Priming with atracurium: improving intubating conditions with additional doses of thiopental

The effects of different intubating doses of atracurium on the time of onset, and the effect of an additional dose of thiopental on intubating conditions, were studied in 72 patients divided into six groups (n = 12 in each). Stratified sampling was used to obtain an even sex distribution. Groups I, III, and V (controls) received atracurium as a single bolus dose of 0.4, 0.5 or 0.6 mg/kg respectively. Groups II, IV, and VI received an initial (priming) dose of 0.05 mg/kg followed 3 min later by 0.35, 0.45, or 0.55 mg/kg respectively. The time of onset, that is the time from the intubating dose to complete suppression of the train-of-four (TOF) response, was significantly accelerated after administration of atracurium in divided doses. Increasing the intubating dose of atracurium after an initial 0.05 mg/kg from 0.35 to 0.55 mg/kg did not result in further significant acceleration of the onset time, but resulted in prolongation of the duration of neuromuscular blockade. When divided doses of atracurium were given, administration of 2 mg/kg thiopental (in addition to the 5 mg/kg used for induction) before the injection of the intubating dose resulted in improvement of intubating conditions as reflected by statistically significant changes in intubating scores. This result was probably due to the increase by thiopental in the depth of anesthesia. Therefore, when thiopental is given as supplement, the priming technique can be made to provide better conditions for tracheal intubation in less than 90 sec.     

The optimal priming dose for atracurium

To determine the optimal priming dose for administration in divided doses, atracurium was given to 77 patients either in a single dose of 0.5 mg X kg-1 or in an initial dose of 0.04, 0.05, 0.06, 0.07, 0.08 or 0.09 mg X kg-1, followed three minutes later by the remainder of the 0.5 mg X kg-1 dose. Patients were anaesthetized throughout the study. When atracurium was given as a single bolus of 0.5 mg X kg-1, the mean time to complete neuromuscular block was 141.5 seconds. Administration in divided doses accelerated the onset time (p less than 0.01), that is the time from the intubating dose to the complete suppression of train-of-four (TOF) response. The TOF ratio decreased slightly but statistically significantly following the priming doses. When the priming dose was 0.05 mg X kg-1, the mean onset time was 70.9 seconds and priming with larger doses did not add any further advantage. It is concluded that 0.05 mg X kg-1 appears to be the optimal priming dose for the administration of atracurium in divided doses. When 0.05 mg X kg-1 is given three minutes before the intubating dose, tracheal intubation can be accomplished in less than 90 seconds.     

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.     

Train-of-four ratio after antagonism of atracurium with edrophonium: influence of different priming doses of edrophonium

This study was designed to investigate the effect of different priming doses of edrophonium on the relationship between the the recovery of the first twitch of the train-of-four (T1) and train-of-four (TOF) ratio. This relationship was studied after the administration of the full dose of the antagonist in all groups. Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I, controls) or in an initial dose of 0.05, 0.1, 0.15 or 0.2 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to V. Reversal was attempted at the ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Of all the groups studied, Group V had a significantly greater recovery in the TOF ratio at any given T1 value. When first twitch tension (T1) had recovered to 100 per cent of the control, it was found for the same tension that the TOF ratio was greater in Group V, being 0.75 compared to 0.63, 0.65, 0.65 and 0.64 in Groups I to IV respectively. The implication is that this differential ability to reverse fade (or prejunctional activity) may be involved in the acceleration of recovery.     

Priming principle with atracurium

In order to substantiate the "priming principle" discussion, 44 patients admitted for elective gynecological surgery under modified neurolept anesthesia were randomized into two groups. In group I, atracurium was administered by a priming technique in which 0.1 mg/kg was given i.v. and, after 6 min, 0.5 mg/kg. In group II was given an atracurium bolus injection of 0.6 mg/kg. In group I onset time (median 61 sec, range 44-160 sec) was significantly more rapid than in group II (median 83 sec, range 60-128 sec). The median train-of-four ratio in group I was 0.80 (range 0.43-1.00, n = 23), 6 min after the priming dose, in 30% of these patients the TOF ratio was above 0.90 and in 22% below 0.70. It is impossible to determine a fixed pretreatment dose per kg body weight owing to the large individual variation in neuromuscular depression. Modification of the priming principle using incremental small doses of non-depolarizing neuromuscular blocking agents, with anesthetic induction, when the train-of-four ratio is between 0.90 and 0.70 or when there is clinical signs of neuromuscular block, might be an alternative in situations where rapid induction is required and where the use of suxamethonium is contraindicated.     

