目的 观察氯胺酮对右美托咪定(Dex)靶控输注患者镇静意识消失时浓度效应关系的影响.方法 择期行椎管内麻醉下腹部或下肢手术者共60例(ASA Ⅰ～Ⅱ级),随机分为D组和KD组,每组30例,每组按Dex靶控浓度的不同随机分为5个亚组(n=6),D组(D1～D5)浓度分别为0.54、0.64、0.76、0.90 和1.07 ng/mL;KD组(KD1～KD5)浓度分别是0.30、0.37、0.46、0.57和0.70 ng/mL.监测脑电双频谱指数(BIS)、心率(HR)、平均动脉压(MAP)和脉搏氧饱和度(SpO2)、警觉/镇静(OAA/S)评分和睫毛反射;以呼之不应(OAA/S评分≤2)和睫毛反射消失作为意识消失指标,观察和记录30 min内每组及其亚组患者意识消失的例数及其对应靶浓度,采用概率单位法(Probit)回归分析计算两组的浓度-效应曲线方程及其意识消失的半数有效浓度(EC50)和95%有效浓度(EC95).结果 D组和KD组中各亚组间随着时间推移和亚组间随着靶浓度增加,意识消失率逐渐上升,BIS值逐渐下降(P<0.05);KD组EC50(0.445 ng/mL) 和EC95(0.603 ng/mL)显著低于D组EC50(0.738 ng/mL)和EC95 (0.990 ng/mL),KD组量效曲线相对D组平行且左移;与基础值比较,两组第3、4、5亚组15 min后MAP逐渐下降(P<0.05),D组第3、4、5亚组5 min后HR逐渐下降,第1、2亚组10 min后HR下降(P<0.05),KD组第3、4、5亚组于20～30 min HR下降明显(P<0.05).SpO2不同时间SpO2≥95%,差异无统计学意义(P＞0.05).结论 随着Dex靶控输注血浆浓度增加,镇静深度增加,小剂量氯胺酮能够降低Dex意识消失所需的靶浓度,增强其镇静效果.%Objective To investigate the effects of ketamine on concentration - response of dexmedetomidine with respect to the loss of consciousness via target-controlled infusion ( TCI ). Methods Sixty patients ( ASA Ⅰ~Ⅱ ) undergoing lower abdominal or extremity operations under combined spinal-epidural anesthesia were randomly divided into 2 groups ( n = 30 ): Group D ( dexmedetomidine alone ) and Group KD ( dexmedetomidine and ketamine ). Patients in Group D were further randomized to 5 subgroups ( n = 6 in each ), in which the subjects received dexmedetomidine via TCI at the respective target plasma concentrations of 0. 54, 0. 64, 0. 76, 0. 90 and 1. 07 ng/mL. Meanwhile, patients in Group KD were randomized 5 subgroups ( n = 6 in each ), in which the subjects with pretreatment of ketamine 0. 4 mg/kg and sustained by 5 μg/kg/min intravenously, received dexmedetomidine via TCI at the respective target plasma concentrations of 0. 30, 0. 37, 0. 46, 0. 57 and 0. 70 ng/mL. The loss of response to verbal command ( OAA/S scores ≤ 2 ) and eyelash stimulation was used as the standard of definite unconsciousness. The number of unconscious patients in each group was recorded during the first 30 mins. Bispectral index ( BIS ), heart rate ( HR ), blood pressure ( BP ), SpO2 , OAA/S scores and eyelash stimulation were monitored during the study. A quantal response model ( probit analysis ) was used to calculate the concentration-effect curve and predict plasma EC50 and EC95 of dexmedetomidine. Results Dexmedetomidine induced significant increase of unconsciousness ratio and reduction of BIS values in concentration-dependent manners ( P < 0. 05 ). The EC50 and EC95 of loss of consciousness of dexmedetomidine were 0. 445 ng/mL and 0. 603 ng/mL in Group rnKD, which were significantly lower than those ( 0. 738 ng/mL and 0. 990 ng/mL, respectively ) in Group D ( P <0. 05 ). A paralleled but left - shift concentration - effect curve was observed in Group KD when compared to that in Group D. Compared to the baseline, the MAP of both groups significantly decreased after 15 min in Subgroup 3, 4 and 5 ( P < 0. 05 ). So did the HR at 5min in the Subgroup 3 , 4 and 5, and at 10 min in the Subgroup 1 and 2 of the Group D. Compared to the baseline, the HR significantly decreased between 20 to 30 min in the Subgroup 4 and 5 ( P <0. 05 ). Conclusion Dex provides concentration-dependent sedative effect on anesthesia, and low dose ketamine enhances this via reduction of target plasma concentration of Dex.
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