Comparative fading responses induced by mivacurium,cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat

PURPOSE: It has been suggested that the different degrees of fade induced by nondepolarizing neuromuscular blocking agents in repetitive muscular contractions may be due to the varying affinities or binding kinetics of presynaptic nicotinic receptors. We compared the degree of fade induced by mivacurium, cisatracurium, and d-tubocurarine in the cat muscular compound action potential (mCAP). METHODS: In 21 cats, mCAPs of the gastrocnemius muscle were evoked by paired (conditioning and test stimuli) and 2 Hz train-of-four (TOF) sciatic nerve stimulation. The interval between the paired stimuli was changed stepwise from 7 to 1000 ms. The ratios of the amplitude evoked by test stimulus to that evoked by the conditioning stimulus (M2/M1 ratios) and TOF ratios were measured. After baseline variables had been obtained, the cat received either mivacurium (0.08 mg x kg(-1), n = 7), cisatracurium (0.05 mg x kg(-1), n = 7), or d-tubocurarine (0.5 mg x kg(-1), n = 7). A series of M2/M1 ratios and TOF ratios were measured at various levels of partial block during recovery. RESULTS: At 10% of baseline amplitude, all agents significantly depressed the M2/M1 ratios (i.e., fade) at relatively longer intervals of paired stimuli (mivacurium, > or = 100 ms; cisatracurium. > or = 40 ms; and d-tubocurarine, > or = 20 ms), when compared with baseline. The order of activity to produce fade was mivacurium < cisatracurium < d-tubocurarine. A similar result was obtained in TOF ratios measured at various levels of neuromuscular block. CONCLUSION: Our results suggest that mivacurium shows a lesser degree of fade during partial neuromuscular block than cisatracurium and d-tubocurarine.     

Timing of reversal with respect to three nerve stimulator end‐points from cisatracurium‐induced neuromuscular block

After elective ear surgery with cisatracurium neuromuscular blockade, 48 adults were randomly assigned to receive neostigmine: (a) at appearance of the fourth twitch of a ‘train‐of‐four’; (b) at loss of fade to train‐of‐four; or (c) at loss of fade to double‐burst stimulation, all monitored using a TOF‐Watch SX^® on one arm. For each of these conditions, the recovery from train‐of‐four (TOF) ratio was measured in parallel objectively using a TOF‐Watch SX placed on the contralateral arm. The median (IQR [range]) time from administration of reversal to a train‐of‐four ratio ≥ 0.9 was 11 (9–15.5 [2–28]) min, 8 (4–13.5 [1–25]) min and 7 (4–10 [2–15]) min in the three groups, respectively. This recovery time was significantly shorter when reversal was given at loss of fade to double‐burst stimulation (c), than when given at the appearance of the fourth twitch (a), p = 0.046. However, the total time to extubation may be unaffected as it takes longer for fade to be lost after double‐burst stimulation than for four twitches subjectively to appear.     

Comparison of double-burst and train-of-four stimulation to assess neuromuscular blockade in children

Double-burst stimulation (DBS), a new technique to evaluate neuromuscular function, consists of two 50-Hz trains of 60-ms duration and 750 ms apart. DBS was compared with train-of-four (TOF) stimulation in 21 children aged 3-10 yr, during halothane anesthesia. On one arm the ulnar nerve was stimulated supramaximally with TOF stimulation every 12 s and the force of the evoked contraction of the adductor pollicis measured with an FTO3 force transducer and recorded on paper. Atracurium (0.4-0.5 mg.kg-1) was administered. During recovery from neuromuscular blockade, TOF stimulation was interrupted periodically and DBS substituted. The same stimulation patterns were applied to the ulnar nerve of the other arm simultaneously, and the clinical anesthesiologist was asked to estimate the degree of fade with both. There was good correlation between the measured TOF ratio (ratio of fourth to first response) and DBS ratio (ratio of second to first response). The TOF and DBS ratios above which fade could no longer be appreciated manually were (mean +/- SEM) 0.44 +/- 0.03 and 0.67 +/- 0.04 (P = 0.0002). Corresponding ranges were 0.3-0.8 for TOF and 0.4-0.9 for DBS, but DBS fade was always apparent if TOF fade could be detected. Therefore, in children, DBS is more sensitive than is TOF stimulation for the clinical assessment of recovery from neuromuscular blockade.     