Neostigmine and edrophonium as antagonists of atracurium and pancuronium

Edrophonium 0.5 mg/kg or neostigmine 0.04 mg/kg were administered to two groups of 30 patients each for antagonism of atracurium- or pancuronium-induced neuromuscular block at 25% single twitch recovery. Neuromuscular block was studied using both single twitch and train-of-four (TOF) nerve stimulation. The times to 100% single twitch recovery were significantly more rapid for patients receiving edrophonium (P less than 0.01) in both groups (atracurium and pancuronium); the TOF ratios were similar for atracurium, but for pancuronium they were greater after neostigmine than after edrophonium, and only at 25 min were these ratios similar. It is concluded that edrophonium in a dose of 0.5 mg/kg antagonizes neuromuscular blockade induced by atracurium, as does neostigmine in a dose of 0.04 mg/kg, but the former does not consistently antagonize neuromuscular blockade induced by pancuronium even at 25% of single twitch recovery.     

Edrophonium priming for antagonism of atracurium neuro-muscular blockade

Edrophonium administered in divided doses has been reported to accelerate antagonism of neuromuscular blockade, i.e., a "priming" effect. Since measured onset times can be affected by the type of stimulation used, this effect was studied using both train-of-four (TOF) and single twitch (ST) stimulation. During thiopentone-nitrous oxide-enflurane anaesthesia 20 adults were given atracurium 0.5 mg.kg-1. Both ulnar nerves were stimulated with TOF every 12 sec until one per cent recovery of first twitch (T1). At this time, ST stimulation was applied to one arm, selected at random. When the mean value of T1 and ST reached ten per cent of control, edrophonium, 1 mg.kg-1, preceded by atropine was given either as a single dose, or in two doses consisting of 0.2 mg.kg-1 followed by 0.8 mg.kg-1 three minutes later. No statistically significant differences were observed between T1 and ST for the next ten minutes, whether edrophonium had been given in single or divided doses. Giving edrophonium in divided doses did not improve recovery significantly, measured with either T1, ST or train-of-four ratio (T4/T1). Five minutes after the first administration of edrophonium, T1 was (mean +/- SEM) 86 +/- 3 and 86 +/- 2 per cent control in the single and divided dose groups respectively. Corresponding values for ST were 89 +/- 1 and 89 +/- 2 per cent (NS), and for TOF, 49 +/- 3 and 57 +/- 3 per cent (NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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)     

Tetanic fade following administration of nondepolarizing neuromuscular blocking drugs

Fade in response to tetanic stimulation was studied following administration of atracurium 120 or 225 micrograms/kg, vecuronium 23 or 40 micrograms/kg, pancuronium 30 or 60 micrograms/kg, or d-tubocurarine 185 or 450 micrograms/kg. Ten patients received each dose and tetanic fade was measured at maximum block in the patients, who received the lower doses of the relaxants or at 10% recovery in those who received the higher doses. Fade during tetanic stimulation was generally similar in all the groups with the exception of the higher dose of pancuronium which showed a significantly greater fade in comparison with the higher doses of atracurium and d-tubocurarine. If fade in response to tetanic stimulation represents a prejunctional effect, the results from the present study suggest that neuromuscular blocking drugs cannot be differentiated with respect to their relative prejunctional effects by measurement of tetanic fade during established block after administration of clinically useful doses as used in the present study.     

Is the priming principle both effective and safe?

This study determined the priming dose of vecuronium (V), pancuronium (P) and atracurium (A) that resulted in the most rapid onset of neuromuscular blockade (NMB) in 150 patients given either V 0.08 mg/kg, P 0.1 mg/kg or A 0.6 mg/kg. Patients were further divided (n = 10 per group) to receive no prime or 5%, 10%, 15% or 20% of the total dose as a prime followed 5-7 minutes later by the remaining (intubating) dose. A further 10 patients received 0.04 mg/kg d-tubocurarine followed by 1.5 mg/kg succinylcholine (S). Priming significantly shortened the onset of NMB. The priming doses producing the most rapid onset were 0.012 mg/kg for V, 0.015 mg/kg for P and 0.09 mg/kg for A. The S resulted in significantly greater NMB at 60 sec than any priming dose of A, V or P. There was no difference between the three nondepolarizing neuromuscular blockers in shortening the onset of NMB produced by priming. To evaluate both the effect of the "optimal" priming dose in awake patients and the effect of increasing intubating doses on NMB an additional 40 patients were given V 0.012 mg/kg followed by V 0.08, 0.1, 0.12 or 0.15 mg/kg. Increasing the intubating dose did not improve onset of NMB. The "optimal" priming dose, however, resulted in a high incidence of symptoms of muscle weakness. We conclude that priming shortens the onset of NMB similarly between V, P and A but the priming dose producing the most rapid onset of NMB also results in a high incidence of side effects and therefore the priming principle should be used with caution.     

