Intravenous ranitidine antagonizes intense atracurium-induced neuromuscular blockade in rats

The neuromuscular action of ranitidine, an H2-receptor antagonist, was investigated by determining its effect on atracurium-induced neuromuscular blockade in urethane-anesthetized and mechanically ventilated male Sprague-Dawley rats. An intravenous bolus and an infusion of atracurium were administered to produce a stable 93 +/- 5% (n = 11) neuromuscular blockade as judged by tibialis anterior muscle twitch response. Ranitidine administered as a 1, 5, or 10 mg/kg normal body weight IV bolus during continuous atracurium infusion produced marked antagonism of neuromuscular paralysis. The percentage of antagonism (25 +/- 9%; n = 4; 53 +/- 19%, n = 4; and 79 +/- 9%, n = 3, respectively) was linearly related to the dose of ranitidine (r = 0.86, P less than 0.05). These results suggest that IV ranitidine has a significant anticholinesterase action against atracurium-induced neuromuscular blockade.     

Factors predicting atracurium reversal time

BACKGROUND: To identify individual factors and combination of factors predictive of reversal time (defined as time from neostigmine administration to train-of-four (TOF) ratio 0.70) from atracurium-induced neuromuscular block, the present study tested the following variables as possible predictors of reversal time: 1) degree of block at the time of antagonism as quantified by first response to TOF or double-burst stimulation (DBS); 2) time from last supplemental dose of atracurium to administration of neostigmine (pre-reversal time); and 3) time from administration of initial atracurium dose to T1 (the magnitude of the first twitch in TOF) recovered to 10% (duration of action of the initial dose of atracurium). METHODS: The study population comprised 83 female patients, ASA physical status 1 or 2, anaesthetized with fentanyl, thiopental, halothane and nitrous oxide. Initial and supplemental doses of atracurium were 0.5 mg x kg(-1) and 0.15 mg x kg(-1), respectively. Evoked responses to TOF or DBS were recorded mechanomyographically. Neuromuscular block was antagonized with neostigmine, 0.07 mg x kg(-1), at varying time intervals (6-50 min) after the final atracurium dose. RESULTS: Multiple linear regression analyses testing T1, D1 (the magnitude of the first twitch in DBS), pre-reversal time and duration of action of the initial dose of atracurium, demonstrated that with superficial block, T1 >15%, T1 is the only significant predictor for reversal time. With moderate block, 0< T1 < or =15%, both T1 and duration of action of the initial atracurium dose are significant predictors for reversal time. With profound block, T1=0, duration of action of the initial dose and pre-reversal time are significant predictors for reversal time. CONCLUSION: 1) T1 is a more important predictor for reversal time from atracurium-induced neuromuscular block than D1; 2) predictors differ with the degree of block: with T1 > 15%, T1 is the only significant predictor; with 0< T1 < or =15%, the duration of action of the initial dose and T1 are predictors for reversal time; with T1=0, the duration of action of the initial dose and pre-reversal time predict reversal time.     

Accelerated reversal of atracurium blockade with divided doses of neostigmine

The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of neuromuscular blockade was investigated. Neostigmine 0.05 mg X kg-1 was administered either in a single bolus dose (Group I, n = 16) or in an initial dose of 0.01 mg X kg-1 followed three minutes later by 0.04 mg X kg-1 (Group II, n = 16) for antagonism of atracurium-induced blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. The mean time (+/- SD) from the first injection of the drug until the train-of-four (TOF) ratio value had reached 0.75 was significantly shorter in Group II (p less than 0.05) than in Group I (391.8 +/- 83.3 and 468.6 +/- 150.3 seconds respectively). The rate of TOF ratio recovery was 2.5 times faster after neostigmine administration in divided doses. It is concluded that administration of neostigmine in divided doses, as described in this study, produced a significantly faster reversal of residual atracurium-induced neuromuscular blockade as compared to a single bolus administration.     

