脑电双频指数反馈调控丙泊酚靶控输注在小儿先心病手术中的应用

目的 探讨脑电双频指数(BIS)反馈调控丙泊酚靶控输注(TCI)在小儿先心病手术中的应用.方法 择期先心病心内直视手术30例,随机均分为BIS反馈调控丙泊酚TCI组(A组)和丙泊酚持续泵入组(B组),比较两组术中血流动力学、术中知晓、血管活性药以及丙泊酚使用剂量.结果 A组血管活性药和丙泊酚用量明显低于B组(P<0.05或P<0.01).两组间术中血流动力学和术中知晓情况差异均无统计学意义.结论 先心病心内直视手术中,BIS反馈调控丙泊酚TCI可降低血管活性药和丙泊酚用量.     

脑电双频指数指导靶控输注丙泊酚用于无痛胃镜的观察

目前国内外陆续将靶控输注(TCI)和脑电双频指数(BIS)应用于临床,但两者结合用于“无痛”胃镜检查的报道甚少。本研究旨在检验在BIS监测指导下丙泊酚TCI用于无痛胃镜检查的可行性。资料与方法一般资料90例ASAⅠ或Ⅱ级自愿接受“无痛”胃镜检查的患者,年龄29~69岁,体重41~88kg,排     

脑电双频指数监测下丙泊酚靶控镇静在眼科手术中的应用

目的 观察丙泊酚靶控输注(TCI)在眼科手术中的镇静效果.方法 成人局麻下眼底手术患者60例,随机均分为Ⅰ、Ⅱ、Ⅲ组,分别TCI丙泊酚0.5、1.0和1.5μg/ml.分别于入室后5 min、球后阻滞、手术开始30 min、眼底激光及手术结束时记录HR、MAP、SpO2、BIS值和Ramsay镇静评分.结果 Ⅲ组术中各时点的Ramsay评分高于Ⅰ组(P＜0.05),但术中4例出现呼吸抑制,2例发生体动反应,而Ⅰ、Ⅱ组未见上述不良反应.结论 在局麻眼底手术中,采用丙泊酚1.0μg/ml TCI镇静较为适宜.     

不同年龄患者靶控输注丙泊酚的血药浓度与脑电双频指数值的相关性

目的研究靶控输注丙泊酚镇静时不同年龄患者的丙泊酚血药浓度与脑电双频指数(BIS)值的相关性。方法60例上腹部手术患者随机分为青壮年组(28~45岁,n=30)和老年组(65~80岁,n=30)。全麻诱导设定丙泊酚血浆靶控浓度3mg/L、雷米芬太尼7μg/L。意识消失后给予维库溴铵0.1mg/kg气管插管后行机械通气。术中雷米芬太尼靶控浓度维持不变,气管插后丙泊酚的靶控浓度降至2.5mg/L,术中调节丙泊酚的量使BIS值维持在45~55,并在调节后5min测定丙泊酚血药浓度。结果两组患者一般情况差异无统计学意义。青壮年组实测丙泊酚血药浓度与BIS值无相关性,老年组呈高度负相关(r=-0.64816)。结论青壮年组丙泊酚实测血药浓度与BIS值无相关性,而老年组有明显的负相关,说明在老年患者实测血药浓度可以评估镇静深度。     

靶控输注雷米芬太尼对脑电双频指数的影响

目的研究不同靶浓度的雷米芬太尼对脑电双频指数（BIS）的影响。方法60例择期行全麻手术的病人随机分成R0、R2、R4、R6四组,每组15例。病人进入手术室静卧5min取得基础数据后,给予血浆靶浓度为3μg／ml的丙泊酚,5min后依分组情况分别给予血浆靶浓度为0、2、4、6ng／ml的雷米芬太尼,3min后行气管插管,并记录数据至气管插管后5min。所有病人均未给予术前药,病人意识消失后给予0．1mg／kg的维库溴铵,研究中应用辅助或机械通气以维持PET CO2在35～45mmHg。记录每分钟的MAP、HR、BIS,并将病人人室后（T0）、给雷米芬太尼前（T1）、气管插管前（T2）及气管插管后5min内的最大值（T3）进行统计分析。结果2～6ng／ml的雷米芬太尼对BIS没有影响。R2组病人气管插管后存在插管反应,BIS明显升高,BIS变化趋势与MAP、HR变化趋势相一致。结论雷米芬太尼对BIS没有影响。BIS可以用来指导丙泊酚的用量,4ng／ml的雷米芬太尼是较佳的气管插管剂量。     

