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.     

Tactile evaluation of train-of-four count as an indicator of reliability of antagonism of vecuronium- or atracurium-induced neuromuscular blockade.

Recent evidence suggests that edrophonium is not the agent of choice to reverse profound neuromuscular blockade but remains an efficacious drug when the level of neuromuscular blockade to be antagonized is modest. We studied 90 healthy adults in an attempt to address the questions: 1) How much variability in such neuromuscular parameters as single twitch height and the train-of-four (TOF) fade ratio (T4/T1) exist when the TOF count first returns to four palpable responses? 2) Is edrophonium a reliable antagonist at this measured point of recovery? 3) What is the optimal dose of edrophonium needed to produce prompt (less than 10 min) and satisfactory (T4/T1 greater than 0.7) reversal when the fourth response of the thumb to indirect TOF stimulation just becomes palpable? Patients were given a bolus atracurium or vecuronium (n = 45 in each group) followed by an iv infusion sufficient to maintain single twitch as measured by electromyography at 10-15% of control values. At the end of surgery, the infusion was terminated and spontaneous recovery was allowed to begin. Once the tactile TOF count was four, edrophonium 0.3, 0.5, or 0.75 mg/kg was administered. At a count-of-four the first twitch averaged 37% of control (+/- 8.5% standard deviation; pooled data from all groups) and the mean T4/T1 ratio was 0.14 +/- 0.049. After atracurium neuromuscular blockade, edrophonium 0.3 mg/kg produced adequate antagonism in 10 min. At this time the mean T4/T1 ratio was 0.79 +/- 0.07 and the lowest observed value was 0.67. Increasing the edrophonium dose to 0.75 mg/kg accelerated recovery by 4-5 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Model-based adaptive closed-loop feedback control of atracurium-induced neuromuscular blockade

Closed-loop control of atracurium-induced neuromuscular blockade by a model-based adaptive feedback algorithm is described. Mean offsets (+/- s.d.) from setpoints at 50, 70 and 90% neuromuscular blocks using the Relaxograph were 1.1 +/- 1.3, 0.2 +/- 0.7 and 0.1 +/- 0.4%, respectively. Correspondingly, the mean steady-state rates of infusion of atracurium were 0.20 +/- 0.06, 0.25 +/- 0.03 and 0.39 +/- 0.10 mg.kg-1.h-1. The described controller provides reasonable control of atracurium dosing at different degrees of neuromuscular blockade. It gives a solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.     

Inflammatory liver disease shortens atracurium-induced neuromuscular blockade in rats.

BACKGROUND: and objective Inflammatory liver dysfunction in rats leads to a prolonged vecuronium-induced neuromuscular blockade due to insufficient metabolism. A coexisting resistance against the drug partly counteracts this prolongation. The present study investigates the pharmacodynamics of atracurium whose metabolism does not depend on liver function. METHODS: Male Sprague-Dawley rats (n=14; 290 +/- 30 g) were randomly allocated to either a group in which liver inflammation was induced by intravenous injection of 60 mg kg(-1) heat-killed Corynebacterium parvum or to a control group. On day 5 after injection, liver function was assessed using the aminopyrine breath test. Under propofol anaesthesia, duration of action of atracurium (4.8 mg kg(-1)) was measured by evoked mechanomyography (stimulation of the sciatic nerve; contraction of the gastrocnemius muscle). Nitric oxide concentrations, as variables for the severity of the inflammation, were assessed by measurement of nitrite/nitrate plasma concentrations. RESULTS: In C. parvum-injected rats, nitrite/nitrate plasma concentrations were increased (972 +/- 597 vs. 25 +/- 7 micromol L(-1)), the aminopyrine turnover was depressed (1.7 +/- 0.4% vs. 3.5 +/- 0.5%), and the atracurium-induced neuromuscular blockade was shortened (372 +/- 128 s vs. 1081 +/- 234 s). CONCLUSIONS: A systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to atracurium. Further investigations are needed regarding a possible up-regulation of acetylcholine receptors or an increased protein binding of atracurium during sepsis to clarify reasons behind this phenomenon.     

