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.     

Effects of succinylcholine on the pharmacodynamics of pipecuronium and pancuronium.

To study the effects of succinylcholine on subsequent pharmacodynamics of nondepolarizing muscle relaxants, a comparative pharmacodynamic study was carried out in patients having balanced anesthesia (thiopental, fentanyl, nitrous oxide/oxygen) in whom equipotent doses of pipecuronium (80 micrograms/kg) and pancuronium (100 micrograms/kg) were given with or without prior administration of succinylcholine (1 mg/kg). Fifty-two patients were randomly assigned to one of the following four groups: 1, pancuronium (100 micrograms/kg); 2, pipecuronium (80 micrograms/kg); 3, succinylcholine (1 mg/kg) plus pancuronium (100 micrograms/kg); and 4, succinylcholine (1 mg/kg) plus pipecuronium (80 micrograms/kg). In groups 3 and 4, the nondepolarizing relaxant was given after succinylcholine when the twitch height recovered to 75% of its control value. For maintenance of neuromuscular blockade, additional increments of pancuronium (20 micrograms/kg) or pipecuronium (15 micrograms/kg) were given. Neuromuscular function was monitored throughout induction, maintenance, spontaneous recovery, and pharmacologic reversal of the neuromuscular block. Mean onset times for pancuronium (group 1) and pipecuronium (group 2) given without succinylcholine were (mean +/- SEM) 2.5 +/- 0.3 and 2.8 +/- 0.2 min, respectively. Mean onset times (times to maximum twitch depression) of the two drugs given after succinylcholine (groups 3 and 4) were significantly shorter (1.4 +/- 0.4 and 1.6 +/- 0.1 min, respectively). Clinical durations (i.e., until 25% twitch recovery of pancuronium and pipecuronium) were not significantly different among the four groups, varying from 81.1 +/- 5.4 (group 4) to 107.0 +/- 17.0 (group 2) min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variability of pipecuronium neuromuscular blockade

The dose-response relationship and the variability of the time variables in pipecuronium neuromuscular blockade were studied in 29 patients (ASA physical status 3) during halothane anaesthesia. The ED₉₅ (twitch tension) was determined in 9 patients using the cumulative dose response technique. Another 20 patients received the resulting ED₉₅ as a single bolus. The mean ED₉₅ was 35 μg-kg^-1 (95% confidence interval: 29–41 μg.kg^-1). Following bolus injection of 1. ED₉₅, an 80–100% twitch depression was achieved within 4.6±1.3 min (mean ± s.d.). The duration from end of injection of pipecuronium to 25% twitch recovery, the time from 25% to 75% twitch recovery, and the time from 25% twitch recovery to the train-of-four ratio (TOF) returning to 0.7 was 35 ± 14, 37 ± 26, and 63 ± 27 min, respectively. The time from end of injection to TOF = 0.7 varied within a 2-h range (54–160 min). Thus, the time variables in pipecuronium neuromuscular blockade were as poorly predictable as those reported in the literature on pancuronium, alcuronium and doxacurium.     

Myasthenia gravis and pipecuronium--report of two cases.

The use of pipecuronium in two patients with myasthenia gravis undergoing thymectomy is described. Neuromuscular function was monitored throughout using the train-of-four (TOF) mechanical twitch response. The cumulative dose-response to pipecuronium was determined in both patients during nitrous oxide-oxygen-narcotic anaesthesia. Both patients were sensitive to pipecuronium. The ED50 doses of pipecuronium were 11.6 and 11.1 micrograms.kg-1 and the ED95 doses were 35 and 33.3 micrograms.kg-1 in patients #1 and 2 respectively. Edrophonium 1 mg.kg-1 and neostigmine 0.06 mg.kg-1 were administered to patients #1 and 2 respectively for antagonism of residual neuromuscular blockade at 25 per cent spontaneous recovery of first twitch (T1) of the TOF stimulation. As with other non-depolarizing muscle relaxants pipecuronium in reduced dosage and with careful neuromuscular monitoring can be used to provide surgical relaxation safely in patients with controlled myasthenia gravis.     