Twitch augmentation and train-of-four fade during onset of neuromuscular block after subclinical doses of suxamethonium

We have studied the train-of-four (TOF) response mechanomyographically during onset of neuromuscular block produced by subclinical doses of suxamethonium in order to follow the augmentation of the first twitch of the TOF (T1) and TOF fade compared with control TOF responses before the drug was given. In the groups given suxamethonium 0.05, 0.1, 0.2 and 0.3 mg kg-1, the increments in T1 after administration of the drug were observed before twitch depression occurred; these were mean 22.3 (SEM 8.1)%, 19.2 (3.3)%, 10.8 (2.0)% and 4.2 (2.2)%, respectively. This effect was more marked with the lower doses (P < 0.05). The degree of TOF fade was moderate during onset of neuromuscular block and depended on the dose of drug. The results of this study suggest that low doses of suxamethonium produced transient increase in muscle tension and twitch depression with significant TOF fade. We conclude that suxamethonium was associated with presynaptic effects as a consequence of brief stimulation of acetylcholine release followed by progressive diminution at the neuromuscular junction.      

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.     

Manual evaluation of residual curarization using double burst stimulation: a comparison with train-of-four

Double burst stimulation (DBS) is a new mode of stimulation developed to reveal residual neuromuscular blockade under clinical conditions. The stimulus consists of two short bursts of 50 Hz tetanic stimulation, separated by 750 ms, and the response to the stimulation is two short muscle contractions. Fade in the response results from neuromuscular blockade as with train-of-four stimulation (TOF). The authors compared the sensitivity of DBS and TOF in the detection of residual neuromuscular blockade during clinical anaesthesia. Fifty-two healthy patients undergoing surgery were studied. For both stimulation patterns the frequencies of manually detectable fade in the response to stimulation were determined and compared at various electromechanically measured TOF ratios. A total of 369 fade evaluations for DBS and TOF were performed. Fade frequencies were statistically significantly higher with DBS than with TOF, regardless of the TOF ratio level. Absence of fade with TOF implied a 48% chance of considerable residual relaxation as compared with 9% when fade was absent with DBS. The results demonstrate that DBS is more sensitive than TOF in the manual detection of residual neuromuscular blockade.     

DIFFERENTIAL EFFECTS OF MYONEURAL BLOCKING DRUGS ON NEUROMUSCULAR TRANSMISSION

The relationship between the depression in the amplitude ofthe compound muscle action potennal and neuromuscular decrement(fade) was studied during the induction of non-depolarizingblockade, using a train of four supramaximal stimuli. Neuromusculardecrement (%) was defined as: {1 — (amplitude of fourthmuscle action potential)/(amplitudc of first muscle action potential)}x 100. When the amplitude of the first action potential wasreduced by M%, mean neuromuscular decrement increased in theorder pancuronium <<alcuronium <<tubocurarine cfazadinium<<gallamine. Similarly, the slope of the regression linerelating the decrease in the amplitude of the action potentialto decrement was least wth pancuronium and greatest with gallarmine.These results may reflects different affinities or intrinsicactivities of the five drugs for prejunctional and postjunctionalreceptors. Thus, pancuronium may have a greater affinity forpostsynaptic receptors, while tubocurarine and gallamine affectselectively the motor nerve terminal. It was confirmed thatfazadinium had a more rapid onset of action than any of theother myoneural blocking drugs studied.     

Posttetanic potentiation and fade in the response to tetanic and train-of-four stimulation during succinylcholine-induced block

We designed this study to confirm anecdotal observations that neuromuscular block after a single administration of succinylcholine is characterized by fade to train-of-four (TOF) or tetanic stimulation, as well as posttetanic potentiation. This prospective, randomized, 2-center observational study involved 100 patients. Patients were allocated to 1 of 5 groups and received 0.1, 0.3, 0.5, 0.75, or 1.0 mg/kg succinylcholine during propofol/fentanyl/nitrous oxide anesthesia. Neuromuscular function was monitored by TOF using mechanomyography. At 10%-20% spontaneous recovery of the first twitch of TOF, the mode of stimulation was changed from TOF to 1-Hz single-twitch stimulation followed by a tetanic stimulus (50 Hz) for 5 s. Three seconds later, the single twitch (1 Hz) was applied again for approximately 30 s followed by TOF stimulation until full recovery of the TOF response. Succinylcholine-induced neuromuscular block had the following characteristics: 1) twitch augmentation before twitch depression, which was seen more frequently in patients given smaller doses (0.1 and 0.3 mg/kg) than in those given larger doses (0.5-1.0 mg/kg); 2) TOF fade during onset and recovery of the block; 3) tetanic fade; and 4) and posttetanic potentiation. Posttetanic potentiation was related to the pretetanic twitch height but was not related to the dose of succinylcholine administered. Some characteristics of Phase II block were detectable during onset and recovery from doses of succinylcholine as small as 0.30 mg/kg. Posttetanic potentiation and fade in response to train-of-four and tetanic stimuli are characteristics of neuromuscular block after bolus administration of different doses of succinylcholine. IMPLICATIONS: Posttetanic potentiation and fade in response to train-of-four and tetanic stimuli are characteristics of neuromuscular block after bolus administration of different doses of succinylcholine. We also conclude that some characteristics of a Phase II block are evident from an initial dose (i.e., as small as 0.3 mg/kg) of succinylcholine.     

