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At least 19 recordsLinked to original sources
PubMed1996

Comparison of the pharmacodynamics and pharmacokinetics of an infusion of cis-atracurium (51W89) or atracurium in critically ill patients undergoing mechanical ventilation in an intensive therapy unit.

We have studied 12 critically ill, sedated patients who required a neuromuscular blocking drug to assist mechanical ventilation in an intensive care unit. Patients were randomized to receive an infusion of cis-atracurium 0.18 mg kg-1 h-1 (group 1, n = 6) or atracurium 0.6 mg kg-1 h-1 (group 2, n = 6) preceded, if necessary, by a bolus dose of 2 x ED95 of the same drug (cis-atracurium 0.1 mg kg-1 or atracurium 0.5 mg kg-1). Neuromuscular block was monitored using an accelerograph and the infusion rate adjusted regularly so that it was possible to detect the first response to train-of-four (TOF) stimulation of the ulnar nerve at the wrist. Blood samples were obtained for estimation of plasma cis-atracurium and laudanosine concentrations (group 1) or the three groups of atracurium isomers and laudanosine (group 2). There was no apparent haemodynamic or allergic response to either drug. The mean infusion time in group 1 was 37.6 h and in group 2, 27.5 h. On termination of the infusion, the time for the TOF ratio to reach 0.7 was similar in the two groups (group 1 = 60 min; group 2 = 62 min). The mean infusion rate of cis-atracurium was 0.19 mg kg-1 h-1 and of atracurium 0.47 mg kg-1 h-1 (expressed as mg of bis-cation): cis-atracurium was 2.5 times more potent than atracurium. Using the NONMEM program, a single compartment pharmacokinetic model was fitted to the plasma concentrations of cis-atracurium and the cis-cis, cis-trans and trans-trans isomers of atracurium. The mean population pharmacokinetic values for cis-atracurium were: volume of distribution (V) = 21,900 (SEM 416) ml; clearance (Cl) = 549 (79) ml min-1; half-life (T1/2) = 27.6 (3.6) min; and for the three groups of atracurium isomers were: cis-cis, V = 15,100 (720) ml, Cl = 449 (42) ml min-1, T1/2 = 23.4 (1.2) min; cis-trans, V = 18,000 (667) ml, Cl = 1070 (43) ml min-1, T1/2 = 11.7 (0.1); trans-trans, V = 13,100 (1280) ml, Cl = 1560 (55) ml min-1, T1/2 = 5.8 (0.4) min. Plasma laudanosine concentrations were lower in the cis-atracurium (peak value 1.3 micrograms ml-1) than in the atracurium (maximum 4.4 micrograms ml-1) group.

Adult↗
PubMed2002

[Cis-atracurium--an equivalent substitution for atracurium in pediatric anesthesia?].

Cis-atracurium is a stereoisomer of atracurium, about five times more potent than the racemate. Whereas cis-atracurium is routinely used in adults, its effects on children are still poorly defined. We compared equipotent doses of atracurium and cis-atracurium in children aged between 2 and 12 years regarding the quality of neuromuscular blockade, the intubation conditions and the occurrence of side-effects. After approval by the ethics committee and with informed parental consent, 84 children (ASA I or ASA II) were randomly allocated to receive either 0.5 mg/kg atracurium (group A, n = 42) or 0.1 mg/kg cis-atracurium (group C, n = 42). In both groups anaesthesia was induced with 15 micrograms/kg alfentanil and 5-7 mg/kg thiopentone. We assessed the intubation conditions according to the Krieg Scale. Anaesthesia was maintained with a nitrous oxide/oxygen mixture of 2:1 and isoflurane in an endexpiratory concentration of approximately 0.6 Vol.%. Neuromuscular blockade was controlled acceleromyographically in response to supramaximal stimulation of the ulnar nerve. We measured the onset time (T1 = 5%), duration of effect (T1 = 25%), recovery index (T1 = 25%-75%) and the recovery time at a train-of-four-ratio (T4/T1) of 0.7. These parameters did not show any significant differences between group A and group C: onset time: 3.1 +/- 1.5 min (group A) versus 3.4 +/- 1.1 min (group C), duration of effect: 34.1 +/- 5.5 min (group A) versus 34.1 +/- 6.5 min (group C), recovery index: 9.3 +/- 3.3 min (group A) versus 9.6 +/- 2.5 min (group C), recovery time at a TOF-ratio of 0.7:49.3 +/- 8.4 min (group A) versus 52.3 +/- 6.6 min (group C). In group A, the intubation conditions were "excellent" or "good" in 98% of the patients, whereas in group C the figure was only 69%. Regarding side-effects, we found significantly more frequent urticaria in group A (6 of the 42 patients) (p < or = 0.05) than in group C, in which no patient showed urticaria. Flush and tachycardia occurred much less frequently and there were no significant differences in the two groups: two patients in group A and only one in group C. The authors conclude that atracurium and cis-atracurium lead to comparable neuromuscular effects in children aged between 2 and 12 years. Only the intubation conditions were better after atracurium, but atracurium was followed by urticaria more often than cis-atracurium.

