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.     

Edrophonium priming alters the course of neuromuscular recovery from a pipecuronium neuromuscular blockade

This study was designed to investigate the effect of divided administration of edrophonium on the course of neuromuscular recovery from a pipecuronium neuromuscular blockade. During thiopentone-nitrous oxide-halothane anaesthesia 48 patients were given pipecuronium 70 micrograms.kg-1. Patients were randomly assigned to one of four groups (n = 12 in each) to receive either edrophonium 1 mg.kg-1 (Groups I and II) or edrophonium 0.75 mg.kg-1 (Groups III and IV). In Groups I and III (single-dose groups), edrophonium was administered as a single bolus dose. In Groups II and IV (divided-dose groups) edrophonium was administered as an initial dose of 0.25 mg.kg-1 followed three minutes later by either 0.75 or 0.50 mg.kg-1 respectively. Reversal was attempted at 20% spontaneous recovery of twitch height. Administration of edrophonium in divided doses (Groups II and IV) accelerated the reversal of the pipecuronium neuromuscular blockade. At ten minutes post-reversal, train-of-four (TOF) ratio recovery reached 0.75 or more in 12 (100%) and in ten (83%) patients in Groups II and IV respectively. Similarly, times to attain a TOF of 0.75 (SEM) were shorter in the divided-dose groups than in the single-dose groups (P less than 0.05), being 354.5 (38.7) and 398.3 (49.1) sec in Groups II and IV vs 705.4 (66.6) and 651.2 (54.3) sec in Groups I and III respectively. Time was counted from the first administration of edrophonium. It is concluded that administration of edrophonium in divided doses produced a faster reversal of residual pipecuronium-induced neuromuscular blockade than single bolus administration. Also, administration in divided doses reduced the requirements of edrophonium needed for reversal of pipecuronium neuromuscular blockade.     

The optimal priming dose for atracurium

To determine the optimal priming dose for administration in divided doses, atracurium was given to 77 patients either in a single dose of 0.5 mg X kg-1 or in an initial dose of 0.04, 0.05, 0.06, 0.07, 0.08 or 0.09 mg X kg-1, followed three minutes later by the remainder of the 0.5 mg X kg-1 dose. Patients were anaesthetized throughout the study. When atracurium was given as a single bolus of 0.5 mg X kg-1, the mean time to complete neuromuscular block was 141.5 seconds. Administration in divided doses accelerated the onset time (p less than 0.01), that is the time from the intubating dose to the complete suppression of train-of-four (TOF) response. The TOF ratio decreased slightly but statistically significantly following the priming doses. When the priming dose was 0.05 mg X kg-1, the mean onset time was 70.9 seconds and priming with larger doses did not add any further advantage. It is concluded that 0.05 mg X kg-1 appears to be the optimal priming dose for the administration of atracurium in divided doses. When 0.05 mg X kg-1 is given three minutes before the intubating dose, tracheal intubation can be accomplished in less than 90 seconds.     

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.      

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.     

Cardiovascular changes at antagonism of atracurium

The cardiovascular changes in the 10 minutes following antagonism of an atracurium-induced block were studied in 32 patients. A 5:1 ratio combination of either 15, 35, 55 or 75 micrograms/kg neostigmine, with a corresponding dose of 3, 7, 11, or 15 micrograms/kg of glycopyrronium was used for antagonism. The least change in heart rate was with neostigmine 15 micrograms/kg with an increase of more than 15 beats/minute found in only one patient. Antagonism with 35, 55 and 75 micrograms/kg neostigmine mixture produced the greatest increase in heart rate at one minute and this was significantly different from the effect of the 15 micrograms/kg dose. Twenty out of 24 patients given the larger doses had heart rate increases in excess of 15 beats/minute and in nine patients this ranged from 30 to 52 beats/minute, representing increases of 46-80% above baseline values. Arterial pressure increases after antagonism were statistically significant in all four groups, with no between-group difference; these were clinically unimportant. When antagonising an atracurium-induced block with clinically useful doses of neostigmine, the standard 5 : 1 ratio combination with glycopyrronium will result in an initial tachycardia.     

Prolonged neuromuscular blockade with atracurium

During general anaesthesia with oxygen, nitrous oxide and enflurane, a 29-year-old woman received a total of 105 mg (1.78mg.kg^-1) of atracurium over a 2.5 hour period. The neuromuscular blockade could not be completely reversed with neostigmine and mechanical venti-latory support was necessary for three hours postopera-tively. The patient received succinylcholine without unusual sequelae before and after this episode. This is the first report of a patient who exhibited prolonged weakness after receiving atracurium.     

Profound atracurium induced neuromuscular blockade

Speed of reversal of profound atracurium induced neuromuscular blockade following edrophonium (0.5 or 1.0 mg/kg) or neostigmine (0.04 or 0.08 mg/kg) was measured using the train-of-four pattern of nerve stimulation. In all patients adequate clinical reversal was present when the ratio of the strength of the fourth to the first twitch (T4 ratio) was 0.5. Both doses of edrophonium were associated with a significantly faster speed of reversal than the smaller dose of neostigmine (p less than 0.05 in both cases). However, the larger dose of neostigmine was associated with a reversal time approaching that of edrophonium. Possible explanations for these findings are discussed in terms of contemporary theories of neuromuscular pharmacology.     

