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.     

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)     

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.     

Dose-response relationships for edrophonium and neostigmine as antagonists of atracurium and vecuronium neuromuscular blockade

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.     

Edrophonium and Neostigmine for Reversal of the Neuromuscular Blocking Effect of Vecuronium

The effect of edrophonium for reversal of the non-depolarizing neuromuscular blockade produced by a continuous infusion of vecuronium was compared to that of neostigmine in 20 adult patients during neurolept anaesthesia. When antagonism was attempted at 10% twitch height recovery, reversal time to a train-of-four ratio of 0.7 was significantly shorter following neostigmine 0.04 mg/kg than after edrophonium 0.75 mg/kg (9.8 min and 18.7 min, respectively) but the same after edrophonium 1.5 mg/kg (10.3 min). There was no statistically significant difference in reversal time between neostigmine 0.04 mg/kg given at 10% twitch height and edrophonium 0.75 mg/kg given at 25% twitch height recovery (6.0 min). Additional doses of atropine were necessary following edrophonium 1.5 mg/kg.     

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)     

The pattern of train-of-four fade after atracurium: influence of different priming doses

This study was designed to investigate the effect of three different priming doses of atracurium--0.06, 0.07, and 0.08 mg/kg--followed 3 min later by the remainder of a 0.5 mg/kg dose on the relationship between the depression in the first twitch of the train-of-four (T1) and train-of-four (TOF) fade. This relationship was studied after the administration of the full dose of the relaxant in all groups. Of all the priming doses, 0.08 mg/kg atracurium, when followed 3 min later by 0.42 mg/kg atracurium, had a significantly greater fade in the TOF ratio at any given T1 value. This may indicate significant prejunctional activity. Acceleration of the onset of neuromuscular blockade was, however, evident in all groups that received atracurium in divided doses. The implication is, therefore, that prejunctional activity may not contribute significantly to the acceleration of onset of neuromuscular blockade after administration of atracurium in divided doses, as described in this study.     

Enzymatic Versus Pharmacologic Antagonism of Profound Mivacurium-induced Neuromuscular Blockade

Background: Mivacurium, a nondepolarizing muscle relaxant, is hydrolyzed by butyrylcholinesterase. The use of butyrylcholinesterase for antagonism of profound mivacurium-induced blockade has not been studied in humans. In part 1 of this two-part study, the authors examined the relationship between the posttetanic count (PTC) and recovery from profound mivacurium-induced blockade. In part 2, an attempt was made to antagonize a quantified level of profound mivacurium-induced blockade using either butyrylcholinesterase, edrophonium, or neostigmine.

Methods: Eighty-seven ASA physical status 1 or 2 adult patients were given 0.15 mg *symbol* kg sup -1 mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. They were randomly assigned to eight groups. Neuromuscular function was monitored by recording the mechanomyographic response of the adductor pollicis to PTC and train-of-four (TOF) stimulation in all patients except those in group 1 where the TOF was the only pattern used. In part 1, neuromuscular function was allowed to recover spontaneously in ten patients (group 1; control-TOF) until TOF ratio (the amplitude of the fourth evoked response as a fraction of the first evoked response: T4/T1) had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 21 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously until TOF ratio had reached 0.75 (group 2; control-PTC). In part 2, the antagonism of mivacurium-induced profound (PTC greater or equal to 1; groups 3-6) and 90% block (groups 7-8) of twitch height were investigated in another 56 patients. Groups 3 and 7 received neostigmine 0.06 mg *symbol* kg sup -1 whereas groups 4 and 8 received edrophonium 1 mg *symbol* kg sup -1, respectively. Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to activity present in 25 or 70 ml *symbol* kg sup -1 of human plasma, respectively.

Results: Neither butyrylcholinesterase nor edrophonium shortened the times from first PTC response to TOF = 0.75 compared to group 2. Neostigmine resulted in prolongation of recovery time. There was a linear relationship (r = -0.80; P = 0.00001) between PTC and time of onset of TOF response.     