脑电双频指数-靶控输注注射泵闭环丙泊酚靶控输注应用于妇科腹腔镜手术的安全效益研究

目的 观察BIS-靶控输注(target controlled infusion,TCI)注射泵闭环丙泊酚TCI对妇科腔镜手术患者丙泊酚的节约效应及血流动力学的影响. 方法 纳入ASA分级Ⅰ、Ⅱ级择期行妇科腔镜手术的患者40例,采用计算机随机数字表分组分为闭环组和开环组,每组20例.闭环组采用BIS监测闭环丙泊酚TCI维持全身麻醉,开环组采用BIS监测下人工调整丙泊酚TCI血浆效应浓度2～5 mg/L维持全身麻醉,BIS目标值50±5;瑞芬太尼血浆效应浓度4μg/L TCI.记录两组在入室后5 min(T0)、诱导后气管插管前(T1)、插管后1 min(T2)、插管后5 min(T3)、手术切皮时(T4)、切皮后30 min(T5)、缝皮(T6)、手术结束(T7)、意识恢复(T8)、拔管即刻(T9)及拔管后5 min(T10)等时点MAP、HR、BIS值的变化,同时记录两组患者诱导及维持丙泊酚用药量、苏醒时间及进入PACU时的疼痛数字评分(numerical rating scale,NRS)及Ramsay镇静评分. 结果 术中维持丙泊酚剂量闭环组[(6.2±1.4) mg· kg-1·h-1]较开环组[(6.9±1.0)mg·kg-1·h-1]降低了10％,两组各时点MAP、HR、BIS差异无统计学意义(P＞0.05),闭环组切皮时MAP、HR、BIS波动明显小于开环组(P＜0.05).两组患者苏醒时间、NRS及Ramsay镇静评分差异无统计学意义(P＞0.05). 结论 BIS-TCI注射泵闭环丙泊酚TCI与常规BIS监测下开环丙泊酚TCI可同样安全地应用于临床,可对患者个体化合理给予全身麻醉药物,并可部分降低术中丙泊酚使用剂量,降低麻醉后手术前的循环波动.同时,避免麻醉医师手动调控TCI靶控血浆浓度,极大地降低了麻醉医师的工作量,并使围麻醉期更加平稳安全.     

脑电双频指数反馈调控丙泊酚靶控输注用于妇科手术病人的清醒镇静

目的　探讨脑电双频指数 (BIS)作为丙泊酚靶控输注的反馈控制变量用于硬膜外麻醉病人清醒镇静的可行性。方法　 4 0例ASAⅠ～Ⅱ级拟在硬膜外麻醉下行妇科手术病人 ,随机分为反馈靶控输注组 (反馈组 )和靶控输注组 (靶控组 ) ,每组 2 0例。BIS作为反馈控制变量设定为 80 ,丙泊酚血浆靶浓度设定为 1 7μg/ml,记录并比较两组间的实时BIS值、术中血压下降、呼吸抑制、术中回忆情况、镇静的满意度以及丙泊酚单位标准化使用剂量。结果　反馈组丙泊酚单位标准化使用剂量明显低于靶控组 (P <0 0 1) ;两组间血压下降、呼吸抑制、术中回忆的发生率及镇静的满意率均无显著性差异 (P >0 0 5 )。结论　BIS作为反馈控制变量用于硬膜外麻醉下妇科手术病人的清醒镇静是可行的 ,具有简单易行、安全有效、节约费用的优点。     

