Primingtechnik mit Cisatracurium

OBJECTIVE: Priming can significantly shorten the onset of nondepolarizing neuromuscular blocking agents (NNBA) measured at the adductor pollicis muscle (APM). In spite of the known risks, priming is very popular especially in cases where NNBAs with a long onset time are used. However, there are no data regarding the onset of action for a priming technique measured at the laryngeal muscles although these muscles are of great importance for conditions of intubation and patient safety. The aim of this study was to compare a bolus application and a priming technique with respect to the laryngeal onset time and peak effect. PATIENT AND METHODS: After approval of the local ethics committee and written informed consent, 36 patients undergoing elective thyroid surgery were enrolled in the study. Anesthesia was induced and maintained with a target controlled infusion of propofol (target concentration 2.7-6.0 microg/ml) and infusion of remifentanil (0.25-0.75 microg/kgbw/min). After loss of consciousness, a tube with a surface electrode was placed into the trachea without the application of any neuromuscular blocking agent. Neuromuscular monitoring consisted of evoked electromyography (EMG) of the laryngeal adductor muscles via the surface electrode and evoked acceleromyography (TOF Guard) of the right adductor pollicis muscle (APM). After transcutaneous stimulation of the recurrent laryngeal nerve and ulnar nerve, either 0.9% NaCl followed by 0.1 mg/kgbw cisatracurium after 3 min (bolus group, n=12), a priming dose of 0.01 mg/kgbw cisatracurium followed by 0.09 mg/kgbw 3 min later (low dose priming group, n=12) or a priming dose of 0.015 mg/kgbw cisatracurium followed by cisatracurium 0.085 mg/kgbw 3 min later (high dose priming group, n=12) were injected. Lag time, onset time and peak effect of NMB were recorded and compared between the groups. RESULTS: Demographic data, lag time and peak effect were comparable between the three groups. Onset time at the laryngeal muscles was significantly shorter in the high dose priming group (80+/-17 s), when compared to the low dose priming group (128+/-23 s) and bolus group (142+/-29 s). Onset time at the APM was also significantly shorter in the high dose priming group (154+/-35 s), when compared with the bolus group (226+/-76 s). The recovery of the neuromuscular function measured at the APM showed no differences between the groups. CONCLUSION: Our results show that only high dose priming of cisatracurium can significantly shorten the laryngeal onset time. However, clinical routine use is not recommended due to possible side-effects.     

Effects of ephedrine on the onset time of neuromuscular block and intubating conditions after cisatracurium: preliminary results

We studied the effects of intravenous ephedrine on the onset time and the intubating conditions 2 min after a bolus dose of cisatracurium (0.15 mg kg-1). Thirty patients anaesthetized with sufentanil and propofol were randomly divided in 2 groups to receive either ephedrine (70 micrograms.kg-1) or saline, 5 s before propofol. Cisatracurium was administered after loss of consciousness. Neuromuscular block was assessed at the adductor pollicis using accelography. Tracheal intubation was performed 2 min after cisatracurium injection and rated as excellent, good, poor or bad. At intubation, neuromuscular block (% height of control T1) was greater in patients receiving ephedrine (36.1 +/- 25.8% vs 57.9 +/- 25.1%) (mean +/- SD). The frequency of excellent intubating conditions was higher after ephedrine (86.6%) than after saline (40.0%). The onset time of cisatracurium was shorter after ephedrine (167 +/- 64.8 s vs 234.9 +/- 63.1 s). Thus, a low dose of ephedrine given before induction of anaesthesia improves the intubating conditions 2 min after 0.15 mg kg-1 cisatracurium and this effect likely relates to a quicker onset of neuromuscular block.     

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.     

