Cost analysis of neuromuscular blocking agents in the operating room: cisatracurium, atracurium, vecuronium and rocuronium

Cisatracurium (C), Atracurium (A), Rocuronium (R) and Vecuronium (V) are four neuromuscular blockers (NMB) used in the operating room with similar efficacy, defined as adequate muscle relaxation, but different pharmacokinetics. C and A have organindependent elimination, A is associated with histamine release and R has a shorter onset time. The objective of this study was to economically compare these four NMB from the hospital point of view in order to facilitate drug selection. A cost analysis was performed. Only direct costs were considered and data were collected through a retrospective chart review. A total of 151 patient charts were randomly selected. Differences between patients receiving one of the four NMB were evaluated by ANOVA or KruskalWallis tests. Then a multiple linear regression analysis was conducted. In the chart review, no significant difference was observed between the four groups of patients in age, weight or surgery duration (p>0.05). Multiple regression analysis revealed that atracurium was on average PTA 237 (1 Euro = PTA 166) cheaper per surgery than any other NMB after adjusting for other factors (p<0.01) and there is no significant difference in cost between the other three NMBs (p>0.1). We recommend the use of rocuronium when a quick onset is needed and the patient does not have hepatic failure, cisatracurium when a haemodynamic instability is possible and atracurium in the remaining cases. If just one NMB can be included in the drug formulary we would select cisatracurium due to its pharmacological advantages over atracurium with a small increment in cost.     

Kinemyography (KMG) versus Electromyography (EMG) neuromuscular monitoring in pediatric patients receiving cisatracurium during general anesthesia

Aim of the workTo compare KMG versus EMG neuromuscular monitoring in pediatric patients receiving cisatracurium during general anesthesia.MethodsAfter approval of the protocol by Ethics Committee 24 pediatric patients of both sexes aged 2–6 years, with a maximum weight 20 kg, were included in the study. Monitoring equipments (Datex-Ohmeda A/S 5?) were attached to the patient. The electromyogram was attached to one hand, while, KMG was attached to the other hand for simultaneous monitoring. Induction of anesthesia with fentanyl 2 μg/kg and propofol 2 mg/kg followed by endotracheal intubation. Anesthesia was maintained by end-tidal isoflurane 1.2%. Ventilation was kept by 50% oxygen in air and was adjusted to maintain end-tidal CO₂ in the range of 35–40 mm Hg. After a stable baseline period of at least 3 min, the 24 patients were received 0.1 mg/kg cisatracurium twice the 95% effective dose (2 × ED₉₅). The following parameters were collected and compared; (1) lag time (time from start of muscle relaxant administration until the first measurable neuromuscular block (NMB), (2) onset time (time from start of muscle relaxant administration until maximal NMB), (3) assessing the recovery period by; train of four (TOF) 0.25, 0.50, 0.75 and 0.90 (time to reach a TOF ratio of 25%, 50%, 75% and 90%, respectively). No top-up doses of muscle relaxants were given.ResultsThere was no statistical difference between both studied groups as regard the demographic data of the patients, the lag time, the onset time, TOF 0.25, 0.5, 0.75 and 0.9 ratios using either EMG or KMG. In addition, there is excellent degree of agreement between EMG and KMG in measuring TOF ratio during both induction and recovery of muscle relaxants.ConclusionsKMG showed an excellent degree of agreement with EMG for determination of onset and recovery of NMB in children.     

顺式阿曲库铵对兔定量药物脑电图δ、θ频段的影响

目的探讨顺式阿曲库铵对兔定量药物脑电图(QPEEG)δ、θ频段的影响。方法采用QPEEG功率谱分析法,分析兔静脉注射顺式阿曲库铵0.3mg/kg前后δ、θ频段功率百分比的变化。结果与给药前相比,枕区δ频段功率百分比在给药后各时间点均增加(P<0.05或P<0.01),而其它各脑区δ频段功率百分比的变化差异均无统计学意义(P>0.05)。与给药前相比,各脑区θ频段功率百分比在给药后各时间点均有所增加,其中枕区和颞区增加最明显(P<0.05或P<0.01)。结论顺式阿曲库铵能够增大兔QPEEG枕区δ频段功率百分比及各脑区θ频段功率百分比。     

Storage at room temperature does not change cisatracurium onset time: a prospective, randomized, double-blind controlled study

Objective

Storage of cisatracurium at room temperature seems to have no effect on its degradation in vitro contrary to the recommendations of storage at +4 °C. The purpose of this study was to evaluate the influence of cisatracurium’ s storage temperature on its onset time.

Study design

Prospective, randomized, double-blind trial study.

Patients and methods

Thirty patients were enrolled. The control group consisted of 15 patients receiving cisatracurium (0.15 mg/kg) stored at room temperature and the intervention consisted of 15 patients receiving cisatracurium (0.15 mg/kg) stored at +4 °C. The primary endpoint was to compare cisatracurium onset time depending on the storage temperature.