Edrophonium and human plasma cholinesterase combination for antagonism of mivacurium-induced neuromuscular block

We have compared the reversal characteristics of mivacurium after administration of an edrophonium-plasma cholinesterase (PCHE) combination with that produced by each antagonist alone. Forty ASA I adults were given mivacurium 0.15 mg kg-1 during fentanyl-thiopentone- nitrous oxide-isoflurane anaesthesia. TOF 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 (T1) reached 10% of its initial control value, patients were allocated randomly to one of four groups (n = 10 in each). Neuromuscular function in patients in group 1 (control group) was allowed to recover spontaneously. Patients in groups 2-4, respectively, received edrophonium 1 mg kg-1 (group ED), exogenous PCHE equivalent to activity present in 25 ml kg-1 of human plasma (group PCHE) or edrophonium 1 mg kg-1 with exogenous human PCHE equivalent to the activity present in 25 ml kg-1 of human plasma (combination group). The time to attain a TOF ratio of 0.75 in the combination group was 4.6 (SD 0.9) min. This was shorter (P < 0.01) than that observed in patients in the control (16.8 (3.3) min), ED (8.9 (3.6) min) and PCHE (9.3 (1.6) min) groups. There was no difference in recovery indices between groups ED and PCHE. We have demonstrated that the edrophonium- PCHE combination significantly accelerated recovery of mivacurium- induced block compared with that observed with the use of individual antagonists.      

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)     

Edrophonium antagonism of vecuronium at varying degrees of fourth twitch recovery

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T₄/T₁ > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-offour (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg · kg^?1, during thiopentone-N₂O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg · kg^?1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg · kg^?1, was given. Two minutes later, edrophonium, 0.1 mg · kg^?1, was given if T₄/T₁ did not reach 0.7. After another two minutes, edrophonium, 0.2 mg · kg^?1, was given if T₄/T₁ did not reach 0.7 or more. Finally, if T₄/ T₁ was still < 0.7, a dose of 0.4 mg · kg^?1 was given. Seventeen patients (42.5%) required 0.1 mg · kg^?1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg · kg^?1 and six patients (15%) required 0.4 mg · kg^?1. Only one patient received 0.8 mg · kg^?1. There was a good correlation between T₄/ T₁ two minutes after the first dose of edrophonium and pre-reversal T₄/T₁ (r = 0.6; P = 0.00014). All patients with pre-reversal T₄/ T₁ > 0.23 required at most 0.2 mg · kg^?1 of edrophonium for successful reversal. We conclude that when all four twitches are clearly visible following train-of-four stimulation, small doses of edrophonium (0.1-0.2 mg · kg^?1) might be sufficient to antagonize vecuronium neuromuscular blockade.     

阿曲库铵与哌库溴铵在预注法中的复合应用

目的 观察阿曲库铵和哌库溴铵在预注法中的复合应用。方法 选择平衡麻醉下择期手术病人70例。研究分两部分：第一部分，将30例病人随机均分为阿曲库铵组和哌库溴铵组，采用累计给药法建立两药量一效关系曲线，计算ED50和ED95；第二部分，根据两药ED95将另40例病人随机均分为单纯阿曲库铵预注组和复合哌库溴铵预注组。观察预注期间肌颤搐抑制值、起效时间和临床作用时间。结果 阿曲库铵ED50和ED95分别为117．5μg／kg和272．8μg／kg，哌库溴铵ED50和ED95分别为23．7μg／kg和42．6μg／kg；复合哌库溴铵预注组起效快于单纯阿曲库铵预注组；复合哌库溴铵预注组临床作用时间长于单纯阿曲库铵预注组。结论 在预注法中采用化学结构不同的肌松药可进一步加快起效，延长临床作用时间。     

Edrophonium antagonizes combined lidocaine-pancuronium and verapamil-pancuronium neuromuscular blockade in cats

The effects of lidocaine or verapamil on pancuronium neuromuscular blockade and the ability of anticholinesterase agents to antagonize these combined blockades were studied in 14 cats using a standard peroneal nerve-anterior tibialis muscle preparation. Pancuronium was infused at a constant rate to produce a stable 50% depression of single twitch tension. In nine cats, intravenous lidocaine boluses followed by a constant infusion produced serum lidocaine levels of 5.09 +/- 1.9 micrograms/ml (mean +/- SD) and resulted in an additional 20.0 +/- 5.5% depression of twitch tension. In the other five cats, intravenous injection of 0.15 mg/kg of verapamil produced an additional 12.8 +/- 8.0% twitch depression of pancuronium-induced neuromuscular blockade. For individual animals, edrophonium antagonism of the combined lidocaine-pancuronium-induced neuromuscular blockade or combined verapamil-pancuronium-induced neuromuscular blockade was not significantly different from antagonism of an equivalent twitch depression produced by pancuronium alone. It is concluded that lidocaine and verapamil augment neuromuscular blockade caused by pancuronium and that anticholinesterase antagonism of this augmented blockade can be expected to occur in a normal fashion.     

Reversal of intense neuromuscular blockade following infusion of atracurium

In order to evaluate reversal time from very intense neuromuscular blockade caused by a continuous infusion of atracurium, the time course of neostigmine induced reversal from different levels of neuromuscular blockade was evaluated using the post-tetanic count (PTC) and the train-of-four (TOF) in 30 patients anesthetized with nitrous oxide, fentanyl, and thiopental. Reversal time (time from administration of neostigmine at different PTC levels to a TOF ratio of 0.7) was found to depend upon the degree of blockade at the time of reversal. Median reversal time from a PTC of 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, and greater than 13 (but less than 10% twitch height) to a TOF ratio of 0.7 was 31, 23, 19, 18, 14, and 13 min, respectively. Spontaneous recovery from PTC level of 1-2, when atracurium infusion was stopped, to a PTC level at which antagonism was induced and reversal time were both correlated to the square root of the PTC. Total recovery time (spontaneous recovery plus reversal time) was not shortened by an early injection of neostigmine. It is concluded that neostigmine administration during intense neuromuscular blockade following atracurium infusion does not shorten total recovery time and offers no clinical advantages.     

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

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