ANTAGONISM OF VERCURONIUM-INDUCED NEUROMUSCULAR BLOCKADE WITH EDROPHONIUM OR NEOSTIGMINE

Antagonism of vecuronium-induced neuromuscular blockade wasattempted, at varying degrees of spontaneous recovery, withedrophonium 0.5 mg kg ^–1 or neostigmine 0.05 mg kg^–1in two groups of 20 patients. Neuromuscular blockade was monitoredusing a train-of-four (TOF) stimulation. Adequate antagonismof neuromuscular blockade, defined as a sustained TOF ratioof 0.7 or more, was attained in all 20 patients given neostigmineand in 13 out of 20 given edrophonium. Five of the remainingseven patients given edrophonium had shown three or less responsesto TOF stimulation before antagonism. While the time to onsetof the action of edrophonium (22 s) was not significantly shorterthan neostigmine (26 s), the time taken to attain a TOF ratioof 0.7 was significantly shorter with edrophonium (67 s comparedwith 194 s with neostigmine). It is concluded that edrophonium0.5 mg kg^–1 does not consistently antagonize vecuronium-inducedneuromusocular blockade, particularly if there are three orless responses to a TOF stimulation present before antagonism.     

Antagonism of pancuronium and tubocurarine blocks by edrophonium or neostigmine: a comparative study

Edrophonium 0.5 and neostigmine 0.05 mg kg-1 were compared as antagonists of pancuronium and tubocurarine-induced neuromuscular blocks, at varying degrees of recovery, in groups of 20 patients each. Adequate antagonism was defined as attaining a sustained train-of-four (TOF) ratio of 0.7 or more. Administration of edrophonium was associated with a more rapid onset of action (17 s with both relaxants with edrophonium, and 31 s and 29 s with neostigmine with pancuronium and tubocurarine, respectively), and a shorter time to attain a TOF ratio of 0.7 (74 s and 48 s with edrophonium and 230 s and 293 s with neostigmine for pancuronium and tubocurarine blocks, respectively). However, whereas neostigmine administration provided adequate antagonism in all 20 patients given pancuronium and in 19 out of 20 patients given tubocurarine, edrophonium failed to achieve adequate antagonism in six patients after pancuronium and eight patients after tubocurarine. The majority of these patients had shown three or less responses to a TOF stimulation prior to antagonism. Two separate groups of 10 patients each with relatively deeper pancuronium or tubocurarine blocks (three or less responses to TOF stimulation) were given edrophonium in a dose of 1.0 mg kg-1. However, adequate antagonism even with this dose of edrophonium was attained in only two out of 10 patients given pancuronium and in five out of 10 patients given tubocurarine. It is concluded that edrophonium is unreliable for antagonism of relatively deep blocks by pancuronium or tubocurarine and that neostigmine is the preferred and more reliable antagonist.     

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.     

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)     

NEOSTIGMINE AND EDROPHONIUM ANTAGONISM OF MODERATE NEUROMUSCULAR BLOCK INDUCED BY PANCURONIUM OR TUBOCURARINE

Edrophonium and neostigmine are anticholin-esterase drugs usedcommonly to antagonize competitive neuromuscular block. Althoughit has a faster onset of action than neostigmine, edrophoniumis unreliable when used to antagonize deep neuromuscular block.We have compared the antagonist characteristics of these twodrugs when used to antagonize a moderate degree of pancuronium-or tubocurarine-induced neuromuscular block. Forty ASA I orII patients undergoing surgical procedures were allocated randomlyto receive either pancuronium 70 kg^-1 or tubo-curarine 0.5 mgkg^-1, and to receive either edrophonium 0.5 mg kg^-1 or neostigmine0.05 mg kgr^-1. Antagonism was attempted when the first responseto train-of-four (TOF) stimulation recovered spontaneously to25% of the control height. Neuromuscular function was monitoredusing the evoked integrated electromyogram of the first dorsalinterosseous muscle of the hand. Adequate recovery was definedas the achievement of a TOF ratio of 0.70 or greater. Only sevenof 20 patients who received edrophonium demonstrated adequaterecovery 30 min after antagonism. Under the conditions describedin this study, edrophonium 0.5 mg kg7 was less effective asan antagonist than neostigmine 0.05 mg kg^-1. (Br. J. Anaesth.1993; 70: 160–162)     

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.     

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).     

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.     

