Influência de diferentes anestésicos locais no bloqueio neuromuscular produzido pelo atracúrio em ratos

IntroductionThe association between Local Anesthetics (LAs) and Neuromuscular Blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose‐dependent manner and may potentiate the effects of NMB drugs.ObjectiveThe aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium.MethodsMale Wistar rats, weighing from 250 g to 300 g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 μg.mL^‐1 (Group I); racemic bupivacaine 5 μg.mL^‐1 (Group II); atracurium 20 μg.mL^‐1 (Group III); atracurium 20 μg.mL^‐1 in a preparation previously exposed to lidocaine 20 μg.mL^‐1 and racemic bupivacaine 5 μg.mL^‐1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane Potentials (MP) and Miniature Endplate Potentials (MEPPs).ResultsLidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive.ConclusionsLidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.     

剖宫产术患者瑞芬太尼-异丙酚-阿曲库铵复合麻醉的效果

目的 探讨瑞芬太尼-异丙酚-阿曲库铵复合麻醉用于剖宫产术患者的效果.方法 全麻剖宫产术患者40例,ASA Ⅰ或Ⅱ级.麻醉诱导:静脉注射瑞芬太尼1 μg/kg、异丙酚1.5 mg/kg和阿曲库铵0.6 mg/kg,气管插管后行机械通气.麻醉维持:静脉输注瑞芬太尼0.15 μg·kg~(-1)·min~(-1),异丙酚4 mg·kg~(-1)·~(-1),间断静脉注射阿曲库铵0.3 mg/kg.取新生儿脐动脉(UA)血样1 ml行血气分析,取UA、脐静脉(UV)和母体动脉(MA)血样各2 ml,以气相色谱.质谱法测定血浆瑞芬太尼浓度(CUV、CUA和CMA).于气管插管前、气管插管即刻、切皮即刻、拔除气管导管即刻记录血液动力学指标,记录苏醒时间和术者满意情况,术后随访术中知晓情况.行新生儿Apgar评分和神经行为学评分(NBNA).结果 所有患者各时点血液动力学平稳,均在正常范围波动.苏醒时间为(5±4)min,未见术中知晓发生.新生儿UA血气分析结果均在正常范围内.新生儿1、5、10 min Apgar评分均大于7分,NBNA均正常.CUV、CUA和CMA分别为(0.65±0.14)、(0.22±0.09)、(0.86±0.25)ng/ml,CUV/CMA和CUA/CUV分别为0.7±0.4和0.35±0.11.结论 瑞芬太尼-异丙酚-阿曲库铵复合麻醉用于削宫产术患者效果良好,对新生儿无不良影响.     

丙泊酚-七氟醚静吸复合麻醉对阿曲库铵药效学的影响

目的 观察七氟醚对阿曲库铵肌松效应的影响.方法 68例择期腹部手术的全麻患者,ASA Ⅰ或Ⅱ级,年龄18～67岁,随机均分为丙泊酚-七氟醚静吸复合麻醉组(七氟醚组)和丙泊酚静脉麻醉组(对照组).监测腩电双频指数(BIS),使用加速度肌松监测仪刺激前臂尺神经,观察拇内收肌的收缩反应,记录阿曲库铵的起效时间、无反应时间、肌松维持时间以及恢复指数等指标.结果 两组肌松起效时间、无反应时间以及T1 25%时间差异无统计学意义,但七氟醚组25%四个成串刺激比(TOFr)恢复时间、恢复指数及拔管时间均比对照组明显延长(P<0.05).结论 七氟醚麻醉能明显增强阿曲库铵的肌松效应.     

维库溴铵和阿曲库铵对骨骼肌细胞膜上成人型和胚胎型乙酰胆碱受体的作用

目的 比较维库溴铵和阿曲库铵对骨骼肌细胞膜上成人型乙酰胆碱受体(ε-nACHR)和胚胎型乙酰胆碱受体(γ-nAChR)的作用。方法先在HEK 293细胞膜上应用脂质体转染技术表达ε—nACHR和γ-nAChA,再采用全细胞膜片钳技术比较维库溴铵和阿曲库铵与这两种受体作用引起峰电流的变化。结果维库溴铵和阿曲库铵均能竞争性抑制ε-nACHR和γ-nAChR。抑制ε-hACHR两药的IC50依次为8.3±2.6和(2,4.2±10.5)μmol/L;抑制γ-nAChR的IC50依次为55.0±28.4和(183.2±39.2)μmol/L。结论 维库溴铵对ε—nACHR和γ-nAChR抑制作用强于阿曲库铵;γ-nAChR对维库溴铵和阿曲库铵的敏感性均低于ε-nACHR。     