The effect of cisatracurium and rocuronium on cisatracurium precurarization and the priming principle

STUDY OBJECTIVE: To demonstrate the effect of administering a precurarizing dose of cisatracurium or rocuronium on the speed of onset of cisatracurium, and to review the possible mechanisms and value of the priming principle. DESIGN: Double-blind, randomized, controlled trial. SETTING: Inpatient anesthesia in a university teaching hospital. PATIENTS: 90 ASA physical status I and II patients undergoing elective surgery requiring endotracheal intubation. INTERVENTIONS: Three groups of 30 patients each were investigated. Following induction of anesthesia with fentanyl and propofol, Group 1 received cisatracurium 0.015 mg.k(-1), Group 2 received rocuronium 0.09 mg. kg(-1), and Group 3 (control) received normal saline. Six minutes after priming, Groups 1 and 2 received cisatracurium 0.135 mg. kg(-1) whereas Group 3 received cisatracurium 0.15 mg. kg(-1). MEASUREMENTS AND MAIN RESULTS: In each group, first twitch height and the train-of-four ratios were recorded every 10 seconds after the initial priming dose. Intubation was attempted after the first twitch height became less than 15% of baseline. The decrease in the train-of-four ratios at 6 minutes was 0.97 for cisatracurium and 0.85 for rocuronium. The onset of muscle relaxation was significantly faster after priming with cisatracurium and rocuronium (71.7 +/- 21.3 and 65 +/- 19.8 sec, respectively) compared with control (148.7 +/- 43.1 sec). Females receiving both muscle relaxants had a faster onset of paralysis than did males (65.9 +/- 20.6 vs. 79.2 +/- 20.6 and 55 +/- 14.5 vs. 71.7 +/- 20.4 sec). Intubation conditions were either excellent or satisfactory in all patients. CONCLUSIONS: Six minutes after precurarization, there is no significant difference between rocuronium and cisatracurium when used as priming drugs. An even faster onset time with both drugs was demonstrated in females. The use of priming doses of 25% to 30% of ED(95) may cause symptomatic muscle weakness. The mechanisms of the priming principle are discussed.     

Comparison of the neuromuscular blocking effect of cisatracurium and atracurium on the larynx and the adductor pollicis

BACKGROUND: Cisatracurium unlike atracurium is devoid of histamine-induced cardiovascular effects and this alone would be the greatest advantage in replacing atracurium for the facilitation of tracheal intubation. On the other hand, 2 ED(95) doses of cisatracurium (100 micro g/kg) do not yield satisfactory intubating conditions such as those seen with equipotent doses of atracurium and therefore the recommended intubating dose of cisatracurium is 3 ED(95). To understand this discrepancy better, we evaluated the potency and onset of atracurium and cisatracurium directly at the larynx adductors in humans. METHODS: The study was conducted in 54 patients (ASA class I or II) undergoing peripheral surgery requiring general anesthesia. Cisatracurium 25-150 micro g/kg or atracurium 120-500 micro g/kg intravenous (i.v.) boluses doses were administered during anesthesia with propofol, nitrous oxide, oxygen and fentanyl. Neuromuscular block was measured by electromyography (single twitch stimulation every 10 s) at the larynx and the adductor pollicis. The dose-response effect measured at both muscles included maximum neuromuscular blockade achieved (Emax), the time to maximum depression of twitch height (onset) and time to spontaneous recovery of the twitch height to 25%, 75% and 90% (T25, T75, T90) of control value. RESULT: The onset at the larynx was of 196 +/- 28 s after the 100 micro g/kg cisatracurium dose compared with 140 +/- 14 s after the 500 micro g/kg atracurium dose (P < 0.05). Emax at the larynx was 92 +/- 1% and 98 +/- 1% after 100 micro g/kg cisatracurium and 500 micro g/kg atracurium, respectively (P < 0.05). The time to onset of maximum suppression Emax = 100 +/- 0% after a 150 micro g/kg cisatracurium dose was 148 +/- 29 s. At the larynx, the ED(50) was 25 micro g/kg for cisatracurium and 180 micro g/kg for atracurium and the ED(95) was 87 micro g/kg for cisatracurium compared with 400 micro g/kg for atracurium. CONCLUSION: The slow onset time at the laryngeal muscles after cisatracurium can be explained by the higher potency as compared with atracurium.     