Neuromuscular Relaxants as Antagonists for M sub 2 and M sub 3 Muscarinic Receptors

Background: Neuromuscular relaxants such as pancuronium bind to M sub 2 and M3 muscarinic receptors as antagonists. Blockade of muscarinic receptors in atria of the M2 subtype mediates tachycardia. In the lung, blockade of M2 receptors on parasympathetic nerves potentiates vagally induced whereas blockade of M sub 3 receptors on bronchial smooth muscle inhibits bronchospasm. The current study was designed to quantify the affinity of a series of neuromuscular relaxants for the M2 and M3 muscarinic receptors, which were individually stably transfected in Chinese hamster ovary cell lines.

Methods: Competitive radioligand binding assays determined the relative binding affinities of the neuromuscular relaxants pancuronium, succinylcholine, mivacurium, doxacurium, atracurium, rocuronium, gallamine, and pipecuronium for the muscarinic receptor in the presence of a muscarinic receptor antagonist (sup 3 H-QNB) in membranes prepared from cells individually expressing either the M2 or M3 muscarinic receptor.

Results: All muscle relaxants evaluated displaced3 H-QNB from muscarinic receptors. The relative order of potency for the M2 muscarinic receptor (highest to lowest) was pancuronium, gallamine, rocuronium, atracurium, pipecuronium, doxacurium, mivacurium, and succinylcholine. The relative order of potency for the M3 muscarinic receptor (highest to lowest) was pancuronium, atracurium, pipecuronium, rocuronium, mivacurium, gallamine, succinylcholine, and doxacurium.     

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.     

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.     

Conditions to optimise the reversal action of neostigmine upon a vecuronium-induced neuromuscular block

Background: Since neostigmine was introduced for reversal of neuromuscular block, there has been controversy about the optimum dose for antagonizing neuromuscular block. The purpose of this study was to characterise recovery of neuromuscular transmission following a vecuronium-induced block 15 min after neostigmine administration using different stimulation patterns, and to determine the effects of different doses of neostigmine given at various pre-reversal twitch heights. Methods: Adductor pollicis (AP) mechanical activity in response to low (0.1 and 2 Hz) and high (50 and 100 Hz) frequency stimulation, was recorded 15 min after 20, 40 and 80 μg/kg neostigmine, given to reverse a vecuronium-induced block at 10, 25 and 50% pre-reversal twitch height (TH). Fifty four ASA class I and II anaesthetised (methohexital, fentanyl, N₂O/O₂) young adult patients were studied and randomly allocated into 9 groups of 6 patients each. Results: In contrast to twitch height (TH) and residual force after 50 Hz, 5 s tetanic stimulation (RF50_Hz), the greater sensitivity of train-of-four (TOF) ratio and residual force after 100 Hz, 5 s tetanic stimulation (RF100_Hz) points out the best reversal conditions (prereversal TH and the optimal neostigmine dose) (P<0.001, two-way analysis of variance). The highest reversal scores (about 0.9 TOF ratio and RF100_Hz) were obtained when 40 μg/ kg of neostigmine was given at 25 and 50% TH. A 0.9 TOF ratio was also observed when 40 μg/kg of neostigmine was given at 10% TH, but, under these conditions, RF100_Hz was only 0.6 (P<0.05, Duncan test). Conclusion: To optimise the reversal action of neostigmine in order to obtain the highest neuromuscular transmission recovery (0.9 TOF ratio and RF100_Hz) during a vecuronium-induced neuromuscular block, the 40 μg/kg dose has to be given at 25 to 50% recovery of TH.     

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)     

Interaction of verapamil with gallamine and pancuronium and reversal of combined neuromuscular blockade with neostigmine and edrophonium

In this in vitro study, the effects and interactions of verapamil with gallamine and pancuronium and reversal by edrophonium and neostigmine of combined neuromuscular blockade, produced by the muscle relaxants and verapamil, were studied in an avian skeletal muscle. The results show that verapamil reduced the amplitude of indirectly-elicited twitch tension and potentiated the neuromuscular blockade produce by the two muscle relaxants. Edrophonium and neostigmine reversed the neuromuscular blockade produce by the muscle relaxants alone, and in combination with verapamil. Edrophonium was more potent than neostigmine in reversing the combined neuromuscular blockade produced by the muscle relaxants with and without verapamil.     

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.     

Neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery with various antagonists in vitro]

We evaluated the neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery by means of washout or by antagonists in vitro, using phrenic nerve-hemidiaphragm preparations of rats. IC50 and IC90 of ORG9426 in single twitch were 10.62 +/- 0.58 microM and 15.75 +/- 0.95 microM; and those in train of four ratio were 9.04 +/- 0.38 microM and 11.87 +/- 0.42 microM, respectively. The potency of ORG9426 in vitro was compared with those of other non-depolarizing muscle relaxants. The order of potency among the non-depolarizing muscle relaxants was the following: d-tubocurarine greater than pipecuronium greater than pancuronium greater than vecuronium greater than ORG9426. There was no difference between ORG9426 and vecuronium in the recovery from block with washout, neostigmine, 4-aminopyridine, 3, 4-diaminopyridine, and edrophonium. In conclusion, the potency of ORG9426 is relatively low, and it can be easily antagonized by anti-cholinesterases and aminopyridines.     

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.     

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.     

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversal of doxacurium and pancuronium neuromuscular blockade with neostigmine in children

Recovery after doxacurium and pancuronium neuromuscular blockade and their acceleration by neostigmine have not been compared in children. Therefore, 60 paediatric surgical patients aged 2–10 yr (ASA 1–2) were studied. They were randomized to receive doxacurium 30 μg · kg^?1 or pancuronium 70 μg · kg^?1 iv during propofol, fentanyl, isoflurane and nitrous oxide anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds using a Datex NMT monitor. Six patients in each relaxant group received neostigmine (0, 5, 10, 20 or 40 μg · kg^?1) with atropine by random allocation when first twitch height (T_I) had recovered to 25% of control. Spontaneous recovery after ten minutes was similar following doxacurium (mean ± SEM values of 45.0 ± 3.9 vs 49.5 ± 10.0 % for T_I and 25.2 ± 3.8 vs 14.8 ± 3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log dose vs logit of T_I or TOF ratio after ten minutes. Neostigmine-assisted recovery was not different in the two groups, with ED₇₀ and ED₉₀ doses for T_I of 14.3 ± 1.8 and 25.7 ± 2.7 μg·kg^?1 for doxacurium and 12.5 ± 1.7 and 25.3 ± 2.3 μg· kg^?1 for pancuronium. Time to recovery of TOF ratio to 70% after neostigmine 40 ng · kg^?1 was 2.3 ± 1.0 and 4.2 ± 1.7 min (P = NS) following pancuronium and doxacurium, respectively. Adjusted recovery due to neostigmine alone (spontaneous recovery subtracted from the total) required two to three times higher doses of neostigmine. Thus, in children, the spontaneous recovery and reversal of neuromuscular blockade is similar with doxacurium and pancuronium. However, compared with previous adult studies, they recover twice as quickly from doxacurium neuromuscular blockade and neostigmine antagonism is achieved at 25–50% of the adult doses.     

Tactile evaluation of the response to double burst stimulation decreases, but does not eliminate, the problem of postoperative residual paralysis

Background: Routine perioperative monitoring with accelero-myography might prevent residual block, whereas routine tactile evaluation of the response to train-of-four (TOF) nerve stimulation does not. The purpose of this prospective, randomised and blinded study was to evaluate the effect of manual evaluation of the response to double burst stimulation (DBS_3.3) upon the incidence of residual block. Methods: Sixty adult patients scheduled for elective abdominal surgery were included in the study. Pancuronium 0.08 to 0.1 mg kg^?1 was given for relaxation and tracheal intubation. For maintenance of neuromuscular block, pancuronium 1–2 mg was administered. The patients were randomly allocated into two groups. In group DBS (double burst stimulation) the degree of block during anaesthesia was assessed by manual evaluation of the response to TOF nerve stimulation. During reversal, when no fade was detectable in the TOF response, the stimulation pattern was changed to DBS_3.3. The trachea was extubated when the anaesthetist judged the neuromuscular function to have recovered adequately and no fade in the DBS_3.3 response could be felt. In group CC (clinical criteria) patients were managed without the use of a nerve stimulator, and the level of neuromuscular block and reversal were evaluated solely on the basis of clinical criteria. In both groups, the TOF ratio was measured by mechanomyography immediately after tracheal extubation. Also, the ability to sustain head lift for 5 s, to protrude the tongue, to open the eyes, and to lift one arm to the opposite shoulder were tested. Results: The TOF ratio, as measured immediately after tracheal extubation, was significantly lower in group CC than in group DBS (means: 0.68 and 0.78, respectively), and the incidence of residual neuromuscular block defined as a TOF ratio <0.7 was significantly higher in group CC than in group DBS (57 and 24%, respectively). The time from the first TOF measurement until the TOF ratio reached 0.8 was significantly longer in group CC than in group DBS (means: 11.5 and 6.2 min, respectively). No significant differences between the two groups of patients were found in duration of anaesthesia, in times from end of surgery to injection of neostigmine, tracheal extubation or TOF ratio 0.8, in dose of pancuronium, or in any other postoperative variable. Conclusion: Routine perioperative manual evaluation of the responses to TOF and DBS_3.3 decreased the incidence and the degree of residual block following the use of pancuronium. It did not, however, exclude clinically significant residual paralysis, nor did it influence the amount of pancuronium used during the operation, the duration of anaesthesia or the time from end of surgery to tracheal extubation or to sufficient recovery of neuromuscular function (TOF=0.8).     

