右旋美托咪啶对丙泊酚靶浓度控制输注的有效靶浓度的影响

作者单位：525200 高州，广东省高州市中医院麻醉科

右旋美托咪啶对丙泊酚靶浓度控制输注的有效靶浓度的影响

莫志伟

【摘要】目的观察不同单次负荷剂量的右旋美托咪啶(DXM)对丙泊酚靶浓度控制输注(TCI)时使患者意识消失的半数有效浓度(EC50)的影响，探讨复合应用两者的安全性。方法选择择期于全身麻醉下行腰椎间盘摘除术的患者80例为研究对象。将患者随机分为D0.25、D0.5、D0.75及D0组各20例，在进行丙泊酚TCI诱导前15 min内采用双盲法分别单次缓慢静脉泵注生理盐水及不同剂量的DXM(0.25、0.5、0.75 μg/kg)，丙泊酚起始血浆靶浓度为3.2 mg/L，根据患者意识消失情况采用序贯法决定下一例的丙泊酚TCI血浆靶浓度，各相邻靶浓度之比为1∶1.25。监测给药前、后患者的血压、心电图、心率、脉搏血氧饱和度(SpO2)等指标。采用加权均数法计算使患者意识消失丙泊酚TCI的EC50及其95%可信区间(95%CI)。记录各组不良反应的发生率。结果D0组使患者意识消失丙泊酚TCI的EC50为3.02 mg/L，95%CI为2.71～3.39 mg/L；D0.25组的EC50为2.88 mg/L、95%CI为2.64～3.15 mg/L；D0.5组的EC50为1.73 mg/L、95%CI为1.57～1.91 mg/L；D0.75组的EC50为1.41 mg/L、95%CI为1.28～1.55 mg/L。4组EC50比较的Z值为13.424，P<0.01。各组的EC50均明显低于D0组(P<0.01)，D0.25组至D0.75组的EC50逐渐减小。4组患者均无出现一过性血压升高，心电图及SpO2均平稳。D0组、D0.25组均无患者出现低血压及心动过缓。D0.5组静脉泵注DXM后1例出现低血压，2例出现心动过缓，使用丙泊酚TCI后2例出现低血压，2例出现心动过缓。D0.75组静脉泵注DXM后5例出现低血压，3例出现心动过缓，使用丙泊酚TCI后5例出现低血压，3例出现心动过缓，D0.5、D0.75的不良反应发生率均高于D0组和D0.25组(P均<0.008)。结论单次静脉泵注DXM能降低丙泊酚TCI时使患者意识消失的EC50，且随着DXM用量的逐渐增加，EC50也逐渐降低，但低血压和心动过缓等不良反应发生率也随之增加，相对于其它剂量的DXM，0.25 μg/kg剂量更安全。

【关键词】右旋美托咪啶；丙泊酚；剂量效应关系；序贯法

DOI:10.3969/g.issn.0253-9802.2015.02.008

通讯作者，莫志伟，E-mail：13929736860@139.com

收稿日期：(2014-08-31)

Effect of dexmedetomidine on effective target conncentration of target-controlled infusion of propofolMoZhiwei.DepartmentofAnaesthesiology，GaozhouCountyHospitalofTraditionalChineseMedicine，Gaozhou525200，China

Correspondingauthor,MoZhiwei,E-mail：13929736860@139.com

Abstract【】ObjectiveTo observe the effect of different single loading doses of dexmedetomidine (DXM) upon half-effective concentration (EC50) when patients lost consciousness during target-controlled infusion (TCI) of propofol and discuss the safety of combined application of DXM and propofol. MethodsEighty patients undergoing lumbar diskectomy under general aneasthesia were selected in this study and randomly divided into D0, D0.25, D0.5 and D0.75 agroups (n=20 for each group). At 15 min before induction of propofol TCI, single intravenous infusion of normal saline and different doses of DXM (0.25, 0.5, 0.75 μg/kg)were conducted using double blind method. Initial target plasma concentration of propofol was 3.2 mg/L. Based upon the situation of loss of consciousness, the target plasma concentration of propofol TCI was determined by sequential method. The ratio of two consecutive concentrations was 1∶1.25. Blood pressure, electrocardiogram, heart rate and pulse oxygen saturation (SpO2) were monitored before and after medicine administration. EC50 and 95% confidence interval (95%CI) of propofol TCI when patients lost consciousness were calculated by weighted average method. The incidence of adverse events in all groups was recorded. ResultsIn D0 group, EC50 was 3.02 mg/L and 95% CI was 2.71-3.39 mg/L when patients lost consciousness, EC50 2.88 mg/L and 95% CI 2.64-3.15 mg/L in D0.25 group, EC50 1.73 mg/L and 95% CI 1.57-1.91 mg/L in D0.5 group, EC50 1.41 mg/L and 95% CI 1.28-1.55 mg/L in D0.75 group. The Z value was 13.424 when comparing EC50 among four groups (P<0.01). The EC50 in other three groups was significantly lower compared with that in D0 group (all P<0.01). The EC50 gradually declined from D0.25, D0.5 to D0.75 groups. No transient elevation of blood pressure was observed in all groups and electrocardiogram and SpO2 were stable. Neither hypotension nor bradycardia was observed in D0 and D0.25 groups. In D0.5 group, one patient presented with hypotension and two bradycardia after intravenous infusion of DXM, two hypotension and two bradycardia after use of propofol TCI. In D0.75 group, one patient presented with hypotension and two bradycardia after intravenous infusion of DXM, five hypotension and three bradycardia after propofol TCI. The incidences pf adverse events in D0.5 and D0.75 groups were significantly higher compared with those in D0 and D0.25 groups (all P<0.008). ConclusionsSingle intravenous infusion of DXM could reduce the EC50 of propofol TCI when patients loss consciousness. EC50 gradually declines whereas the incidence of adverse reaction, such as hypotension and bradycardia, increases along with the steady elevation of DXM dose. The dose of 0.25 μg/kg DXM is relatively safer compared with alternative concentrations.

【Key words】Dexmedetomidine; Propofol;Dose-effect relationship; Sequential method

目前，丙泊酚已被广泛应用于手术室内全身麻醉的诱导、维持及手术室外的镇静[1]。靶浓度控制输注(TCI)可以使血浆或效应室药物浓度快速达到和维持于所设定的目标浓度，并能够根据药效学效果和可能出现的刺激改变进行调整，从而起到麻醉与镇静深度平稳的效果。丙泊酚具有起效快、代谢迅速和持续给药后时量相关半衰期小的特点，已成为TCI静脉麻醉的最常用药物[2]。……