DOSE-RESPONSE RELATIONSHIPS FOR NEOSTIGMINE ANTAGONISM OF VECURONIUM-INDUCED NEUROMUSCULAR BLOCK IN ADULTS AND THE ELDERLY

We have studied the dose-response relationship for neostigminein 36 adult (ages 18-50 yr) and 36 elderly (ages > 70 yr)subjects during antagonism of neuromuscular block induced byvecuronium. All patients received vecuronium 0.08 mg kg^–1and neuromuscular block was monitoredmechanomyo-graphicallyusing the train-of-four (TOF) mode of stimulation. Six patientsof each age group were allocated randomly to receive neostigmine5, 15, 25, 35 or 45 µg kg^–1 or saline at 10% recoveryof T1 (first response in the TOF). TOF ratios were recordedcontinuously over the next 10 min and the values at 1-min intervalsfrom 5 min onwards were used to construct the dose-responserelationships. There was a significant difference (P < 0,05)in the time to spontaneous recovery of T1 to 10% between theadults (24 (SD 5.5) min) and the elderly (33 (7.8) min). Dose-responsecurves for neostigmine were parallel in the two age groups,but those for the. elderly were significantly to the right ofthe curves for the adults. This sggests an apparently lesserrelative potency of neostigmine, or the requirement of a largerdose, in the elderly for attaining antagonism of a moderatelyintense vecuronium block at the same time as in adults.     

Recovery from vecuronium neuromuscular blockade following neostigmine administration in infants, children, and adults during halothane anesthesia

To determine whether neostigmine had different effects in pediatric patients during vecuronium neuromuscular blockade, the rate of recovery following neostigmine administration was compared in infants (n = 8), children (n = 10), and adults (n = 10) during nitrous oxide-halothane anesthesia. After induction of anesthesia, patients received 100 micrograms/kg of vecuronium. The EMG response of the adductor pollicis was monitored after train-of-four (TOF) stimulation of the ulnar nerve every 20 s. When the first twitch of TOF spontaneously recovered to 10% of control value, neostigmine was injected (40 micrograms/kg in adults, 30 micrograms/kg in infants and children). During the first few minutes following neostigmine administration, no differences were observed between the three groups. After the 8 min, recovery was more rapid in children than in infants and adults up to and including the 15th min. Ten minutes after neostigmine administration, the first twitch (mean +/- SD) reached 97 +/- 3%, 99 +/- 2%, and 97 +/- 5% of control value in infants, children, and adults, respectively; TOF ratio was greater in children (0.96 +/- 0.03) than in either adults (0.82 +/- 0.17) or in infants (0.83 +/- 0.14) (P less than 0.05). During the first minutes after neostigmine administration, the lack of difference in TOF recovery in the three groups suggests that neostigmine is the main factor of recovery. In contrast, the more complete recovery after the eighth minute in children could be due to the faster rate of spontaneous recovery from vecuronium induced neuromuscular blockade in children.     

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.     

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.     

Vecuronium infusion requirements in paediatric patients in intensive care units: the use of acceleromyography

Neuromuscular blocking drugs in intensive care units (ICU) may cause complications, including prolonged neuromuscular block as a result of overdosage and post-ventilation muscle weakness. These may be increased by using inappropriately high infusion rates for infants, in whom published studies are scarce, and by failure to monitor neuromuscular block. There is little ICU experience of acceleromyography, which may permit more reliable monitoring. To determine appropriate vecuronium infusion rates, 12 neonates/infants (median age 4 (interquartile range (IQR) 2-5) months) and 18 children (median age 3.07 (2-10 yr) were studied. The vecuronium infusion rate was adjusted to maintain train-of- four (TOF) at 1 response using the TOF guard accelerometer. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 0.7. Neonates and infants required 45% less vecuronium (mean infusion rate 54.7 (SEM 4.23) micrograms kg-1 h-1) than older children (98.7 (7.07) micrograms kg-1 h-1) and had faster recovery to 70% T4/T1 (45 (IQR 20-51) min vs 65 (55-103) min), with no evidence of prolonged weakness. Routine monitoring of neuromuscular block in ICU is essential; acceleromyography is convenient and reliable.      

