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.     

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.     

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 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.     

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)     

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)     

Dose-response relationships for neostigmine antagonism of rocuronium-induced neuromuscular block in children and adults

Dose-response relationships for the antagonism of intermediate-acting neuromuscular blocking agents have not been evaluated previously in children. We have examined the dose-response relationships for neostigmine antagonism of 90% rocuronium-induced neuromuscular block in children and adults, during nitrous oxide-1 MAC of isoflurane anaesthesia. We studied 40 children, aged 2-10 yr, and 50 adults, aged 18-60 yr; all received a single bolus dose of rocuronium 0.6 mg kg-1 and accelerometry was used to monitor neuromuscular transmission. When the first twitch of the train-of-four (TOF) response (T1) recovered to 10% of its control (T0), one of five doses of neostigmine 0, 5, 10, 20 or 50 micrograms kg-1 was given by random allocation to each of the study groups (n = 8 children and n = 10 adults). Recovery of T1 and TOF ratio (T4/T1%) was recorded for 10 min after initial administration of neostigmine. Onset time of rocuronium-induced block was faster in children than in adults (mean 64.6 (95% confidence intervals 57.7-71.5) s vs 83.7 (70.7-96.6) s; P < 0.05). The time to 10% recovery of T1/T0 was shorter in children than in adults (25.4 (22.9-27.9) min vs 38.8 (36.1-41.4) min; P < 0.001). Spontaneous and antagonist-assisted recovery were more rapid in children than in adults. Adequate recovery (T4/T1 of 80%) occurred in children at 4, 5 and 8 min after neostigmine 50, 20 and 10 micrograms kg-1, respectively. Adequate recovery was not produced in adults by any dose of neostigmine within 10 min. The effective doses of neostigmine required to achieve a TOF ratio of 80% (ED80) after 10 min in children and adults were, respectively, 7.10 (5.2-9.8) micrograms kg-1 and 56.56 (45.5-71.9) micrograms kg-1 (P < 0.001). There was no advantage in administering doses of neostigmine greater than 20 micrograms kg-1 to antagonize 90% rocuronium-induced neuromuscular block in children. In contrast, it appeared prudent to use neostigmine 50 micrograms kg-1 or more for adequate antagonism of a similar degree of block in adults.      

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)     

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 Responses for Neostigmine and Edrophonium as Antagonists of Mivacurium in Adults and Children

Background: Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children.

Methods: Fifty-four adults, aged 40.1+/-10.9 yr, and 54 children, aged 4.9+/-0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg *symbol* kg sup -1 intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micro gram *symbol* kg sup -1) or edrophonium (100, 200, 400, and 1,000 micro gram *symbol* kg sup -1) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min.

Results: Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97+/-2% (SD) in children compared with 69+/-11% in adults and train-of-four to 84 +/-5% versus 30+/-13% (P < 0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children.     

Predicting recovery from deep neuromuscular block by rocuronium in children and adults

STUDY OBJECTIVE: To compare the response to motor nerve stimulation at a rate of 1 Hz after 50 Hz tetanus [posttetanic count (PTC)] and 2 Hz for 2 seconds [train-of-four (TOF)] in children and adults during spontaneous recovery from blockade caused by rocuronium. DESIGN: Prospective, clinical, observational, multicenter study. SETTING: Operating rooms of two university hospitals. PATIENTS: 22 children (ASA physical status I and II) aged 2 to 5 years, scheduled to undergo dental treatment and 20 adults aged 18 to 60 years, scheduled to undergo elective general or orthopedic surgery during general anesthesia with tracheal intubation. MEASUREMENTS: Neuromuscular blockade was evaluated with accelerometry of the thumb, using PTC and TOF stimulation of the ulnar nerve, in patients who received rocuronium 1 mg x kg(-1). MAIN RESULTS: The first response to posttetanic and TOF nerve stimulation appeared earlier in children than in adults. The time from injection of rocuronium to appearance of the fourth response to TOF ranged from 27 to 62 minutes in children and from 37 to 94 minutes in adults. The average interval between the appearance of a posttetanic response and the first detectable response to TOF stimulation (T1) was also shorter in children, 7 minutes, than in adults, 16 minutes. The relationship between PTC and the time interval between a given PTC and the first detectable TOF response in both children and adults was exponential (R = -0.64 and R = -0.81, respectively). CONCLUSIONS: Children recover faster than adults from neuromuscular blockade after administration of 1 mg x kg(-1) rocuronium. The relationship between PTC and time to first response to TOF is exponential both in children and adults during recovery from neuromuscular blockade caused by rocuronium.     

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)     

Intubating conditions after pipecuronium bromide: the influence of dose and time.