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).     

Spontaneous recovery of residual neuromuscular blockade after atracurium or vecuronium during isoflurane anaesthesia

With atracurium and vecuronium, spontaneous recovery of residual neuromuscular blockade monitored electromyographically during 0.5% isoflurane anaesthesia was studied in 60 patients undergoing plastic surgery. After thiopentone, in random order, either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 was administered and isoflurane added to N2O and O2 mixture. Following spontaneous recovery of both the single twitch amplitude (T1) to 75% of the control value and the train-of-four ratio (TOF ratio) to 75%, incremental doses of the relaxant were given to maintain the T1 at less than 10%. Before the end of surgery, the blockade was again permitted to recover spontaneously. During the initial spontaneous recovery, the mean recovery time of T1 from 25% to 75% (the recovery index) with atracurium was longer (P less than 0.001) than that with vecuronium (13.2 min and 10.1 min, respectively) but, during the second recovery, the mean recovery index was shorter (P less than 0.05) with atracurium than with vecuronium (16.1 min and 19.8 min, respectively). The recovery time from T1 75% to TOF ratio 75%, indicating the recovery rate of residual neuromuscular blockade, with atracurium was about 15 min after both the initial and the second recoveries. With vecuronium, the respective recovery times were significantly (P less than 0.001) longer (25.6 min and 38.5 min, respectively). It is concluded that with vecuronium there is slower spontaneous recovery of residual neuromuscular blockade than with atracurium.     

Antagonism of an intubation dose of vecuronium

To study the problem of rapid antagonization of an intubation dose of vecuronium (0.08 mg/kg), 36 surgical patients undergoing barbiturate/halothane anesthesia were given edrophonium 0.5, 0.75, and 1.0 mg/kg or neostigmine 0.04, 0.06, and 0.08 mg/kg precisely 5 min following injection of the muscle relaxant. T1 twitch (T1/Tc) and train-of-four (TOF) ratios (T4/T1) of the hypothenar muscle were monitored every 20 s with the aid of a commercially available EMG monitor (Datex-Relaxograph). As documented by T1 and T4/T1 follow-up curves (Figs. 1 and 2) and derived parameters of relaxation as well (Dur25, Dur50, Dur75, recovery index, and reversal time; Table 4), both edrophonium and neostigmine resulted in a significantly shorter duration of vecuronium blockade (P less than 0.001). The mean time for recovery of TOF ratio to above 0.7 was between 10.8 +/- 6.0 (neostigmine 0.08 mg/kg) and 21.2 +/- 7.8 (neostigmine 0.06 mg/kg) min (mean +/- SD) following injection of the antagonist as compared to 58 +/- 18.4 min in the control group (P less than 0.001). Recurarization did not occur. Differences between drugs and dose-dependent effects were minimal; edrophonium did not prove superior to neostigmine with the exception of less pronounced muscarinic side effects, hence less bradycardia and a minimum heart rate of 57 +/- 8.2 bpm 20 min after the injection of neostigmine as opposed to 72 +/- 8.2 bpm following edrophonium (P less than 0.05; Fig. 4). As to the restitution of a ventilatory force sufficient to allow spontaneous breathing, no definite conclusions can be made.(ABSTRACT TRUNCATED AT 250 WORDS)     

Edrophonium priming alters the course of neuromuscular recovery from a pipecuronium neuromuscular blockade