Antagonism of pancuronium- and pipecuronium-induced neuromuscular block

We have compared the antagonism of neuro muscular block producedby pipecuronium with pancuronium in 80 anaesthetized surgicalpatients using mechanomyography and electromyography. Pancuronium0.1 mg kg or pipecuronium 0.07 mg kg^–1 was given afterinduction of anaesthesia and neuromuscular block was adjustedto 75% twitch depression at the time of antagonism. The followingregimens were used: edrophonium 0.5 and 1.0 mg kg^–1, neostigmine0.04 mg kg^–1 pyridostigmine 0.3 mg kg^–1 and edrophonium0.25 mg kg^–1 with pyridostigmine 0.15 mg kg^–1. Antagonismwas evaluated also by the head lift test. There was no differencebetween the reversibility of neuromuscular block produced bypancuronium or pipecuronium. Edrophonium produced a significantlyfaster antagonism than neostigmine or pyridostigmine but onsetof action was not significantly faster than that of edrophoniumwith pyridostigmine. All regimens produced 100% (or near 100%)antagonism of twitch response within 15 min. However, TOF fadeantagonism was more complete with pyridostigmine, neostigmineand edrophonium 1.0 mg kg^–1 than with edrophonium 0.5mg kg^–1. The head lift test indicated somewhat less antagonismwith edrophonium 0.5 and 1.0 mg kg^–1. Using five monitoringmethods, the rank order of reversal potency was: pyridostigmine neostigmine > edrophonium 1.0 mg kg^–1 edrophonium+ pyridostigmine > edrophonium 0.5 mg kg^–1.     

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)     

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.     

Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children

Background: The rapid recovery from mivacurium-induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit.

Methods: In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg *symbol* kg sup -1 edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode.

Results: Children arrived in the postanesthesia care unit 8.2 +/-3.4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/-0.05 vs. 0.93+/-0.01, P < 0.01), TOF was > 0.7 in all children. Adults arrived in the postanesthesia care unit 12.9+/- 5.3 min after reversal of neuromuscular block (P < 0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was < 0.7 in four others), compared with TOF < 0.7 in only one of the edrophonium group (P < 0.05).     

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)     

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.     

Edrophonium effectively antagonizes neuromuscular block at the laryngeal adductors induced by rapacuronium, rocuronium and cisatracurium, but not mivacurium

PURPOSE: To examine the efficacy of antagonism of rapacuronium-, mivacurium-, rocuronium- and cisatracurium-induced neuromuscular block at the laryngeal adductors (LA). METHODS: One hundred four patients were randomly assigned to one of eight study groups. They either received rapacuronium 1.5 mg x kg(-1), mivacurium 0.25 mg x kg(-1), rocuronium 0.9 mg x kg(-1) or cisatracurium 0.15 mg x kg(-1). Patients in each treatment group either received edrophonium (0.5 mg x kg(-1)) at 10% recovery of the first twitch (T1) of train-of-four (TOF) at the LA or were allowed to recover spontaneously from neuromuscular block. The effect of antagonism on speed of recovery of neuromuscular function at the LA was evaluated. RESULTS: The time to recovery to a TOF ratio of 0.9 at the LA, when compared to the spontaneous recovery group, was significantly shortened by the administration of edrophonium in patients receiving rapacuronium [19.2 +/- 7.8 vs 26.2 +/- 4.9 (mean +/- SD) min], rocuronium (24.7 +/- 14.3 vs 44.4 +/- 13.0 min) and cisatracurium (24.2 +/- 5.7 vs 35.1 +/- 7.6 min). Edrophonium administration did not shorten complete recovery from mivacurium-induced block (15.7 +/- 8.0 vs 17.6 +/- 6.1 min). CONCLUSION: Recovery from rapacuronium-, rocuronium- or cisatracurium- induced neuromuscular block to a TOF ratio of 0.9 as measured at the LA was shortened by the administration of edrophonium, when compared to spontaneous recovery.     

Priming with anticholinesterases — the effect of different combinations of anticholinesterases and different priming intervals

This study was designed to investigate the effect of different combinations of neostigmine and edrophonium when administered in divided doses and the effect of different intervals (priming intervals) between the doses. Seventy-two patients divided into 12 groups (n = 6 in each) were included in the study. An initial dose of neostigmine 0.012 mg.kg-1 or edrophonium 0.2 mg.kg-1 was administered, followed at different priming intervals (1, 2 or 3 min) by either edrophonium 0.8 mg.kg-1 or neostigmine 0.048 mg.kg-1 for antagonism of atracurium-induced neuromuscular blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. Adequate reversal of neuromuscular block (train-of-four ratio of 0.75) was achieved in all patients. Significant (p less than 0.05) acceleration of the recovery index (time taken for the twitch height to recover from 25 to 75 per cent of control) and reversal time (time taken from the end of injection of the priming dose until TOF ratio value had reached 0.75) was obtained in groups which received edrophonium-edrophonium combination. Recovery indices and reversal times were found to be significantly shorter (p less than 0.05) with a 1 min priming interval. In two additional groups of patients premedicated and anaesthetized as the others equipotent mixtures of the antagonists were administered as a single bolus dose. Reversal times were significantly longer (p less than 0.05) when compared to those given the same amounts of the combination but in divided doses with a 1 min priming interval.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effects of neostigmine and edrophonium on the duration of action of suxamethonium