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.     

Neostigmine and edrophonium for reversal of pipecuronium neuromuscular blockade

Neostigmine 0.06 mg.kg-1 or edrophonium 1 mg.kg-1 were administered to two groups of 15 patients each for antagonism of pipecuronium-induced neuromuscular block at 20% spontaneous recovery of the first twitch (T1) of the train-of-four (TOF) stimulation. The mean onset of action (+/-SEM) of edrophonium (18.1 +/- 2.4 sec) was significantly more rapid (P less than 0.01) than that of neostigmine (47.6 +/- 4 sec), as were the times taken to attain a TOF ratio of 0.25 and 0.5. Nevertheless, the reversal time (time taken from the end of injection of the antagonist until TOF ratio value had reached 0.75) was significantly shorter (P less than 0.01) in the neostigmine than in the edrophonium group (499.3 +/- 62 vs 767 +/- 52 sec respectively). The TOF ratio ten minutes after reversal was greater in the neostigmine group than in the edrophonium group (P less than 0.01), 0.78 +/- 0.02 vs 0.68 +/- 0.02 min respectively. At that time, 33% (5 out of 15) and 80% (12 out of 15) patients failed to be reversed adequately (TOF ratio of 0.75) after neostigmine 0.06 mg.kg-1 and edrophonium 1 mg.kg-1, respectively. Administration of one additional dose (one-third of the initial dose) of the same antagonist resulted in adequate antagonism in the remaining five patients in the neostigmine group and in nine patients in the edrophonium group. Two such doses were required in the remaining three patients in the latter group. The mean total dose of neostigmine and edrophonium employed in this study was 0.067 +/- 0.002 and 1.3 +/- 0.05 mg.kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myasthenia gravis and pipecuronium--report of two cases.

The use of pipecuronium in two patients with myasthenia gravis undergoing thymectomy is described. Neuromuscular function was monitored throughout using the train-of-four (TOF) mechanical twitch response. The cumulative dose-response to pipecuronium was determined in both patients during nitrous oxide-oxygen-narcotic anaesthesia. Both patients were sensitive to pipecuronium. The ED50 doses of pipecuronium were 11.6 and 11.1 micrograms.kg-1 and the ED95 doses were 35 and 33.3 micrograms.kg-1 in patients #1 and 2 respectively. Edrophonium 1 mg.kg-1 and neostigmine 0.06 mg.kg-1 were administered to patients #1 and 2 respectively for antagonism of residual neuromuscular blockade at 25 per cent spontaneous recovery of first twitch (T1) of the TOF stimulation. As with other non-depolarizing muscle relaxants pipecuronium in reduced dosage and with careful neuromuscular monitoring can be used to provide surgical relaxation safely in patients with controlled myasthenia gravis.     

Dose Responses for Neostigmine and Edrophonium as Antagonists of Mivacurium in Adults and Children

Background: Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children.

Methods: Fifty-four adults, aged 40.1+/-10.9 yr, and 54 children, aged 4.9+/-0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg *symbol* kg sup -1 intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micro gram *symbol* kg sup -1) or edrophonium (100, 200, 400, and 1,000 micro gram *symbol* kg sup -1) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min.

Results: Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97+/-2% (SD) in children compared with 69+/-11% in adults and train-of-four to 84 +/-5% versus 30+/-13% (P < 0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children.     