不同体温对兔不同剂量顺式阿曲库铵肌松效应的影响

目的 评价不同体温对兔不同剂量顺式阿曲库铵肌松效应的影响.方法 健康成年新西兰大白兔72只,体重2.0～2.2 kg,雌雄各半,随机分为低体温组(L组)、常温组(N组)和高体温组(H组),每组24只,各组直肠温度依次为34.5、38.5和41.8℃,各组随机分为4个亚组,L<1～4组、N1～4组和H1～4组,每组6只.各亚组分别于直肠温度稳定20 min后静脉注射顺式阿曲库铵0.33、0.66、0.99和1.32 mg/kg,于改变动物体温前5 min、给药前2 min、给药后5、10、30、60、90 min时监测平均动脉压(MAP)、心率(HR)及直肠温度,记录肌松起效时间、从注药毕到T1恢复至基础值5%、25%和95%的时间及恢复指数.结果 不同体温下相同剂量组间比较:与N组比较,H组肌松起效时间、从注药毕到T1恢复至基础值5%、25%和95%的时间及恢复指数缩短,L组延长(P<0.05或0.01);相同体温下不同剂量组间比较:随顺式阿曲库铵剂量增加,各组肌松起效时间缩短、从注药毕到T1恢复至基础值5%、25%和95%的时间延长(P<0.01);剂量与体温因素的交互作用对起效时间的影响差异有统计学意义(P<0.01);相同剂量不同体温下MAP、HR比较:与N组比较,H组各时点MAP降低、HR升高,L组各时点MAP、HR升高(P<0.05或0.01).结论 体温升高时顺式阿曲库铵的肌松效应降低,体温降低时顺式阿曲库铵的肌松效应升高;相同体温下顺式阿曲库铵(0.33～1.32 mg/kg)的肌松效应呈剂量依赖性;两因素间存在交互作用.     

Efficacy of different doses of atracurium on intubating conditions of burned patients

BackgroundBurned patients exhibit resistant response to nondepolarizing muscle relaxants. This study was designed to investigate the efficacy of high dose atracurium (3 and 4 times ED95) with and without application of the priming principle on the intubating conditions and the onset times in burned patients.MethodsASA physical status I and II patients undergoing burn related surgery, were randomly allocated into one of four groups of 20 patients each. Group I received 1 ml placebo followed 3 min later by atracurium 0.75 mg/kg, group II received atracurium 0.04 mg/kg as the priming dose followed 3 min later by atracurium 0.71 mg/kg, group III received 1 ml placebo followed 3 min later by atracurium 1 mg/kg and group IV received atracurium 0.04 mg/kg as the priming dose followed 3 min later by atracurium 0.96 mg/kg. Datex relaxograph was used at the adductor pollicis to monitor and record the twitch response to the train of four (TOF) stimulation.ResultsThe conditions for intubation improved significantly with increasing the dose of atracurium, as we seen, when comparing patients in group IV and group I. Onset times were significantly delayed in groups I and II compared with groups III and IV.ConclusionCombinations of 4 times ED95 of atracurium together with the application of the priming principle are required to overcome the resistance and produce satisfactory intubating conditions in burned patients.     

The infusion requirements and recovery characteristics of cisatracurium or atracurium in intensive care patients

Objective To investigate the infusion requirements and recovery characteristics of cisatracurium compared with atracurium when both are administered by prolonged continuous infusion.Design A prospective, randomised, single-blind study.Settings The Intensive Care Unit of the Manchester Royal Infirmary.Patients 20 patients requiring a continuous infusion of a neuromuscular blocking agent to facilitate mechanical ventilation. 12 patients received cisatracurium and 8 received atracurium.Interventions Cisatracurium or atracurium was administered by continuous infusion for a minimum of 24h. The level of neuromuscular blockade was measured by recording the train-of-four responses using acceleromyography, the aim being to maintain 1–2 twitch responses of the adductor pollicis. At the end of the infusion period, the train-of-four was recorded until the ratio was greater than 0.7.Measurements and results The mean infusion rate of cisatracurium was 0.23 mgkg^–1 h^–1, compared to 0.62 mgkg^–1 h^–1. No time-related increase in infusion requirements was seen for either drug. The mean recovery time to a train-of-four ratio greater than 0.7 was the same (46 min). There was no correlation between recovery time and age, duration of infusion or mean infusion rate.Conclusions Cisatracurium provides a satisfactory level of neuromuscular blockade in adult ICU patients at approximately one-third the infusion rate of atracurium and with a similar recovery time.This work was completed with the support of a grant from the Wellcome Foundation ple     

室温对阿曲库铵制剂的药物效价的影响

本文研究了室温保存和低温保存的阿曲库铵的累积剂量单位－效应曲线。选择ＡＳＡⅠ～Ⅱ级的择期手术病人２０例，麻醉维持为Ｎ２Ｏ－硫喷妥钠－芬太尼。结果表明，室温保存的阿曲库铵的ＥＤ５０和ＥＤ９５值显著大于低温保存的阿曲库铵（Ｐ＜０．０５）。本研究认为阿曲库铵应严格按照低温保存，才能保持其药物效价。     

The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

阿曲库铵与哌库溴铵在预注法中的复合应用

目的 观察阿曲库铵和哌库溴铵在预注法中的复合应用。方法 选择平衡麻醉下择期手术病人70例。研究分两部分：第一部分，将30例病人随机均分为阿曲库铵组和哌库溴铵组，采用累计给药法建立两药量一效关系曲线，计算ED50和ED95；第二部分，根据两药ED95将另40例病人随机均分为单纯阿曲库铵预注组和复合哌库溴铵预注组。观察预注期间肌颤搐抑制值、起效时间和临床作用时间。结果 阿曲库铵ED50和ED95分别为117．5μg／kg和272．8μg／kg，哌库溴铵ED50和ED95分别为23．7μg／kg和42．6μg／kg；复合哌库溴铵预注组起效快于单纯阿曲库铵预注组；复合哌库溴铵预注组临床作用时间长于单纯阿曲库铵预注组。结论 在预注法中采用化学结构不同的肌松药可进一步加快起效，延长临床作用时间。