Dose-response relationships for edrophonium and neostigmine antagonism of atracurium and cisatracurium- induced neuromuscular block

PURPOSE: To study the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by atracurium and cisatracurium. METHODS: One hundred and twenty eight, ASA group 1 or 2 adults were given either 0.5 mg x kg(-1) atracurium or 0.1 mg x kg(-1) cisatracurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. The neuromuscular block was measured by an acceleration-responsive transducer. Responses were defined in terms of percent depression in the first twitch (T1) and train-of-four (TOF) response. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg x kg(-1)) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg x kg(-1)) was administered by random allocation. Neuromuscular function in another sixteen subjects was allowed to recover spontaneously. RESULTS: At five minutes, unlike edrophonium, neostigmine was equally effective against atracurium and cisatracurium with respect to T1 recovery. The neostigmine T1-ED50 was 10.3 +/- 1.06 (SEM) microg x kg(-1) after atracurium and 11.2 +/- 1.06) microg x kg(-1) after cisatracurium. The edrophonium ED50 was 157 +/- 1.07 microg x kg(-1) with atracurium and 47.4 +/- 1.07 microg x kg(-1) with cisatracurium, giving a neostigmine:edrophonium potency ratios of 15.2 +/- 1.7 and 4.2 +/- 0.41 (P < 0.001) for atracurium and cisatracurium, respectively. At 10 min neostigmine was 13 +/- 1.4 times as potent as edrophonium for achieving 50% TOF recovery after atracurium paralysis. After cisatracurium the potency ratio was 11.8 +/- 1.3 (NS). CONCLUSIONS: Although there were differences at five minutes, neostigmine:edrophonium potency ratios at 10 min, were similar in both relaxants studied.     

Postoperative residual curarization with cisatracurium and rocuronium infusions

BACKGROUND AND OBJECTIVE: Monitoring of neuromuscular blockade still often relies on clinical judgement. Moreover, there are substantial national differences in the use of agents to 'reverse' their effects. We investigated the recovery characteristics and incidence of postoperative residual curarization after cisatracurium and rocuronium infusions for long duration interventions without systematic antagonism. METHODS: In 30 patients undergoing major surgery, we measured infusion dose requirements for rocuronium and cisatracurium during propofol anaesthesia. Infusions were discontinued at the beginning of surgical closure; spontaneous recovery of neuromuscular function was awaited in both groups. Neostigmine (50 microg kg(-1)) was administered only when a patient started to wake without a train-of-four ratio (TOF) of 0.9. RESULTS: In the cisatracurium and rocuronium groups, four (27%) and one (7%) patients, respectively, had a TOF ratio > or = 0.9 at the end of surgery. The TOF ratio in each group at that time was 51 +/- 32% for cisatracurium and 47 +/- 31% for rocuronium (P = 0.78). Six patients (40%) in the cisatracurium group and seven (47%) in the rocuronium group required neostigmine. The TOF ratio at the time of reversal was 63 +/- 7% for cisatracurium and 40 +/- 19% for rocuronium (P = 0.01). The time interval between the end of surgery and a TOF ratio of 0.9 was 10 +/- 9 min for cisatracurium and 18 +/- 13 min for rocuronium (P = n.s.). CONCLUSIONS: Patients receiving a cisatracurium or rocuronium infusion have a high incidence of postoperative residual curarization when the block is not antagonized. When 'reversal' is not attempted, cisatracurium seems to be safer than rocuronium.     

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.     

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.     

Dose-response relationship and infusion requirement of cisatracurium besylate in infants and children during nitrous oxide-narcotic anesthesia

BACKGROUND: To determine the effect of age on the dose-response relation and infusion requirement of cisatracurium besylate in pediatric patients, 32 infants (mean age, 0.7 yr; range, 0.3-1.0 yr) and 32 children (mean age, 4.9 yr; range, 3.1-9.6 yr) were studied during thiopentone-nitrous oxideoxygen-narcotic anesthesia. METHODS: Potency was determined using a single-dose (20, 26, 33, or 40 microg/kg) technique. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor pollicis to supramaximal train-of-four stimulation of the ulnar nerve at 2 Hz. RESULTS: Least-squares linear regression analysis of the log-probit transformation of dose and maximal response yielded median effective dose (ED50) and 95% effective dose (ED95) values for infants (29+/-3 microg/kg and 43+/-9 microg/kg, respectively) that were similar to those for children (29+/-2 microg/kg and 47+/-7 microg/kg, respectively). The mean infusion rate necessary to maintain 90-99% neuromuscular block during the first hour in infants (1.9+/-0.4 microg x kg(-1) x min(-1); range: 1.3-2.5 microg x kg(-1) x min(-1)) was similar to that in children (2.0+/-0.5 microg x kg(-1) x min(-1); range: 1.3-2.9 microg x kg(-1) x min(-1)). CONCLUSION: The authors conclude that cisatracurium is equipotent in infants and children when dose is referenced to body weight during balanced anesthesia.     

