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.     

Neostigmine and edrophonium as antagonists of atracurium and pancuronium

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

Edrophonium 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.     

Dose-response curves for edrophonium, neostigmine, and pyridostigmine after pancuronium and d-tubocurarine

To determine the potencies of neostigmine, pyridostigmine, and edrophonium in reversing pancuronium and d-tubocurarine blockade, dose-response curves were established for first twitch height recovery and train-of-four ratio. One hundred and twenty ASA physical status I or II patients scheduled for elective surgery received either 0.06 mg/kg pancuronium or 0.36 mg/kg d-tubocurarine during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height had recovered spontaneously to 10% of its initial value, neostigmine (0.005, 0.01, 0.02 or 0.05 mg/kg), pyridostigmine (0.02, 0.04, 0.1, or 0.2 mg/kg), or edrophonium (0.1, 0.2, 0.4 or 1 mg/kg) was injected by random allocation. Recovery was measured 10 min after the injection of the antagonist. First twitch ED50's were 0.013, 0.085, and 0.17 mg/kg after pancuronium, and 0.017, 0.11, and 0.27 mg/kg after d-tubocurarine, for neostigmine, pyridostigmine, and edrophonium, respectively. The ED50 for pyridostigmine and edrophonium obtained after d-tubocurarine was significantly larger (P less than 0.05) than that after pancuronium. The train-of-four dose-response curves were significantly flatter for edrophonium than for the other two agents, indicating a greater ability of edrophonium to antagonize fade at low doses. It is concluded that the potency of reversal agents may be different for different relaxants, and that potency ratios might depend upon the end-point chosen as full neuromuscular recovery.     

Twitch depression and train-of-four ratio after antagonism of pancuronium with edrophonium, neostigmine, or pyridostigmine

During N2O-O2-halothane anesthesia pancuronium (3 mg/70 kg) was antagonized with neostigmine (2.5 or 5 mg/70 kg), pyridostigmine (10 or 20 mg/70 kg), or edrophonium (50 or 100 mg/70 kg) in 36 human subjects (6 in each group). Reversal was attempted at 10% spontaneous recovery of muscle twitch, which was measured using train-of-four stimulation. When first twitch tension was less than 70% of the control it was found that for the same tension, the train-of-four ratio was greater with edrophonium than with neostigmine, and greater with neostigmine than with pyridostigmine. It was concluded that the three antagonists have different mechanisms of action. In comparison with neostigmine, edrophonium is more and pyridostigmine is less effective at presynaptic (or fade) receptors.     

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)     

Antagonism of an intubation dose of vecuronium

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

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.     

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.     

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

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

Dose requirements of vecuronium, pancuronium, and atracurium during orthotopic liver transplantation.

To further elucidate the role of the liver in the clearance of vecuronium, atracurium, and pancuronium, 30 patients undergoing orthotopic liver transplantation were randomly assigned to three comparable groups to receive a continuous infusion of vecuronium, atracurium, or pancuronium. The evoked integrated compound action potential of the hypothenar eminence in response to train-of-four ulnar nerve stimulation was measured and recorded. Anesthesia was induced with 3-5 mg/kg of thiopental, 50 micrograms/kg of midazolam, and 1-5 micrograms/kg of fentanyl IV and was maintained with continuous infusions of midazolam and fentanyl while the lungs were ventilated with an air-oxygen mixture. The infusion rates of vecuronium, atracurium, and pancuronium were adjusted to achieve a T1/Tc ratio of between 0.02 and 0.10 (T1 = height of first twitch, Tc = height of control twitch). Vecuronium and pancuronium requirements, which were 0.072 +/- 0.022 and 0.042 +/- 0.015 mg.kg-1.h-1 (mean +/- standard deviation) respectively during the dissection phase, decreased significantly during the anhepatic phase to 0.036 +/- 0.021 and 0.018 +/- 0.012 mg.kg-1.h-1 and returned toward the initial values in the postreperfusion phase (0.055 +/- 0.018 and 0.032 +/- 0.012 mg.kg.-1.h-1); whereas atracurium requirements remained unchanged during the three phases (0.667 +/- 0.199, 0.567 +/- 0.142, and 0.692 +/- 0.254 mg.kg-1.h-1). These data suggest that the liver has an important role in the elimination of vecuronium and pancuronium, whereas the elimination of atracurium is unaltered during exclusion of the liver from the circulation.     

Train–of–four fade during onset of neuromuscular block with nondepolarising neuromuscular blocking agents

Fade in the train-of-four (TOF) responses during onset of neuromuscular block was studied following administration of atracurium (225 or 450 micrograms/kg), vecuronium (40 or 80 micrograms/kg), pancuronium (60 or 120 micrograms/kg) and tubocurarine (450 micrograms/kg). TOF ratios were measured at approximate heights of T1 (first response in the TOF) of 75, 50 and 25%. Fade in TOF increased as the height of T1 decreased, with maximum fade being observed at T1 of 25%. The greatest difference between relaxants was observed at T1 of 25%, vecuronium showing the least fade and pancuronium, atracurium and tubocurarine showing increasing fade, in that order. The difference between atracurium and tubocurarine or between vecuronium and pancuronium was not significant, but the degree of TOF fade was significantly greater with atracurium and tubocurarine in comparison to vecuronium or pancuronium.     

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

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

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.     

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.     

Edrophonium antagonism of pancuronium-induced neuromuscular blockade in man: a reappraisal.

The ability of edrophonium to reverse the nondepolarizing neuromuscular blockade produced by pancuronium was studied in 40 adult patients during light nitrous oxide--enflurane anesthesia. Antagonism of paralysis was attempted when the train-of-four fade ratio had spontaneous recovered in various extents. Edrophonium was administered in incremental doses intravenously either until the fade ratio increased to 0.70 or more or until the total dose of drug amounted to 0.5 mg/kg. All patients who had spontaneous recovery of train-of-four fade ratios to at least 0.10 had adequate reversal with edrophonium. When the train-of-four count was three or fewer visible twitches, the response to endrophonium was unpredictable. No evidence of recurarization was seen.     

The potencies of edrophonium and neostigmine as antagonists of pancuronium

Dose response curves were constructed for edrophonium and neostigmine when used to antagonise pancuronium, 0.07 mg/kg during thiopentone-nitrous oxide-halothane anaesthesia. The antagonist was given when 10% twitch height had been restored and the effect was measured 10 minutes later. Recoveries to 50% and 90% twitch height were achieved with 167 and 828 micrograms/kg of edrophonium, and 10.5 and 51 micrograms/kg of neostigmine. The dose response curves were parallel and neostigmine was 16 times more potent than edrophonium. Combinations of equipotent doses of edrophonium and neostigmine were also administered and produced additive but not synergistic effects. It is concluded that either edrophonium or neostigmine may be used for the reversal of pancuronium neuromuscular blockade, but the combination of the two offers no advantage.     

Postoperative neuromuscular function in pediatric day-care patients.

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.     

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.