Neuromuscular sensitivity to atracurium in humans

The relation between plasma concentration and the effects of atracurium was studied in seven patients anaesthetised with thiopentone, fentanyl and nitrous oxide-oxygen. The response to train-of-four stimulation at ten-second intervals with tetanic stimuli applied every five minutes were recorded. The first sign of transmission returning after complete blockade was usually the post-tetanic facilitated twitch, which was noted when the mean atracurium concentration was 1.15 mg 1(-1) (SD 0.77). The most sensitive parameter was the train-of-four ratio, which recovered to 0.5 when the concentration was 0.217 mg 1(-1) (SD 0.56), compared with a concentration of 0.271 (SD 0.85) at 50% recovery for twitch height, 0.221 (SD 0.029) for tetanic peak and 0.231 (SD 0.079) for tetanic fade. The value for the train-of-four ratio differed significantly (P less than 0.05) from that for the twitch height, but other differences were not significant. Once recovery commenced, these four parameters recovered at similar rates, with recovery indices (25 to 75% responses) of 14.8 (SD 1.7), 14.0 (SD 1.0), 14.3 (SD 1.8) and 13.7 (SD 2.1) minutes respectively. Post-tetanic facilitation was most marked during severe but incomplete blockade and tetanic stimulation temporarily reversed the atracurium-induced decrease in train-of-four ratio. Clinically, the use of tetanic stimulation did not improve the sensitivity of neuromuscular monitoring, but post-tetanic count may be useful where monitoring of profound relaxation is required.     

Neuromuscular effects of atracurium during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia in humans

To compare the effect of halothane and enflurane on an atracurium-induced neuromuscular blockade, the authors studied 40 patients during elective surgery. During 1.25 MAC enflurane-nitrous oxide (n = 20) or halothane-nitrous oxide (n = 20) (MAC value includes contribution from 60% nitrous oxide), the doses depressing twitch tension 50% (ED50S) for atracurium were 70 and 77 micrograms/kg, respectively. The difference was not significant. Time from injection to peak effect did not differ between groups. However, the duration of action of atracurium (expressed as duration 50 or the duration of a 50% blockade) was longer during enflurane-nitrous oxide anesthesia (34.2 min) than during halothane-nitrous oxide anesthesia (25.5 min) (P less than 0.05). The authors conclude that the potency of atracurium does not differ during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia. Combining the results of this study with a previous study (atracurium ED50 = 68 micrograms/kg and 83 micrograms/kg during isoflurane-nitrous oxide and fentanyl-nitrous oxide anesthesia respectively), the potency of atracurium does not differ by more than 20% among the four anesthetic techniques studied. The background anesthetic appears to have less effect on an atracurium-induced neuromuscular blockade than on one produced by other longer-acting nondepolarizing muscle relaxants (e.g., pancuronium and d-tubocurarine).     

Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium-induced neuromuscular block

Study Objective: (1) To determine the time to peak effect of neostigmine (time to peak antagonism) during atracurium- or vecuronium-induced neuromuscular block; and (2) to determine the effect on time to peak effect of neostigmine during atracurium-induced neuromuscular block, when the dose of neostigmine is increased from 35 μg/kg to 70 μg/kg.

Design: Prospective, randomized clinical study.

Setting: Gynecologic operating room suite at a university hospital.

Patients: 45 ASA I and II women admitted for gynecologic laparotomy.

Interventions: Anesthesia was performed with thiopental sodium, fentanyl, halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF) stimulation and mechanomyography were used to monitor neuromuscular transmission. Neostigmine was administered while a constant degree of neuromuscular block was maintained at a twitch height at a point between 4% and 11% of the control twitch height, using a continuous infusion of atracurium or vecuronium. The patients were randomized to three groups, with 15 patients in each group. Group 1 received atracurium block antagonized with neostigmine 35 μg/kg; group 2 received vecuronium block antagonized with neostigmine 35 μg/kg; and group 3 received atracurium block antagonized with neostigmine 70 μg/kg.