Neuromuscular effects of atracurium during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia in humans

To compare the effect of halothane and enflurane on an atracurium-induced neuromuscular blockade, the authors studied 40 patients during elective surgery. During 1.25 MAC enflurane-nitrous oxide (n = 20) or halothane-nitrous oxide (n = 20) (MAC value includes contribution from 60% nitrous oxide), the doses depressing twitch tension 50% (ED50S) for atracurium were 70 and 77 micrograms/kg, respectively. The difference was not significant. Time from injection to peak effect did not differ between groups. However, the duration of action of atracurium (expressed as duration 50 or the duration of a 50% blockade) was longer during enflurane-nitrous oxide anesthesia (34.2 min) than during halothane-nitrous oxide anesthesia (25.5 min) (P less than 0.05). The authors conclude that the potency of atracurium does not differ during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia. Combining the results of this study with a previous study (atracurium ED50 = 68 micrograms/kg and 83 micrograms/kg during isoflurane-nitrous oxide and fentanyl-nitrous oxide anesthesia respectively), the potency of atracurium does not differ by more than 20% among the four anesthetic techniques studied. The background anesthetic appears to have less effect on an atracurium-induced neuromuscular blockade than on one produced by other longer-acting nondepolarizing muscle relaxants (e.g., pancuronium and d-tubocurarine).     

Atracurium: neuromuscular blockade in repeated administration

The neuromuscular blocking action of repeated injections of atracurium and vecuronium was studied in 74 surgical patients during balanced anaesthesia (methohexitone or etomidate, intubation after suxamethonium, fentanyl, droperidol, N2O). The initial bolus dose (ID) of atracurium was 0.25 mg/kg and of vecuronium 0.05 mg/kg followed by repeated increments (RD) of atracurium 0.1 mg/kg and vecuronium 0.0125 mg/kg when neuromuscular function (EMG) had recovered to about 30% of pre-relaxant control. Dose-response relationships revealed atracurium to be about 1/5 as potent as vecuronium; the ED50 of atracurium was 0.13 +/- 0.03 mg/kg and of vecuronium 0.023 +/- 0.007 mg/kg. The ID of both relaxants produced a neuromuscular blockade of about 90% within 4 min. The duration from the time of injection to 30% recovery was slightly longer in atracurium 26 +/- 9 min. In all patients the RD produced within 3.5 min satisfactory muscle relaxation with a neuromuscular block of about 85%. The mean duration of atracurium (18 min) was 5-10 min longer than of vecuronium (12 min). To maintain good surgical relaxation (more than 70% blockade) atracurium 0.32 mg/kg X h and vecuronium 0.056 mg/kg X h were required. No cumulation could be measured after repeated injections. The recovery time of atracurium and vecuronium at the end of anaesthesia was 10-12 min. Neither cardiovascular side-effects nor signs of histamine release were observed after both relaxants in our particular dose range. It is concluded, that atracurium is a favourable blocker for anaesthetic practice: The time of onset is approximately the same compared with vecuronium. The duration of action, however, is slightly longer but still truly intermediate long.(ABSTRACT TRUNCATED AT 250 WORDS)     

Closed-loop infusion of atracurium with four different anesthetic techniques

A new proportional-integral-derivative (PID) controller for the automated closed-loop delivery of atracurium was tested in 32 patients. Groups of 8 patients received halothane, enflurane, isoflurane, or N2O/morphine anesthesia. After induction of anesthesia with sodium thiopental 3-5 mg.kg-1, a bolus of atracurium 0.2 mg.kg-1 was delivered by the controller; this was followed by an infusion calculated by the controller to maintain the electromyogram (EMG) at a setpoint of 90% neuromuscular blockade. The average overshoot for the controller was 10.1% and the mean steady-state error 3.0%. The mean infusion rates for atracurium to maintain 90% blockade were calculated for each anesthetic group, with the inhalation anesthetics at 1 MAC. Infusion rates for N2O/morphine, halothane 0.8%, enflurane 1.7%, and isoflurane 1.4% at 90% blockade were 5.7 +/- 0.6, 4.9 +/- 0.3, 3.5 +/- 0.3, and 4.1 +/- 0.5 micrograms.kg-1.min-1, respectively (mean +/- SE). The infusion rate for atracurium at 90% blockade under N2O/morphine anesthesia was in general agreement with published values. The other infusion rates at 90% blockade have not been reported previously, but correspond to the known potencies of these inhalation anesthetics for augmentation of neuromuscular blockade. This controller performed well in comparison to previously developed controllers, and in addition was used as a research tool for rapid estimation of infusion rates.     

Postoperative neuromuscular function in pediatric day-care patients.

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.     