丙泊酚靶控输注在冠状动脉搭桥术麻醉中的应用

目的 以特定脑电双频指数（BIS）作为麻醉终点指标,丙泊酚为主要麻醉药物,对丙泊酚靶控输注（TCI）在心脏冠状动脉搭桥术（CABG）麻醉中的可行性进行评价,并试图探索出安全的麻醉方案,以指导临床。方法 选择30例40～60岁ASA Ⅱ～Ⅲ级择期CABG患者。麻醉诱导及维持均采用TCI丙泊酚,维持目标BIS在45～55。分别在气管插管前、手术切皮前和关胸前辅助给予芬太尼3～7μg／kg。观察目标BIS下丙泊酚浓度、血液动力学变化、血管活性药的应用,并测定血浆儿茶酚胺水平。结果 目标BIS下TCI丙泊酚血浆浓度麻醉诱导为1．6μg／ml,心肺转流（CPB）前为2．0～2．4μg／ml,CPB期间为2．2μg／ml,CPB后为2．3μg／ml。诱导期间30%患者需要少量山莨菪碱和去氧肾上腺素。CPB前及CPB中有55％患者应用尼卡地平。血浆儿茶酚胺水平在CPB结束时达峰值,手术结束时回落,与术前无显著性差异。结论 丙泊酚TCI技术可以安全用于CABG麻醉诱导和维持,该方法可以获得满意的麻醉效果,同时维持平稳的血液动力学。     

老年人丙泊酚效应室靶控浓度与脑电双频指数变化的关系

目的探讨老年人靶控输注(TCI)丙泊酚时不同效应室靶控浓度与脑电双频指数(BIS)变化的关系,以及镇静和麻醉时效应室靶控浓度的适宜设置值。方法18例老年病人静脉TCI丙泊酚,血浆靶控浓度的设定从0·5μg/ml开始,当效应室靶控浓度上升到血浆靶控浓度水平时,将血浆靶控浓度调高0·5μg/ml,使丙泊酚血浆靶控浓度阶梯式上升,直到效应室靶控浓度达到3·5μg/ml。记录每个效应室靶控浓度水平时的MAP、HR、RR、SpO2、BIS值和Ramsay镇静评级,同时测定丙泊酚血药浓度。结果丙泊酚效应室靶控浓度与实测血药浓度呈高度直线相关(r=0·9982,P<0·01),预测误差中位数(MDPE)=5%,预测误差绝对值的中位数(MDAPE)=12·7%,摇摆率(Wobble)=12·0%。效应室靶控浓度与BIS值呈高度直线负相关(r=-0·9985,P<0·01),回归方程:BIS值=92·94-17·77×效应室靶控浓度值(R2=0·9771,P<0·01)。当效应室靶控浓度达到0·5μg/ml时,50%的病人镇静评级达到3级。效应室靶控浓度达到3·5μg/ml时,MAP的降幅达到基础值的34%,自主呼吸率稍有降低,吸氧条件下SpO2保持在95%以上。结论丙泊酚效应室靶控浓度与BIS值呈负相关,可以用其评估镇静深度。对于老年病人,丙泊酚效应室靶控浓度在0·5~1·0μg/ml时已获得临床镇静效果,2·0~2·5μg/ml时达到全麻诱导的要求。     

单纯靶控输注瑞芬太尼对脑电双频指数（BIS）的影响

目的：观察单纯靶控输注（TCI）瑞芬太尼对患者脑电双频指数（BIS）的影响。方法：40例择期全麻手术患者，按不同的瑞芬太尼预计血浆浓度随机分为4组（R2 、R4、 R6组，、即2、4、4、8ng/ml）。首先靶控输注瑞芬太尼，待瑞芬太尼血浆与效应室浓度达平衡后，记录患者BIS值。随后持续呼唤患者一分钟，并记录呼唤一分钟后患者的BIS值。结果：与基础BIS值相比，R8组患者BIS值明显降低（P〈0.05）,R6、R8组BIS值组间丝袜无统计学差异（P〉0.05）。R6、R8组组内患者对瑞芬太尼反应个体差异很大。结论：当单纯血浆单纯靶控输注瑞芬太尼时，血浆和效应室浓度小于4ng/ml时不会引起起BIS值下降，5－8ng/ml有镇静作用，可以引起BIS值明显下降，但个体间差异较大。     