Clinical study of interaction between rocuronium and some commonly used antimicrobial agents

The onset and duration of clinical relaxation and reversibility of rocuronium bromide (ORG 9426) 0.6 mg kg-1 were studied following administration of netilmicin 2 mg kg-1 (n = 10) or cefuroxime 20 mg kg-1 (n = 10) in patients undergoing urological surgery; and cefuroxime 20 mg kg-1 (n = 10) metronidazole 7.5 mg kg-1 (n = 10), metronidazole 7.5 mg kg-1 and cefuroxime 20 mg kg-1 (n = 10), or placebo (n = 10) in patients undergoing abdominal surgery under anaesthesia with thiopentone, nitrous oxide in oxygen, fentanyl and halothane. The antimicrobial agents were administered intravenously 5 min before rocuronium. Neuromuscular function was monitored using mechanomyography and train-of-four (TOF) mode of stimulation. Onset of neuromuscular block occurred in approximately 60 s with all patients achieving complete block. The mean clinical duration (+/- SD) was 50 +/- 10.7 and 44 +/- 6.7 min following netilmicin and cefuroxime respectively in patients undergoing urological surgery; and 49 +/- 13.7, 44 +/- 11.1, 48 +/- 11.1 and 38 +/- 7.3 min in the groups undergoing abdominal surgery receiving cefuroxime, metronidazole, cefuroxime and metronidazole combination and placebo respectively. There were no statistically significant differences between the groups in either the onset or the duration of clinical relaxation. Reversal of neuromuscular block with neostigmine carried out at spontaneous recovery of T1 (first response in the TOF) of 25% or more was easily achieved in all groups in 2-4 min. It is concluded that there is no significant interaction between rocuronium and single doses of the antimicrobial agents used in the present study.     

Sevoflurane increases fade of neuromuscular response to TOF stimulation following rocuronium administration in children. A PK/PD analysis

BACKGROUND: Sevoflurane enhances neuromuscular block produced by rocuronium, affecting not only single twitch response but also the response to high-frequency stimulation, increasing tetanic [or train-of-four (TOF)] fade. METHODS: We compared the degree of fade during spontaneous recovery from rocuronium-induced neuromuscular block in 24 children (3-11 years old, ASA groups I and II), anesthetized with nitrous oxide-sevoflurane (one MAC, endtidal concentration) or nitrous oxide-fentanyl. Neuromuscular transmission was monitored electromyographically (EMG), stimulating the ulnar nerve at the wrist with TOF, 2 Hz for 2 s, repeated at 20-s intervals and recording EMG potential from adductor pollicis brevis. Depression of the fourth twitch, T4, was used as a measure of fade. Following an intubating dose of rocuronium, 0.6 mgxkg(-1), continuous infusion of rocuronium was given to maintain stable 90-99% T1 depression. Plasma concentration of rocuronium was determined with high performance liquid chromatography with electrochemical detection (HPLC-EC) method at the moment of discontinuation of rocuronium infusion and 10, 20, 30, 40, 50, 60, and 75 min afterwards. A two compartment model was used for pharmacokinetic (PK) calculations. PK parameters were fixed and pharmacodynamic data were fitted to effect compartment model proposed by Sheiner. RESULTS: Sevoflurane reduced rocuronium concentration in effect compartment producing 50% inhibition of both T1 and T4 response and significantly delayed not only T1, but also T4 recovery. CONCLUSIONS: Potentiating effect of sevoflurane on rocuronium-induced neuromuscular block influences not only postsynaptic, but also the presynaptic part of the neuromuscular junction, enhancing fade of neuromuscular response to high-frequency stimulation. The intensity of this latter effect is clinically relevant.     

Experimental pharmacology of atracurium dibesylate

Atracurium dibesylate is a new non depolarizing muscle relaxant, metabolized by a non enzymic pathway, the Hofmann elimination. The potency of atracurium in animals was similar to d-tubocurarine and six times less than that of pancuronium. In the cat, the ED50 was 130 micrograms . kg-1; an intravenous dose of 250 micrograms . kg-1 atracurium was sufficient to cause complete neuromuscular block; its duration was 29 min. Single twitch block was readily antagonized by neostigmine 50-100 micrograms . kg-1 or edrophonium 200 micrograms . kg-1. Halothane potentiated the block given by atracurium. Dose ratio for 50% vagal block (ED50) and 50% neuromuscular block was 24; atracurium had weak ganglioplegic effects. 2,000 micrograms . kg-1 atracurium (eight times the neuromuscular blocking dose) reduced mean aortic pressure, heart rate, cardiac output and peripheral resistance. Such effects could be prevented by giving histamine receptor blockers prior to injecting atracurium.     