Train-of-four fade of non depolarizing muscle relaxants: an insight into the mechanism of precurarization

This study was carried out to assess the prejunctional effect of non depolarizing muscle relaxants during the onset of neuromuscular blockade using the train-of-four ratio (TR). The prejunctional effect was compared with previous results concerning the ability of the relaxants to prevent suxamethonium-induced fasciculations. Fifty-three adult patients were relaxed with small incremental doses of either alcuronium (0.03 mg.kg-1), atracurium (0.04 mg.kg-1), pancuronium (0.01 mg.kg-1), d-tubocurarine (0.05 mg.kg-1) or vecuronium (0.01 mg.kg-1) during anaesthesia with thiopentone, fentanyl and nitrous oxide in oxygen. The muscle relaxant was given after recovery from an initial suxamethonium blockade needed for tracheal intubation. The evoked integrated EMG response to supramaximal train-of-four (2 Hz) stimulation was recorded every 20 s. TR % was calculated at different first twitch (T1) levels during the onset of neuromuscular blockade. Significant changes occurred at the 100% and 90% T1 levels, alcuronium having the lowest mean TR values. Atracurium, pancuronium and vecuronium gave similar TR values. Results with d-tubocurarine placed it between alcuronium and the others. These train-of-four ratio results were compared with the ability of non depolarizing muscle relaxants to prevent fasciculations. In conclusion, the stronger the train-of-four fade, the greater was the ability of the relaxant to prevent suxamethonium-induced fasciculations. This supports the theory that the blockade of prejunctional cholinergic receptors is the mechanism of action of precurarization.     

Atracurium in the myasthenic patient

The use of the new competitive muscle relaxant, atracurium, is described in five myasthenic patients presenting for thymectomy. With an initial dose of 0.1 mg/kg, that is approximately one-fifth of that normally used, and incremental doses of 0.02-0.04 mg/kg, satisfactory clinical conditions were achieved. Neuromuscular function was monitored throughout using the train-of-four mechanical twitch response, and residual neuromuscular blockade was reversed satisfactorily at the end of the procedure with neostigmine 5.0 mg. A marked increase in the magnitude of the first twitch of the train-of-four to greater than control levels, accompanied by pronounced fade, was found on reversal. In reduced dosage and with careful neuromuscular monitoring, atracurium is safe to use in the myasthenic patient.     

Neuromuscular blocking effects and train-of-four fade with cisatracurium: comparison with other nondepolarising relaxants

Neuromuscular blocking drugs exhibit different degrees of fade in response to train-of-four stimulation believed to represent their relative prejunctional effects. The present study was designed to compare the train-of-four fade after cisatracurium and compare this with other commonly used muscle relaxants. Train-of-four fade during onset and recovery of block were recorded after administration of cisatracurium 0.05 or 0.1 mg.kg-1, atracurium 0.5 mg.kg-1, vecuronium 0.08 mg.kg-1, mivacurium 0.15 mg.kg-1 or rocuronium 0.6 mg.kg-1 to patients anaesthetised with fentanyl, nitrous oxide and a propofol infusion. Neuromuscular monitoring was by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The onset and recovery of block were also measured. Train-of-four fade during onset of block was greater with the lower dose of cisatracurium compared with the higher dose of cisatracurium and all other relaxants. Train-of-four fade during recovery was similar. The median times (and ranges) for the onset of maximum block were 3.4 (2.1-5.6), 1.5 (1.2-2.3), 2.1 (1.2-2.6), 2.0 (1.5-2.7) and 1.0 (0.7-1.3) min for cisatracurium 0.1 mg.kg-1 and atracurium, mivacurium, vecuronium and rocuronium, respectively. The median times (and ranges) for the recovery of T1 to 25% of control and to a train-of-four ratio of 0.8 were 41 (21-50) and 65 (40-78); 43 (37-54) and 69 (58-79); 15 (11-20) and 25 (19-30); 31 (23-46) and 60 (45-117); and 33 (18-57) and 50 (28-76) min following cisatracurium, 0.1 mg.kg-1, atracurium, mivacurium, vecuronium and recuronium, respectively.     

