Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane, and halothane anesthesia in adults and children

To determine in adults and children the dose-response relationship and the duration of action of pipecuronium bromide during fentanyl-nitrous oxide (N2O), isoflurane, and halothane anesthesia, the authors studied 30 ASA Physical Status 1-2 adults (age: 16-55 yr) and 30 ASA Physical Status 1-2 children (age: 1.7-11.5 yr) during minor elective surgery. Patients were anesthetized with N2O/O2 (60:40) supplemented with either fentanyl (4 micrograms/kg), or isoflurane (adults, 0.9%; children, 1.2%), or halothane (adults, 0.6%; children, 0.7%). Neuromuscular (NM) blockade was measured by electromyography. Incremental iv doses of pipecuronium were administered to determine the cumulative dose-response relationship of pipecuronium until a 95% twitch depression (ED95) had been obtained. In adults, ED50 was 31.7 +/- 2.9 micrograms/kg (mean +/- SE) during fentanyl-N2O/O2, reduced by isoflurane (18.0 +/- 4.8 micrograms/kg, P less than 0.05) but not by halothane (25.0 +/- 2.6 micrograms/kg, NS). ED95 was 59.4 +/- 5.4 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (42.3 +/- 2.5 micrograms/kg, P less than 0.05), but not by halothane (49.7 +/- 3.1 micrograms/kg, NS). In children, ED50 was 43.9 +/- 4.7 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (23.1 +/- 1.6 micrograms/kg, P less than 0.05), and halothane (33.2 +/- 3.2 micrograms/kg, P less than 0.05). ED95 was 79.3 +/- 9.8 micrograms/kg during fentanyl-N2O/O2, and reduced by isoflurane (49.1 +/- 3.1 micrograms/kg, P less than 0.05), but not by halothane (62.5 +/- 7.3 micrograms/kg, NS). Comparison between adults and children reveals no statistically significant differences, except for ED50 during fentanyl-N2O/O2 anesthesia which was increased in children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Onset and duration of neuromuscular blockade following high-dose vecuronium administration

To determine the onset time and duration of high doses of vecuronium, 40 ASA Physical Status 1 and 2 patients were randomly assigned to receive either 100, 200, 300, or 400 micrograms/kg of vecuronium bromide for muscle relaxation during elective general surgery. Neuromuscular blockade was continuously quantitated by recording the electromyographic response to stimulation of the ulnar nerve train-of-four. The rate of onset of neuromuscular blockade, endotracheal intubating conditions, duration of neuromuscular blockade, and hemodynamic effects of vecuronium at each dose were evaluated and compared. The time from vecuronium administration to complete abolition of twitch tension (T1 = 0%) decreased from 208 +/- 41 to 106 +/- 35 s as the vecuronium dose was increased from 100 to 400 micrograms/kg (P less than 0.01). Corresponding times to endotracheal intubation (T1 less than 20%) also decreased from 183 +/- 24 to 96 +/- 31 s with increasing doses (P less than 0.01). Recovery time (T1 = 25%) increased from 37 +/- 13 to 138 +/- 24 min with increasing doses (P less than 0.01). No significant hemodynamic differences between the four groups were observed. Endotracheal intubating conditions were good or excellent in all patients. High doses of vecuronium may, therefore, be a useful alternative to succinylcholine when a rapid onset of neuromuscular blockade is required.     

Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans

To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).     

Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children

The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1–12 yr. All received premedication with midazolam, 0.5 mg · kg⁻¹ po and an inhalational induction with up to 3 MAC of either agent in 70% N₂O and O₂. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg · kg⁻¹) iv. The onset of maximal blockade occurred in 2.4 ± 1.26 (mean ± SD) min with halothane and 1.8 ± 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 ± 2.6, 19.5 ± 4.4, and 24.2 ± 4.8 min) were greater than during halothane anaesthesia (7.2 ± 2.2, 15.0 ± 4.0, 19.2 ± 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T₁ > 95%, T₄/T₁ > 75%) during the surgery which lasted 24–63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary. L’activité neurobloquante du mivacurium pendant l’anesthésie au sévoflurane ou à l’halothane fait l’objet de cette étude réalisée chez 38 enfants de 1 à 12 ans. Tous ont été prémédiqués au midazolam 0,5 mg · kg⁻¹ et l’anesthésie est induite avec un agent volatil jusqu’à MAC 3 de l’un des agents dans du N₂O à 70%. Le nerf cubital était stimulé au poignet au train de quatre aux dix seconds et la force de l’adduction du pouce mesurée avec un transducteur de force Myotrace. L’anesthésie était entretenue avec l’équivalent MAC I d’un des deux agents volatils pendant cinq minutes avant l’administration de mivacurium (0,2 mg · kg⁻¹). Le début du bloc maximum est survenu dans 2,4 ± 1,26 (moyenne ± SD) min avec l’halothane et 1,8 ± 0,54 min avec le sévoflurane (NS). Quatre patients n’ont pas été bloqués à 100% (trois avec l’halothane, un avec le sévoflurane). L’intervalle séparant l’injection à 5; 75, et 95% de la récupération pendant l’anesthésie au sévoflurane (9,8 ± 2,6, 19,5 ± 4,4 et 24,2 ± 4,8 min) a été plus long que pendant l’anesthésie à l’halothane (7,2 ± 2,2, 15,0 ± 4,0, 19,2 ± 4,9 min, respectivement (P < 0,005). An moniteur, chez tous les patients, la fonction neuromusculaire a récupéré spontanément (T₁ > 95%, T₄/T₁ > 75%) au cours de la chirurgie qui a duré de 24–63 min. Tous les patients montraient aussi les signes cliniques d’une récupération complète (par ex., levée de la tête, réflexe pharyngé ou toux). Aucun antagoniste pharmacologique n’a été requis. Il est conclu que le délai jusqu’à la relaxation maximum après une seule dose d’intubation de mivacurium ne diffère pas entre l’anesthésie à l’halothane et l’anesthésie au sévoflurane; les délais de retour à 5, 75 et 95% de la hauteur du twitch sont plus longs pendant l’anesthésie au sévoflurane et il n’est pas nécessaire d’antagoniser le bloc neuromusculaire.

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Supported in part by a grant from Abbott Laboratories, Chicago, Illinois.     

Recovery of neuromuscular function and postoperative morbidity following blockade by atracurium, alcuronium and vecuronium

Recovery of neuromuscular function and postoperative morbidity were studied in 51 fit female patients who had nonemergency gynaecological laparoscopy as inpatients. They were allocated randomly to one of three groups to receive either atracurium 0.31 mg/kg, alcuronium 0.25 mg/kg, or vecuronium 0.06 mg/kg as part of an otherwise standard anaesthetic technique. There were neither differences in intubation conditions nor in the occurrence of postoperative diplopia whichever muscle relaxant was used. Deficits in grip strength and expiratory force were seen at one hour after reversal with atropine 1.2 mg and neostigmine 2.5 mg in all patients, deficits which persisted for 3 hours in those who received alcuronium. The recovery of inspiratory force was slower and less complete at up to 3 hours in those who received alcuronium and there was a high incidence of minor postoperative morbidity at up to 24 hours in each of the three groups. The only statistical difference in symptomatic morbidity was an increase in muscle weakness in those who received alcuronium compared with atracurium at 3 hours after laparoscopy. Only 25%, 20% and 31% of the patients who received atracurium, alcuronium and vecuronium respectively said that they would have liked to be day stay patients.     