Does discontinuation of desflurane at the time of neostigmine administration speed recovery from cisatracurium block compared to that with a propofol‐based technique?

BACKGROUND: Volatile anaesthetics are known to influence the effect of neostigmine as an antagonist of neuromuscular block. The aim of the present study was to investigate whether discontinuation of desflurane at the time of neostigmine administration shortens reversal time from cisatracurium block, compared to that with a propofol-based anaesthesia. METHODS: Ten volunteers were studied twice. For one study, anaesthesia was induced with alfentanil and propofol and maintained with nitrous oxide 70% and propofol 150 microg. kg-1. min-1. For the other study, experimental conditions were replicated except that desflurane 6% was administered and the dose of propofol was only 50 microg. kg-1. min-1. The evoked mechanical response of the adductor pollicis to train-of-four (TOF) stimulation was recorded. Neuromuscular block was induced with cisatracurium 0.2 mg. kg-1. When the magnitude of the first TOF response (T1) had recovered to 10%, the block was antagonized with neostigmine 70 microg. kg-1. At this time, propofol was decreased to 50 microg. kg-1. min-1, or the desflurane was discontinued. RESULTS: There were no significant differences between the two techniques of anaesthesia in the rate of neostigmine-induced recovery of the TOF ratio. The times (mean+/-SD) to achieve TOF ratios of 0.7, 0.8, and 0.9 were (propofol first, desflurane second) 6.1+/-2.2 and 6.5+/-1.6 min; 10.4+/-4.2 and 9.6+/-2.7 min; 17.1+/-6.9 and 21.0+/-13.0 min, respectively. CONCLUSION: Discontinuing desflurane does not speed neostigmine-induced recovery from cisatracurium neuromuscular block, when compared to that during propofol-based anaesthesia.     

肝移植术患者罗库溴铵不同给药方式肌松效果的比较

目的 比较肝移植术患者间断静脉注射(Ⅳ)、静脉输注(CI)和靶控输注(TCI)罗库溴铵的肌松效果.方法 拟行肝移植术的患者36例,性别不限,年龄21～63岁,体重48～80 kg,Child-Pugh评分7～9分,肝功能Child分级B或C级,随机分为3组(n=12):Ⅳ组、CI组和TCI组.采用TOF模式进行肌松监测,Ⅳ组:麻醉诱导时静脉注射罗库溴铵0.6 mg/kg,无肝前期T1恢复至25%时、无肝期和新肝期T4/T1(TOFR)恢复至25%时追加0.15 mg/kg.TCI组:麻醉诱导时靶控输注罗库溴铵,初始效应室靶浓度3μg/ml,调整靶浓度,维持T1 5%～10%;无肝期和新肝期开始时暂停TCI,随后以效应室靶浓度0.1μg/ml再次输注,调整靶浓度,维持T15%～10%.CI组:麻醉诱导时静脉注射罗库溴铵0.6 mg/kg,无肝前期以30μg·kg-1·min-1的速率开始静脉输注,调节输注速率,维持T1 5%～10%,无肝期和新肝期开始时暂停CI,随后以1μg·kg-1·min-1的速率静脉再次输注,调整输注速率,维持T15%～10%.各组于肌松达最大效应时行气管插管,于缝合腹膜后停止给药.记录麻醉诱导时罗库溴铵肌松起效时间、T1最大抑制程度和气管插管条件满意情况;记录各组无肝期T1 25%恢复时间及TOFR 25%恢复时间,新肝期停药后T125%恢复时间、TOFR 25%恢复时间、TOFR 75%恢复时间、TOFR90%恢复时间及恢复指数;记录罗库溴铵总用量.结果 与Ⅳ组比较,TCI组和CI组气管插管条件满意率、罗库溴铵总用量、麻醉诱导时罗库溴铵起效时间、T1最大抑制程度和各期肌松恢复情况差异均无统计学意义(P＞0.05).肌松效应监测图显示Ⅳ组各期罗库溴铵肌松效应波动较大,TCI组和CI组各期肌松效应较为平稳.结论 采用Ⅳ、CI和TCI给药时,肝移植术患者罗库溴铵肌松起效和恢复情况无差异,而采用TCI或CI给药时,肌松效应较Ⅳ更加平稳.     