Measurements and Main Results: The degree of neuromuscular block at antagonism was similar in the three groups. Time to peak effect (mean ± SD) on TOF ratio was significantly longer in Group 1 (9.7 ± 3.0 minutes) versus Group 2 (6.6 ± 1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium-induced block was reduced from 9.7 ± 3.0 minutes to 6.3 ± 2.0 minutes when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3 compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2.

Conclusion: The time to peak effect of neostigmine 35 μg/kg is about 6 to 10 minutes when antagonizing a constant degree of atracurium- or vecuronium-induced neuromuscular block at a twitch height at a point between 4% and 11%. Even though the time to peak effect was longer with atracurium than with vecuronium, clinically significant differences between the antagonizing effect of atracurium versus vecuronium block were not demonstrated. The time to peak effect during atracurium-induced block decreased when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg.     

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)     

RECOVERY CHARACTERISTICS FOLLOWING ANTAGONISM OF ATRACURIUM WITH NEOSTIGMINE OR EDROPHONIUM

The evoked reversal characteristics of atracurium were studiedin 21 patients using edrophonium or neostigmine and a train-of-fourpattern of stimulation. Reversal of residual atracurium-inducedneuromuscular blockade was significantly more rapid using edrophoniumcompared with neostigmine. The ratio of the fourth twitch inthe train-of-four to the first twitch—the T₄ ratio—wassignificantly greater when the first twitch (T₁) had recoveredto 75% of control T₁, using edrophonium compared with neostigmine.A T₄ ratio of 0.5 was confirmed to be compatible with the reliableand safe reversal of atracurium-induced neuromuscular blockade.     

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.     

The effect of epidural bupivacaine on vecuronium–induced neuromuscular blockade in children

The efTect of epidural bupivacaine on potency and duration of action of vecuronium–induced neuromuscular blockade (NMB) was evaluated in 30 general surgical paediatric patients (ASA I–II) of three to ten years of age. Premedication was midazolam 0.5 μg kg^-1 orally (max 15 mg). In addition to general anaesthesia, 15 of the children received a lumbar epidural block with 0.5% bupivacaine 2.5 mg kg^-1. Anaesthesia was induced and maintained with N₂O:o₂ (2:1), propofol and alfentanil. NMB was monitored by adductor pollicis EMG with the train–of–four stimulus every 20 sec. Thirty minutes following the epidural bupivacaine injection (mean plasma concentration 0.86 μg ml^-1) or induction of anaesthesia a cumulative dose–response curve of vecuronium was established to achieve a 95% depression of the twitch response. Thereafter, NMB was allowed to recover spontaneously. ED doses of vecuronium were 19–22% greater in the control group than in the epidural group. ED^ doses were 33.8 (s.e.mean 1.3) μg kg"¹ and 28.4 (2.2) μg kg"', respectively ( P <0.05). There were no differences in recovery times from NMB between control and epidural group, the recovery index (time of twitch height to recover from 25 to 75%) being 6.4 (0.4) min and 7.0 (0.9) min, respectively. However, a negative correlation was found between bupivacaine plasma concentration and an ED₅₀ dose of vecuronium ( P =0.01). Our results indicate that vecuronium is slightly more potent in children with bupivacaine epidural block than in children without it.     

Optimum time for neostigmine reversal of atracurium-induced neuromuscular blockade

Purpose

The aim of the study was to determine the optimum time for administration of neostigmine during recovery from atracurium-induced neuromuscular blockade.

Methods

The study comprised 103 patients anaesthetised with midazolam, fentanyl, thiopentone, halothane, and nitrous oxide. Relaxation was induced with atracurium 0.5 mg·kg^?1 and maintained with supplements of 0.15 mg·kg^?1. The ulnar nerve was stimulated with train-of-four (TOF) and double burst stimulation (DBS). Evoked MMG responses were recorded. Patients were randomized to spontaneous recovery (n = 20) or to assisted recovery by neostigmine (0.07 mg ·kg^?1) at varying intervals (6–50 min) from the last atracurium dose (n = 83).