Clinical evaluation of different doses of pipecuronium bromide during nitrous-oxide-fentanyl anaesthesia in adult surgical patients.

The neuromuscular and cardiovascular effects of three different doses of pipecuronium were studied in 60 adult patients. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 0.1 Hz and 2 Hz. Three subgroups (A, B, C) of 20 patients received pipecuronium doses of 60, 80 and 100 micrograms kg-1, respectively, as an intubating dose and, when necessary, maintenance doses were administered at 25% single twitch recovery in a dose of one-quarter of the initial one. The onset time was 5.4 +/- 2.0 min for 60 micrograms kg-1 and similar for 80 and 100 micrograms kg-1 (3.9 +/- 1.1 and 3.6 +/- 1.1 min). The duration of action was 45 +/- 10 min for 60 micrograms kg-1, 74 +/- 25 and 94 +/- 21 for 80 and 100 micrograms kg-1, respectively. The recovery indices were measured in all patients after neostigmine administration (Groups B and C) and after neostigmine and edrophonium (Subgroup A, 10 patients each). TOF ratio was significant only 2 min after edrophonium administration in Group A patients. Variations of heart rate and blood pressure were not significant.     

Sugammadex比新斯的明更快逆转维库溴铵所致神经肌肉阻滞的多中心随机对照研究

背景 Sugammadex是一种具有特异结构的γ-环糊精,能选择性地与肌松药结合快速逆转罗库溴铵所致的神经肌肉阻滞,并较小程度地逆转维库溴铵所致的神经肌肉阻滞.该研究中,我们对比了行择期手术的患者中sugammadex和新斯的明对逆转维库溴铵所致神经肌肉阻滞的作用.方法 年龄≥18岁,ASA分级Ⅰ～Ⅲ级拟行择期手术的患...     

Accelerated reversal of atracurium blockade with divided doses of neostigmine

The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of neuromuscular blockade was investigated. Neostigmine 0.05 mg X kg-1 was administered either in a single bolus dose (Group I, n = 16) or in an initial dose of 0.01 mg X kg-1 followed three minutes later by 0.04 mg X kg-1 (Group II, n = 16) for antagonism of atracurium-induced blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. The mean time (+/- SD) from the first injection of the drug until the train-of-four (TOF) ratio value had reached 0.75 was significantly shorter in Group II (p less than 0.05) than in Group I (391.8 +/- 83.3 and 468.6 +/- 150.3 seconds respectively). The rate of TOF ratio recovery was 2.5 times faster after neostigmine administration in divided doses. It is concluded that administration of neostigmine in divided doses, as described in this study, produced a significantly faster reversal of residual atracurium-induced neuromuscular blockade as compared to a single bolus administration.     

Can early administration of neostigmine, in single or repeated doses, alter the course of neuromuscular recovery from a vecuronium-induced neuromuscular blockade?