性别因素对七氟醚增强顺阿曲库铵或罗库溴铵肌松效应的影响

目的 探讨性别因素对七氟醚增强顺阿曲库铵或罗库溴铵肌松效应的影响.方法 择期全麻手术患者240例,年龄20～60岁,ASA分级Ⅰ或Ⅱ级,BMI 20～30 kg/m2,随机分为2组(n=120):顺阿曲库铵组和罗库溴铵组,各组按性别和麻醉药再分4个亚组(n=30):女性异丙酚组、男性异丙酚组、女性七氟醚组和男性七氟醚组.各异丙酚组靶控输注异丙酚,血浆靶浓度2～6 μg/ml,各七氟醚组吸入七氟醚,于靶控输注或待呼气末七氟醚浓度稳定于1.71%5 min后,静脉注射顺阿曲库铵0.15 mg/kg或罗库溴铵0.6 mg/kg.记录肌松起效时间、肌松作用峰值时间、T1 25%恢复时间和TOFR25%恢复时间.结果 与异丙酚麻醉比较,女性患者七氟醚麻醉时,罗库溴铵TOFR 25%恢复时间延长,顺阿曲库铵肌松作用峰值时间、T1 25%恢复时间和TOFR 25%恢复时间延长,男性患者七氟醚麻醉时,罗库溴铵起效时间缩短,肌松作用峰值时间、T1 25%恢复时间和TOFR 25%恢复时间延长,顺阿曲库铵肌松作用峰值时间、T1 25%恢复时间和TOFR 25%恢复时间延长(P＜0.05或0.01);七氟醚麻醉时与男性患者比较,女性患者罗库溴铵T1 25%恢复时间和TOFR 25%恢复时间缩短,顺阿曲库铵起效时间缩短(P＜0.05或0.01).结论 七氟醚对罗库溴铵肌松的增强作用存在性别差异,男性强于女性;对顺阿曲库铵肌松的增强作用无明显性别差异.     

Total intravenous anesthesia with remifentanil, propofol and cisatracurium in end-stage renal failure

PURPOSE: To compare recovery parameters of total intravenous anesthesia (TIVA) with remifentanil and propofol, hemodynamic responses to perioperative events, and pharmacodynamic parameters of cisatracurium in 22 end-stage renal failure and 22 normal renal function patients. METHODS: Anesthesia was induced with 2-3 mg x kg(-1) propofol and 1 microg x kg(-1) remifentanil and maintained with 75 microg x kg(-1) x min(-1) propofol and propofol initial infusion of 0.2 microg x kg(-1) x min(-1) propofol. Arterial pressure and heart rate were maintained by remifentanil infusion rate adjustments. The first twitch (T1) was maintained at 25% by an infusion of cisatracurium. RESULTS: There was no difference in the time to maintenance of adequate respiration, date of birth recollection, first analgesic administration, between the renal failure (4.8+/-2.5, 7.8+/-3.2, 12.3+/-5.3 min respectively) and the control group (5.2+/-2.8, 8.1+/-3.1, 12.7+/-5.5 min): nor were there any differences in the time to 25% T1 recovery, T1 recovery from 25% to 75%, or cisatracurium infusion rate between the renal failure group (32.1 +/-10.8 min, 18.2+/-5.5 min, 0.89+/-0.29 microg x kg(-1) min(-1) respectively) and the control group (35.9 (7.9 min, 18.4+/-3.8 min, 0.95+/-0.22 microg x kg(-1) x min(-1)). CONCLUSION: End-stage renal failure does not prolong recovery from TIVA with remifentanil and propofol, or the recovery from cisatracurium neuromuscular block.     

Effect of an intravenous infusion of lidocaine on cisatracurium‐induced neuromuscular block duration: a randomized‐controlled trial

Background: Intravenous lidocaine can be used intraoperatively for its analgesic and antihyperalgesic properties but local anaesthetics may also prolong the duration of action of neuromuscular blocking agents. We hypothesized that intravenous lidocaine would prolong the time to recovery of neuromuscular function after cisatracurium. Methods: Forty‐two patients were enrolled in this randomized, double‐blind, placebo‐controlled study. Before induction, patients were administered either a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2 mg/kg/h infusion or an equal volume of saline. Anaesthesia was induced and maintained using propofol and remifentanil infusions. After loss of consciousness, a 0.15 mg/kg bolus of cisatracurium was administered. No additional cisatracurium injection was allowed. Neuromuscular function was assessed every 20 s using kinemyography. The primary endpoint was the time to spontaneous recovery of a train‐of‐four (TOF) ratio ≥0.9. Results: The time to spontaneous recovery of a TOF ratio ≥0.9 was 94 ± 15 min in the control group and 98 ± 16 min in the lidocaine group (P=0.27). Conclusions: No significant prolongation of spontaneous recovery of a TOF ratio ≥0.9 after cisatracurium was found in patients receiving intravenous lidocaine.     