Narcotrend监测下丙泊酚靶控输注技术在肾移植患者全麻诱导期的应用

目的探讨Narcotrend监测下丙泊酚靶控输注(TCI)技术在肾移植患者全麻诱导期的应用对心血管及应激反应的影响。方法选择择期行亲属活体肾移植手术的尿毒症患者40例,男25例,女15例,年龄21~38岁,ASAⅢ或Ⅳ级,随机分为A、B两组,每组20例。A组在Narcotrend监测下采用Diprifusor TCI输注泵输注丙泊酚,B组人工推注丙泊酚。记录麻醉诱导前(T_0)、气管插管前(T_1)、气管插管后1 min(T_2)、3 min(T_3)、5 min(T_4)的HR、MAP、Narcotrend指数(NTI)及血糖(Glu)、血浆皮质醇(Cor)浓度。结果与T0时比较,T1时两组患者HR明显减慢,MAP明显下降(P0.05),且B组明显低于A组(P0.05);T_2、T_3时B组HR明显增快,MAP明显升高(P0.05),且B组明显高于A组(P0.05)。与T_0时比较,T2~T4时A组Glu、Cor略有升高,但差异无统计学意义;T_2~T_4时B组Glu、Cor浓度明显升高(P0.05),且B组明显高于A组(P0.05)。结论 Narcotrend监测下丙泊酚TCI用于肾移植患者全麻诱导时,麻醉深度可控性强,能有效减轻气管插管引起的机体应激反应,维持血流动力学平稳。     

BIS指导下丙泊酚闭环靶控输注在老年患者开腹手术中的应用

目的探讨BIS指导下丙泊酚闭环靶控输注在老年患者开腹手术中的应用效果。方法择期全麻下行开腹手术的老年患者60例,男38例,女22例,年龄65~80岁,ASAⅠ~Ⅲ级,随机分为两组:闭环组(A组)和开环组(B组),每组30例。两组采用相同的诱导方式。BIS下降至60且连续15s小于或等于60时A组丙泊酚以BIS值45~55为目标自动闭环反馈输注,B组手动调节丙泊酚维持BIS在45~55之间。两组均用肌松监测反馈仪闭环输注顺阿曲库铵,手动调节瑞芬太尼。记录入室后5min(T0)、插管即刻(Tl)、插管后3min(T2)、切皮后3min(T3)、腹腔探查时(T4)、缝皮结束时(T5)的BIS值、MAP、HR,记录两组麻醉时间、拔管时间及丙泊酚、瑞芬太尼、顺阿曲库铵、阿托品、麻黄碱、乌拉地尔和硝酸甘油等使用量,统计闭环系统性能指标:总体分数(GS),充分麻醉(40BIS60)所占时间比例。用MMSE表对两组患者术前1d、术后第3天和第5天的认知功能进行评分。结果两组患者各时点HR差异无统计学意义。T4时A组MAP、BIS明显高于B组(P0.05)。A组丙泊酚用量和靶控浓度明显低于B组(P0.05),两组患者瑞芬太尼、顺阿曲库铵使用量,麻黄碱、阿托品、乌拉地尔、硝酸甘油的使用例数差异无统计学意义。A组术后拔管时间[(27±8)min]明显短于B组[(36±10)min](P0.05),A组GS[(28±10)分]明显低于B组[(49±11)分](P0.05),充分麻醉(40BIS60)所占时间比例A组(82%±9%)明显高于B组(67%±9%)(P0.05)。术后第5天MMSE,A组[(28.57±0.87)分]明显高于B组[(26.83±0.91)分](P0.05),但术后认知功能障碍的发生率差异无统计学意义。结论 BIS指导下丙泊酚闭环靶控输注用于开腹手术的老年患者,麻醉效果良好,但在腹腔探查时患者血压有波动;BIS指导下丙泊酚闭环靶控输注可很好地维持BIS在设定的范围内;可减少全身麻醉药物的使用,缩短拔管时间,减轻对术后早期认知功能的影响。     

丙泊酚靶控输注全麻诱导时BIS值与机体应激反应的关系

目的观察丙泊酚靶控输注(TCI)用于全麻诱导时,脑电双频指数(BIS)值与应激反应的关系。方法30例气管插管全麻下手术患者随机分为三组,每组10例。Ⅰ组BIS值维持在36~45,Ⅱ组46~55,Ⅲ组56~65,分别于麻醉诱导前(T0)、插管即刻(T1)以及插管后1min(T2)、3min(T3)、5min(T4)和10min(T5)记录HR和MAP,同期抽取桡动脉血测定血糖和皮质醇。结果Ⅰ组MAP、HR于T3、T4时持续下降(P<0.05),且T3、T4时MAP低于Ⅲ组(P<0.05);Ⅱ组T4时MAP低于T0时(P<0.05);Ⅲ组血糖和皮质醇水平T2、T3时高于T0时(P<0.05或P<0.01),血糖T2~T4时较Ⅰ组升高(P<0.05或P<0.01),T3、T4时较Ⅱ组升高(P<0.05),T2、T3时皮质醇水平明显高于Ⅰ组和Ⅱ组(P<0.05或P<0.01)。结论丙泊酚TCI用于全麻诱导时,将BIS值控制在46~55,在有效减轻应激反应的同时,能维持血流动力学的相对稳定。     