Atropine and neuromuscular fade in the mouse phrenic nerve-diaphragm

Purpose

These studies were intended to resolve the conflict between the reasonable inference from the scientific literature that atropine might alter neuromuscular fade and the expectation from informal clinical experience that it does not.

Methods

We examined the effect of a high concentration of atropine (20 μM) on moderate neuromuscular block and fade produced by d-tubocurarine (dTC). Isometric twitch tension was measured in the mouse phrenic nerve-diaphragm preparation. In one set of experiments, the phrenic nerve was stimulated with trains of 5 pulses at 10 Hz every second. Block and fade were measured in two groups, control and with atropine (n = 6 each). In another set of experiments, the phrenic nerve was stimulated with standard train-of-four stimulation (TOF, 4 pulses at 2 Hz every 11.5 seconds). Block and fade were measured first in a control period and then in a treatment period with either saline (n = 4) or atropine (n = 4).

Results

During 10 Hz train stimulation, atropine had no significant effect on either the block of the first twitch (control: 62 ± 17; atropine: 75 ± 4) or fade (control: 55 ± 12: atropine; 57 ± 14) produced by dTC. Similarly, atropine did not differ significantly from saline in altering dTC-induced block of first twitch (saline: 92.5 ± 14; atropine 92.5 ± 9.6% control) or fade (saline 119 ± 50; atropine 102 ± 30% control) during TOF stimulation.

Conclusions

While atropine may alter ACh release under some conditions, its action is not great enough to alter either block or fade.     

Train–of–four fade during onset of neuromuscular block with nondepolarising neuromuscular blocking agents

Fade in the train-of-four (TOF) responses during onset of neuromuscular block was studied following administration of atracurium (225 or 450 micrograms/kg), vecuronium (40 or 80 micrograms/kg), pancuronium (60 or 120 micrograms/kg) and tubocurarine (450 micrograms/kg). TOF ratios were measured at approximate heights of T1 (first response in the TOF) of 75, 50 and 25%. Fade in TOF increased as the height of T1 decreased, with maximum fade being observed at T1 of 25%. The greatest difference between relaxants was observed at T1 of 25%, vecuronium showing the least fade and pancuronium, atracurium and tubocurarine showing increasing fade, in that order. The difference between atracurium and tubocurarine or between vecuronium and pancuronium was not significant, but the degree of TOF fade was significantly greater with atracurium and tubocurarine in comparison to vecuronium or pancuronium.     

Effect of atracurium on twitch, tetanic and post-tetanic twitch responses at the rat neuromuscular junction

The effect of atracurium on the phenomenon of post-tetanic potentiation, which is believed to be of a presynaptic origin, i.e. due to endogenous transmitter release, was investigated to see if atracurium had a presynaptic inhibitory mechanism at the rat neuromuscular junction. The results showed that atracurium (0.8-80 microM) reduced the indirectly elicited twitch, tetanic and post-tetanic twitch tensions, in a dose-dependent manner. Atracurium (1 microM) produced a tetanic fade in the preparations stimulated at 20 Hz and above. The acetylcholine (ACh) released at high frequencies of nerve stimulation was collected, in the presence of physostigmine (0.77 microM), added to a rat ileum preparation, in which it produced a small contraction which was blocked by atracurium (1 microM), which in turn blocked the contracture produced by ACh (1 microM) added directly to the organ bath. It was concluded that, in addition to its well-known competitive blockade of postsynaptic ACh receptors, atracurium may also have a presynaptic inhibitory effect at the neuromuscular junction.     