This study was designed to investigate the effect of divided administration of edrophonium on the course of neuromuscular recovery from a pipecuronium neuromuscular blockade. During thiopentone-nitrous oxide-halothane anaesthesia 48 patients were given pipecuronium 70 micrograms.kg-1. Patients were randomly assigned to one of four groups (n = 12 in each) to receive either edrophonium 1 mg.kg-1 (Groups I and II) or edrophonium 0.75 mg.kg-1 (Groups III and IV). In Groups I and III (single-dose groups), edrophonium was administered as a single bolus dose. In Groups II and IV (divided-dose groups) edrophonium was administered as an initial dose of 0.25 mg.kg-1 followed three minutes later by either 0.75 or 0.50 mg.kg-1 respectively. Reversal was attempted at 20% spontaneous recovery of twitch height. Administration of edrophonium in divided doses (Groups II and IV) accelerated the reversal of the pipecuronium neuromuscular blockade. At ten minutes post-reversal, train-of-four (TOF) ratio recovery reached 0.75 or more in 12 (100%) and in ten (83%) patients in Groups II and IV respectively. Similarly, times to attain a TOF of 0.75 (SEM) were shorter in the divided-dose groups than in the single-dose groups (P less than 0.05), being 354.5 (38.7) and 398.3 (49.1) sec in Groups II and IV vs 705.4 (66.6) and 651.2 (54.3) sec in Groups I and III respectively. Time was counted from the first administration of edrophonium. It is concluded that administration of edrophonium in divided doses produced a faster reversal of residual pipecuronium-induced neuromuscular blockade than single bolus administration. Also, administration in divided doses reduced the requirements of edrophonium needed for reversal of pipecuronium neuromuscular blockade.     

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)     

Dose-response relationships for edrophonium and neostigmine as antagonists of moderate and profound atracurium blockade

To measure the ability of neostigmine and edrophonium to reverse moderate and profound atracurium blockade, dose-response relationships were established for these reversal agents given at 1% and 10% twitch height recovery. Eighty-five ASA I and II adult patients received atracurium, 0.4 mg/kg, during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 seconds, and the force of contraction of the adductor pollicis muscle was recorded. Edrophonium, 0.1, 0.2, 0.4, or 1 mg/kg; neostigmine, 0.005, 0.01, 0.02 or 0.05 mg/kg; or no reversal agent was given when there was either 1% or 10% recovery of the first twitch response. With profound blockade, the slope of the edrophonium dose-response relationship was significantly flatter (P less than 0.05) than that of neostigmine. The dose of neostigmine required to achieve 80% first twitch recovery (ED80) after 10 minutes was 0.013 +/- 0.003 mg/kg (mean +/- SEM) if given at 10% recovery, and 0.032 +/- 0.004 mg/kg if given at 1% recovery. The ED80 for edrophonium was 0.22 +/- 0.04 mg/kg and 1.14 +/- 0.33 mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 16.6 +/- 3.5 and 35.3 +/- 8.9 at 90% and 99% blockade respectively (P less than 0.006). We conclude that the relative potency of neostigmine is greater than that of edrophonium for antagonism of profound atracurium blockade.     

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.     

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)     

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.     

Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia

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

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.     

ANTAGONISM OF VECURONIUM AND ATRACURIUM: COMPARISON OF NEOSTIGMINE AND EDROPHONIUM ADMINISTERED AT 5% TWITCH HEIGHT RECOVERY

In 39 healthy patients antagonism, by neostig-mine 0.07 mg kg^–1or edrophonium 0.8 mg kg^–1, of neuromuscular blockadeinduced by vecuronium or atracurium, was compared. Reversalwas attempted when the height of the single twitch (TH) hadrecovered spontaneously to 5% of the control value. The evokedresponses, initially single twitch, then train-of-four (TOF)were observed until the TOF ratio was 70%. Induced recoveryfrom TH 5% to 25% was shorter following edrophonium than followingneostigmine with both vecuronium (P < 0.05) and atracurium(P < 0.05). The recovery indices and times until TH was 75%of control and until the TOF ratio was 70% were not different.The time from a TH of 75% to a TOF ratio of 70% was shorterfollowing neostigmine than following edrophonium with both vecuronium(P < 0.01) and atracurium (P < 0.01). Edrophonium hada much more variable effect on vecuronium than on atracurium.These results show that although the onset of action of edrophoniumwas faster than that of neostigmine, this did not lead to afaster clinical recovery, and antagonism by edrophonium maybe delayed in a number of patients if vecuronium is the neuromuscularblocker.