Comparative evaluation of the cerebral state index and the bispectral index during target-controlled infusion of propofol

Background. Cerebral state index (CSI) has recently been introducedas an intra-operative monitor of anaesthetic depth. We comparedthe performance of the CSI to the bispectral index (BIS) inmeasuring depth of anaesthesia during target-controlled infusion(TCI) of propofol. Methods. Twenty Chinese patients undergoing general anaesthesiawere recruited. CSI and BIS, and predicted effect-site concentrationof propofol were recorded. The level of sedation was testedby Modified Observer's Assessment of Alertness/Sedation Scale(MOAAS) every 20 s during stepwise increase (TCI, 0.5 µgml^–1) of propofol. The loss of verbal contact (LVC) andloss of response (LOR) were defined by MOAAS values of 2–3and less than 2, respectively. Baseline variability and theprediction probability (P_K) were calculated for the BIS andCSI. The values of BIS₀₅ and CSI₀₅, BIS₅₀ and CSI₅₀, BIS₉₅ andCSI₉₅ were calculated at each end-point (LVC and LOR). Results. Baseline variability of CSI was more than that of BIS.Both CSI and BIS showed a high prediction probability for thesteps awake vs LVC, awake vs LOR, and LVC vs LOR, and good correlationswith MOAAS values. Conclusion. Despite larger baseline variation, CSI performedas well as BIS in terms of P_K values and correlations with stepchanges in sedation.     

Geographic differences in the target-controlled infusion estimated concentration of propofol: bispectral index response curves

Purpose

Variability in drug responses could result from both genetic and environmental factors. Thus, drug effect could depend on geographic location, although regional variation is not generally acknowledged as a basis for stratification. There is evidence that the pharmacokinetic set developed in a European population for the target-controlled infusion (TCI) of propofol does not apply in Chinese patients; however, we are not aware of previous studies comparing the estimated concentration-bispectral index (BIS) response of Caucasian patients in Europe with that of Chinese patients in China.

Methods

The Diprifusor^TM TCI pump, incorporating the pharmacokinetic model proposed by Marsh et al., was applied to 30 Caucasian patients in Austria and 30 Chinese patients in China. The estimated plasma concentration (C_p) of propofol for the two groups was set at 1 μg·mL^?1 and increased by 1 μg·mL^?1 every minute to gradually reach 5 μg·mL^?1 after 5 min. The BIS values were fitted against the estimated C_p and the predicted effect-site concentration (C_e) in a sigmoid E_max model.

Results

The sigmoid E_max curves were shifted significantly to the left in the Chinese group compared with the Austrian group. After 5 min, the BIS value in the Chinese group was lower than in the Austrian group (mean ± standard deviation [SD], 47.2 ± 3.6 vs 63.6 ± 5.4, respectively; P = 0.0006). The estimated C_p at loss of consciousness (LOC), predicted C_e at LOC, and time to LOC, were lower in the Chinese group than in the Austrian group (3.3 ± 0.8 μg·mL^?1, 1.6 ± 0.4 μg·mL^?1, 2.8 ± 0.6 min, respectively, vs 4.6 ± 2.8 μg·mL^?1, 2.4 ± 1.5 μg·mL^?1, 3.9 ± 0.5 min, respectively; P < 0.0001).

Conclusion

When propofol is given using the same TCI protocol, Chinese patients in China lost consciousness faster and at a lower estimated plasma concentration than Caucasians in Austria. Larger studies are needed to map geographically appropriate TCI infusion models.     

