联合应用顺阿曲库铵与维库溴铵后ED50和ED95的改变

目的：观察顺式阿曲库铵联合维库溴铵用药后ED50和ED95的变化。方法将75例择期手术患者（ASAⅠ~Ⅱ级）随机分为3组：顺式阿曲库铵组、维库溴铵组和顺式阿曲库铵＋维库溴铵组,每组各25例。麻醉诱导后,以单次给药法观察起效时间和T1达到最大抑制的时间,描绘3组患者的量-效曲线,求得各自的ED50和ED95值,并运用等效图法和代数法对两药相互作用进行分析。结果单用顺式阿曲库铵组、维库溴铵组ED50值分别为32.35、28.78μg/kg,ED95值分别为52.67、51.20μg/kg。联合用药时ED50值为16.81、12.17μg/kg,ED95值为23.49、22.16μg/kg,与单独用药相比,差异均有统计学意义。联合用药时ED50和ED95的合用代数值分别为0.942、0.879。结论联合使用顺式阿曲库铵和维库溴铵具有协同作用,且量-效曲线产生左移。     

苯磺顺阿曲库铵合成工艺的优化

目的 对苯磺顺阿曲库铵合成工艺的优化 方法 以3,4-二甲氧基苯乙胺和3,4-二甲氧基苯乙酸为原料,依次经酰化、脱水环化及还原制得四氢罂粟碱。采用半量拆分法,以D-(+)-二对甲基苯甲酰酒石酸为拆分剂,进行拆分,得到R-四氢罂粟碱,经过麦克加成,氮甲基化反应得苯磺酸阿曲库铵。 结果 目标产物结构通过质谱法、核磁共振氢谱、碳谱和DEPT谱对结构进行了确证,产物的纯度经 HPLC检测为99.18 %,总产率为24.79%。结论 优化后的工艺反应条件温和、操作简便,反应产率高,为工业化生产提供了信息和依据。     

预注法联合限时法缩短顺苯磺酸阿曲库铵起效时间疗效观察

目的：研究预注法联合限时法缩短顺苯磺酸阿曲库铵起效时间的效果。方法：成年择期手术全麻患者112例按入院先后顺序分为甲乙丙3组,3组患者均使用芬太尼4μg·kg-1和丙泊酚2 mg·kg^-1作为诱导药。甲组采用预注法联合限时法,患者先静注顺苯磺酸阿曲库铵20μg·kg-1,3 min后再先后注射诱导药和顺苯磺酸阿曲库铵80μg·kg-1;乙组采用预注法,患者先静注顺苯磺酸阿曲库铵100μg·kg-1,1.5 min后注入诱导药;丙组采用限时法,患者先后注入诱导药与顺苯磺酸阿曲库铵l00μg·kg-1。观察比较各组诱导前T1百分比,肌肉颤搐抑制90%和100%的时间、气管插管评级以及药品不良反应。结果：3组患者气管插管优秀率比较,差异无统计学意义（P〉0.05）。与甲、乙组比较,丙组诱导前不存在T1抑制,乙组（9.8±2.6）多于甲组（3.2±1.5）（P〈0.01）;达肌肉颤搐抑制90%与100%时间,丙组明显长于甲、乙两组（P〈0.01）。丙组不良反应发生率明显高于甲、乙两组（P〈0.05）。结论：应用预注法以及限时法,均可有效缩短顺苯磺酸阿曲库铵的起效时间,效果显著,且安全性高。     

Comparison of the variability of the onset and recovery from neuromuscular blockade with cisatracurium versus rocuronium in elderly patients under total intravenous anesthesia

This study was designed to compare the variability of the onset and offset of the effect of two neuromuscular blocking drugs with different elimination pathways in adult and elderly patients during total intravenous anesthesia (TIVA). After Ethics Committee approval and patients'' informed consent, the drugs were compared in 40 adult and 40 elderly patients scheduled for elective surgery under TIVA with tracheal intubation who were randomized to receive a single bolus dose of 0.15 mg/kg cisatracurium or 0.9 mg/kg rocuronium. The time of onset of maximum depression, duration of action, and recovery index time were measured and recorded for each patient and variability is reported as means ± standard deviation. Time of onset was significantly shorter for rocuronium than cisatracurium for the adult and elderly groups (P = 0.000), but the variability of cisatracurium was significantly greater compared with rocuronium for the same age groups (93.25 vs 37.01 s in the adult group and 64.56 vs 33.75 s in the elderly group; P = 0.000). The duration of the effect in the elderly group receiving rocuronium was significantly longer than in the elderly group receiving cisatracurium, and the variability of the duration was significantly greater in the rocuronium group than in the cisatracurium group. Mean time of recovery was significantly longer for the elderly group receiving rocuronium than for the elderly group receiving cisatracurium (P = 0.022), and variability was also greater (P = 0.002). Both drugs favored good intubating conditions. In conclusion, cisatracurium showed less variability in these parameters than rocuronium, especially in the elderly, a fact that may be of particular clinical interest.     

