Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine
Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine
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DOI：
10.1097/00000539-199711000-00033
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发表时间：
1997-11-01
影响因子：
5.7
通讯作者：
Fisher, DM
中科院分区：
文献类型：
--
作者：
Talke, P;Richardson, CA;Fisher, DM
右美托咪定是一种选择性α（2）-肾上腺素受体激动剂，具有中枢介导的交感神经阻滞、镇静和镇痛作用。本研究评价了：I）手术患者血浆和脑脊液（CSF）中右美托咪定的药代动力学; 2）术后即刻期间右美托咪定计算机控制输注方案（CCIP）的精确度; 3）该期间右美托咪定的交感神经阻滞作用。术后通过CCIP向8名女性输注右美托咪定60分钟，目标血浆浓度（C-p）为600 pg/mL。在输注前、输注期间和输注后，采集血液样本以测定去甲肾上腺素、肾上腺素和右美托咪定的血浆浓度，采集CSF样本以测定右美托咪定浓度（C-CSF）。从输注前5 min开始至输注结束后3 h连续测量心率和动脉血压。输注期间，C-p值通常超过目标值：平均百分比误差中位数为21%，范围为-2%至74%;平均绝对百分比误差中位数为23%，范围为4%至74%。输注后，C-CSF为C-p的4% +/- 1%。由于C-CSF几乎未超过测定的定量限，因此未测定CSF药代动力学。输注期间，去甲肾上腺素从2.1 +/- 0.8降至0.7 +/- 0.3 nmol/L;肾上腺素从0.7 +/- 0.5降至0.2 +/- 0.2 nmol/L;心率从76 +/- 15降至64 +/- 11 bpm;收缩压从158 ± 23毫米汞柱降至140 ± 23毫米汞柱。我们得出结论，使用已发表的药代动力学参数，通过CCIP输注右美托咪定会在术后早期超过目标右美托咪定浓度。血流动力学和儿茶酚胺结果表明，右美托咪定可在术后即刻减弱交感神经活动。含义：我们研究了右美托咪定在术后即刻的药代动力学和交感神经阻滞作用，发现在此期间，已发表的药代动力学数据略微超过了目标血浆右美托咪定浓度。我们还发现右美托咪定输注期间心率、血压和血浆儿茶酚胺浓度降低。
Dexmedetomidine is a selective alpha(2)-adrenoceptor agonist with centrally mediated sympatholytic, sedative, and analgesic effects. This study evaluated: I) pharmacokinetics of dexmedetomidine in plasma and cerebrospinal fluid (CSF) in surgical patients; 2) precision of a computer-controlled infusion protocol (CCIP) for dexmedetomidine during the immediate postoperative period; and 3) dexmedetomidine's sympatholytic effects during that period. Dexmedetomidine was infused postoperatively by CCIP for 60 min to eight women, targeting a plasma concentration (C-p) of 600 pg/mL. Before, during, and after infusion, blood was sampled to determine plasma concentrations of norepinephrine, epinephrine, and dexmedetomidine, and CSF was sampled to determine dexmedetomidine concentrations (C-CSF). Heart rate and arterial blood pressure were measured continuously from 5 min before until 3 h after the end of infusion. During the infusion, C-p values generally exceeded the target value: median percent error averaged 21% and ranged from -2% to 74%; median absolute percent error averaged 23% and ranged from 4% to 74%. After infusion, C-CSF was 4% +/- 1% of C-p. Because C-CSF barely exceeded the assay's limit of quantitation, CSF pharmacokinetics were not determined. During the infusion, norepinephrine decreased from 2.1 +/- 0.8 to 0.7 +/- 0.3 nmol/L; epinephrine decreased from 0.7 +/- 0.5 to 0.2 +/- 0.2 nmol/L; heart rate decreased from 76 +/- 15 to 64 +/- 11 bpm; and systolic blood pressure decreased from 158 +/- 23 to 140 +/- 23 mm Hg. We conclude that infusion of dexmedetomidine by CCIP using published pharmacokinetic parameters overshoots target dexmedetomidine concentrations during the early postoperative period. Hemodynamic and catecholamine results suggest that dexmedetomidine attenuates sympathetic activity during the immediate postoperative period. Implications: We studied the pharmacokinetic and sympatholytic effects of dexmedetomidine during the immediate postoperative period and found that during this period, the published pharmacokinetic data slightly overshoot target plasma dexmedetomidine concentrations. We also found that heart rate, blood pressure, and plasma catecholamine concentrations decrease during dexmedetomidine infusion.