Anesthesia, General↗
PubMed1997

A comparison of the infusion pharmacokinetics and pharmacodynamics of cisatracurium, the 1R-cis 1'R-cis isomer of atracurium, with atracurium besylate in healthy patients.

We have compared the pharmacokinetics of cisatracurium with atracurium when given by bolus dose followed by continuous infusion. Twenty healthy patients were anaesthetised with thiopentone, midazolam, fentanyl and 70% nitrous oxide in oxygen. Ten patients (Group C) were randomly allocated to receive cisatracurium 0.1 mg.kg-1 and 10 patients (Group A) were given atracurium 0.5 mg.kg-1. Neuromuscular block was monitored using a mechanomyograph. When the first twitch of the train-of-four had recovered to 5% of control, an infusion of cisatracurium 3 micrograms.kg-1.min-1 was started in Group C and an infusion of atracurium 10 micrograms.kg-1.min-1 was started in Group A. The infusion rates were adjusted to maintain the first twitch of the train-of-four at 5% of control. The times to 90% and maximum depression of the first twitch of the train-of-four were significantly longer after cisatracurium than atracurium (2.2 and 3.4 min compared with 1.3 and 1.8 min, respectively; p < 0.01 in each instance). No significant differences were found in recovery parameters between the two groups. Blood samples were taken at regular intervals following the bolus, during the infusion and for 8 h thereafter. The plasma samples were analysed using high-performance liquid chromatography for cisatracurium and atracurium (using a method which distinguishes between the three geometric isomer groups), laudanosine and monoquaternary alcohol. The results were analysed using the Non-linear Mixed Effects Model program. A two-compartment model was fitted to the data. The different isomer groups of atracurium have different pharmacokinetics, the trans-trans group having the highest clearance (1440 ml.min-1) and the cis-cis group the lowest (499 ml.min-1). The clearance of cisatracurium (425 ml.min-1) is less than that of cis-cis atracurium and its elimination half-life is longer (34.9 min and 21.9 min, respectively). The plasma concentration of laudanosine after cisatracurium was one-fifth of that after atracurium.

Adult↗
PubMed1998

Laudanosine and atracurium concentrations in a patient receiving long-term atracurium infusion.