Desflurane reduces the effective therapeutic infusion rate (ETI) of cisatracurium more than isoflurane, sevoflurane, or propofol

PURPOSE: The present study investigated the interaction between the cumulative dose requirements of cisatracurium and anesthesia with isoflurane, sevoflurane, desflurane or propofol using closed-loop feedback control. METHODS: Fifty-six patients (18-85 yr, vitrectomies of more than one hour) were studied. In the volatile anesthetics groups, anesthesia was maintained by 1.3 MAC of isoflurane, sevoflurane or desflurane; in the propofol group, anesthesia was maintained by a continuous infusion of 6-8 mg.kg(-1).hr(-1) propofol. After bolus application of 0.1 mg.kg(-1) cisatracurium, a T1%-level of 10% of control level (train-of-four stimulation every 20 sec) was maintained using closed-loop feedback controlled infusion of cisatracurium. The effective therapeutic infusion rate (ETI) was estimated from the asymptotic steady-state infusion rate Iss. The Iss was derived from fitting an asymptotic line to the measured cumulative dose requirement curve. The ETI of the different groups was compared using Kruskal-Wallis- test, followed by rank sum test, corrected for the number of comparisons, P <0.05 was regarded as showing significant difference. RESULTS: ETI in the isoflurane group was 35.6 +/- 8.6 microg.m(-2).min(-1), in the sevoflurane group 36.4+/- 11.9 microg m(-2).min(-1), in the desflurane group 23.8 +/- 6.3 microg.m(-2).min(-1). The ETI of the volatile anesthetic groups were all significantly lower than the ETI in the propofol group at 61.7 +/- 25.3 microg.m(-2).min(-1) (P <0.002). The ETI in the desflurane group was significantly lower than in all other groups (P <0.02). CONCLUSION: In comparison to propofol, isoflurane, sevoflurane and desflurane reduce the cumulative dose requirements of cisatracurium to maintain a 90% neuromuscular blockade by 42%, 41% and 60%, respectively.     

Large bolus dose vs. continuous infusion of cisatracurium during hypothermic cardiopulmonary bypass surgery

BACKGROUND AND OBJECTIVE: We investigated whether a high bolus dose of cisatracurium (8x ED95) given at induction can provide muscle relaxation for the major part of a cardiac procedure with hypothermic cardiopulmonary bypass, avoid important postoperative residual curarization and cause no waste of product. METHODS: Twenty patients were randomly assigned either to Group 1 (n = 10) or Group 2 (n = 10). Those in Group 1 were given cisatracurium in a high bolus dose (0.4 mg kg(-1)). Those in Group 2 received cisatracurium 0.1 mg kg(-1) at induction followed after 30 min by a continuous infusion of cisatracurium. As an escape medication in case of patient movement, a bolus dose of cisatracurium 0.03 mg kg(-1) was given. RESULTS: In Group 1 (large cisatracurium bolus dose), the clinical duration of effect (until T1/T0 = 25%) was 110 min. Six of 10 patients in Group 1 required additional boluses of cisatracurium intraoperatively. Four of these six had received an additional bolus near the end of surgery and had a train-of-four (TOF) ratio = 0 at the end. The other four patients in Group 1 had a final TOF ratio >0.9. In Group 2 (continuous cisatracurium infusion), only two patients had a TOF ratio >0.9 at the end of surgery, no patient moved and none received additional boluses. The total amount of cisatracurium used in the bolus and infusion Groups was 34.5 +/- 7.8 and 21.3 +/- 5.7 mg, respectively (P = 0.0004). CONCLUSIONS: For continued neuromuscular block during hypothermic cardiac surgery, a high bolus dose of cisatracurium appears to be safe, although it is not an alternative to a continuous infusion, as its neuromuscular blockade does not cover the intraoperative period and a high incidence of movements occurs. In the patients who received a high bolus dose of cisatracurium, postoperative residual curarization appeared after additional boluses had been given. The consumption of cisatracurium by high bolus was significantly greater than with continuous infusion.     