Recovery from neuromuscular blockade: residual curarisation following atracurium or vecuronium by bolus dosing or infusions

We conducted a survey of the incidence of Postoperative Residual Curarisation (PORC) in two groups of patients following the use of atracurium or vecuronium. In the first group (B) the neuromuscular blocking drugs were administered by bolus dosing, and in the second group (I) by continuous infusion. On arrival in the recovery room, neuromuscular function was assessed both by compound evoked electromyogram (EMG) in a train of four pattern and also clinically, by the ability to sustain a headlift for >5 seconds, and to cough. Results were obtained from 150 patients (100 in group B and 50 in group I). The incidence of PORC, as defined by a train of four ratio of <0.7, on arrival in the recovery room was 12% in group B, and 24% in group I. Clinical criteria of adequate neuromuscular reversal revealed different results, with the majority of patients being unable to perform either clinical test on arrival in recovery. Those patients in whom a peripheral nerve stimulator was used intra-operatively did not have a reduced incidence of PORC. We have demonstrated that PORC is still a common occurrence even with intermediate duration of action neuromuscular blocking drugs.     

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.     

Clinical,electrical and mechanical correlations during recovery from neuromuscular blockade with vecuronium

In order to determine correlations between electromyographic (EMG), mecanomyographic (MMG) and clinical criteria of adequate recovery from neuromuscular blockade with vecuronium, seven young healthy conscious volunteers were given subparalysing doses of vecuronium. During recovery from neuromuscular blockade, vital capacity, negative inspiratory pressure, peak expiratory flow rate and five-second head lift were assessed. Neuromuscular monitoring included the evoked EMG response of the adductor digiti minimi and the simultaneous evoked MMG response of the adductor pollicis on the same side. We found that all subjects maintained head lift for five seconds at EMG T4T1 of 0.70, and they achieved normal respiratory tests at EMG T4/T1 of 0.90. The MMG T4/T1 needed for the subjects to perform normal respiratory tests was found to be 0.50, at which time six of the seven subjects were able to perform adequately the head lift test.     

Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, enflurane, isoflurane, and halothane anesthesia in surgical patients.

This study was designed to determine the capacity of several anesthetics to augment pipecuronium neuromuscular blockade. The potency of pipecuronium was determined with single-bolus administration of 20-50 micrograms/kg in 160 patients. Patients were anesthetized with N2O/O2 (60:40) supplemented with fentanyl (4-5 micrograms/kg), halothane (0.8%), isoflurane (1.2%), or enflurane (1.7%). Neuromuscular blockade was measured by an acceleration-responsive transducer (the Accelograph, Biometer International, Odense, Denmark). Responses were defined in terms of percent depression in first-twitch height and train-of-four response, and the dose-response curves were constructed after probit transformation of the responses. The dose-response curves were found to be parallel for both first twitch height and train-of-four responses. The dose-response lines for the enflurane and isoflurane groups were displaced significantly (P less than 0.01) to the left of the line for the fentanyl-N2O group. The calculated doses producing 50% depression of first twitch height were 21.9, 21.2, 18.9, and 17.8 micrograms/kg for the N2O-fentanyl, halothane, isoflurane, and enflurane groups, respectively. Corresponding calculated doses for 50% depression of train-of-four response were significantly smaller (15.5, 14.4, 13.7, 11.9 micrograms/kg, respectively). The enhancing effects of the volatile anesthetics were reflected by significant prolongation of the clinical duration of neuromuscular blockade by pipecuronium. It is concluded that the potency of pipecuronium is enhanced more by enflurane and isoflurane than halothane or fentanyl-N2O anesthesia.     

Duration of halothane anesthesia and neuromuscular blockade with d-tubocurarine.

Cumulative d-tubocurarine dose-response curves were determined in 35 unpremedicated adult surgical patients. In five awake patients with and five awake patients without ulnar nerve block the median effective doses of d-tubocurarine necessary for 50 per cent depression of twitch tension (ED50) were 8.3 and 9.1 mg/m2, respectively. The presence of an ulnar nerve block did not significantly alter ED50, which suggests that the central nervous system has little influence on the d-tubocurarine dose-response curve. The ED50's of d-tubocurarine were 4.8, 4.5, 2.5, 3.2, and 3.8 mg/m2 in patients anesthetized with 1.0 to 1.3 per cent alveolar concentrations of halothane for 10, 20, 40, 80, and 160 minutes, respectively. It is concluded that duration of anesthesia has no effect on neuromuscular blockade by d-tubocurarine.     