OBJECTIVE: Atracurium is sometimes used for muscle relaxation in patients undergoing mechanical ventilation. Use of atracurium in high doses or for a long period of time has raised the possibility of the accumulation of laudanosine, a breakdown product known to cause seizure activity in animals. The objective of this report was to see if laudanosine accumulation and seizure activity had occurred in a patient who had received a long-term, relatively high-dose infusion of atracurium. DESIGN: Case report. The patient received atracurium for 38 days, at rates ranging from 0.3 to 0.96 mg/kg/hr. An electroencephalogram (EEG) was done before the discontinuation of the infusion, and plasma concentrations of atracurium and laudanosine were measured at, and after, the termination of the atracurium infusion. The laudanosine elimination half-life was calculated. SETTING: Intensive care unit. PATIENT: A 23-yr-old woman admitted with sickle cell crisis, complicated by acute chest syndrome, acute respiratory distress syndrome, and hepatic and renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: As expected, laudanosine concentrations were increased but were below the level reported to cause seizure activity in animals. Laudanosine elimination half-life was prolonged to 617 mins, which was consistent with previously reported values. The patient's EEG was normal, with no ictal pattern. CONCLUSIONS: Despite long-term use of high doses of atracurium infusion and the increased elimination half-life of laudanosine, only moderate accumulation of laudanosine occurred, and the EEG was normal. Hence, it appears unlikely that toxic concentrations of laudanosine would be reached, even in a critically ill patient.

Adult↗
PubMed1990

Quantitation of the interaction between atracurium and succinylcholine using closed-loop feedback control of infusion of atracurium.

The authors used closed-loop feedback control of infusion of atracurium to study the effect of prior administration of succinylcholine on neuromuscular blockade induced by atracurium in patients undergoing otolaryngologic surgery. Anesthesia was maintained with nitrous oxide in oxygen, flunitrazepam, and fentanyl. Of 14 patients given atracurium, seven were given prior administration of succinylcholine and seven were not. Interaction between the two drugs was quantified by determining the asymptotic steady-state rate of infusion necessary to produce a constant 90% neuromuscular blockade. This was accomplished by applying nonlinear curve-fitting to data on the cumulative dose requirement during anesthesia. The neuromuscular blocking effect of atracurium was found to be greater after prior administration of succinylcholine. The asymptotic steady-state rate of infusion (+/- SD) for atracurium was 0.27 +/- 0.06 mg.kg-1.h-1 for patients given succinylcholine and 0.38 +/- 0.10 mg.kg-1.h-1 for those not given succinylcholine. The clinical implication of this study is that the clinician should be aware of the fact that an induction dose of 1 mg/kg of succinylcholine does reduce atracurium requirement for 90% neuromuscular blockade by approximately 30%.

Adult↗
PubMed2002

Pharmacodynamics and atracurium and laudanosine concentrations during a fixed continuous infusion of atracurium in mechanically ventilated patients with acute respiratory distress syndrome.

The present study was designed to assess the pharmacodynamics and the plasma levels of atracurium and laudanosine found during a 72-hour fixed rate infusion of atracurium in acute respiratory distress syndrome patients without renal or liver failure. Nine sedated and mechanically ventilated acute respiratory distress syndrome patients without renal or liver failure were paralysed with a bolus of atracurium (1 mg x kg(-1)) followed by a 72-hour continuous infusion (1 mg x kg(-1) x h(-1)). The count of train-of-four (TOF) and TOF ratio were monitored by an accelerograph until full neuromuscular recovery (T4/T1 > or = 0.7). Atracurium and laudanosine concentrations were measured from the onset to four days after cessation of the infusion. An electroencephalogram was recorded daily. Analysis showed that TOF count was always < or = 3 until cessation of the infusion. Following cessation, neuromuscular recovery occurred between 31 and 96 minutes (median value = 45 min). The highest atracurium and laudanosine concentrations ranged from 3.3 to 5.8 microg x ml(-1) and from 3 to 20 microg x ml(-1) respectively. In four patients with renal impairment, the highest laudanosine concentration was > 10 microg x ml(-1). No seizure was recorded. A fixed infusion rate of atracurium in acute respiratory distress syndrome patients provided an effective muscle paralysis with a rapid neuromuscular recovery but can lead to accumulation of laudanosine in patients with renal impairment.

Aged↗
PubMed1994

Assessment of the interaction between atracurium and suxamethonium at 50% neuromuscular block using closed-loop feedback control of infusion of atracurium.