Comparative Pharmacology of Cisatracurium (51W89), Atracurium, and Five Isomers in Cats

Background: Atracurium has four chiral centers and the marketed product is a mixture of ten optical and geometric isomers. Six of the isomers were prepared and evaluated for neuromuscular blocking activity and autonomic effects in anesthetized cats. This study reports the comparative pharmacology of the six isomers and atracurium that led to the selection of one isomer, cisatracurium (Nimbex, 51W89) for clinical development.

Methods: Purpose bred cats, anesthetized with alpha-chloralose (80 mg/kg) and pentobarbital sodium (7 mg/kg) administered intraperitoneally, were used in this study. Neuromuscular blocking effects were assessed from the effects on the tibialis anterior twitch evoked at 0.15 Hz. Inhibition of the autonomic nervous system was assessed from the effects on the nictitating membrane contraction, in response to preganglionic sympathetic nerve stimulation and the bradycardia/vasodepressor responses to vagal nerve stimulation. Cardiovascular effects and plasma histamine concentrations were determined after a bolus injection of cisatracurium or atracurium.

Results: Like atracurium, all six isomers produced dose-dependent neuromuscular block (NMB). The calculated ED95 NMB values varied approximately tenfold (43+/-2 micro gram/kg-488+/-56 micro gram/kg). The "R-series" isomers were more potent than the corresponding "S series" isomers. With the exception of the S,Trans-S', Trans isomer, the NMB effects, i.e., onset times (range 2.6+/-0.2 min to 4.7+/-0.3 min) and total durations (range 9.9+/- 1.4 min to 14+/-0.9 min), of the other five isomers were very similar to that of atracurium. The former isomer had a relatively short duration of action. The 25-75% recovery times after cisatracurium at 1x ED sub 95 (4.4+/-0.4 min), 4x ED95 (4.5+/-0.4 min), and continuous infusions lasting at least 60 min that maintained 95-99% NMB (4.8+/-0.4 min) indicated a noncumulative effect. The vagal ID50: NMB ED95 ratios for atracurium and the six isomers ranged from 2 to 27. The sympathetic ID25: NMB ED95 ranged from 2.7 to 60. Atracurium and all of the isomers, except cisatracurium, produced cardiovascular effects after intravenous bolus administration at large doses (700-4,800 micro gram/kg). In contrast to atracurium, there were no changes in plasma histamine concentrations associated with the administration of doses of cisatracurium equivalent to 60x the NMB ED95 (62+/-8 micro gram/kg).     

Influence of the priming technique on pharmacodynamics and intubating conditions of cisatracurium

STUDY OBJECTIVES: To determine the effects of the priming technique on the intubating conditions and pharmacodynamics of different doses of cisatracurium. DESIGN: Open-label, randomized study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 60 ASA physical status I, II, and III female patients. INTERVENTIONS: Patients were randomly assigned to one of four groups. Patients from Groups 1, 2, and 3 received 0.01 mg/kg cisatracurium as a priming dose, and patients from Group 4 received placebo. Four minutes later, patients from Groups 1, 2, 3, and 4 received the following intubating doses of cisatracurium: 0.09 mg/kg, 0.14 mg/kg, 0.19 mg/kg, and 0.2 mg/kg, respectively. Anesthesia was induced with thiopental sodium, sufentanil, droperidol, and nitrous oxide (N2O; 6 L/min) in oxygen (O2; 4 L/min) and maintained with isoflurane up to 0.7%, N2O in O2, and sufentanil. Mechanomyography assessed the neuromuscular function of the adductor pollicis with train-of-four supramaximal impulses. The trachea was intubated when the amplitude of the first twitch decreased to 10% to 15% of control. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among the groups regarding the demographic data, the value of the first twitch at 60 seconds, the time to 90% block, and the onset time. Clinical duration of cisatracurium was significantly different between Group 3 and Groups 1 and 2, whereas Group 4 differed significantly from Group 1. Intubating conditions did not differ significantly among the groups. CONCLUSION: When primed, cisatracurium 0.09 mg/kg and 0.14 mg/kg produced an onset time comparable with that of 0.2 mg/kg and allowed an earlier spontaneous recovery (p < 0.05). In this study, there was no benefit in priming cisatracurium 0.19 mg/kg.     