The authors sought to determine whether neostigmine, given at a time when no response to peripheral nerve stimulation could be elicited, hastened recovery from a vecuronium-induced neuromuscular blockade (NMB). The effect of neostigmine (70 micrograms/kg) in antagonizing a profound (no-twitch) vecuronium-induced (0.1 mg/kg) NMB in 40 healthy patients was studied. Patients were randomly assigned to one of four groups specifying the sequence of neostigmine administration. Fifteen minutes after the administration of vecuronium, when there was no detectable twitch response, each patient received either neostigmine (70 micrograms/kg) with glycopyrrolate (15 micrograms/kg) or an equivalent volume of normal saline (placebo). When T1 (the first response in the train-of-four [TOF] sequence) recovered to 10% of control, patients again received either neostigmine with glycopyrrolate in the same doses as before or the placebo. The following variables were measured: times from vecuronium injection until T1 recovered to 10% (t [10]) and 90% (t [90]) of control, and time until the TOF ratio was equal to 75% (t [TOF75]). Mean values of t (90) and t (TOF75) were shorter (54.7-75.2 min and 60.4-79.5 min, respectively) for the three groups who received neostigmine as compared with patients who received two doses of placebo (104.3 and 122.6 min, respectively). There were no differences in the t (90) and t (TOF75) values among the three groups who received neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-tetanic count and train-of-four responses during neuromuscular block produced by vecuronium and infusion of nicardipine

We have examined onset and recovery of neuromuscular block produced by vecuronium using either post-tetanic count (PTC), or the first twitch of the train-of-four (TOF) (T1/T0) and TOF ratio (T4/T1) during continuous infusion of nicardipine. Sixty adult patients were allocated to one of four groups of 15 patients each: nicardipine-PTC, nicardipine- TOF, control-PTC and control-TOF. In the nicardipine-PTC and nicardipine-TOF groups, nicardipine 0.03 mg kg-1 was given before vecuronium 0.1 mg kg-1 and a continuous infusion of nicardipine was started immediately at a rate of 2 micrograms kg-1 min-1. Mean time from administration of vecuronium to onset of neuromuscular block in the nicardipine-PTC and nicardipine-TOF groups was significantly shorter than in the control-PTC and control-TOF groups (166 (SD 39) vs 220 (28) s; P < 0.05). There was no significant difference in recovery of PTC between the nicardipine-PTC and control-PTC groups or in recovery of TOF ratio in the nicardipine-TOF and control-TOF groups. However, during recovery, T1/T0 in the nicardipine-TOF group was significantly less than that in the control-TOF group, 60-100 min after administration of vecuronium.      

Antagonism of rapacuronium using edrophonium or neostigmine: pharmacodynamics and pharmacokinetics

We have studied the pharmacodynamics and pharmacokinetics of rapacuronium (Org 9487) in 70 healthy patients. Neuromuscular transmission was monitored using TOF stimulation of the ulnar nerve and mechanomyography of the adductor pollicis muscle. Half of the patients were given a single dose of rapacuronium 1.5 mg kg-1 and the remainder rapacuronium 1.5 mg kg-1 with three incremental doses of 0.5 mg kg-1, each given when T1/T0 had recovered to 25%. In all patients, neuromuscular block was antagonized using neostigmine 0.05 mg kg-1 or edrophonium 1.0 mg kg-1 (allocated randomly), 2 min after the final dose of rapacuronium. All patients developed complete block after rapacuronium 1.5 mg kg-1. Mean onset time was 66 (SD 24) s. In patients who received an antagonist 2 min after the first dose of rapacuronium, time to recovery of T1/T0 to 25% was similar after neostigmine (9.8 (3.8) min) and edrophonium (10.3 (4.3) min): in patients who received incremental doses of rapacuronium, spontaneous recovery of T1/T0 to 25% after the first dose was 18.9 (4.7) min. In those who received an antagonist 2 min after the first dose of rapacuronium, times to recovery of T4/T1 to 0.7 were also similar after neostigmine (23.7 (7.7) min) and edrophonium (29.1 (10.7) min). After three incremental doses of rapacuronium, there was a longer time to recovery of T1/T0 = 25% after neostigmine compared with edrophonium (5.1 (1.0) vs 3.3 (1.3) min; P < 0.05) but more rapid recovery to T1/T0 = 75% (10.1 (2.9) vs 16.8 (10.1) min; P < 0.05) and T4/T1 = 0.7 (19.8 (6.3) vs 35.1 (10.4) min; P < 0.05). A three-compartment pharmacokinetic model was justified. Typical values for clearance and initial volume of distribution (V1) were 4.4 ml kg-1 min-1 and 94.8 ml kg-1, respectively. In females, clearance was decreased by 38.5% compared with males and V1 was decreased by 25% in patients aged more than 65 yr.      

