Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique)

Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them.     

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.     

Postoperative Resistenzentwicklung gegenüber Atracurium

Zusammenfassung Zwei F?lle einer postoperativ aufgetretenen Atracuriumresistenz werden vorgestellt. In beiden F?llen handelte es sich um Patienten, welche nach einem intrathorakalen Elektiveingriff eine septische Komplikation entwickelten. Kasuistik: Beim ersten Patienten (39 Jahre) entwickelte sich wenige Tage nach einer Pneumonektomie eine Bronchusfistel mit einer Superinfektion der Thoraxresth?hle. Zum Zeitpunkt des Revisionseingriffs war die Wirkung von Atracurium im Vergleich zur Prim?roperation deutlich ver?ndert: Die Anschlagzeit war verl?ngert (7 vs. 3,5 min), die Erholungszeit (DUR 10%) war verkürzt (14 vs. 28 min), und die Infusionsrate zur Aufrechterhaltung der Relaxation mu?te um ca. das 3fache gesteigert werden (14,3 vs. 5,0 μg/kg·min). Beim zweiten Patienten (56 Jahre) kam es im Anschlu? an eine Oberlappenresektion rechts zu einer Gangr?n des Mittellappens, welcher operativ entfernt werden mu?te. Die zur Intubation erforderliche Atracuriumdosis mu?te im Vergleich zur Prim?roperation deutlich gesteigert werden (70 vs. 40 mg), ohne da? hierdurch eine komplette neuromuskul?re Blockade zu erzielen war. Darüber hinaus war zur Ruhigstellung des Patienten eine wesentlich h?here Erhaltungsdosis als beim Ersteingriff erforderlich (11,8–16,5 vs. 5,5 μg/kg·min). Schlu?folgerung: Die Beispiele zeigen, da? sich innerhalb relativ kurzer Zeit eine Resistenz gegenüber Atracurium entwickeln kann, und wir nehmen an, da? diese Ver?nderungen durch die schweren, entzündlichen Komplikationen ausgel?st wurden.      

Quantitative determination of atracurium in human plasma using high-performance liquid chromatography

The authors have established a new method for extraction and determination of atracurium in human plasma that employs a reversed phase high-performance liquid chromatography (HPLC). This method made use of a fluorescent spectrophotometer at an excitation wavelength of 240nm and an emission wavelength of 310nm. The mobile phase was made of a phosphate buffer, distilled water and acetonitrile (20V:30V:50V). The analytical column used was a Little Champ C₁₈.In a Bond Elute C₁₈ extraction column, which had been prewashed with a phosphate buffer and a 50% methanol solution, atracurium was extracted from acidified plasma samples using a mixture of methanol and phosphate buffer. A standard curve was prepared by the internal standard method using metocurine. A high linear correlation between atracurium concentration and the ratio of the atracurium peak height to the metocurine peak height was observed (r = 0.9994). The lowest threshold for detection of atracurium was 15ng/ml. When the plasma concentrations of atracurium were determined in 2 clinical cases, t_1/2 was 2.10 and 1.73min and t_1/2 was 15.57 and 21.57min, respectively. These results indicate that this method of extraction and determination is appropriate for studying the pharmacokinetics of atracurium because it allows a high reproducibility, and provides an extremely accurate, simple and quick analysis.(Okutani R, Kono K, Frederic M. deBros et al.: Quantitative determination of atracurium in human plasma using high-performance liquid chromatography. J Anesth 2: –, 1988)     

The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat

Sevoflurane was compared to isoflurane anesthesia alone and in combination with atracurium or vecuronium in 84 rats using the sciatic nerve—anterior tibialis muscle preparation. Both bolus injection and infusion rate techniques were used to evaluate these drug interactions. The ED₅₀ (dose which produced a 50% depression of twitch tension) of atracurium was 311 ± 31 and 360 ± 32µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The ED₅₀ of vecuronium was 190 ± 27 and 149 ± 14µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The mean infusion rates of atracurium and vecuronium required to maintain a 50% depression of twitch tension were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1. These infusion rates were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1 during 1.25MAC sevoflurane and 3.73 ± 0.3 and 1.81 ± 0.4mg·kg^–1·hr^–1 during 1.25MAC isoflurane anesthesia respectively. With both atracurium and vecuronium, the infusion rate required to maintain a 50% depression twitch of tension was inversely related to the concentrations of isoflurane and sevoflurane. The authors conclude that sevoflurane is similar in potency to that of isoflurane in augmenting a vecuronium or atracurium induced neuromuscular blockade in a dose-dependent manner.(Shin YS, Miller RD, Caldwell JE, et al.: The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat. J Anesth 6: 1–8, 1992)     