STUDY OBJECTIVE: To determine the intubating conditions following the administration of pipecuronium bromide in doses of two (0.07 mg/kg) or three (0.1 mg/kg) times ED95 (average dose that gives 95% block of the first twitch). DESIGN: To compare intubating conditions at 11/2 and 21/2 minutes in 41 patients receiving balanced anesthesia. SETTING: Surgical patients at Thomas Jefferson University Hospital. PATIENTS: Forty-one patients undergoing surgical procedure who received general anesthesia. INTERVENTIONS: After obtaining a stable baseline of train-of-four (TOF), 41 patients randomly received either 0.07 mg/kg or 0.1 mg/kg of pipecuronium as a single intravenous (IV) bolus dose, and the trachea was intubated either at 11/2 or 21/2 minutes. MEASUREMENTS AND MAIN RESULTS: Intubating conditions at 21/2 minutes appeared significantly better than those at 11/2 minutes, regardless of the pipecuronium dose. The mean time for T1 (first twitch of TOF) to reach 50% and 90% suppression was 1.36 +/- 0.51 minutes and 2.29 +/- 0.8 minutes, respectively, for the 0.07 mg/kg dose and 1.07 +/- 0.27 minutes and 1.72 +/- 0.45 minutes, respectively, for the 0.1 mg/kg dose. This did not make a significant difference in intubating conditions at either time. The time to 25% recovery of T1 was 68.2 +/- 22 minutes for the 0.07 mg/kg dose and 121.5 +/- 49 minutes for the 0.1 mg/kg dose. In patients who had spontaneous recovery of T1 to between 10% and 25% of control, administration of neostigmine or edrophonium resulted in identical recovery in 10 minutes. However, in patients with less than 10% spontaneous recovery of T1, neostigmine appeared to be superior to edrophonium. CONCLUSION: Pipecuronium has a relatively rapid onset. The trachea could be intubated successfully in 11/2 minutes with a dose of either 0.07 mg/kg or 0.1 mg/kg. If the clinical situation requires perfect relaxation with no movement or bucking, we recommend waiting at least 21/2 minutes.     

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.     

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.     

Edrophonium antagonism of intense mivacurium-induced neuromuscular block in children

We have studied the time course of recovery after administration of edrophonium during intense mivacurium block in children aged 2-10 yr, using thumb acceleration in response to train-of-four (TOF) stimulation. Forty-three children receiving alfentanil, propofol, nitrous oxide, isoflurane anaesthesia and mivacurium 0.2 mg kg-1 were allocated randomly to one of three groups. Patients in group 1 (n = 15) received edrophonium 1 mg kg-1, 2 min after maximum block (intense block group). At the time of administration of edrophonium in this group, there was no response to TOF stimulation (100% block) and the post-tetanic count was 10.7 (range 0-20). Patients in group 2 received the same dose of edrophonium after 10% recovery of the first twitch (T1) in the TOF (conventional reversal). Patients in group 3 (n = 13) recovered spontaneously. All patients developed complete suppression of twitch height in response to the bolus dose of mivacurium. All recovery times were measured from the point of maximum block after mivacurium. Mean time for 25% recovery of T1 (clinical duration) was 3.8 (SD 1.1) min in the intense block group. This was significantly shorter than the conventional reversal (8.3 (2.4) min) and spontaneous recovery (9.2 (3.5) min) groups (P < 0.001). The times for 75% and 90% recovery of T1 were shorter in the intense block group (9.4 (2.8), 12.3 (4.2) min) compared with the conventional (13.1 (3.8), 17.3 (4.8) min) and spontaneous recovery (14.9 (4.5), 17.9 (5.2) min) groups (P < 0.01). Total recovery time required for 70% recovery of the TOF ratio (T4/T1) was 8.8 (2.4) min in the intense block group. This was significantly shorter than the conventional reversal (11.9 (3.2) min) (P < 0.05) and spontaneous recovery (17.1 (4.0) min) groups (P < 0.001). Conventional reversal was associated with a shorter total recovery time compared with spontaneous recovery (P < 0.01). The recovery index (time interval between T1 25% and 75%) was comparable in groups 1-3 (5.5 (2.0), 4.8 (2.1) and 5.7 (1.4) min respectively). Ten minutes after development of maximum block, the numbers of patients who recovered adequately (TOF ratio 70% or more) were, respectively, 12 (80%), 8 (53%) and 1 (8%) in groups 1-3. We conclude that edrophonium antagonized intense (no response to TOF stimulation) mivacurium-induced block in children, with significant reduction in the recovery times of T1 and TOF ratio compared with conventional reversal and spontaneous recovery.      