Potency and time course of action of rocuronium during desflurane and isoflurane anaesthesia

We have studied the potency and onset and duration of action of rocuronium in patients anaesthetized with 1 MAC of desflurane or isoflurane (in 66% nitrous oxide). Potency was estimated using the single bolus dose technique. Neuromuscular block was measured by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The ED50 and ED95 of rocuronium were estimated as 138 (95% confidence limits 117-162) micrograms kg-1 and 281 (241-328) micrograms kg-1, and 126 (105-151) micrograms kg-1 and 283 (236-339) micrograms kg-1 during desflurane and isoflurane anaesthesia, respectively. The mean times to onset of maximum block after rocuronium 0.6 mg kg-1 were 1.0 (SD 0.10) min and 1.1 (0.15) min, respectively, during anaesthesia with desflurane and isoflurane. The respective times to recovery of T1 (the first response in the train-of- four (TOF) stimulation) to 25% and 90% were 36 (8.3) min and 54 (15.4) min during desflurane anaesthesia and 31 (8.2) min and 45 (12.7) min during isoflurane anaesthesia. The times to recovery of the TOF ratio to 0.7 were 66 (13.4) min and 52 (16.3) min and the 25-75% recovery indices 14 (5.3) min and 10 (3.2) min, respectively, in the desflurane and isoflurane groups. There were no differences in the estimated potency or onset of action of rocuronium during desflurane and isoflurane anaesthesia. However, duration of action tended to be longer curing desflurane anaesthesia although only the differences in times to TOF ratio of 0.7 and the recovery indices were close to being significantly different (P = 0.0503 and 0.0560).      

Train-of-Four recovery after pharmacologic antagonism of pancuronium-, pipecuronium-, and doxacurium-induced neuromuscular block in anaesthetized humans

Previous studies have suggested that the increased duration of action of long-acting neuromuscular relaxants may make their pharmacologic antagonism more difficult and, thus, increase the likelihood of residual block. This hypothesis was tested in healthy, adult humans who received a background of isoflurane/N₂O/fentanyl anaesthesia.
Study subjects were paralyzed with either pancuronium (N=8), pipecuronium (N=8), or the longer-acting relaxant, doxacurium (N=8). Neuromuscular function was monitored, and, using a blinded, randomized study design, the relaxants were titrated to identify the ED₉₅ dose in each patient. Thereafter, spontaneous recovery was observed until there was 25% ofbaseline response to the first supramaximal twitch (Tl) in a train-of-four (TOF). At this time, the block was antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 0.014 mg/kg i.v., and recovery of TOF was recorded.
Spontaneous recovery to 25% of the baseline Tl response occurred at 52± 14 min (mean±SD) following administration of either pancuronium and pipecuronium, and 85 ±33 min following doxacurium ( P <0.05 for doxacurium versus pancuronium and pipecuronium). In doxacurium-rreated patients, reversal of block with neostigmine was less predictable and less complete than with the other two relaxants. For example, the ratio of the fourth to first twitch (T4/T1) of the TOF at 10 and 15 min after reversal was significantly less with doxacurium (59 ±14% and 61±16%, respectively) than with either pancuronium (75±6% and 75±10%) or pipecuronium (76±9% for both). At 30 min post-neostigmine, the incidence of residual block (i.e. T4/T1 <0.70) was: pancuronium 2 patients, pipecuronium 1 patient, and doxacurium 5 patients.
These studies support the hypothesis that incomplete reversal of neuromuscular block is more likely with longer-acting neuromuscular relaxants.