We have studied the effect of prior administration of suxamethonium on the infusion requirements of atracurium at 50% neuromuscular block in patients undergoing elective general surgery. Anaesthesia was maintained with nitrous oxide in oxygen, propofol and fentanyl. Of 20 patients given atracurium, only 10 were given prior administration of suxamethonium 1 mg kg-1. At the beginning of the infusion, atracurium 0.3 mg kg-1 was given by bolus administration. Interaction between the two drugs was assessed by determining the steady state rate of infusion necessary to produce a constant 50% neuromuscular block. This was accomplished by applying non-linear curve fitting to data on the cumulative dose requirements during anaesthesia. The neuromuscular blocking effect was found to be similar with or without prior administration of suxamethonium. The mean steady-state rate of infusion for atracurium was 0.19 (SD 0.03) mg kg-1 h-1 for patients given suxamethonium and 0.18 (0.09) mg kg-1 h-1 for those who were not given suxamethonium. Thus prior administration of suxamethonium did not affect the infusion requirements of atracurium at 50% neuromuscular block, unlike the situation at constant 90% neuromuscular block.

Adolescent↗
PubMed2002

Tracheal intubation condition--a comparison between one minute after rocuronium alone, one minute after rocuronium combined with atracurium and one minute after atracurium with rocuronium at one minute priming interval.

BACKGROUND: Rocuronium, a monoquaternary steroid analogue of vecuronium, is designed to provide a rapid onset of action. Experimentally, it has been shown that two non-depolarizing neuromuscular relaxants administered together can produce either a neuromuscular block of a size expected to be the sum of the individual doses (additive effect) or a larger neuromuscular block (synergistic effect). Experimental observations have suggested that during onset rocuronium acts synergistically with other nondepolarizing agents, but that at a steady state the combined action is additive. METHODS: To investigate whether rocuronium can speed up the onset of atracurium for intubation, 120 patients who consented to receive elective surgery requiring tracheal intubation were randomly assigned to 3 equally divided groups to receive one of the following three different combinations of muscle relaxants: twice ED95 of rocuronium (0.6 mg/kg group 1), an equipotent mixture of ED95 of rocuronium and atracurium (0.3 mg/kg and 0.25 mg/kg respectively, group 2), and rocuronium 0.1 mg/kg to prime atracurium 0.42 mg/kg at 1 min interval. Intubation conditions were assessed 1 minute after intravenous muscle relaxant injection, and scored as good, acceptable and poor based on four clinical evaluators: the ease of laryngoscopy (score of 1-3), the relaxation of vocal cord (1-3), the degree of coughing (1-3), and movement of extremity (1-3). Adding up together, intubation condition that scored 4-5 was considered to be good, 6-7 acceptable, and 8-12 poor. RESULTS: The conditions produced in the rocuronium and the mixture groups were similar and both were moderately better than those of the priming group. Good intubation conditions were achieved in 58% patients of the rocuronium group, 63% of the mixture group and 43% of the priming group. By Pearson Chi-square test, the comparisons did not show statistical significance between groups. CONCLUSIONS: Statistically, rocuronium alone, mixture of equipotent atracurium and rocuronium, and using rocuronium to prime atracurium all provided similar onset for satisfactory intubation.

Adult↗
PubMed1993

Atracurium after an anticholinesterase. Does prior reversal with edrophonium or neostigmine influence the response to atracurium?

This study documents the response to atracurium (75 micrograms.kg-1) administered 30 min after a pancuronium- or tubocurarine-induced neuromuscular block has been reversed with either neostigmine (50 micrograms.kg-1) or edrophonium (0.5 mg.kg-1). Twenty-one ASA 1 or 2 patients were studied, of whom 11 received neostigmine and 10 edrophonium. The degree of neuromuscular block was measured electromyographically from the first dorsal interosseous muscle of the hand using train-of-four stimulation of the ulnar nerve. When atracrium was administered, the single twitch response compared with control was 100% in all patients and the mean train-of-four ratios were 91% and 65% in the neostigmine and edrophonium groups respectively. After atracurium (75 micrograms.kg-1), minimum values for the single twitch response compared with control were 52% and 66% in the neostigmine and edrophonium groups respectively. Prior administration of atracurium appears to potentiate the neuromuscular blocking effects of atracurium administered 30 min later.