Results

Cisatracurium onset time was 235 (180–292) seconds in the “room temperature” group vs. 240 (210–292) seconds in the “refrigerated” group. There was no difference between the onset of cisatracurium depending on the temperature of storage (p = 0.51). Subgroups analysis in the “room temperature” group did not show any difference in cisatracurium onset depending on whether it was stored at room temperature for one, two or three weeks. Excellent intubation score was obtained for 100% of the patients.

Conclusion

This study demonstrated that cisatracurium's storage at room temperature had no influence on its onset time. It provides an argument for the preservation of cisatracurium at room temperature for a period not exceeding 21 days. Monitoring the onset of curarization may increase the quality score of intubation.     

新斯的明拮抗老年患者术后肌松药残留阻滞作用的量效研究

目的 研究老年患者术后使用新斯的明拮抗顺式阿曲库铵肌松药残留阻滞作用的量效关系。方法 选择深圳市第二人民医院2013年2~9月在全凭静脉麻醉下行腹腔镜胆囊摘除术的老年患者80例,分为4组,每组各20例,即T0,T5,T10和T20组。术后当4个成串刺激比值(TOFR)恢复至0.5时,T5,T10和T20组患者分别静脉注射新斯的明5,10,20μg/kg,而T0组注射生理盐水。记录TOFR恢复到1.0的时间,记录给药前及给药后第3、5、10分钟的心率(HR),血压(BP)的变化,计算各组10 min内TOFR成功恢复到1.0的百分率,以及术后6 h恶心呕吐的发生率。结果 1T0组比较,T20组TOFR恢复到1.0时间明显缩短,T20组中10 min内TOFR成功恢复到1.0的百分率增加,差异有统计学意义(P<0.05);而T5组及T10组在TOFR恢复到1.0时间以及10 min内TOFR成功恢复到1.0的百分率与T0组比较,差异无统计学意义(P>0.05)。2T20组在第3、5、10分钟的HR与给药前比较明显降低,差异有统计学意义(P<0.05)。T0组、T5组及T10组在给药前后HR变化差异无统计学意义(P>0.05),各组给药前后BP变化差异无统计学意义(P>0.05)。3各组术后6 h恶心呕吐发生率差异无统计学意义(P>0.05)。结论 在老年患者腹腔镜胆囊切除术后,当TOFR恢复至0.5时,使用20μg/kg新斯的明可有效的拮抗顺式阿曲库铵的残留作用,20μg/kg剂量新斯的明可导致老年患者心率减慢,但不增加术后恶心呕吐发生率。     

增大顺阿曲库铵剂量与罗库溴铵麻醉诱导效果的比较

目的通过观察不同剂量顺阿曲库铵的起效时间、临床有效时间的变化,并与罗库溴铵比较,为临床手术患者个体化选择肌松药物及剂量提供理论依据。方法ASAI～Ⅱ级择期妇科手术女性患者120例,随机分为4组,每组30例,分别予顺阿曲库铵0．1mg／kg（A组）、0．15mg／kg（B组）、O．2mg／kg（c组）和罗库溴铵0．9mg／kg（D组）,咪达唑仑、芬太尼、异丙酚诱导麻醉,观察心率、血压和全身皮肤情况以及TOF的变化,并进行气管插管条件评级。结果各组肌松药起效时间分别是（226±57）s、（184±56）s、（135±45）s、（80-．I-25）S,C组分别与A、B、D相比较均有统计学意义（P〈0．05）;各组临床有效时间分别是（334±5）min、（41±8）min、（534±8）min、（42±11）min,C组分别与A、B、D相比较差异均有统计学意义（P〈0．05）。c组临床有效时间的离差与D组相比较差异有统计学意义（P〈0．05）。结论增大剂量法明显缩短顺阿曲库铵的插管起效时间,但与罗库溴铵相比,临床作用时间延长,便不适于短小外科手术的麻醉,而罗库溴铵临床作用时间的变异性较大,顺阿曲库铵的可控性优于罗库溴铵。     

Die klinische Pharmakologie von Cisatracurium

Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED₉₅ of cisatracurium was determined to be about 50?μg/kg (cation, molecular weight 929), while the ED₉₅ of atracurium (besylate salt, molecular weight 1245) was 250?μg/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED₉₅ of about 40?μg/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145?h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio >0.7 (68±18?min) was on average only some 70% longer than after an infusion of cisatracurium for 2?h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED₉₅.     

