依托咪酯对新生大鼠认知功能的影响及其机制研究

目的 探讨新生大鼠依托咪酯麻醉后近远期认知功能及烟碱型乙酰胆碱受体（nAChR）功能的变化。方法 将7 d龄新生大鼠随机分对照组、依托咪酯组、激动剂组,分别单次腹腔注射生理盐水10 ml/kg、依托咪酯5 ml/kg、依托咪酯5 ml/kg+α7nAChR激动剂PNU-282987 5 ml/kg,每组16只。麻醉清醒后2 h和4周,各组随机取8只大鼠进行行为学测试,完成测试后立即取双侧海马组织,采用qRT-PCR和Western blotting检测α7nAChR、乙酰胆碱酯酶（AChE） mRNA和蛋白。结果 麻醉清醒后2 h,依托咪酯组洞板实验探洞次数少于对照组和激动剂组（P <0.05）;3组Y电迷宫实验中正确反应次数和全天总反应时间比较,差异无统计学意义（P >0.05）。麻醉清醒后4周,3组洞板实验探洞次数、Y电迷宫实验中正确反应次数和全天总反应时间比较,差异无统计学意义（P >0.05）。麻醉清醒后2 h,依托咪酯组海马组织α7nAChR mRNA相对表达量低于对照组和激动剂组（P <0.05）,AChE mRNA和蛋白相对表达量高于对照组和激动剂组（P <0.05）。麻醉清醒后4周,3组α7nAChR、AChE mRNA和蛋白相对表达量比较,差异无统计学意义（P >0.05）。结论 新生大鼠依托咪酯麻醉对近期学习记忆能力和远期认知能力无明显影响,但可一过性影响新生大鼠近期探索能力,其机制可能与抑制海马nAChR功能有关。     

输注速度和刺激对全麻诱导时依托咪酯所致肌阵挛的影响

目的 通过观察不同给药速度以及在麻醉诱导过程中给予刺激对依托咪酯进行全麻诱导时发生肌阵挛的影响,分析肌阵挛的诱发因素.方法 200例ASA Ⅰ～Ⅱ级的患者随机分为四组：慢诱导组（S组）、慢诱导刺激组（S-s组）、快诱导组（F组）、快诱导刺激组（F-s组）,各50例.四组患者麻醉诱导均采用依托咪酯0.3 mg/kg.S组与S-s组输注时间均为1 min,F组与F-s组输注时间为10s.S组与F组待睫毛反射消失、呼吸变浅后开始行辅助通气,S-s组与F-s组待意识消失即刻开始行正压机械通气.记录四组患者麻醉前、依托咪酯注药后3 min内平均动脉压（MAP）、心率（HR）、脉搏血氧饱和度（SPO2）变化;观察静脉注射依托咪酯后肌阵挛的发生情况以及严重程度.结果 S组患者与F组患者肌阵挛发生率无明显差异,S-s组与S组相比以及F-s组与F组相比,其肌阵挛发生率均增高（P＜0.01）,但S-s组与F-s组相比肌阵挛发生率稍低（P＜0.01）.此外S-s组与F-s组注药后MAP及HR较基础值有所升高,SPO2则呈下降趋势（P＜0.01）,其余两组无明显变化.结论 全麻诱导时,加快输注速度并不会增加依托咪酯所致肌阵挛的发生率,但若在麻醉深度不够时给予了刺激则易诱发肌阵挛的发生.     

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate,in healthy subjects

Background

Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers.

HPLC梯度洗脱法测定依托咪酯乳状注射液的有关物质

目的:建立测定依托咪酯乳状注射液中的有关物质的HPLC方法。方法:色谱柱为Waters SpherisorbC₈(4.6 mm×250 mm, 10μm);流动相为磷酸二氢钾溶液-乙腈-80%-四氢呋喃,梯度洗脱;柱温为40℃;检测波长为220 nm,采用外标法与自身对照法。结果:依托咪酯与依托咪酸能较好分离,依托咪酸相邻各峰间分离度均大于1.5;依托咪酸的线性范围为10.0～100.0μg·mL^-1(r=0.999 9);平均回收率(n=9)为99.5%。结果表明,B企业产品中依托咪酸的含量相对较高,其他杂质也高于A企业产品。结论:所建方法简便快捷、专属性强、重复性好,可用于依托咪酯乳状注射液中的有关物质检查。     

The effects of etomidate in the cat middle cerebral artery occlusion model of brain ischaemia: An experimental study

The effects of etomidate on focal cerebral ischaemia following transorbital occlusion of the cat middle cerebral artery were investigated. Etomidate had no effect on CBF before or after onset of ischaemia by comparison with controls, but caused a greater fall in CBF in cats with high preocclusion or initial ischaemic CBF than in those in which CBF was lower. There were more sustained rises in Kp on SG. The established flow threshold for water accumulation was lost; more gyri with CBF above and fewer gyri with CBF below the flow threshold accumulated water. The relationship between mean occlusion CBF and in vitro GABA uptake was lost; uptakes from MC were lower and from SG and EG higher than expected. In the ischaemic penumbra there was a trend towards reduction in CBF, disruption of ion homeostasis and cerebral oedema formation, whilst in areas of lower flow there was some recovery of GABA uptake and less cerebral oedema following administration of etomidate.     