Cisatracurium in cardiac surgery--continuous infusion vs. bolus administration

The aim of this study was the comparison of infusion vs. intermittent bolus administration of cisatracurium (CA) following cardiac surgery with regard to total intraoperative dose and time of recovery from neuromuscular blockade. From June 2005 to April 2006 sixty ASA II-III patients who were undergoing coronary bypass graft and valve replacement surgery, were equally divided and randomized to receive either intermittent bolus (Group A, n = 30) or continuous infusion (Group B, n = 30) of CA in Madani Heart Center in the Tabriz (Iran). Total intraoperative dose of CA and time to TOF ratio = 0.8 after operation were measured. Anesthesia technique in two groups was the same. All of the patients underwent cardiopulmonary bypass. Intensity of neuromuscular blockade maintained on one train-of-four (TOF) twitch response of adductor pollicis during operation. Mean received dose of CA was 32.8 +/- 20.6 micro/kg/hr in Group A and 89.7 +/- 39.4 micro/kg/hr in Group B (p = 0.003). Total intraoperative dose of CA was 23.6 +/- 4.9 mg in Group A and 39.2 +/- 10.1 mg in Group B (p = 0.001). Spontaneous recovery from neuromuscular blockade in ICU (TOF ratio = 0.8) was reached in 43.8 +/- 9.2 min in Group A, and 64.2 +/- 15.1 min in Group B (p = 0.0001). Intubation time in ICU was not significantly different (Group A = 8.3 +/- 5.1 hrs vs. Group B = 10.2 +/- 6.2 hrs, p = 0.256). These results support the intermittent bolus administration of cisatracurium in cardiac surgery following cardiopulmonary bypass.     

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.     

Intubation with low-dose atracurium in children

The objective of this study was to compare intubating conditions and neuromuscular effects using smaller doses of atracurium (0.25 mg/kg and 0.3 mg/kg) with the recommended dose of 0.4 mg/kg for intubation in children anesthetized with halothane, N2O and oxygen undergoing strabismus repair. All patients (10 in each group) had good or excellent intubating conditions at 80% depression of twitch height [T1 of train-of-four (TOF) stimulation]. Mean times to intubation were 2.6 +/- 0.2 minutes following 0.25 mg/kg and 2.2 +/- 0.2 minutes following 0.3 mg/kg. These times were significantly longer (P less than 0.05) than the mean intubation time of 1.5 +/- 0.2 minutes following 0.4 mg/kg. Mean times to recovery, defined as times from injection of atracurium to return of T1 of TOF to 10%, 25%, and 95% of control measurements, were significantly shorter with the smaller doses. Atracurium at these low doses may provide an alternative to succinylcholine for intubating children during halothane anesthesia for surgical procedures lasting 20-30 min.     

The relationship of posttetanic count and train-of-four responses during recovery from intense cisatracurium-induced neuromuscular blockade

Posttetanic count (PTC) has been used to quantify intense degrees of nondepolarizing neuromuscular blockade. Our objective in the present investigation was to discern whether PTC correlates with recovery from intense cisatracurium-induced neuromuscular blockade under both inhaled and IV anesthesia. In 60 patients, anesthesia was induced with propofol 2 mg/kg and fentanyl 1.5 micro g/kg IV. Recovery from intense neuromuscular blockade induced by cisatracurium (0.15 mg/kg) was studied in 2 groups. Group 1 (n = 30) had anesthesia maintained with propofol 100-200 micro g x kg(-1) x min(-1) and 60% N(2)O in O(2), whereas Group 2 (n = 30) had anesthesia maintained with isoflurane (end-tidal concentration 0.8%) and 60% N(2)O in O(2). Neuromuscular functions were monitored using acceleromyography. Cycles of posttetanic stimulation were repeated every 6 min with train-of-four (TOF) stimulation in between. Measurement included times to posttetanic responses and to the first response to TOF stimulation (T(1)), as well as the correlation between PTC and T(1). In Group 1, the mean times to PTC(1) and T(1) were 35.6 +/- 7.5 and 46.9 +/- 6.5 min, respectively. Corresponding times in Group 2 were 39.5 +/- 6.8 and 56.7 +/- 5.4 min, respectively. There was a good time correlation, r = 0.919 for propofol (Group 1) and r = 0.779 for isoflurane (Group 2), between PTC and T(1) recovery in both groups. The PTC when T(1) appeared ranged between 8 and 9 in Group 1 and 8 and 14 in Group 2. Conforming to original observations with other neuromuscular blocking drugs, there is a correlation between PTC and TOF recovery from intense cisatracurium-induced neuromuscular blockade allowing better monitoring of this intense degree of blockade during both IV (propofol) and isoflurane anesthesia. IMPLICATIONS: Monitoring posttetanic count during intense neuromuscular blockade allows the clinician to estimate the intensity of the blockade and estimate recovery time. The relationship between posttetanic count and train-of-four recovery from intense cisatracurium-induced neuromuscular blockade was documented under both IV and inhaled anesthesia.     