ORG 9487 Neuromuscular Block at the Adductor Pollicis and the Laryngeal Adductor Muscles in Humans

Background: ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis.

Methods: In 30 adults, anesthesia was induced with propofol (2-5 mg/kg) and fentanyl (2-3 micro gram/kg). After train-of-four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group).

Results: Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P < 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/- 14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/- 20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P <0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/- 7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min at the adductor pollicis muscle.     

Effects of bolus administration of ORG-9426 in children during nitrous oxide-halothane anesthesia.

ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose-response relationship of ORG-9426 in 62 children (aged 1-5 yr) during nitrous oxide-halothane anesthesia by means of log-probit transformation and least-squares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 micrograms/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. To determine the dose-response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) micrograms/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 micrograms/kg, respectively. Time from administration of 600 micrograms/kg to onset of 90% and 100% neuromuscular block was 0.8 +/- 0.1 (0.5-1.3) and 1.3 +/- 0.2 (0.7-2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 +/- 1.9 (17.2-39.0) min. The recovery index (T25-75) was 11.0 +/- 1.6 (6.0-22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) greater than or equal to 0.75 was 41.9 +/- 3.2 (26.5-57.7) min.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of anesthetic technique on recovery from neuromuscular blockade with cisatracurium

OBJECTIVES: To assess the effect of four anesthetic techniques on recovery after a single dose of 0.2 mg/kg of cisatracurium. PATIENTS AND METHOD: After giving informed consent, 96 patients of both sexes, ASA I-III, were enrolled. Anesthesia was induced with fentanyl, propofol O2-N2O (FiO2 40%) after which the patients were randomly assigned to four groups according to maintenance technique: propofol by infusion, sevoflurane, desflurane or isoflurane at 1.3 MAC. Neuromuscular block was monitored (electromyographic recording of the pollicis adductor). Variables recorded were time of maximum block, duration of action of 1% and 25%, and recovery indices at T0-TR75 andT25%-T75%. ANOVA was performed ( = 0.05 and beta = 0.1). RESULTS: The groups were homogeneous. Time until recovery of 25% of baseline amplitude of the first response to a train of four (TOF) (T1) was longer in the desflurane group (68.4 +/- 11.1 min) than in the propofol group (60.2 +/- 9.4 min; p < 0.05). Time until recovery of 75% of the TOF-ratio was longer in the sevoflurane (96.8 +/- 13.1 min), desflurane (101.5 +/- 14.4 min) and isoflurane (94.1 +/- 13.9 min) groups than in the propofol group (83.7 +/- 1.3 min) (p < 0.0001).Times until recovery of T1 up to 1% were not statistically different: 45.8 +/- 10.7 (propofol), 50.6 +/- 11.0 (sevoflurane), 51.3 +/- 11.5 (desflurane) and 46.5 +/- 11.2 min (isoflurane). The 25% - 75% recovery index was also similar at 19.0 +/- 9.3 (propofol), 20.0 +/- 5.1 (sevoflurane), 25.7 +/- 12.4 (desflurane) and 20.9 +/- 7.9 (isoflurane). CONCLUSIONS: The inhaled anesthetics studied prolong the duration of clinical effect of cisatracurium more than does propofol.     