Muscle relaxation and increasing doses of propofol improve intubating conditions

PURPOSE: Muscle relaxants and anesthetics are usually associated during intubation. However, their relative role to facilitate the process is not clearly defined. This study was designed to determine, during intubation: i). the relative role of anesthetics and atracurium-induced neuromuscular block and; ii). the effect of different doses of propofol in the presence of complete muscle block. METHODS: Patients were randomized to four groups and received fentanyl and a standardized anesthetic procedure. Patients from groups high (H; n = 45), medium (M; n = 48) and low (L; n = 47) received 2.5 mg x kg(-1), 2.0 mg x kg(-1), and 1.5 mg x kg(-1) of propofol respectively. Atracurium (0.5 mg x kg(-1)) was then injected and tracheal intubation performed once complete block was achieved at the orbicularis oculi. Patients from group without atracurium (WA; n = 20) received propofol as in group H. Intubation was performed at the expected onset time of action of atracurium. RESULTS: Using the same dose of propofol, the incidence of good or excellent intubating conditions was 35% without atracurium and 95% with atracurium (P < 0.0001). In patients receiving atracurium, clinically acceptable intubating conditions were more frequently achieved in groups receiving the highest propofol doses (group H or M vs group L; P < 0.03). CONCLUSION: Our study confirms the interaction between anesthesia and muscle relaxation to produce adequate intubating conditions. In the conditions described, intubating conditions were more dependent on atracurium-induced neuromuscular blockade than on anesthetics, but both atracurium and propofol improved intubating conditions.     

Neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium

To compare the time course of neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium, the authors studied 98 patients anesthetized with nitrous oxide (60%) and halothane or enflurane. Neuromuscular blockade, as monitored by single stimulus-induced twitch tension (TT), was antagonized at varying degrees of spontaneous recovery (2-80% of control TT). Time to antagonism (time from injection of neostigmine or edrophonium to 90% recovery of control TT) was not different between edrophonium, 0.5 mg/kg, and neostigmine, 0.04 mg/kg, when spontaneous recovery had been allowed to occur to at least 11% of control TT prior to antagonist administration (P greater than 0.05). For profound neuromuscular blockade (TT less than or equal to 10% of control) induced by pancuronium or vecuronium, time (mean +/- SD) to antagonism with neostigmine, 0.04 mg/kg, was 7.0 +/- 2.2 min and 5.6 +/- 1.7 min, respectively, while the same for edrophonium, 0.5 mg/kg, was 20.0 +/- 8.0 min and 15.0 +/- 12.5 min, respectively (P less than 0.05). Time to antagonism of profound atracurium-induced neuromuscular blockade was 8.5 +/- 3.3 min for neostigmine, 0.04 mg/kg, and 9.8 +/- 7.0 min for edrophonium, 0.5 mg/kg, (P less than 0.05). For profound vecuronium-and pancuronium-induced neuromuscular blockade, time to antagonism by edrophonium, 1.0 mg/kg, was 4.6 +/- 3.0 min and 3.9 +/- 1.6 min respectively. The authors conclude that neostigmine, 0.04 mg/kg, antagonizes neuromuscular blockade within 12 min when TT is greater than 2% of control at time of reversal. When TT is greater than 10% of control, edrophonium, 0.5 mg/kg, produces similar time to antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentrations of pancuronium and neuromuscular blockade after injection into the isolated arm, bolus injection, and continuous infusion.

To establish whether the plasma concentration of pancuronium reflects magnitude of neuromuscular blockade, the authors determined times of recovery from neuromuscular blockade and associated plasma concentrations following equipotent doses of pancuronium using three methods of pancuronium administration: the isolated-arm technique in conscious volunteers (n = 4), and the bolus intravenous injection (n = 7) and continuous-infusion methods (n = 3) in anesthetized patients. Although maximum depressions of twitch tension were similar (85 +/- 11,91 +/- 6, and 92 +/- 4 per cent, respectively) with the three techniques, times to recovery from neuromuscular blockade differed significantly, being 10 +/- 2 min with the isolated-arm technique, 23 +/- 7 min with the bolus-injection technique, and 46 +/- 5 min with the continuous-infusion method. The plasma concentration of pancuronium necessary for neuromuscular blockade was least with the isolated-arm technique and greatest with continuous infusion. At 25 and 75 per cent recovery, mean plasma concentrations were 0.07 +/- 0.01 and 0.04 +/- 0.01 microgram/ml in the isolated arm; 0.13 +/- 0.04 and 0.09 +/- 0.02 microgram/ml after bolus injection, and 0.20 +/- 0.04 and 0.11 microgram/ml during continuous infusion, respectively. It is concluded that the relationship between plasma concentration of pancuronium and magnitude of neuromuscular blockade depends on the method of pancuronium administration.     