The prolonged duration of rocuronium in Chinese patients

We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0. 12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T(1)) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T(1) 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P<0.05 for T(1) of 10%, 25%, 75%, and 90% and TOF to 0.7). The 50% effective dose was smaller in Chinese adults (125+/-63 vs. 159+/-66 microg/kg) and Chinese children (171+/-43 vs. 191+/-46 microg/kg) than in Caucasian adults and children, but the difference was not statistically significant. In adults, time to 25% T(1) recovery was 43+/-13 min in Chinese patients and 33+/-10 min in Caucasian patients (P<0.05). The corresponding values were more rapid for children: 30+/-10 and 24+/-6 min (P<0.05). We conclude that the recovery from rocuronium neuromuscular blockade was longer in Chinese compared with Caucasian patients and in adults compared with children.     

Mivacurium infusion during nitrous oxide-isoflurane anesthesia: a comparison with nitrous oxide-opioid anesthesia.

STUDY OBJECTIVE: To determine the potentiation of the neuromuscular blockade induced by a titrated infusion of mivacurium in the presence of isoflurane versus a nitrous oxide (N2O)-opioid anesthesia. DESIGN: An open-label, controlled study. SETTING: The inpatient anesthesia service of two university medical centers. PATIENTS: Thirty adults divided into two groups. INTERVENTION: An intravenous infusion of mivacurium during anesthesia with N2O-opioid or N2O-isoflurane. MEASUREMENTS AND MAIN RESULTS: A neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. The mivacurium infusion rate was significantly less in the presence of isoflurane [4.0 +/- 0.8 micrograms/kg/min (mean +/- SEM)] than during N2O-opioid anesthesia (6.4 +/- 0.6 micrograms/kg/min). The recovery rates did not differ between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 of at least 0.75 occurred in an average of 17.9 +/- 1.5 minutes, with a mean recovery index (T25-75) of 6.0 +/- 0.7 minutes. CONCLUSION: Isoflurane anesthesia reduces the infusion rate of mivacurium required to produce about 95% depression of neuromuscular function.     

Double-blind comparison of the variability in spontaneous recovery of cisatracurium- and vecuronium-induced neuromuscular block in adult and elderly patients

BACKGROUND: This study was designed to compare variability in the offset of two neuromuscular blocking agents with different elimination pathways. METHODS: The spontaneous recovery profiles of cisatracurium and vecuronium were compared in adult (18-64 years) and elderly (> or =65 years) patients receiving N2O/O2/fentanyl/propofol anaesthesia. Patients were randomised to receive an initial bolus dose and maintenance doses of 3xED95, respectively, 0.6xED95 for cisatracurium (0.15 and 0.03 mg.kg-1) or 2xED95, respectively, and 0.4xED95 for vecuronium (0.1 and 0.02 mg.kg(-1)), as recommended in their prescribing information. Administration of the study drugs was double-blinded, and neuromuscular transmission was monitored using mechanomyography of the evoked response of the adductor pollicis, following ulnar nerve stimulation. RESULTS: The clinically effective duration (minutes) of the initial bolus dose, defined as the mean time to 25% T1 recovery (+/-SD), for the adult and elderly patients was 53.5+/-9.8 and 57.3+/-11.5 for cisatracurium, respectively, and 34.1+/-9.0 and 47.5+/-14.4 for vecuronium, respectively. The duration of spontaneous sufficient recovery (SSR), defined as the mean (+/-SD) time interval in minutes from 25% T1 recovery to a T4:T1 ratio > or =0.8 after the last bolus dose, for the adult, respectively, elderly patients was 28.3+/-8.0 and 31.7+/-10.0 for cisatracurium and 38.5+/-13.2 and 60.3+/-26.1 for vecuronium. CONCLUSION: Whereas both the clinically effective duration and the duration of SSR are comparable between the adult and the elderly patients receiving cisatracurium, they differ substantially between these two age groups for vecuronium. Furthermore, the variability in offset is significantly lower in patients receiving cisatracurium, especially in the elderly, which may be of particular clinical interest.     