Neuromuscular blocking agents

Clearly, many aspects of the action of neuromuscular blockers remain poorly understood at the molecular level. In the case of competitive blockers, blockade of EPPs by competitive binding to the ACh receptor site accounts for the most clinically important aspect of blockade. Although train-of-four fade produced by curare and some other competitive agents probably represents a presynaptic action, the molecular mechanisms underlying this effect have not been addressed. Depolarizing blockade is inherently more complicated than competitive blockade. Simple depolarization and inactivation of the mechanism for generation of the action potential probably account for the major clinical effect seen in phase I block. Furthermore, the relative balance between activation of channels and desensitization may also provide a qualitative explanation for phase II block and tachyphylaxis. However, effects that are more likely to be explained by presynaptic actions of depolarizing blockers have also been described, and it is not yet possible to assess quantitatively whether the rates of onset of the different postsynaptic actions can account for most aspects of depolarizing block. This discussion has raised several issues which need to be addressed in future studies. 1. What are the presynaptic effects of cholinergic drugs? Do these drugs act through a specific receptor or, on other ion channels in the terminal membrane, or do they operate by mechanisms distinct from effects on membrane conductance? Can any of the observations be explained by indirect effects mediated through postsynaptic ACh receptors, e.g., K+ release? 2. What are the factors that influence variability in sensitivity to neuromuscular blockers among species, muscles within species, and during development? Many of the potential factors, e.g., differences in safety factor, resting conductances, ACh receptor type, and differences in the presence and absence of presynaptic receptors, have been outlined, but definitive tests of the contribution of any particular mechanisms are lacking. 3. Does modulation of desensitization play a role in any components of neuromuscular blockade? 4. Can trapping of blocking agents in ion channels in some cases account for slowly reversible components of blockade? 5. Can closed-channel block provide an effective mechanism of neuromuscular block?     

FADE PROFILES DURING SPONTANEOUS OFFSET OF NEUROMUSCULAR BLOCKADE: VECURONIUM AND GALLAMINE COMPARED

The characteristics of the train-of-four (TOF) response havebeen studied electromyographically during the onset and thespontaneous offset of neuromuscular blockade indued with vecuroniumor gallamine. During the onset of blockade, at 75% depressionof initial twitch height, gallamine was associated with significantlymore TOF fade than vecuronium. Both agents were associated withsignificantly less fade during onset than during spontaneousoffset. When the two neuromuscular blocking drugs were comparedduring spontaneous offset they showed a similar degree of fadeduring early offset (up to 50% recovery of initial twitch height).However, during late spontaneous offset, when the initial twitchheight had recovered to 75% of control values, vecuronium wasassociated with more fade than gallamine.     

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)     

TRAIN-OF-FOUR FADE DURING ONSET AND RECOVERY OF NEUROMUSCULAR BLOCK: A STUDY IN NON-ANAESTHETIZED SUBJECTS

The actions of alcuronium, vecuronium and tubocurarine havebeen studied in the isolated forearms of six healthy, non-anaesthetizedvolunteers. The responses of adductor pollicis were measuredduring onset and recovery of neuro-muscular block for each agent.There was a drug-related disparity between mechanomyo-gram (MMG)and electromyogram (EMG) measurement of the first response ofthe train-of-four (T1) and of the ratio of the fourth (T4) tothe first response (TOF ratio). There were significantly higherT1 values for the EMG than for MMG during alcuronium blockade(P = 0.03). For tubocurarine, however, the relationship wasreversed. The relationship between T1 and TOF ratio during onsetand recovery of neuromuscular block was a hysteresis. The TOFratio at 50% T1 was significantly higher during onset than duringrecovery for all three drugs, measured by MMG or EMG (P <0.005). Analysis of variance of the differential fade loopsfailed to show a drug-related effect. We conclude that careshould be taken in assuming interchangeability between MMG andEMG measurement of T1. Relationships between T1 and TOF ratioderived during recovery do not necessarily apply during onsetand may lead to error in estimating the degree of muscle relaxation.     

Relationship between single twitch depression and train-of-four fade: influence of relaxant dose during onset and spontaneous offset of neuromuscular blockade

The characteristics of the train-of-four (TOF) response were studied electromyographically during onset and spontaneous offset of neuromuscular blockade with bolus doses of vecuronium (ED95, and ED95 X 2). During onset of blockade there was less fade with the larger than the smaller dose of vecuronium, demonstrating a variable and dose-related relationship between the ratio of height of the initial twitch, T1, and fourth twitch, T4. With both doses TOF fade was more pronounced during recovery than during onset of block, but at the same T1 values during offset, both doses were associated with similar degrees of fade during recovery. Thus with bolus doses of vecuronium the T4 ratio during recovery bears a fixed relationship to initial T1 depression that is independent of dose.     