Rapid sequence induction of anaesthesia necessitating the use of suxamethonium may occasionally be needed soon after antagonism of neuromuscular block with anticholinesterase agents. The onset and duration of action of 1 mg kg^-1 of suxamethonium was recorded in groups of 10 patients each, 5 or 10 min after the administration of edrophonium 1 mg kg^-1 or neostigmine 40 μg kg^-1 given for the antagonism of atracurium-induced neuromuscular block. Plasma cholinesterase activity was measured before, and 5 and 10 min after the administration of the anticholinesterases. A further 10 patients received suxamethonium 1 mg kg^-1 without prior atracurium or anticholinesterase administration to serve as controls. The onset of action of suxamethonium was significantly prolonged when administered 5 min after both anticholinesterases, compared to the control group ( P <0.01). Recovery of suxamethonium block was delayed significantly after neostigmine, compared to both the edrophonium and the control groups ( P <0.05–0.001). Plasma cholinesterase activity was significantly reduced with the use of neostigmine but not with edrophonium ( P <0.001).     

Edrophonium antagonism of cisatracurium-induced neuromuscular block: dose requirements in children and adults

This randomized, controlled study compared edrophonium dose requirements to antagonize cisatracurium-induced neuromuscular block in children and adults. Sixty children, aged two to 10 years, and 60 adults aged 20 to 60 years, all subjects ASA physical status 1 or 2, having propofol, fentanyl and isoflurane-N2O anaesthesia, were studied. Cisatracurium 0.1 mg x kg(-1) was given for muscle relaxation. Neuromuscular block was monitored with accelerometry. Edrophonium 0.1, 0.2, 0.4 or 1 mg x kg(-1) or no anticholinesterase (controls) was given by random allocation to antagonize 90% neuromuscular block in each of the study groups (n=12). Atropine 5 to 10 microg x kg(-1) was given according to edrophonium dose. Onset time of cisatracurium-induced block in children was mean (SD) 2.4 (0.8) versus 4.1 (2.3) minutes in adults, P<0.01. The times to 10% spontaneous recovery of the first twitch (T1) were respectively, 28.4 (5.2) and 41.8 (6.1) minutes in children and adults, P<0.01. Spontaneous and antagonist assisted neuromuscular recovery was more rapid in children. Adequate neuromuscular recovery (train of four (TOF) ratio 80%) was achieved in children at 3 and 10 minutes after edrophonium 1.0 mg kg(-1) and 0.4 mg x kg(-1), respectively. A TOF ratio of 80% was not achieved, within 10 minutes, with any of the four dose levels of edrophonium in adults. The dose of edrophonium to achieve a TOF ratio of 80% (ED(TOF-80)) after 5 and 10 minutes in children were, respectively, mean (SD) 0.85 (0.38) and 0.38 (0.19) mg x kg(-1). The equivalent ED(TOF-80) in adults was outside the edrophonium dose range studied.     

Edrophonium and plasma cholinesterase activity

Plasma cholinesterase activity was estimated following administration of edrophonium 0.5 or 1.0 mg X kg-1 given for antagonism of atracurium-induced neuromuscular block. There was no inhibition of enzyme activity for up to three hours following edrophonium administration. This is in contrast to profound and prolonged inhibition of enzyme activity seen following neostigmine and pyridostigmine.     

Conditions to optimise the reversal action of neostigmine upon a vecuronium-induced neuromuscular block

Background: Since neostigmine was introduced for reversal of neuromuscular block, there has been controversy about the optimum dose for antagonizing neuromuscular block. The purpose of this study was to characterise recovery of neuromuscular transmission following a vecuronium-induced block 15 min after neostigmine administration using different stimulation patterns, and to determine the effects of different doses of neostigmine given at various pre-reversal twitch heights. Methods: Adductor pollicis (AP) mechanical activity in response to low (0.1 and 2 Hz) and high (50 and 100 Hz) frequency stimulation, was recorded 15 min after 20, 40 and 80 μg/kg neostigmine, given to reverse a vecuronium-induced block at 10, 25 and 50% pre-reversal twitch height (TH). Fifty four ASA class I and II anaesthetised (methohexital, fentanyl, N₂O/O₂) young adult patients were studied and randomly allocated into 9 groups of 6 patients each. Results: In contrast to twitch height (TH) and residual force after 50 Hz, 5 s tetanic stimulation (RF50_Hz), the greater sensitivity of train-of-four (TOF) ratio and residual force after 100 Hz, 5 s tetanic stimulation (RF100_Hz) points out the best reversal conditions (prereversal TH and the optimal neostigmine dose) (P<0.001, two-way analysis of variance). The highest reversal scores (about 0.9 TOF ratio and RF100_Hz) were obtained when 40 μg/ kg of neostigmine was given at 25 and 50% TH. A 0.9 TOF ratio was also observed when 40 μg/kg of neostigmine was given at 10% TH, but, under these conditions, RF100_Hz was only 0.6 (P<0.05, Duncan test). Conclusion: To optimise the reversal action of neostigmine in order to obtain the highest neuromuscular transmission recovery (0.9 TOF ratio and RF100_Hz) during a vecuronium-induced neuromuscular block, the 40 μg/kg dose has to be given at 25 to 50% recovery of TH.