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)     

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.     

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)     

Neostigmine and edrophonium as antagonists of atracurium and pancuronium

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

Neostigmine and edrophonium for reversal of pipecuronium neuromuscular blockade

Neostigmine 0.06 mg.kg-1 or edrophonium 1 mg.kg-1 were administered to two groups of 15 patients each for antagonism of pipecuronium-induced neuromuscular block at 20% spontaneous recovery of the first twitch (T1) of the train-of-four (TOF) stimulation. The mean onset of action (+/-SEM) of edrophonium (18.1 +/- 2.4 sec) was significantly more rapid (P less than 0.01) than that of neostigmine (47.6 +/- 4 sec), as were the times taken to attain a TOF ratio of 0.25 and 0.5. Nevertheless, the reversal time (time taken from the end of injection of the antagonist until TOF ratio value had reached 0.75) was significantly shorter (P less than 0.01) in the neostigmine than in the edrophonium group (499.3 +/- 62 vs 767 +/- 52 sec respectively). The TOF ratio ten minutes after reversal was greater in the neostigmine group than in the edrophonium group (P less than 0.01), 0.78 +/- 0.02 vs 0.68 +/- 0.02 min respectively. At that time, 33% (5 out of 15) and 80% (12 out of 15) patients failed to be reversed adequately (TOF ratio of 0.75) after neostigmine 0.06 mg.kg-1 and edrophonium 1 mg.kg-1, respectively. Administration of one additional dose (one-third of the initial dose) of the same antagonist resulted in adequate antagonism in the remaining five patients in the neostigmine group and in nine patients in the edrophonium group. Two such doses were required in the remaining three patients in the latter group. The mean total dose of neostigmine and edrophonium employed in this study was 0.067 +/- 0.002 and 1.3 +/- 0.05 mg.kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonism of pancuronium- and pipecuronium-induced neuromuscular block

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

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.     

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.     

Priming with anticholinesterases — the effect of different priming doses of edrophonium

The effect of different priming doses of edrophonium were studied in 77 patients divided into seven groups (n = 11 in each). Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I; controls) or in an initial dose of 0.05, 0.1, 0.15, 0.2, 0.25 or 0.3 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to VII respectively. Reversal was attempted at ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Increasing the size of the priming dose from 0.05 to 0.2 mg.kg-1 resulted in a stepwise increase (p less than 0.05) in recovery of T1 and train-of-four (TOF) ratio. Higher priming doses (0.25 and 0.3 mg.kg-1) were not associated with further improvement in T1 and TOF recovery. Reversal time, that is the time taken from the first injection of edrophonium until the TOF ratio value had reached 0.75 was significantly faster (p less than 0.01) following priming with edrophonium 0.2 mg.kg-1 (Group V) when compared to Groups I, II, III, IV and VI. Reversal times were also significantly faster in Groups IV and VI when compared to the control group. It is concluded that 0.2 mg.kg-1 appears to be the optimal priming dose for administration of edrophonium in divided doses.     

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

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

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)     

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.     

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)     

Train-of-four ratio after antagonism of atracurium with edrophonium: influence of different priming doses of edrophonium

This study was designed to investigate the effect of different priming doses of edrophonium on the relationship between the the recovery of the first twitch of the train-of-four (T1) and train-of-four (TOF) ratio. This relationship was studied after the administration of the full dose of the antagonist in all groups. Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I, controls) or in an initial dose of 0.05, 0.1, 0.15 or 0.2 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to V. Reversal was attempted at the ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Of all the groups studied, Group V had a significantly greater recovery in the TOF ratio at any given T1 value. When first twitch tension (T1) had recovered to 100 per cent of the control, it was found for the same tension that the TOF ratio was greater in Group V, being 0.75 compared to 0.63, 0.65, 0.65 and 0.64 in Groups I to IV respectively. The implication is that this differential ability to reverse fade (or prejunctional activity) may be involved in the acceleration of recovery.     

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.     