Effect of different doses of cisatracurium on intraocular pressure in sedated patients

BACKGROUND AND OBJECTIVE: The aim was to examine the course of intraocular pressure after relaxation with different doses of cisatracurium. METHODS: The investigation was carried out as a prospective, randomized double-blind study in a crossover design in 30 postoperative patients with stable haemodynamic and respiratory function (ASA I and II). To exclude any disrupting factors, patients remained intubated and continuously sedated. Twenty patients received an intubation dose (2 x ED95) of cisatracurium (0.1 mg kg(-1)) compared with atracurium (0.5 mg kg(-1)). In a second series, 10 patients were given an effective dose, ED95 (0.05 mg kg(-1)), and a repeat dose (0.02 mg kg(-1)) of cisatracurium. The intraocular pressure was determined before (T0) as well as 1 (T1), 5 (T5), 10 (T10), 15 (T15), 20 (T20) and 45 (T45) min after bolus administration. RESULTS: Intraocular pressure decreased after an intubation dose of either cisatracurium or atracurium, and reached a minimum after 10 min (6.7 +/- 2.2 and 7.9 +/- 2.1 mmHg, respectively). There was no significant difference between either muscle relaxant (P = 0.27). When lower doses of cisatracurium (0.05 and 0.02 mg kg(-1)) were applied, the intraocular pressure also decreased, albeit to a lesser extent and with a delayed onset (8.4 +/- 1.9 mmHg after 10 min, 9.9 +/- 3.4 mmHg after 15 min). There was no significant difference between dosages (p = 0.44). CONCLUSIONS: Cisatracurium is a useful drug in patients when a decrease of intraocular pressure is wanted and where muscle relaxation is necessary and acceptable.     

Pharmacodynamic interactions between cisatracurium and rocuronium

The onset and duration of maintenance doses of neuromuscular blocking drugs may be influenced by the original neuromuscular blocking drug used. We assessed the effect of the interaction between steroidal and benzo-isoquinolinium compounds on the clinical duration of maintenance doses of cisatracurium. Sixty adult patients undergoing anesthesia with isoflurane, nitrous oxide, and oxygen were randomized to receive the following: Group I = rocuronium 0.6 mg/kg followed by cisatracurium 0.03 mg/kg when the first twitch in the train-of-four (TOF) recovered to 25%, Group II = cisatracurium 0.15 mg/kg followed by cisatracurium 0.03 mg/kg, and Group III = rocuronium 0.6 mg/kg followed by rocuronium 0.15 mg/kg. Neuromuscular blockade was monitored using acceleromyography (TOF-Guard, Boxtel, The Netherlands). The clinical duration (mean +/- SD) of the first 2 maintenance doses was 41 +/- 10, 31 +/- 7++, and 25 +/- 8++ min, and 39 +/- 11, 30 +/- 6+, 29 +/- 9* min in Groups I-III, respectively (*P < 0.05, +P < 0.01, ++P < 0.001; Group I versus II and III). Thus, the clinical duration of the first two maintenance doses of cisatracurium was prolonged when administered after rocuronium. IMPLICATIONS: We assessed the clinical effect of administering cisatracurium after an intubating dose of rocuronium in 60 patients undergoing isoflurane/nitrous oxide and oxygen anesthesia. The clinical duration of the first two maintenance doses of cisatracurium administered after rocuronium was significantly prolonged. This supports the contention that combinations of structurally dissimilar neuromuscular blocking drugs result in a synergistic effect.     

Assessment of neuromuscular and haemodynamic effects of cisatracurium and vecuronium under sevoflurane-remifentanil anaesthesia in elderly patients

BACKGROUND AND OBJECTIVE: Neuromuscular block times, quality of muscle relaxation for tracheal tube insertion, and the haemodynamic effects after cisatracurium and vecuronium under sevoflurane-remifentanil anaesthesia were compared in elderly patients. METHODS: The study was performed in 40 patients over 65 yr of age. Anaesthesia was induced with thiopental, and maintained with sevoflurane in N2O/O2 and remifentanil. Cisatracurium 0.15 mg kg(-1) or vecuronium 0.1 mg kg(-1) were administered after induction. Intubation was attempted when neuromuscular block was 95%. Onset time, clinical duration of action, recovery index, spontaneous recovery time and tracheal intubation conditions were assessed. Haemodynamic parameters were also monitored. RESULTS: The average ages of the patients were 72.5 +/- 5.1 and 73.6 +/- 6.3 in the cisatracurium and vecuronium groups, respectively. Onset time was significantly shorter after vecuronium, 158 +/- 34 s vs. 200 +/- 50s, respectively. Recovery index was significantly shorter after cisatracurium, 19.5 +/- 7.5 s vs. 33.7 +/- 18.6 s (P < 0.05). Clinical duration and spontaneous recovery time were similar in both groups as well as haemodynamic variables. CONCLUSIONS: In elderly patients, vecuronium has a faster onset time while cisatracurium has a shorter recovery index under sevoflurane-remifentanil anaesthesia.     