Clinical pharmacology of pipecuronium in infants and children during halothane anesthesia

We determined the cumulative dose-response relations of pipecuronium in infants and children during nitrous oxidehalothane anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Patients were stratified into four groups according to age: 3 mo or older but not yet 6 mo (n = 10), 6 mo or older but not yet 12 mo (n = 10), 1 yr or older but not yet 3 yr (n = 10), and 3 yr or older but not yet 6 yr (n = 9). The mean ED50 of pipecuronium in these age groups was 18, 20, 21, and 24 micrograms/kg, respectively; the mean ED95 was 33, 38, 47, and 49 micrograms/kg, respectively. The ED95 of pipecuronium was statistically significantly less for the 3-6-mo-old patients than for children between 1 and 6 yr of age. Similarly, pipecuronium dosage requirements calculated on the basis of body surface area were significantly less in infants 3-12 mo of age than in children 1-6 yr of age. Thus, compared with children, infants appear to be more sensitive to the neuromuscular blocking effects of pipecuronium. Duration (T25) of action after cumulative dosing with pipecuronium was approximately 20 min in infants and 30 min in children. Spontaneous recovery indices were not prolonged in the younger patients. The average T25-75 recovery index was 27.1 +/- 9.6 min. There were no changes in cardiac rhythm, heart rate, or blood pressure attributable to pipecuronium during this study.     

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.     

新斯的明拮抗国产阿曲库铵效果及对Q-T离散度的影响

目的研究不同剂量新斯的明拮抗国产阿曲库铵肌松恢复作用的效果及对QT离散度(QTd)的影响.方法30例ASA Ⅰ～Ⅱ级患者,随机分为三组,每组10例.分别给予新斯的明20μg/kg(N20组)、30μg/kg(N30组)和40μg/kg(N40组),观察拮抗阿曲库铵肌松作用恢复时间及对QTd的影响.结果新斯的明20μg/kg产生的肌松恢复效果弱于30μg/kg和40μg/kg,而30 μg/kg和40μg/kg所产生的效果相似.新斯的明20 μg/kg、30μ/kg对QTd的影响不明显,而40μg/kg新斯的明明显增大QTd.结论新斯的明剂量由20μg/kg增加到40 μg/kg,肌松恢复加快,但增大QTd.     

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)     

Recovery of neuromuscular blockade caused by vecuronium is delayed in patients with hypertriglyceridemia

We investigated the effects of hypertriglyceridemia on the onset and recovery of neuromuscular blockade, induced by vecuronium, over the adductor pollicis muscle, electromyographically. Eighteen adult patients with hypertriglyceridemia (hypertriglyceridemia group) and 18 healthy patients with normal serum triglyceride (control group) were studied. The supramaximal stimulating current for train-of-four (TOF) in the hypertriglyceridemia group was significantly higher than that in the control group (45.7 ± 16.7 vs 31.5 ± 9.8 mA; mean ± SD; P = 0.004). The onset of vecuronium 0.1 mg·kg⁻¹-induced neuromuscular blockade in the hypertriglyceridemia group did not significantly differ from that in the control group (240 ± 60 vs 279 ± 88 s; P = 0.132). Times from vecuronium to the return of T1, T2, T3, and T4 in the hypertriglyceridemia group were significantly longer than those in the control group (31.4 ± 6.2 vs 25.5 ± 6.2 min for T1; P = 0.008). During recovery from neuromuscular blockade, T1/control did not differ between the two groups. However, the TOF ratios (T4/T1) in the hypertriglyceridemia group were significantly lower than those in the control group 80–120 min after vecuronium (P < 0.05). We conclude that, in patients with hypertriglycemidemia, a higher current is needed to elicit supramaximal response of the adductor pollicis muscle, and recovery from vecuronium-induced neuromuscular blockade is delayed.