Stabilité physico-chimique des solutions injectables de bésilate de cisatracurium dans les conditions cliniques d’utilisation

Objectives

To assess the stability of cisatracurium besilate solution stored at 5 °C and 25 °C.

Materials and methods

Cisatracurium solutions at 2, 5 and 0.1 mg/mL in 0.9 % sodium chloride or 5 % glucose were exposed to 5 °C and 25 °C under 60 % relative humidity for seven days. The physicochemical stability was assessed at 24, 48 hours and seven days with dosage of the active substance, detection of degradation products and a possible racemization, measuring pH, osmolality and turbidity, assessment of coloration, visible particles and invisible particles count.

Results

Cisatracurium besilate present good stability for 24 hours at 5 °C and 25 °C for concentrations between 0.1 and 5 mg/mL. Beyond 24 hours, the solutions at 2 and 5 mg/mL remained stable for seven days at 5 °C. At 25 °C, potentially toxic degradation products appear in solutions of 0.1 mg/mL between 24 and 48 hours. No racemization was detected, the drug remains in its active form cis.

Conclusion

Cisatracurium solutions at 2 and 5 mg/mL may be stored at 5 °C or 25 °C for seven days. It's advisable to keep the solutions in a dilution of 0.1 mg/mL in 0.9 % sodium chloride or 5 % glucose in the refrigerator. No diluted solution should be stored at room temperature beyond 24 hours.     

体温对老年人顺式阿曲库铵与罗库溴铵恢复时相影响的比较

目的比较不同体温对老年患者术后顺式阿曲库铵和罗库溴铵肌肉松弛恢复的影响。方法择期在全身麻醉下行手术的老年患者80例,随机分为顺式阿曲库铵不保温、顺式阿曲库铵保温、罗库溴铵不保温及罗库溴铵保温组,每组20例。采用全身麻醉联合硬脊膜外腔阻滞麻醉,全身麻醉诱导气管插管时给予顺式阿曲库铵0.15mg/kg或罗库溴铵0.6mg/kg,术中肌肉松弛药经静脉输液泵输注维持,持续监测肌肉松弛和鼻咽温度,记录患者的药物累积剂量,手术时间,静脉注射肌肉松弛药到第1个肌颤搐高度(T1)最大抑制的时间(起效时间),T1从25%恢复到75%的时间(肌肉松弛恢复指数),T1恢复至25%到4个成串刺激(TOF)比值(TOFR,即TOF中第4个肌颤搐高度与T1的比值)恢复至90%的时间(完全恢复时间),以及麻醉诱导时、T1恢复至25%时、TOFR恢复至90%时的温度。结果术毕两个不保温组的体温显著低于两个保温组(P值均<0.01)。顺式阿曲库铵不保温、顺式阿曲库铵保温组的起效时间均显著长于罗库溴铵不保温、罗库溴铵保温组(P值均<0.01),肌肉松弛恢复指数则显著短于罗库溴铵不保温、罗库溴铵保温组(P值均<0.01)。顺式阿曲库铵保温组的完全恢复时间显著短于罗库溴铵保温组(P<0.01)。给予同一肌肉松弛药的两个保温组间起效时间的差异无统计学意义(P>0.05),而肌肉松弛恢复指数和完全恢复时间均显著短于两个不保温组(P值均<0.05)。结论老年患者容易发生术中低体温,保温有助于肌肉松弛的恢复,且应用于顺式阿曲库铵的效果尤佳。     

术中保温对持续输注顺式阿曲库铵代谢的影响

目的:观察患者术中保温对顺式阿曲库铵代谢过程的影响。方法:选择ASA(Ⅰ～Ⅱ)级行择期手术的患者24例,随机分为两组,Ⅰ组为对照组,Ⅱ组为术中保温组。Ⅱ组术中用保温毯保温,术中冲洗用盐水加温至37℃,用输液加温器加温输注液体,Ⅰ组对照组不做上述保温处理。选用四个成串刺激方式监测尺神经-拇内收肌神经传递功能,TOF频率为2Hz,串间间隔15s,刺激电流为50mA,当T1值恢复至10%时持续静脉泵注顺式阿曲库铵,并调节微泵速度,维持T1 10%,至缝合肌层后停止泵注,并记录顺式阿曲库铵的泵注量,T1恢复至25%、75%,TOF 90%的时间和患者的食道温度。结果:两组患者年龄、性别比例、体重差异及顺式阿曲库铵用量的差异均无统计学意义(P>0.05),Ⅰ组患者手术结束时的体温在36℃以下,Ⅱ组患者手术结束时体温在36℃以上。与Ⅰ组患者比较,Ⅱ组患者的肌松恢复时间明显缩短,差异有统计学意义(P<0.05)。结论:手术中对患者进行保温对于药物的代谢消除,减少药物残留造成围术期并发症有着重要的意义。     