Die klinische Pharmakologie neuer Benzylisochinolin-Diester-Verbindungen Unter besonderer Berücksichtigung von Cisatracurium und Mivacurium

The benzylisochinoline muscle relaxants have a highly selective affinity to the motor endplate which is associated with an absence of autonomic side effects such as ganglionic and vagus block. The requirement of only low clinical doses also reduces histamine liberation. Muscle relaxants with high neuromuscular blocking potency have a slow onset. Both atracurium and cisatracurium undergo Hofmann-Elimination in the plasma whereas mivacurium is hydrolyzed by pseudocholinesterase. The difference in kinetics between these pathways render atracurium and cisatracurium muscle relaxants of intermediate duration of action while mivacurium is short acting. Cisatracurium, one of the ten stereoisomeres of atracurium, is 3 to 4 times as potent as atracurium, does not release histamine, has no cardiovascular side effects and, due to the small clinical doses resulting from its high neuromuscular blocking potency, produces only negligible quantities of laudanosine. Its ED₉₅ is 0.05 mg/kg. Good intubation conditions can be expected within 1.5 to 2 min following 3- to 4-times the ED₉₅. Thereafter is takes about 65 min for T1 to recover to 25% of control. Maintenance doses of 0.02 to 0.04 mg/kg have a duration of action of 15 to 20 min. An infusion of cisatracurium of 1.0 to 2.0 mcg/kg/min, is adequate to maintain a 90 to 95% neuromuscular block. The time of recovery is largely independent on the total dose of cisatracurium administered by either repeated injection or infusion. – Mivacurium is a racemate of 3 stereoisomeres of which the trans-trans- and the cis-trans-compound account for 95% of the neuromuscular blocking effect. In adults the ED₉₅ is 0.08 mg/kg. The ensuing recovery of T1 to 25% of control is about 15 min. Rapid injection of 3×ED₉₅ may transiently lower the arterial blood pressure and may produce skin flushing in an incidence of 30 to 40%. Larger doses should be injected slowly with 30 to 60 s. The onset of mivacurium neuromuscular block following 3×ED₉₅ is relatively slow (2 min). Maintenance doses of 0.05 to 0.1 mg/kg have a duration of action of 5 to 10 min. A 95% neuromuscular block may be maintained by an infusion of 3 to 12 μg/kg/min. The time of recovery does not depend on the total cumulative dose given by either repeated injection or by infusion. The duration of mivacurium neuromuscular block may be drastically prolonged in the presence of low or atypical plasmacholinesterase. Both neostigmine and edrophonium are suitable reversal agents. ? None of the presently available benzylisochinoline muscle relaxants has the potential to completely replace succinylcholine.     

预注不同剂量顺式阿曲库铵对其起效时间的影响

目的探讨预注不同剂量顺式阿曲库铵对其起效时间的影响。方法选择2014年11月至2015年4月南京医科大学第一附属医院择期手术全麻患者80例,男41例,女39例,年龄18~60岁,随机均分为四组,每组20例。对照组(C组)预注生理盐水3 ml,C1组、C2组、C3组分别预注顺式阿曲库铵15、30、50μg/kg,1min后再分别静脉注射剩余剂量顺式阿曲库铵0.15、0.135、0.12、0.10mg/kg,麻醉诱导顺序静脉注射咪达唑仑0.05mg/kg、芬太尼5.0μg/kg、依托咪酯0.3mg/kg,采用四个成串刺激(TOF)监测,记录静脉注射剩余插管剂量后T4/T1=0的时间,记录呼吸困难、荨麻疹、心律失常等不良反应的情况。结果C3组起效时间为(114.2±14.1)s,明显短于C2组(136.3±28.1)s、C1组(164.6±26.9)s和C组(165.9±10.8)s(P0.01)。四组患者均未见呼吸困难、荨麻疹、心律失常等不良反应。结论与顺式阿曲库铵15和30μg/kg比较,顺式阿曲库铵50μg/kg预注能明显缩短肌松起效时间。     

顺式阿曲库铵预注射联合无通气诱导在全麻剖宫产中的应用

目的：探讨顺式阿曲库铵预注射联合无通气快速诱导用于全麻剖宫产术的安全性和可行性。方法拟行全麻下剖宫产手术的产妇22例,诱导前给予1/8-1/10诱导剂量的顺式阿曲库铵预注射,面罩吸入纯氧3min后行静脉快速诱导,诱导期间不实施正压辅助通气,观察并记录诱导前后HR、SpO2、BP的变化及诱导过程中呛咳、呕吐、返流、误吸发生率。结果T0、T1、T2与T3各时点的SpO2分别为（96.57±0.61）%、（98.78±0.42）%、（97.94±0.35）%和（99.63±0.14）%。诱导过程平稳,气管插管前后SpO2无显著变化;诱导过程中无缺氧、呕吐、返流、误吸发生,且插管条件较为理想。结论对拟行全麻剖宫产的非困难气道产妇,采用顺式阿曲库铵预注射联合无通气快速诱导技术是安全、可行的。