Results

The reversal time (time from administration of neostigmine to TOF ratio 0.7) was always < 13 min, when T₁ (first twitch in TOF) was detectable or when D₁ (first twitch in DBS) was > 5%. Total assisted recovery time (time from last supplemental atracurium dose to TOF ratio 0.7) increased with increasing T₁ and D₁ twitch heights (P < 0.05). The curve fitted to the scattergram with total assisted recovery time vs time from last atracurium supplement to neostigmine administration decreased to reach a minimum after which it increased to approach the line of identity. The minimum of the curve (total assisted recovery time 30.7 min) was reached when neostigmine was given 18.6 min after last atracurium supplement. At this time the T₁ and D₁ twitch height averaged 4 and 8% respectively. If prolongation of the minimum total recovery time of 2.5% is accepted, neostigmine can be given at T₁ and D₁ twitch height values of 0 to 8% and 4 to 15%, respectively.

Conclusion

The optimum time for neostigmine administration, taking both the reversal time and total recovery time into consideration, is when 0 < T₁ < 8% or when 5 < D₁ < 15%. Giving neostigmine at more profound degrees of blockade prolongs reversal time, while giving neostigmine later in the recovery phase prolongs total recovery time.     

Administration of vecuronium, atracurium and pancuronium in divided doses: effect on onset and duration of action

The time to onset of neuromuscular block (as assessed by single twitch stimulation at 0.1 Hz) and the duration to 25% recovery of twitch height were measured after administration of vecuronium 0.1 mg kg-1, atracurium 0.5 mg kg-1 or pancuronium 0.1 mg kg-1, administered either as a single bolus or in divided doses, 10% being administered 4 min prior to the remaining 90%. The patients were anaesthetized with thiopentone, nitrous oxide in oxygen and i.v. fentanyl. There was no significant difference between the single- and divided-dose groups, either in the onset times (2.8 and 2.9 min for vecuronium, 2.7 and 2.4 min for atracurium and 3.3 min each for pancuronium for single- and divided-dose groups, respectively) or the duration to 25% recovery of twitch height (35 and 29 min for vecuronium, 45 and 39 min for atracurium and 87 and 93 min for pancuronium for single- and divided-dose groups, respectively).     

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.     

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.     

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)     

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)     

Continuous infusions of atracurium and vecuronium,compared with intermittent boluses of pancuronium: dose requirements and reversal

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidurally administered mepivacaine delays recovery of train-of-four ratio from vecuronium-induced neuromuscular block

BACKGROUND: The aim of this study was to examine the efficacy of epidurally administered mepivacaine on recovery from vecuronium-induced neuromuscular block. METHODS: Eighty patients were randomly assigned to one of two study groups. They were either given epidurally a bolus of 0.15 ml kg(-1) of mepivacaine 2%, followed by repetitive injections of 0.1 ml kg(-1) h(-1) throughout the study, or were not given epidurally. General anaesthesia was induced and maintained with fentanyl, propofol and nitrous oxide. Neuromuscular block was induced with vecuronium 0.1 mg kg(-1) and monitored using acceleromyographic train-of-four (TOF) at the adductor pollicis. Patients in each treatment group were randomized to receive neostigmine 0.04 mg kg(-1) at 25% recovery of the first twitch of TOF or to recover spontaneously to a TOF ratio of 0.9. The effect of epidural mepivacaine on speed of spontaneous and facilitated recovery of neuromuscular function was evaluated. RESULTS: The time from administration of vecuronium to spontaneous recovery to a TOF ratio of 0.9 was significantly longer in the epidural mepivacaine group [105.4 (14.2) min] as compared with the control group [78.5 (9.1) min, P < 0.01]. Neostigmine administered at 25% of control in T1 shortened recovery from neuromuscular block, however the time required for facilitated recovery to a TOF ratio of 0.9 in the epidural group was significantly longer than that in the control group [7.6 (1.6) min vs 5.8 (2.1) min, P < 0.01]. CONCLUSIONS: In clinical anaesthesia, it should be recognized that epidurally administered mepivacaine delays considerably the TOF recovery from neuromuscular block.     

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 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.