Effect of partial neuromuscular blockade on intraoperative electromyography in patients undergoing resection of acoustic neuromas.

Intraoperative electromyographic monitoring of the facial nerve during acoustic neuroma excision provides early detection of nerve injury and improved outcome. To determine whether a useful level of peripheral neuromuscular blockade could be achieved without compromise of facial electromyographic monitoring, we studied 10 patients undergoing resection of acoustic neuroma. Facial nerve monitoring was accomplished by placement of wire electrodes in the orbicularis oris, orbicularis occuli, and mentalis muscles. Peripheral neuromuscular blockade was assessed by recording unprocessed hypothenar compound muscle action potentials (CMAPs). After induction of anesthesia, an infusion of atracurium (1.0 micrograms.kg-1.min-1) accompanied by a bolus dose of 50 micrograms/kg was administered. The infusion was then increased in increments of 0.5 micrograms.kg-1.min-1 until a 50% reduction in hypothenar single-twitch CMAP was obtained. Facial nerve function was continuously monitored by comparison of facial CMAPs produced by stimulation of the nerve proximal and distal to the tumor bed. The mean (+/- SD) infusion rate of atracurium was 2.55 +/- 0.75 micrograms.kg-1.min-1. Decrements in facial nerve CMAPs were detected in 6 of 10 patients, and all demonstrated moderate to severe facial nerve dysfunction. In no patient was an unexpected deficit present postoperatively. Moderate degrees of peripheral neuromuscular blockade can be achieved without compromising facial nerve electromyographic monitoring.     

A double-blind, randomized comparison of low-dose rocuronium and atracurium in a desflurane anesthetic

STUDY OBJECTIVES: To compare the neuromuscular and hemodynamic effects of rocuronium and atracurium when administered during a desflurane-based anesthetic. DESIGN: Randomized, double-blind clinical trial. PATIENTS: 51 adult ASA physical status I and II patients scheduled for general surgical operations. SETTING: University-based NCI-designated cancer center. INTERVENTIONS: Patients received either 0.45 mg/kg rocuronium (n = 28) or atracurium 0.5 mg/kg (n = 23). Induction of anesthesia was accomplished by 2 microg/kg fentanyl intravenously (IV) and 1.5 mg/kg propofol IV and maintained by a nitrous oxide/oxygen desflurane anesthetic. MEASUREMENTS AND MAIN RESULTS: A neuromuscular monitor was used at the adductor pollicis to monitor and record twitch response to train-of-four electrical stimulation. Baseline heart rate (HR) and blood pressure (BP) were measured and again at 2, 5, 10, and 15 minutes after muscle relaxant administration. Patients in the rocuronium group were found to have shorter times to 80%T(1)depression (109 +/- 53 vs. 135 +/- 47 sec), although those differences did not reach statistical significance (p = 0.07). Percent of the first twitch (T(1) ) was significantly lower in the patients receiving rocuronium at 60 seconds (53 +/- 24 vs. 73 +/- 27 sec; p = 0.006) and 90 seconds (25 +/- 22 vs. 47 +/- 29 sec; p = 0.003) than in the patients receiving atracurium. Duration was shorter in rocuronium-treated patients (25% T(1) recovery = 32 +/- 12 vs. 54 +/- 14 min; p < 0.001) than the patients receiving atracurium. Intubation scores were better at 60 seconds after muscle relaxant administration in the rocuronium group. No significant differences in HR or BP were seen between the patients in the two groups. CONCLUSIONS: Rocuronium at a dose of 0.45 mg/kg possesses a fairly rapid onset of neuromuscular blockade and has short:intermediate duration of action when used with a desflurane anesthetic. This quality makes it a desirable drug for operations of relatively short duration. Rocuronium at a dose of 0.45 mg/kg has a faster onset and shorter duration than atracurium, at 0.5 mg/kg, when used with a desflurane anesthetic.     