Adult↗
PubMed1995

Intubating conditions following 1R CIS, 1'R CIS atracurium (51W89). A comparison with atracurium.

51W89 besylate, a new intermediate acting non-depolarising muscle relaxant, consisting of a single stereo-isomer of the commercial preparation of atracurium has been assessed in respect of intubating conditions during nitrous oxide-propofol-isoflurane anaesthesia. Intubating conditions at 2 min were acceptable in 67% of patients following a dose of 0.1 mg.kg-1 and in 90% of patients following a dose of 0.15 mg.kg-1. Intubating conditions at 1.5 min were acceptable in 76% of patients following a dose of 0.2 mg.kg-1. In comparison, intubating conditions at 2 min were acceptable in 95% of patients following 0.5 mg.kg-1 of atracurium. The intubating conditions at 2 min following a dose of 0.1 mg.kg-1 51W89 besylate were significantly worse than the other three groups (p < 0.05); however, there was no significant differences between the scores in the other three groups. There was no clinical evidence of histamine release in the groups receiving 51W89 besylate compared to two out of the 19 patients who had cutaneous flushing following the administration of atracurium. Our results suggest that 51W89 besylate provides acceptable intubating conditions at 2 min following a dose of 0.15 mg.kg-1 and may prove to be an acceptable alternative to atracurium if studies in progress confirm its greater cardiovascular stability and reduced propensity to release histamine than its parent compound.

Adolescent↗
PubMed1987

Closed-loop administration of atracurium. Steady-state neuromuscular blockade during surgery using a computer controlled closed-loop atracurium infusion.

The advent of newer muscle relaxants with predictable rates of metabolism and times of offset of neuromuscular blockade now makes it possible to use intravenous infusion safely as a mode of delivery. This has many advantages over administration by intermittent bolus. Moreover, it is feasible to use a servo system for their delivery. We have developed and evaluated such a system which is portable and requires little computer expertise to set up and use. It is a useful adjunct to routine anaesthesia, as well as a potentially powerful research tool.

Adolescent↗
PubMed1991

Interaction of the neuromuscular blocking drug atracurium with muscarinic acetylcholine receptors.

On isolated rat heart atria, atracurium competitively antagonized the negative chronotropic effect of methylfurmethide, shifting the concentration-response curve to the right without diminishing the agonist's maximal effect; Kd calculated from dose ratios was 3.0 mumol/l. On the longitudinal muscle of rat ileum, atracurium antagonized the effect of methylfurmethide in a non-competitive manner; at 50 mumol/l atracurium, the maximum response to methylfurmethide was diminished by about 50%. Atracurium antagonized the binding of (3H)quinuclidinyl benzilate [3H)QNB) to muscarinic binding sites in the atria, ileal longitudinal muscle and cerebellum with IC50 values of 5-8 mumol/l, and in brain cortex of 25 mumol/l. Atracurium was little efficient, however, in antagonizing the binding of N-(3H-methyl) scopolamine [3H)NMS) to muscarinic binding sites. Complete blockade was not achieved at concentrations up to 1 mmol/l. Concentrations required to diminish the binding by 50% were 10 - 1000 times higher for (3H)NMS than for (3H)QNB. Atracurium brought about the dissociation of (3H)QNB-receptor complexes, but its effect was considerably stronger at a concentration of 30 mumol/l than at 1 mmol/l. Atracurium slowed down the dissociation of (3H)QNB-receptor complexes observed after the addition of atropine. The effects of atracurium on the dissociation of (3H)NMS-receptor complexes were similar to those on (3H)QNB-receptor complexes, but a high concentration of atracurium (1 mmol/l) produced a transient increase in (3H)NMS binding preceding its subsequent dissociation. Although the observations of the antagonism by atracurium of the effect of methylfurmethide on the heart atria, and of the inhibition of the specific binding of (3H)QNB to the atria, ileal smooth muscle, cerebellum and brain cortex are compatible with the assumption of a competitive interaction, the discrepancy between the effects of atracurium on the binding of (3H)QNB and (3H)NMS indicates that atracurium does not bind to the same binding site as (3H)QNB and (3H)NMS. It appears that most effects of atracurium on muscarinic receptors are allosteric and that both negative and positive cooperatives play a role in interactions between atracurium and muscarinic ligands.