常温不同贮存时间对国产顺阿曲库铵肌松效应的影响

目的 评价常温不同贮存时间对国产顺阿曲库铵肌松效应的影响.方法 择期全麻手术患者120例,年龄18～64岁,性别不限,ASA分级Ⅰ或Ⅱ级,BMI＜ 30 kg/m2,采用随机数字表法,将患者分为3组(n=40):低温60d组(LT组)、室温30 d组(RT30组)和室温60 d组(RT60组).顺阿曲库铵置于冰箱4～8 ℃贮存60 d(LT组)、室温21 ～ 24℃存放30 d(RT30组)或60 d(RT60组).采用TOF-Watch SX肌松监测仪,采用单次超强电刺激观察拇内收肌的肌松程度.待患者麻醉诱导意识消失时静脉注射顺阿曲库铵0.2 mg/kg,当肌颤搐达到最大抑制时行气管插管.记录顺阿曲库铵起效时间、肌颤搐最大抑制程度、临床作用时间、恢复指数和75％恢复时间.评价气管插管条件,记录低血压、心动过缓和皮肤过敏的发生情况.结果 与LT组比较,RT30组顺阿曲库铵起效时间、临床作用时间、恢复指数、75％恢复时间差异无统计学意义(P＞0.05),RT60组起效时间延长,临床作用时间和75％恢复时间缩短(P＜0.05),恢复指数差异无统计学意义(P＞0.05).与RT30组比较,RT60组起效时间延长,临床作用时间缩短(P＜0.05).3组气管插管条件均为优良,且差异无统计学意义,3组低血压和心动过缓发生率比较差异无统计学意义(P＞0.05),均未发生皮肤过敏.LT组和RT30组最大肌颤搐抑制均达到100％,RT60组除1例最大肌颤搐抑制程度为95％外,其余均达到100％.结论 室温贮存30 d对国产顺阿曲库铵肌松效应无明显影响,而贮存60 d可降低其肌松效应.     

罗库溴铵和阿曲库铵联合应用的肌松效应分析

目的探讨罗库溴铵和阿曲库铵联合应用时的肌松效应。方法择期全麻手术女性成年患者147例,丙泊酚和舒芬太尼静脉诱导,输注丙泊酚维持麻醉。面罩辅助或控制呼吸,用加速度仪以连续4次刺激(TOF)方式透皮刺激腕部尺神经,获取肌松药作用起效时间和T1最大抑制程度(Tmax)。按观测项目将患者均分成四组。结果阿曲溴铵ED95为(220.8±3.6)μg/kg,罗库溴铵ED95为(286.3±3.1)μg/kg。0.5×ED95的罗库溴铵与阿曲库铵联合使用,肌松效应达到T1抑制93%~97%时,阿曲库铵的剂量为63.6μg/kg。罗库溴铵0.5×ED95与阿曲库铵63.6μg/kg联合使用,Tmax为(95.3±0.9)%,变异系数1.0%。Ⅳ组中三个亚组的Tmax基本相同,合用组作用起效时间比阿曲库铵组快(P<0.01)。给予肌松药前和注药后5min内,MAP和HR的波动幅度均小于5%。结论罗库溴铵与阿曲库铵合用呈协同作用。当罗库溴铵剂量为0.5×ED95时,为获得T1抑制95%的肌松效应,阿曲库铵的合理用量为63.6μg/kg,比阿曲库铵的ED95减少71.2%。     