Recovery times following edrophonium and neostigmine reversal of pancuronium, atracurium, and vecuronium steady-state infusions

The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and vecuronium was studied in 71 adult patients anesthetized with nitrous oxide and halothane. Infusion rates of blocking drugs were adjusted so that single twitch depression as measured by the evoked integrated EMG of the hypothenar muscles was kept at 10% of control. Two minutes after the termination of the infusion either edrophonium (0.75 mg/kg) or neostigmine (0.05 mg/kg) was administered. Single twitch depression and train-of-four (T4/T1) fade was recorded during the recovery period. T4/T1 fade ratios observed at 20 min postreversal were 0.80 (atracurium-edrophonium); 0.76 (vecuronium-edrophonium); 0.44 (pancuronium-edrophonium); 0.95 (atracurium-neostigmine); 0.89 (vecuronium-neostigmine); and 0.68 (pancuronium-neostigmine). Under conditions of this study neostigmine produced more rapid and complete recovery than did edrophonium. Although edrophonium produced adequate antagonism of atracurium if 20-30 min were allowed to elapse, edrophonium reversal of pancuronium was rarely acceptable even at 30 min. Increasing the dose of edrophonium to 1.0 mg/kg produced single twitch values of 0.90 at 5 min postreversal but did not increase the rate of recovery of the train-of-four fade ratio. Neostigmine reversal of pancuronium, on the other hand, generally produced T4/T1 ratios of greater than 0.70 in 20-30 min. Although the pattern of recovery seen after reversal of vecuronium was in general quite similar to that seen after atracurium, two patients in the vecuronium-edrophonium group showed delayed recovery and also failed to respond significantly to subsequent doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Intubationsbedingungen nach Gabe von Atracurium und Vecuronium Bolusmethode vs. Primingtechnik

Prompted by the ongoing discussion of the pros and cons of using succinylcholine, this study was conducted to compare the responses to bolus injections of atracurium or vecuronium with those after sequential injection of these drugs (priming principle). We evaluated the earliest possible intubation times, intubating conditions, and the onset times (i.e. times from the end of injection to the maximum blockade) under conditions approaching real use as closely as possible. Methods. The randomized and double-blind study was carried out with 80 ASA risk class 1 and 2 patients. Approval of the institutional ethics committee was obtained, and each patient gave informed consent. Patients were randomly allocated to four study groups of 20 patients each. Isotonic saline was administered to those patients assigned to the atracurium or vecuronium bolus groups, whereas the patients assigned to the other two groups received a priming injection of either atracurium (0.05 mg/kg) or vecuronium (0.01 mg/kg). We observed the patients for signs of incipient muscular weakness before the induction of anaesthesia. Anaesthesia was induced with thiopental 3.5 min after the first injection (5 mg/kg and 50–100?mg before intubation). After a further 1 min during which adequate mask ventilatin with oxygen was assured, corresponding to a priming interval of 4.5?min, 0.5 mg/kg of atracurium or 0.1 mg/kg of vecuronium was administered to the patients in the bolus groups and 0.45 mg/kg of atracurium or 0.09 mg/kg of vecuronium as intubating doses to those in the priming groups. Intubation was attempted at 90, 120, 150 and 180?s thereafter. Intubating conditions were evaluated on the basis of laryngoscopy, vocal cord movement and coughing or bucking of the patients. Neuromuscular function was monitored via accelerometry at the adductor pollicis muscle (TOF stimulation of the ulnar nerve every 15?s). Results. The priming doses did not diminish the elicited twitches of the adductor pollicis muscle, but led to heavy eyelids and double vision in 35% of the atracurium patients and 47% of the vecuronium patients; these symptoms were well tolerated by the patients. At the time of intubation the adductor pollicis muscle was relaxed to approximately the same degree in all groups (mean±SD for the TOF ratios in the bolus groups was 0.46±0.37 for atracurium, 0.45±0.4 for vecuronium; in the priming groups 0.52±0.39 for atracurium, 0.53±0.36 for vecuronium). The administration of the relaxants in divided doses significantly shortened the intubating time after atracurium (100 vs 124?s) and improved the intubating conditions of vecuronium (good vs tolerable), but had no effect on the time course of the neuromuscular blockade (onset times in the bolus groups 224±84?s for atracurium and 209±64 s for vecuronium; in the priming groups 249±112?s for atracurium and 205±52 s for vecuronium). Conclusions. The priming technique presented here is clinically superior to the bolus method and therefore should be preferred in all elective cases and in those patients in whom succinylcholine is contraindicated.     

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.     

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.     

Profound atracurium induced neuromuscular blockade

Speed of reversal of profound atracurium induced neuromuscular blockade following edrophonium (0.5 or 1.0 mg/kg) or neostigmine (0.04 or 0.08 mg/kg) was measured using the train-of-four pattern of nerve stimulation. In all patients adequate clinical reversal was present when the ratio of the strength of the fourth to the first twitch (T4 ratio) was 0.5. Both doses of edrophonium were associated with a significantly faster speed of reversal than the smaller dose of neostigmine (p less than 0.05 in both cases). However, the larger dose of neostigmine was associated with a reversal time approaching that of edrophonium. Possible explanations for these findings are discussed in terms of contemporary theories of neuromuscular pharmacology.