Intubation with low-dose atracurium in children

The objective of this study was to compare intubating conditions and neuromuscular effects using smaller doses of atracurium (0.25 mg/kg and 0.3 mg/kg) with the recommended dose of 0.4 mg/kg for intubation in children anesthetized with halothane, N2O and oxygen undergoing strabismus repair. All patients (10 in each group) had good or excellent intubating conditions at 80% depression of twitch height [T1 of train-of-four (TOF) stimulation]. Mean times to intubation were 2.6 +/- 0.2 minutes following 0.25 mg/kg and 2.2 +/- 0.2 minutes following 0.3 mg/kg. These times were significantly longer (P less than 0.05) than the mean intubation time of 1.5 +/- 0.2 minutes following 0.4 mg/kg. Mean times to recovery, defined as times from injection of atracurium to return of T1 of TOF to 10%, 25%, and 95% of control measurements, were significantly shorter with the smaller doses. Atracurium at these low doses may provide an alternative to succinylcholine for intubating children during halothane anesthesia for surgical procedures lasting 20-30 min.     

Influence of epidural lidocaine injection on vecuronium-induced neuromuscular blockade

BACKGROUND: We investigated vecuronium-induced neuromuscular blockade in patients with continuous epidural lidocaine injection and those without epidural lidocaine. METHODS: Lower thoracic epidural injection of lidocaine was commenced at a rate of 2-3 mg x kg(-1) x h(-1) following its bolus injection (1.5-2 mg x kg(-1)) only in epidural group. Neuromuscular function was monitored by acceleromyographic train-of-four (TOF) responses of the adductor pollicis muscle to ulnar nerve stimulation after induction of general anesthesia. RESULTS: Neuromuscular block was obtained by vecuronium 0.1 mg x kg(-1) as an intubating dose and was maintained 5-10% of baseline first twitch (T 1) of TOF responses by continuous vecuronium administration. The maximum depression of T 1 response and onset time obtained by vecuronium 0.1 mg x kg(-1) were not different between the groups, but mean clinical duration from administration of the first dose to T 1 recovery to 5% of baseline was significantly prolonged in group with epidural lidocaine (49.5 min), compared to that without lidocaine (32.3 min). Furthermore, maintenance dose of vecuronium obtained in the group with epidural lidocaine (0.034 mg x kg(-1) x h(-1)) was significantly smaller than that in the group without lidocaine (0.060 mg x kg(-1) x h(-1)). CONCLUSIONS: Based on our results, we conclude that lidocaine injected continuously into the epidural space potentiates vecuronium-induced neuromuscular block.     

Influence of neostigmine on the course of neuromuscular blockade with rocuronium or cisatracurium: a randomized, double-blind trial

OBJECTIVES: To compare the time-course of neuromuscular blockade with rocuronium or cisatracurium during intravenous anesthesia, in terms of both the time to spontaneous recovery or time to reversal after administration of neostigmine. MATERIAL AND METHODS: Patients classified as ASA 1-2 were randomized to receive blinded administration of a single injection of twice the 95% effective dose of rocuronium or cisatracurium for general anesthesia, and then neostigmine plus atropine at recovery of the first train-of-4 (TOF) twitch at 5% or 25%, or normal saline solution as placebo at recovery of the first TOF twitch at 25%. The neuromuscular blockade was monitored by acceleromyography. Intergroup comparisons were carried out by Student t test and analysis of variance. RESULTS: Sixty patients were enrolled. Mean (SD) time to onset was faster with rocuronium at (1.04 [0.32] minutes) compared with cisatracurium at (2.58 [0.81] minutes) and duration was shorter: time to the first twich at 5% was 30 (6.4) minutes with rocuronium and 38.1 (9.7) minutes with cisatracurium. The total duration of blockade (time to the 80% TOF ratio) was also shorter with rocuronium when the neuromuscular blockade was reversed, but there were no differences in the time to block reversal when neostigmine was not used: 62 (18.9) minutes to recovery from the rocuronium blockade vs 66.96 (15.9) minutes to recover from a cisatracurium blockade. A high percentage of patients had less than an 80% TOF ratio at 60 and 90 minutes of administration of the neuromuscular blockerswhen reversal was not used (patients receiving rocuronium, 60% at 60 minutes, and 20% at 90 minutes; patients receiving cisatracurium, 80% at 60 minutes, and 40% at 90 minutes). CONCLUSION: Not antagonizing a rocuronium- or cisatracurium-induced neuromuscular blockade in surgical procedures lasting less than 90 minutes can lead to a high percentaje of residual blockade (TOF ratio <80%).