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.     

Comparison of respiratory sparing effect between pancuronium and three new nondepolarizing muscle relaxants in rats

Purpose There is a large difference in sensitivity between respiratory muscles and other limb muscles. This phenomenon, known as the respiratory sparing effect (RSE), is well established withd-tubocurarine, pancuronium, and succinylcholine. The purpose of this study is to evaluate the RSE of these new relaxants, vecuronium, pipecuronium, and ORG9426. Methods The study was done in vivo using rats. Mechanical twitch responses of tibialis anterior muscle and diaphragm stimulated with the sciatic nerve and phrenic nerve, respectively, were recorded simultaneously to monitor neuromuscular transmission. Changes of mechanical twitch responses from both muscles were compared following the injection of four kinds of muscle relaxants (pancuronium, picuronium, recuronium, and ORG9426). Results T, D (%) represents the maximum depression in tibialis anterior and diaphragm, respectively. T−D (%), which means the sensitivity difference between the two kinds of muscle, was calculated by subtracting D from T. The T−Ds of pancuronium, pipecuronium, vecuronium, and ORG9426 were 86.0±2.6%, 81.4±1.9%, 77.7±2.1%, and 74.6±2.7%, respectively. Conclusions The results indicated that the blockade produced by each muscle relaxant was lower in the diaphragm than in the anterior tibialis muscle. T−D was significantly smaller with vecuronium or ORG9426 than with pancuronium.     

Pretreatment with pancuronium before suxamethonium administration in patients heterozygous for the usual and the atypical plasma cholinesterase gene

The object of this study was to investigate whether pretreatment with pancuronium before i.v. injection of suxamethonium could cause prolonged neuromuscular blockade in patients heterozygous for the usual and the atypical plasma cholinesterase gene (E1uE1a). Forty-three patients, 23 with genotype E1uE1a and 20 with normal genotype (E1uE1u), were pretreated with pancuronium 0.01 mg.kg-1 followed by suxamethonium 1.5 mg.kg-1, and received either neurolept anaesthesia or halothane anaesthesia. Seven patients (E1uE1a) were given suxamethonium 1.5 mg.kg-1 without pretreatment. The duration and type of neuromuscular block were evaluated using train-of-four (TOF) nerve stimulation. Type of anaesthesia did not significantly influence the results. The duration of block following pretreatment was significantly longer in heterozygous patients than in normal patients. Time to 90% twitch height recovery was 10.7 +/- 1.2 min (mean +/- s.d.) in genotypically normal patients, and 18.0 +/- 4.2 min in patients with genotype E1uE1a. Pretreatment with pancuronium caused a significantly slower recovery of the TOF ratio (phase II block). Thus, a TOF ratio of 0.7 was always reached within 13 min in genotypically normal patients. In genotypically abnormal patients, the same TOF ratio was reached within 20 min in all but three patients. In these three patients time to 90% twitch height recovery was prolonged (18-31 min), and TOF ratio did not return to normal, but stabilized at about 0.35, 0.50, and 0.65, respectively. Injection of edrophonium restored normal neuromuscular function in 10 min. It is concluded that in patients heterozygous for the usual and the atypical gene, pretreatment with pancuronium in combination with an increased dose of suxamethonium may cause a phase II block and thus a prolonged neuromuscular block.