Ester und Stereoisomere

This review discusses concepts of isomers, stereoisomers, chirality, and enantiomers as applied to drugs used in anaesthesia. The inhalational anaesthetics enflurane and isoflurane are examples of stereoisomers. A chiral centre is formed when a carbon or quaternary nitrogen atom is connected to four different atoms. A molecule with one chiral centre is then present in one of two possible configurations termed enantiomers. A racemate is a mixture of both enantiomers in equal proportions. Many of the drugs used in anaesthesia are racemic mixtures (the inhalational anaesthestics, local anaesthetics, ketamine, and others). The shape of the atracurium molecule is comparable to that of a dumb-bell: the two isoquinoline groups representing the two bulky ends connected by an aliphatic chain. In each isoquinoline group there are two chiral centres, one formed by a carbon and the other by a quaternary nitrogen atom. From a geometric point of view, the connections from the carbon atom to a substituted benzene ring and from the quaternary nitrogen to the aliphatic chain may point in the same direction (cis configuration) or in opposite directions (trans configuration). The two isoquinoline groups in atracurium are paired in three geometric configurations: cis-cis, trans-trans, or cis-trans. However, the two chiral centres allow each isoquinoline group to exist in one of four stereoisomeric configurations. In the symmetrical atracurium molecule, the number of possible stereoisomers is limited to ten. Among these, 1 R-cis, 1′ R-cis atracurium was isolated and its pharmacologic properties studied. This isomer, named cis-atracurium, offers clinical advantages over the atracurium mixture, principally due to the lack of histamine-releasing propensity and the higher neuromuscular blocking potency. The ester groups appear in one of two steric configurations true and reverse esters. In the true esters, oxygen is positioned between the nitrogen atom and the carbonyl group, while in the reverse esters it is positioned on the other side of the carbonyl group. True esters, suxamethonium and mivacurium, are hydrolysed by the enzyme plasma cholinesterase (butyrylcholinesterase), albeit at different rates. The more rapid degradation of suxamethonium is responsible for its fast onset and short duration of action in comparison with mivacurium. The reverse esters, atracurium, cisatracurium, and remifentanil, are hydrolysed by nonspecific esterases in plasma (carboxyesterases). Remifentanil is hydrolysed rapidly; the degradation leads to its inactivation and short duration of action. Cis-atracurium is preferentially degraded and inactivated by a process known as Hofmann elimination. In a second step, one of the degradation products, the monoester acrylate, is hydrolysed by a nonspecific esterase.     

Effects of cisatracurium on cerebral and cardiovascular hemodynamics in patients with severe brain injury

Background : For neuroanesthesia and neurocritical care the use of drugs that do not increase or preferentially decrease intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) are preferred. The current study investigates the effects of a single rapid bolus dose of cisatracurium on cerebral blood flow velocity, ICP, CPP, mean arterial pressure (MAP) and heart rate (HR) in 24 mechanically ventilated patients with intracranial hypertension after severe brain trauma (Glasgow coma scale 6) under continuous sedation with sufentanil and midazolam.
Methods : Patients were randomly assigned to receive either 2XED95 (n=12) or 4XED95 (n=12) of cisatracurium as a rapid i.v. bolus injection. Before and after bolus administration mean cerebral blood flow velocity (BFV, cm/s) was measured in the middle cerebral artery using a 2–MHz transcranial Doppler sonography system, ICP (mm Hg) was measured using an extradural probe, and MAP (mm Hg) and HR (b/min) were measured during a study period of 20 min. Cerebral perfusion pressure (CPP=MAP–ICP) was also calculated.
Results : Our data show that a single bolus dose of up to 4 × ED95 cisatracurium caused no significant (P<0.05) changes in BFV, ICP, CPP, MAP and HR. Possible histamine-related events were not observed during the study.
Conclusions : The results from this study suggest that cisatracurium is a safe neuromuscular blocking agent for use in adult severe brain–injured patients with increased ICP under mild hyperventilation and continuous sedation.     

顺式阿曲库铵和阿曲库铵用于全麻气管插管腹腔镜胆囊切除术中效果比较

目的 探讨顺式阿曲库铵和阿曲库铵在全麻气管插管腹腔镜胆囊切除术中的肌松效果及不良反应发生情况.方法 回顾性分析2014年2月-2015年10月行全麻气管插管的腹腔镜胆囊切除患者120例的临床资料,根据用药情况分为研究组68例和对照组52例,研究组给予顺式阿曲库铵,对照组给予阿曲库铵.观察2组气管插管完成率、气管插管条件、插管时声门暴露程度及肌松药起效时间,记录诱导前(T1)、插管后1 min(T2)、插管后15 min(T3)时血氧饱和度(SpO2)及心率变化情况,分析2组不良反应发生情况.结果 2组气管插管完成率、气管插管条件及插管时声门暴露程度良好率比较差异无统计学意义(P＞0.05).研究组起效时间长于对照组,总不良反应发生率低于对照组(P＜0.05).2组T1-3时点SpO2、心率组内及组间比较差异均无统计学意义(P＞0.05).结论 顺式阿曲库铵和阿曲库铵均可在全麻气管插管腹腔镜胆囊切除术中发挥理想的肌松效果,但顺式阿曲库铵安全性更高.