Closed-loop titration of propofol guided by the bispectral index

This review analyzes the clinical studies concerning the automated perfusion, or closed-loop, of propofol guided by the bispectral index (BIS). To carry out the maintenance of general anaesthesia by a closed loop propofol-BIS is feasible as shown by studies comprising few low risk patients. We showed that induction of anaesthesia is feasible with a closed loop, haemodynamic stability being similar to a manual titration. A second study, bearing on the whole of the anaesthesia of patients ASA I to III undergoing very diverse surgical acts, showed that the closed loop propofol-BIS was more precise than a manual perfusion. This confirms that the closed loop propofol-BIS is not an esoteric research and that it represents a tool with a future for the clinician.     

右美托咪啶对靶控输注异丙酚意识消失时BIS值的影响

目的 评价右美托咪啶对靶控输注异丙酚意识消失时脑电双频谱指数(BIS)值的影响.方法 择期行普外科手术患者120例,性别不限,年龄25～50岁,体重41～68 kg,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将患者随机分为3组(n=40):异丙酚组(P组)、右美托咪啶0.5μg/kg+异丙酚(D1P组)和右美托咪啶1.0μg/kg+异丙酚(D2P组).每组再分为5个亚组(n=8):异丙酚效应室靶控浓度0、1、2、3和4 mg/L组(P0～4组).P0～4组靶控输注异丙酚,效应室靶浓度分别为0、1、2、3和4 mg/L;D1 P0～4组静脉输注右美托咪啶0.5 μg/kg,输注速率0.05μg·kg-1·min-1,输注结束后5min时靶控输注异丙酚,效应室靶浓度分别为0、1、2、3和4 mg/L;D2 P0～4组静脉输注右美托咪啶1.0μg/kg,输注速率0.1 μg· kg-1 ·min-1,输注结束后5min时靶控输注异丙酚,效应室靶浓度分别为0、1、2、3和4mg/L.异丙酚靶控输注3 min时记录OAA/S评分和BIS值,OAA/S评分≤2分判定为意识消失.采用Probit法计算半数患者意识消失时异丙酚的效应室靶浓度(EC50)和半数患者意识消失时的BIS值(BIS50)及其95％可信区间,采用Smith法计算BIS值对意识消失的预测概率.结果 与P组比较,D1P组和D2P组EC50降低,BIS50升高(P＜0.05或0.01),预测概率差异无统计学意义(P＞0.05);D1P组和D2P组EC50、BIS50和预测概率比较差异无统计学意义(P＞0.05).结论 右美托咪啶复合靶控输注异丙酚时BIS 值可准确预测患者的意识水平,而意识消失时的BIS值增加.     

Bispectral index in patients with target-controlled or manually-controlled infusion of propofol

In this prospective, randomized study we compared bispectral index (BIS), hemodynamics, time to extubation, and the costs of target-controlled infusion (TCI) and manually-controlled infusion (MCI) of propofol. Forty patients undergoing first-time implantation of a cardioverter-defibrillator were included. Anesthesia was performed with remifentanil (0.2-0.3 micro g. kg(-1). min(-1)) and propofol. Propofol was used as TCI (plasma target concentration, 2.5-3.5 micro g/mL; n = 20) or MCI (3.0-4.0 mg. kg(-1). h(-1); n = 20). BIS, heart rate, and arterial blood pressure were measured at six data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the two groups. BIS was significantly lower at T3 and T4 in the TCI group than in the MCI group. The mean dose of propofol was larger in TCI patients (5.8 +/- 1.4 mg. kg(-1). h(-1)) than in the MCI patients (3.7 +/- 0.6 mg. kg(-1). h(-1)) (P < 0.05), whereas doses of remifentanil did not differ. Time to extubation did not differ between the two groups (TCI, 13.7 +/- 5.3 min; MCI, 12.3 +/- 3.5 min). One patient in the MCI group had signs of intraoperative awareness without explicit memory after first defibrillation (BIS before shock, 49; after shock, 83). Costs were significantly less in the MCI group (34.83 US dollars) than in the TCI group (39.73 US dollars). BIS failed to predict the adequacy of anesthesia for the next painful stimulus. IMPLICATIONS: In this prospective, randomized study, bispectral index (BIS), hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) and manually-controlled infusion of propofol were compared. TCI increased the amount of propofol used. BIS failed to predict the adequacy of anesthesia for the next painful stimulus.