Reversal of intense neuromuscular blockade following infusion of atracurium

In order to evaluate reversal time from very intense neuromuscular blockade caused by a continuous infusion of atracurium, the time course of neostigmine induced reversal from different levels of neuromuscular blockade was evaluated using the post-tetanic count (PTC) and the train-of-four (TOF) in 30 patients anesthetized with nitrous oxide, fentanyl, and thiopental. Reversal time (time from administration of neostigmine at different PTC levels to a TOF ratio of 0.7) was found to depend upon the degree of blockade at the time of reversal. Median reversal time from a PTC of 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, and greater than 13 (but less than 10% twitch height) to a TOF ratio of 0.7 was 31, 23, 19, 18, 14, and 13 min, respectively. Spontaneous recovery from PTC level of 1-2, when atracurium infusion was stopped, to a PTC level at which antagonism was induced and reversal time were both correlated to the square root of the PTC. Total recovery time (spontaneous recovery plus reversal time) was not shortened by an early injection of neostigmine. It is concluded that neostigmine administration during intense neuromuscular blockade following atracurium infusion does not shorten total recovery time and offers no clinical advantages.     

Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade

The effect of epidurally administered bupivacaine on duration, intensity and reversal characteristics of atracurium-induced neuromuscular blockade was studied in 30 healthy patients anaesthetized with thiopentone, fentanyl, midazolam and nitrous oxide. Fifteen patients received, in addition, epidural anaesthesia with bupivacaine. The remaining patients served as controls. The ulnar nerve was stimulated at the wrist and the evoked twitch response from the adductor pollicis was measured with a force displacement transducer. Neuromuscular blockade was induced with atracurium 0.5 mg i.v. and maintained with repeated doses of atracurium 0.15 mg/kg whenever the twitch height had recovered to 15% of the initial twitch height. After operation, the neuromuscular blockade was reversed with neostigmine when the twitch height had recovered to 15%. In the epidural group the clinical duration of neuromuscular blockade, time until first response to train-of-four (TOF) and reversal time were all significantly prolonged (P less than 0.05). Post-tetanic count (PTC) after 20 min was also significantly lower in the epidural group (P less than 0.05). It is therefore concluded that epidurally administered bupivacaine prolongs atracurium-induced neuromuscular blockade. The clinical implication of the modest prolongation is, however, limited.     

The Maximum Depth of an Atracurium Neuromuscular Block Antagonized by Edrophonium to Effect Adequate Recovery

Background: The inability of edrophonium to rapidly reverse a deep nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling effect to antagonism of neuromuscular block by edrophonium. A ceiling effect means that only a certain level of neuromuscular block could be antagonized by edrophonium. Neuromuscular block greater than this could not be completely antagonized irrespective of the dose of edrophonium administered. The purpose of this study was to determine whether a ceiling effect occurred for antagonism of an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum level of block that could be antagonized by edrophonium.

Methods: In 30 adult patients, atracurium was administered to maintain a constant neuromuscular block. The level of block varied between patients. Evoked adductor pollicis twitch tension was monitored. Incremental doses of edrophonium were administered while the infusion of atracurium continued. Increments were given until adequate recovery occurred, as defined by a train-of-four (TOF) ratio greater or equal to 70%, or until no further antagonism of the block could be achieved. The probability of being able to effect adequate recovery by antagonism with edrophonium was determined using a logistic regression model. Cumulative dose-response curves were constructed using the logit transformation of the neuromuscular effect versus the logarithm of the cumulative dose of edrophonium.

Results: In 14 patients with a block of 25-77% depression of the first twitch response, antagonism by edrophonium to a TOF ratio greater or equal to 70% was possible, whereas in 16 patients with a 60-92% depression of T1, a TOF ratio > 70% was not achievable, indicating that a ceiling effect for antagonism by edrophonium occurred. A block of 67 plus/minus 3% (mean plus/minus SE) had a 50% probability of adequate antagonism. In patients in whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic effect occurred with an edrophonium dose of 0.8 plus/minus 0.33 mg *symbol* kg sup -1 (mean plus/minus SD).     

Accelerated onset of non-depolarizing neuromuscular blocking drugs: pancuronium, atracurium and vecuronium. A comparison with succinylcholine

