右美托咪啶对机械性疼痛刺激的镇痛有效浓度测定

DETERMINATION OF EC_(50) OF DEXMEDETOMIDINE FOR PAIN RELIEF OF MECHANICAL STIMULUS IN VOLUNTEERS

目的：测定右美托咪啶对志愿者机械性疼痛刺激的镇痛有效浓度.方法：征集健康志愿者50名（ASA-I级）随机分为5个组,每组10例,并接受机械性疼痛刺激和视觉模拟评分（visual analoguescale,VAS）分别以血浆靶浓度（0.9 ng/ml、1.04 ng/ml、1.2 ng/mi、1.39 ng/ml和1.6 ng/ml）靶控输注右美托咪啶,于靶控输注后5min （T1）、10min （T2）、15min （T3）、20min （T4）和30min （T5）等时点唤醒VAS评分,若唤醒困难或任何时间点VAS ＜10 mm为镇痛有效,并记录为阳性,并于相应时间点记录BIS值、HR、MAP和SpO2.采用概率单位法（probit）回归分析计算两组的浓度-效应曲线方程及其痛觉消失的EC50和EC95.结果：五组间随着靶浓度增加和时间推移,BIS值逐步下降,痛觉消失发生率逐渐上升（P＜0.05）.痛觉消失的EC50、EC9s分别为1.162（1.063～1.267） ng/ml和1.572（1.402～2.075） ng/ml.与基础值比较,各组MAP、HR于靶控输注10min时后开始逐渐下降（P＜0.05）.结论：DEX对机械性疼痛刺激具有明显的镇痛作用,EC50、EC95分别为1.162 ng/ml和1.572 ng/ml,合并血压和心率下降.

Objective： To determine the median effective concentration （ECs0） of dexrnedetomidine for pain relief of mechanical stimulus in volunteers. Methods： Fifty volunteers （ASA-I） provided informed consent in the tests were randomly divided into 5 groups （10 in each group） according to different plasma concentrations of dexmedetomidine： 0.9 ng/ml （group D1）, 1.04 ng/ml （group D2）, 1.2 ng/ml （group D3）, 1.39 ng/ml （group D4） and 1.6 ng/ml （group D5）. The VAS pain scores were assessed by giving a vertically mechanical stimulus （ 150 g ） of electronic Von Frey on the palm of left hand. Dexmedetomidine was administered intravenously via a computer-controlled infusion pump as defined. The values of MAP （mean arterial pressure）, HR （heart rate）, SpO2 （pulse oxygen saturation） and BIS （bispectral index） and the VAS pain scores were repeatedly assessed every 5 minutes in 30 minutes after TCI began. If it was difficult to awake patient during sedation or the VAS pain scores were below 10 mm at any time points at 5 min, 10 rain, 15 min, 20 min, 25 min and 30 min, it was recorded as loss of pain effectively. A quantal response model （probit analysis） was used to calculate the concentration-effect curve and predict plasma ECs0 and EC95 of lOSS of pain of dexmedetomidine. Results： With increasing plasma concentration of dexmedetomidine and the time elapsed, the values of BIS decreased and the rate of pain relief increased gradually among the five groups （P 〈 0.05）. EC50 and EC95 ofdexmedetomidine for loss of pain were 1.162 （ 1.063 ~ 1.267 ） ng/ml and 1.572 （ 1.402 ~ 2.075 ） ng/ml. Compared to the baseline values, the values of MAP and HR in each group decreased gradually beginning from 10 min after TCI began （P 〈 0.05 ） . Conclusion： Dexmedetomidine can relieve pain of mechanical stimulus with a concentration-response relationship, which was acompanied by hypotension and bradycardia during TCI. ECs0 and EC95 ofdexmedetomidine for loss of pain was 1.162 ng/ml and 1.572 ng/ml.