration-time curve were negatively correlated with age (r = -0.53; 95% CI, 0.70 to -0.29; P < .001). Median (IQR) maximal reduction in Comfort-B sedation scores was 8 (6-9), which was achieved 45 minutes (40-48 minutes) after dosing. Median (IQR) decrease in heart rate was 15% (9%-23%) from the baseline.
Conclusion:
Dexmedetomidine is relatively rapidly absorbed after IN administration and provides clinically meaningful but short-lasting sedation in pediatric patients.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
麻醉学文献进展分享
贵州医科大学高鸿教授课题组
翻译：唐剑 编辑：何幼芹 审校：王贵龙