“Priming” with neostigmine: failure to accelerate reversal of single twitch and train-of-four responses

Train-of-four stimulation can shorten the apparent onset time of neuromuscular blocking drugs. This study was designed to verify whether the same occurred with neostigmine-assisted recovery, and whether this apparent acceleration could explain the previously reported effectiveness of the priming technique for reversal agents. Fourteen adults received atracurium, 0.5 mg.kg-1, during a thiopentone-nitrous oxide-enflurane anaesthetic. The ulnar nerves of both arms were stimulated with train-of-four stimulation every 12 seconds until 1 per cent recovery of first twitch, at which time stimulation in one arm was switched to single twitch. When mean first twitch height reached 10 per cent of control, neostigmine, 0.04 mg.kg-1, was administered either as a single bolus, or as a "priming" dose of 0.01 mg.kg-1, followed 3 min later by 0.03 mg.kg-1. No statistically significant differences were observed between single twitch in one arm and first twitch height of the train-of-four in the other arm for the next 10 min. With priming, first twitch height was 45 +/- (SEM) 5 per cent at 5 min and 85 +/- 6 per cent at 10 min, compared with 72 +/- 5 per cent (p less than 0.05) and 91 +/- 2 per cent (NS) respectively without priming. Train-of-four ratio was 28 +/- 3 per cent at 5 min and 65 +/- 5 per cent at 10 min with priming, versus 53 +/- 4 per cent (P less than 0.05) and 73 +/- 3 per cent (NS) respectively without priming.(ABSTRACT TRUNCATED AT 250 WORDS)     

4-Aminopyridine potentiates neostigmine and pyridostigmine in man.

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 +/- 6 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevent a change in heart rate by 68 and 70 per cent, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.     

Neuromuscular blockade for rapid tracheal intubation in children: comparison of succinylcholine and pancuronium

To compare the effectiveness of succinylcholine and pancuronium for rapid intubation in children, 49 healthy children ages two to eight years were studied. After induction of anaesthesia with thiopentone and atropine, and administration of droperidol, fentanyl, nitrous oxide, and oxygen, each child received one of the following muscle relaxants: succinylcholine 1.5 mg X kg-1 (n = 12), succinylcholine 1.0 mg X kg-1 (n = 13), pancuronium 0.15 mg X kg-1 (n = 11), or pancuronium 0.10 mg X kg-1 (n = 13). The force of thumb adduction was measured by stimulating the ulnar nerve with repetitive supramaximal single twitches (0.15 Hz). The time to 95 per cent twitch depression (mean +/- S.D.) was most rapid with succinylcholine 1.5 mg X kg-1 (40.8 +/- 3.0 seconds) and succinylcholine 1.0 mg X kg-1 (51.8 +/- 14.0 seconds), slowest with pancuronium 0.10 mg X kg-1 (150.9 +/- 38.0 seconds), and intermediate with pancuronium 0.15 mg X kg-1 (80.3 +/- 21.8 seconds) (p less than 0.005). The intubating conditions were excellent in 100% of the children who received succinylcholine 1.5 and 1.0 mg X kg-1, and pancuronium 0.15 mg X kg-1, but were excellent in only 69 per cent of those who received pancuronium 0.10 mg X kg-1. We conclude that succinylcholine 1.5 mg X kg-1 produces the most rapid onset of excellent intubating conditions in children. In children in whom succinylcholine is contra-indicated, pancuronium 0.15 mg X kg-1 provides excellent intubating conditions within 80 seconds.     

A comparative evaluation of intubating doses of atracurium,d-tubocurarine,pancuronium and vecuronium in children

To determine the onset and recovery times and haemodynamic effects of intubating doses of atracurium (0.4 mg.kg-1), d-tubocurarine (0.8 mg.kg-1), pancuronium (0.12 mg.kg-1), and vecuronium (0.07 mg.kg-1), sixty-seven children aged one to eight years were studied under halothane and nitrous oxide anaesthesia. The time to maximum twitch depression and the time to recovery to T1/Tc 25 per cent were recorded with an integrated evoked EMG recorder. The heart rate and systolic blood pressure were recorded for five minutes after drug administration and prior to intubation. There was no difference in onset times between drugs. The recovery time to T1/Tc 25 per cent following vecuronium (25.5 +/- 6.3 min) was shorter than following atracurium (37.5 +/- 7.0 min). Recovery times for d-tubocurarine and pancuronium were greater than sixty minutes. Elevation of heart rate occurred after administration of pancuronium (+29.8 per cent to +38.6 per cent) and d-tubocurarine (+31 per cent to +34.9 per cent), but no change was observed after atracurium or vecuronium. Elevation of blood pressure was greatest following pancuronium (+10.8 to +14.8 per cent). No significant change was observed following atracurium or vecuronium. A transient lowering of blood pressure (-9.3 per cent) occurred following d-tubocurarine.