Nondepolarizing neuromuscular blocking drugs and train-of-four fade

The aim of this study was to examine differences in prejunctional effects of different relaxants by measuring the train-offour (TOF) fade during the onset and recovery of neuromuscular block. The relaxants studied were atracurium (225 μg · kg^?1), mivacurium (65 μg · kg^?1) rocuronium (300 μg · kg^?1)) and vecuronium (40 μg · kg^?1)). The TOF ratios were measured at approximate heights of T₁) (first response in the TOF) of 90, 75, 50, and 25%. The TOF fade (as shown by lower TOF ratios) increased with a decrease in the T₁) during onset of neuromuscular block. Although there was a slightly greater fade with atracurium and rocuronium during the onset of block, the differences among the relaxants were insignificant. It is concluded that the relative prejunctional effects of these relaxants are similar.     

Train-of-four fade and neuromuscular block in rats: a comparison between pancuronium, vecuronium, and rocuronium

PURPOSE: To clarify the relationship between neuromuscular block and train-of-four fade and to investigate the causes of these drug-dependent differences, we compared the neuromuscular block and TOF fade after pancuronium, vecuronium and rocuronium. METHODS: In 24 anesthetized rats, the sciatic nerve was stimulated, and the twitch of left tibialis anterior muscle was recorded. After T1 (first twitch response) was kept constant at 95% block by administration of pancuronium, vecuronium, or rocuronium (n=8, in each), the TOF fade was measured when T1 block was decreased to 40% and 20%. In addition, using 24 phrenic nerve-diaphragm preparations, the fade was measured when the T1 block increased to 20% and 40% by titrating of either one of the three drugs (n=8, in each). RESULTS: In in vivo experiments, the fade produced by pancuronium was greater than that by vecuronium or rocuronium when T1 block was at 40% (81 +/- 9 vs 63 +/- 15 and 63 +/- 6%, respectively) and at 20% (66 +/- 13 vs 34 +/- 17 and 40 +/- 6%, respectively). In contrast, in in vitro experiments, the differences did not reach significant levels among the three drugs either at 20% (32 +/- 19 vs 33 +/- 10 and 32 +/- 17%) or 40% of block (62 +/- 29 vs 65 +/- 14 and 55 +/- 14%). CONCLUSIONS: For vecuronium and rocuronium, the results were similar in vivo and in vitro. For pancuronium, fade was greater in vivo. These results suggest that different neuromuscular blocking agent have different relationships between the fade and the block. In vitro results might not be the same as in vivo, possibly due to pharmacokinetic differences.     

A case report of monitoring neuromuscular blockade during anesthesia in a patient with facioscapulohumeral muscle dystrophy]

Facioscapulohumeral muscle dystrophy (FSHMD) is characterized by slowly progressive wasting of facial, pectoral and shoulder-girdle muscles that begins in adolescence. A 31 year-old man with FSHMD had dystrophic changes in the deltoid, anterior serratus and pectoralis major muscles but not in the distal muscle of his arms and legs. He underwent an operation for thoraco-scapula fixation under enflurane-nitrous oxide anesthesia with vecuronium 6 mg. At the end of the surgical procedure, the train-of-four (TOF) responses of a thumb and a toe, as measured by using an acceleration transducer, were recorded simultaneously. TOF stimulation in an arm demonstrated an apparent fade phenomenon (TOF; 0.54), while a TOF test in the leg showed complete recovery of the TOF ratio (TOF; 1.0). The patient revealed no clinical signs of residual neuromuscular blockade. It was clear that there was a difference in the degree of neuromuscular block between the arm and the leg in a FSHMD patient. Use of the peripheral nerve stimulator only in the arm may be an unreliable guide to assess neuromuscular block in FSHMD patients. Therefore, two sites should be chosen for monitoring neuromuscular blockade in a FSHMD patient.     

COMPARISON OF THE TRAIN-OF-FOUR FADE PROFILES PRODUCED BY VECURONIUM AND ATRACURIUM

In this double-blind study, we have allocated randomly 40 ASAI-III patients to one of four groups. After a standard anaestheticinduction, patients received vecuronium 0.08 mg kg^–1 or0.10 mg kg^–1, or atracurium 0.4 mg kg^–1 or 0.5 mgkg^–1. Using an electromyogram (Datex Relaxograph) thetrain-of-four (TOF) response was measured during onset of andrecovery from neuromuscular block. A greater degree of fadeof TOF was observed with atracurium during onset of neuromuscularblock than with equivalent doses of vecuronium. During recoveryof neuromuscular transmission, vecuronium was associated withmore fade than atracurium. The differences in the TOF profilesof these two drugs may be important when judging the adequacyof antagonism of neuromuscular block using the TOF response.