丙泊酚、瑞芬太尼复合阿曲库铵加高频喷射通气在小儿气管异物取出术的应用

目的研究丙泊酚、瑞芬太尼复合阿曲库铵加高频喷射通气用于小儿气管异物取出术的临床效果。方法随机选择行气管异物取出术患儿40例，分为丙泊酚、瑞芬太尼复合阿曲库铵（P组）和氯胺酮联合r-羟基丁酸钠（R组）各20例。两组均采用高频喷射通气，比较其手术时间、苏醒时间、术中术后心率（HR）、血氧饱和度（SpO2）、血压（BP）的变化及发生呛咳、屏气呼吸暂停、支气管痉挛的次数、最低SpO2。结果两组HR、SpO2、BP和手术时间无显著差异，但R组置镜、退镜时屏气，术中屏气、呛咳、支气管痉挛和最低SpO2的例数等明显高于P组（P〈0．05），且苏醒时间较P组明显延迟（P〈0．05）。结论丙泊酚、瑞芬太尼复合阿曲库铵加高频喷射通气是小儿气管异物取出术的的一种较为安全可行的麻醉方法。     

急性高容量血液稀释对全麻患者顺式阿曲库铵药效学的影响

目的 探讨急性高容量血液稀释(AHH)对全麻患者顺式阿曲库铵药效学的影响.方法 择期腹部手术患者印例,年龄18～60岁,ASAI或Ⅱ级,随机分为对照组(C组)和AHH组,每组30例,各组按顺式阿曲库铵首剂量(首剂量分别为30、40、50μg/kg,总用量100 μg/kg)分为3个亚组,每亚组10例.采用TOF-Wateh~(R)SX肌松监测仪监测神经肌肉阻滞情况.AHH组经30～40 min静脉输注6%羟乙基淀粉130/0.4 15 ml/kg行血液稀释,AHH后各亚组分别给予首剂量顺式阿曲库铵,当T_1达最大抑制后再注入余量.记录肌松起效时间、临床肌松作用时间、体内作用时间及恢复指数.采用概率单位法计算T_1抑制50%、90%、95%时顺式阿曲库铵的用量(ED_(50)、ED_(90)、ED_(95).结果 与C组比较,AHH组顺式阿曲库铵ED_(50)、ED_(90)、ED_(95)升高,肌松起效时间延长,临床肌松作用时间及体内作用时间缩短(P<0.05或0.01),恢复指数差异无统计学意义(P>0.05).结论 AHH可降低顺式阿曲库铵的肌松效应.     

不同性别患者预注顺阿曲库铵加快起效的半数有效剂量

目的 探讨不同性别患者预注顺阿曲库铵加快起效的半数有效剂量(ED50).方法 择期拟在全身麻醉下行腹部手术的患者90例,年龄18～55岁,分为2组(n=45):男性组(M组)和女性组(F组).采用TOF-Watch SX型加速度肌松监测仪对尺神经行单次颤搐刺激,监测拇内收肌肌颤搐情况.静脉注射咪达唑仑0.04 mg/kg、芬太尼1 μg/kg,患者意识消失后开启加速度肌松监测仪,静脉注射顺阿曲库铵预注剂量,3 min后静脉注射芬太尼5 μg/kg、异丙酚2 mg/kg,静脉注射预注量后4 min,静脉注射顺阿曲库铵剩余插管剂量(3×ED95即0.15 mg/kg减去预注量),当单刺激颤搐值与对照值的比值下降至10%,行气管插管.静脉输注异丙酚、瑞芬太尼,吸入异氟烷维持麻醉.预注量根据序贯法确定,预注量从5μg/kg(10%ED95)开始,各相邻剂量比值为1.2.记录给予预注量后4min时单刺激颤搐值与对照值的比值、90%起效时间、起效时间、最大阻滞程度、临床作用时间.计算预注顺阿曲库铵加快起效的ED50及其95%可信区间(CI).结果 M组90%起效时间长于F组(P＜0.05),其余肌松效应指标两组比较差异无统计学意义(P＞0.05).预注顺阿曲库铵加快起效的ED50:男性为21.36μg/kg,95%CI为20.52～22.23μg/kg;女性为14.53 μg/kg,95%CI为13.77～15.33μg/kg,男性高于女性(P＜0.05).结论 预注顺阿曲库铵加快起效的ED50:男性为21.36μg/kg,女性为14.53 μg/kg,男性高于女性.