Neuromuscular effects of cisatracurium in morbidly obese patients

Obesity is associated with significant changes in body composition and function that may alter the pharmacodynamics and pharmacokinetics of various drugs. In this study, we investigated the neuromuscular effects of cisatracurium in morbidly obese as compared to control group of normal body weight patients. In the morbidly obese group (n = 20), corrected weight was used to calculate the drug doses. In the control group (n = 20), the dose was calculated on ideal body weight (IBW). 0.15 mg/kg(-1) cisatracurium was administered as the neuromuscular blocker. Neuromuscular effects were recorded at T0 (onset time), T1 (appearance of first stimulus of TOF), T25 (25% recovery of T1) and T25-75 (time of T25 to T75, recovery time). T0 was determined as 177 +/- 23 s and 168 +/- 19 s in the morbidly obese, and control group, respectively. T25 was determined as 46 +/- 7 min and 56 +/- 8 min, in the morbidly obese and control group, respectively (p < 0.05). T25-75 was determined as 11 +/- 5 min and 14 +/- 6 min in the morbidly obese and control group, respectively (p < 0.05). Intubation conditions were determined as good in 13, excellent in 7 patients in the morbidly obese group, and as good in 4 and excellent in 16 patients in the control group (p < 0.05). As different neuromuscular effects of cisatracurium were detected, we conclude that ne uromuscular agents must be monitored in the morbidly obese patients.     

Early and late reversal of rocuronium with pyridostigmine during sevoflurane anaesthesia in children

This study investigated the effect of pyridostigmine administered at different levels of recovery of neuromuscular function after rocuronium during sevoflurane anaesthesia in children. Fifty-one patients aged 3 to 10 years, ASA physical status 1 or 2 were randomized to 4 groups: a spontaneous recovery group; or, reversal with pyridostigmine 0.25 mg/kg with glycopyrrolate 0.01 mg/kg at one of three times: 5 minutes after rocuronium administration; at 1% twitch height (T1) recovery; or at a 25% twitch height (T25) recovery. Anaesthesia was induced with thiopentone (5-7 mg/kg) and maintained with 2-3% sevoflurane and 50% nitrous oxide. Atropine (0.015 mg/kg) and, after calibrating the TOF-Watch, rocuronium (0.6 mg/kg) were then administered. Maximal block occurred 1.1+/-0.5 min (mean, SD) after rocuronium administration. In the spontaneous recovery group, the clinical duration (recovery to T25) was 40.1+/-8.8 min and the recovery index (time between T25 and T75) 19.9+/-9.8 min. Recovery to TOF >0.9 from the time of rocuronium administration was reduced by approximately 30% in the pyridostigmine groups compared to the spontaneous recovery group. There was no significant difference among the three pyridostigmine groups. When pyridostigmine was given at T1 or T25, the time from pyridostigmine administration to TOF >0.9 was shorter than for the group receiving pyridostigmine 5 minutes after rocuronium.     

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.     

Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia

BACKGROUND: The use of volatile anesthetics for maintenance of anesthesia can enhance the action of non-depolarizing muscle relaxants and interfere with the reversal of neuromuscular blockade. In this study, we studied the antagonism of rocuronium with edrophonium-atropine during propofol- versus sevoflurane-based anesthesia. METHODS: Following induction of anesthesia with propofol (2-2.5 mg kg(-1), i.v.) and fentanyl (1-2 microg kg(-1) i.v.), rocuronium 0.6 mg kg(-1) i.v. was administered to facilitate tracheal intubation. Patients were then randomized to receive either a propofol infusion (100 microg kg(-1) min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular blockade was monitored using electromyography at the wrist, and reversed with edrophonium 1.0 mg kg(-1) and atropine 0.015 mg kg(-1) when the first twitch hight (T1) of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. Anesthetic maintenance with propofol or sevoflurane was continued following reversal until a TOF ratio of 0.7 was attained. RESULTS: The clinical duration of action (i.e., time to 25% T1 recovery) was similar during both propofol- (39.3+/-14.6 min) and sevoflurane-based (48.1+/-19.7 min) anesthesia. However, the reversal time from 25% T1 to TOF ratio of 0.7 was significantly longer with sevoflurane [Median 2.8 (range 0.5-18.8) min] compared with propofol [1.5 (0.75-3) min] (P<0.05). CONCLUSIONS: We conclude that the clinical duration of action after a single dose of rocuronium, 0.6 mg kg(-1) i.v., was similar during both propofol- and sevoflurane-based anesthesia. However, the reversal of rocuronium-induced residual blockade was slower and more variable in the presence of sevoflurane.     

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.