The time of onset and degree of neuromuscular blockade (NMB) in 80 anaesthetized patients, following either a single bolus injection of pancuronium 0.95 mg kg-1, atracurium 0.53 mg kg-1 or vecuronium 0.07 mg kg-1, or divided doses of pancuronium 0.15 mg kg-1, atracurium 0.07 mg kg-1 or vecuronium 0.01 mg kg-1 administered 3 min or 5 min before the second dose of pancuronium 0.08 mg kg-1, atracurium 0.46 mg kg-1 or vecuronium 0.06 mg kg-1, were determined and compared to the same parameters measured following succinylcholine administration (1 mg kg-1). The time to maximum NMB (100%) following the administration of succinylcholine was 58.1 +/- 5.3 s, whereas the time to maximum NMB (100%) following a single bolus injection of either pancuronium, atracurium or vecuronium was 130.6 +/- 22.2, 93.0 +/- 6.4, 127.5 +/- 13.0 s, respectively. These values for time to maximum NMB are significantly longer than the time required for succinylcholine to achieve maximal blockade. The time to attain maximum NMB following divided doses of pancuronium, atracurium or vecuronium separated by 3 min decreased significantly to 77.9 +/- 4.3, 77.5 +/- 7.6, 89.0 +/- 8.6 s, respectively. However, when the two doses of drug were separated by 5 min, only small, non-significant further decreases occurred in the time required to achieve maximum blockade. Although the time to maximum NMB following divided doses of pancuronium, atracurium or vecuronium is significantly longer than that for succinylcholine, divided dosing significantly decreases the time required to reach maximal NMB.     

A comparison of edrophonium and neostigmine for the antagonism of atracurium-induced neuromuscular block

Edrophonium, 0.5 mg/kg, or neostigmine, 0.05 mg/kg, was administered to groups of 20 patients each, for antagonism of atracurium-induced block at varying degrees of spontaneous recovery. Neuromuscular block was studied using train-of-four (TOF) stimulation. Adequate reversal of neuromuscular block (TOF ratio of 0.7) was achieved in all patients given neostigmine but only in 13 of the 20 given edrophonium. The onset of action of edrophonium (23 sec) was significantly more rapid than that of neostigmine (40 sec), as was the time taken to attain a TOF ratio of 0.7 in those in whom adequate antagonism was achieved (68 sec for edrophonium and 246 sec for neostigmine). Five of the seven patients in the edrophonium group who failed to be reversed adequately had shown three or fewer twitches to a TOF stimulation. It is concluded that edrophonium in a dose of 0.5 mg/kg does not consistently antagonize neuromuscular blockade induced by atracurium, particularly if all four responses to a TOF stimulation are not elicited prior to antagonism of the block.     

Effects of propofol and isoflurane on the neuromuscular block induced by atracurium]

Speed of onset, duration of action and recovery time for a bolus injection of atracurium were measured in two groups of patients. In group I anaesthesia considered of propofol, fentanyl, nitrous oxide and oxygen mixture. The induction dose of propofol was 2 mg/kg-1 followed by an infusion of 9.0 mg/kg-1/h-1 for first half hour and 4.5 mg/Kg-1/h-1 subsequently. In group II anaesthesia consisted of isoflurane, fentanyl, nitrous oxide and oxygen mixture. Isoflurane was given upon clinical needs. Speed of onset, duration of action, and recovery time for atracurium were measured in the two groups. No statistically significant differences between speed of onset and duration of action between the two groups were found. The recovery period from T1 = 10% to T1 = 70% twitch response was considerably longer with isoflurane (25 min +/- 6) than with propofol (18 min +/- 3) (p less than 0.01). Results obtained suggest that for adequate relaxation during tracheal intubation smaller doses of atracurium are not needed during isoflurane than propofol administration. Because of the longer recovery period of residual neuromuscular blockade during isoflurane anaesthesia decreasing doses of atracurium and careful monitoring of twitch depression tension are also suggested.     

Continuous infusion of atracurium in children

Atracurium infusion requirements were determined in 28 children anesthetized with N2O:O2 narcotic, N2O:O2 halothane (1% inspired), and N2O:O2 enflurane (2% inspired). When the patient was recovering from a bolus dose of 0.4 mg/kg atracurium, a continuous infusion of atracurium was started and the rate was adjusted to maintain 90-99% muscle twitch depression. Patients receiving enflurane anesthesia required atracurium at an infusion rate of 4.9 +/- 0.3 micrograms X kg-1 X min-1 which was a significantly lower rate (P = 0.0001) than those anesthetized with halothane (8.3 +/- 0.4 micrograms X kg-1 X min-1) or with N2O:O2 and narcotic (9.3 +/- 0.5 micrograms X kg-1 X min-1). At the onset of neuromuscular blockade, the twitch response disappeared faster after train-of-four stimulation repeated every 10 s than after single twitch rates of stimulation at 0.1 Hz. In children, during halothane anesthesia after 0.4 mg/kg atracurium, the response of the adductor of the thumb was ablated in 2.0 +/- 0.3 min with train-of-four stimulation, and in 3.7 +/- 0.4 min with single twitch stimulation. The authors recommend the use of a nerve stimulator during continuous infusion of atracurium because of the marked interpatient differences in infusion-rate requirements.