Priming with atracurium efficiently suppresses etomidate-induced myoclonus

IntroductionEtomidate is a hypnotic drug widely used as an intravenous anesthetic induction agent. The incidence of etomidate-induced myoclonus has been reported as much as 50–80% after induction making it an undesirable drug for induction.ObjectiveOur aim is to use a priming dose of atracurium to suppress etomidate-induced myoclonus during induction of anesthesia.MethodsIn a double-blinded clinical trial 80 patients were randomly given either atracurium (20% of ED95 × kg) or saline as a priming agent. Then, induction of anesthesia was performed using 0.4 mg/kg etomidate. Age, weight, body mass index, bispectral index (BIS) monitor, and duration and grade of myoclonus were recorded.ResultsThe demographic characteristics, age, body mass index, BIS score, and weight were not significantly different between the atracurium (ATRA) priming group and control groups. The binomial regression model showed that BMI was an independent predictor variable for myoclonus (OR: 2.1, CI 95%: 1.7–7.5, p = 0.032). In this model, adjusted odds ratios (OR) of myoclonus (multivariate logistic regression analysis) in the control group was 6.6 (95% CI: 1.5–9.7, p = 0.013).ConclusionLow-dose atracurium priming could effectively suppress etomidate-induced myoclonus.     

依托咪酯语言及记忆评估的Wada试验在癫痫外科运动、语言和记忆评估中的初步应用

目的 依托咪酯语言及记忆评估的Wada试验(etomidate speech and memory-Wada testing, eSAM-Wada)在我国还未见相关报道,而血管超选下eSAM-Wada试验国内外还未见报道。探讨eSAM-Wada试验的安全性及其对运动、语言和记忆功能评估的效果。 方法 本文通过回顾性分析我中心5例行eSAM-Wada试验的难治性癫痫患者,观察操作过程中患者运动、语言及记忆功能的改变和术中的不良反应。结果：5例患者均可完成整个评估流程,智商偏低的患者仍可配合完成。2例患者完成血管超选下的eSAM-Wada试验。3例左利手患者中,2例(66.7%)语言优势侧仍位于左侧半球,2例(100%)右利手患者语言优势侧均位于左侧半球。4例左侧半球病变的患者,2例(50%)记忆的优势侧仍位于左侧颞叶,1例(25%)记忆为双侧优势,1例(25%)记忆优势侧转移至右侧颞叶。2例患者进行了后续切除性手术,1例患者进行了立体定向脑电图电极引导下热凝毁损术,1例患者出现左下肢一过性无力,运动、语言及记忆功能改变均与eSAM-Wada试验预测结果相符。2例患者(40%)出现癫痫发作可能与操作流程中依托咪酯静脉推注给药速度过快有关,后给药速度改为>30秒后,患者再无癫痫发作。不良反应需要进一步观察。结论：eSAM-Wada试验是全面评估运动、语言及记忆评估较为可靠且相对安全的方法。与血管超选技术结合,可以更加有效的指导涉及功能区的颅脑外科手术治疗。由于病例数量有限,结论尚需进一步观察。     

Comparison of etomidate and midazolam for prehospital Rapid-sequence intubation

Objective

This study compares etomidate with midazolam for prehospital rapid-sequence intubation (RSI).

Methods

The authors conducted a retrospective review of consecutive intubations at a university-based air medical program from January 1995 to December 2000. Exclusion criteria were patients not undergoing RSI, age <15 years, and incomplete chart data. Outcome measures included intubation success, incidence of hypotension, and percentage of change in heart rate (HR) and systolic blood pressure (SBP).

Results

The intubation success rate was 110 out of 112 (98%) with etomidate, and 96 out of 97 (99%) with midazolam. Mean ages, patient gender distributions, and initial SBPs and HRs did not differ between the two groups. The mean dose of etomidate was 24 mg, the mean percentage of change in HR was −1% (95% confidence interval [CI], −6 to 4), and the mean percentage of change in SBP was 2% (95% CI, −3 to 7). The mean dose of midazolam was 3.5 mg, the mean percentage of change in HR was 1% (95% CI, −5 to 7), and the mean percentage change in SBP was 3% (95% CI, −3 to 9). The number of hypotensive episodes with etomidate (7 out of 74) compared with midazolam (3 out of 56) did not differ significantly (Fisher's exact test, p = 0.51).

Conclusion

Intubation success rate was very high with both etomidate (98%) and midazolam (99%). There was no statistically significant mean percentage of change in SBP or HR with either agent. The authors found a low incidence of hypotension with both agents, although the mean dose of midazolam used was considerably less than typically recommended for induction.     

地佐辛联合依托咪酯在老年患者无痛胃镜术中应用

目的观察地佐辛联合依托咪酯用于无痛胃镜检查的有效性及安全性。方法行无痛胃镜检查患者184例,随机分为观察组和对照组各92例,对照组静脉注射依托咪酯0．3mg／kg;观察组静脉注射地佐辛30μg／kg,密切观察10min后静脉注射依托咪酯0．2mg／kg;观察2组血流动力学指标,比较2组苏醒时间、定向恢复时间、满意程度评分及不良反应发生情况。结果2组均顺利完成检查,检查期间血流动力学指标稳定;与对照组比较,观察组满意程度评分高,苏醒时间、定向恢复时间短,依托咪酯用量少,术中烦躁发生率低（P〈0．05）。结论地佐辛联合依托咪酯用于老年患者无痛胃镜检查可提高患者的满意程度,降低不良反应发生率。