Muscle relaxation does not influence venous oxygen saturation during cardiopulmonary bypass

STUDY OBJECTIVE: To examine whether the omission of neuromuscular blocking drugs during cardiopulmonary bypass (CPB) is associated with increased anesthetic requirements, higher frequency of intraoperative movements, and lower venous oxygen saturation (SvO(2)). DESIGN: Prospective, randomized study. SETTING: Large community hospital. PATIENTS: 30 ASA physical status III and IV patients scheduled for cardiac surgery. INTERVENTIONS: Patients were randomized to one of two groups: group 1 (n = 15) received a 3xED(95) bolus dose of cisatracurium at induction and thereafter no more neuromuscular blocking drug; group 2 (n = 15) received a continuous infusion of cisatracurium during the entire procedure. INTERVENTIONS: Both groups received a standardized anesthetic with bispectral index-guided propofol target-controlled infusion and a remifentanil infusion steered by hemodynamic changes. Venous oxygen saturation was continuously determined during CPB. MEASUREMENTS AND MAIN RESULTS: Propofol consumption was 5.4 +/- 1.7 and 4.4 +/- 1.0 mg/(kg/h) in groups 1 and 2, respectively (P = 0.07). Remifentanil consumption was 0.15 +/- 0.05 and 0.17 +/- 0.05 mug/(kg/min) in groups 1 and 2, respectively (P = 0.19). In groups 1 and 2, no patient recalled any intraoperative phenomena; none moved or had diaphragmatic contractions. During CPB, SvO(2) was 81.3 +/- 3.2% (76%-85%) in group 1 and 80.6 +/- 3.1% (73%-85%) in group 2 (P = 0.53). CONCLUSIONS: Omitting the continuous administration of neuromuscular blocking drugs during CPB did not increase anesthetic requirements. No intraoperative movements occurred, nor was there decreased SvO(2).     

A randomized double-blinded multicenter comparison of remifentanil versus fentanyl when combined with isoflurane/propofol for early extubation in coronary artery bypass graft surgery

We compared a fentanyl/isoflurane/propofol regimen with a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in a prospective, randomized, double-blinded study on patients undergoing elective coronary artery bypass graft surgery. Anesthesia was induced with a 1-min infusion of 0.5 mg/kg propofol followed by 10-mg boluses of propofol every 30 s until loss of consciousness. After 0.2 mg/kg cisatracurium, a blinded continuous infusion of remifentanil at 1 microg. kg(-1). min(-1) or the equivalent volume rate of normal saline was then started. In addition, a blinded bolus syringe of 1 microg/kg remifentanil or 10 microg/kg fentanyl, respectively, was given over 3 min. Blinded remifentanil, 1 microg. kg(-1). min(-1) (or the equivalent volume rate of normal saline), together with 0.5% isoflurane, were used to maintain anesthesia. Significantly more patients (P < 0.01) in the fentanyl regimen experienced hypertension during skin incision and maximum sternal spread compared with patients in the remifentanil regimen. There were no differences between the groups in time until extubation, discharge from the surgical intensive care unit, ST segment and other electrocardiogram changes, catecholamine levels, or cardiac enzymes. The remifentanil-based anesthetic (consisting of a bolus followed by a continuous infusion) resulted in significantly less response to surgical stimulation and less need for anesthetic interventions compared with the fentanyl regimen (consisting of an initial bolus, and followed by subsequent boluses only to treat hemodynamic responses) with both drug regimens allowing early extubation. IMPLICATIONS: Both fentanyl and the newer opioid remifentanil, when each is combined with isoflurane and propofol, allowed for fast-track cardiac anesthesia. The remifentanil regimen used in this study resulted in significantly less hemodynamic response to surgical stimulation.