Animals↗
PubMed1991

Atracurium decay and the formation of laudanosine in humans.

Several groups of investigators have reported that the plasma concentrations of laudanosine, a metabolite of atracurium, are high immediately after administration of atracurium and thereafter decline. Such a time profile of a metabolite in plasma is very unusual. The authors describe a model of atracurium decay and laudanosine disposition that satisfactorily explains these data. The model reveals the following: 1) each atracurium molecule is degraded into two of laudanosine; 2) the generation of laudanosine occurs through two processes--a rapid one, involving approximately 31% of the atracurium dose and proceeding with a half-life of 0.25 min, and a slower one, involving the residual 69% and proceeding with a half-life of 51 min; 3) atracurium degradation by Hofmann elimination proceeds in the central and the noncentral compartments; 4) laudanosine formed from atracurium gains access to its central compartment and disappears from plasma in a biexponential pattern; 5) in cirrhotic patients, only 18% of the atracurium dose is degraded rapidly and laudanosine is disposed of more slowly. The authors propose that the rapid degradation of atracurium in plasma proceeds through a nucleophilic substitution reaction, with plasma nucleophiles substituting for the laudanosine moiety in atracurium. Because both laudanosine moieties in atracurium are required to establish and sustain plasma concentrations of laudanosine, excretion of atracurium or its degradation through pathways not generating laudanosine must be small.

Atracurium↗
PubMed1996

[Intubation conditions following administration of atracurium and vecuronium. Bolus method versus priming technique].

Prompted by the ongoing discussion of the pros and cons of using succinylcholine, this study was conducted to compare the responses to bolus injections of atracurium or vecuronium with those after sequential injection of these drugs (priming principle). We evaluated the earliest possible intubation times, intubating conditions, and the onset times (i.e. times from the end of injection to the maximum blockade) under conditions approaching real use as closely as possible. METHODS. The randomized and double-blind study was carried out with 80 ASA risk class 1 and 2 patients. Approval of the institutional ethics committee was obtained, and each patient gave informed consent. Patients were randomly allocated to four study groups of 20 patients each. Isotonic saline was administered to those patients assigned to the atracurium or vecuronium bolus groups, whereas the patients assigned to the other two groups received a priming injection of either atracurium (0.05 mg/kg) or vecuronium (0.01 mg/kg). We observed the patients for signs of incipient muscular weakness before the induction of anaesthesia. Anaesthesia was induced with thiopental 3.5 min after the first injection (5 mg/kg and 50-100 mg before intubation). After a further 1 min during which adequate mask ventilating with oxygen was assured, corresponding to a priming interval of 4.5 min, 0.5 mg/kg of atracurium or 0.1 mg/kg of vecuronium was administered to the patients in the bolus groups and 0.45 mg/kg of atracurium or 0.09 mg/kg of vecuronium as intubating doses to those in the priming groups. Intubation was attempted at 90, 120, 150 and 180 s thereafter. Intubating conditions were evaluated on the basis of laryngoscopy, vocal cord movement and coughing or bucking of the patients. Neuromuscular function was monitored via accelerometry at the adductor pollicis muscle (TOF stimulation of the ulnar nerve every 15 s). RESULTS. The priming doses did not diminish the elicited twitches of the adductor pollicis muscle, but led to heavy eyelids and double vision in 35% of the atracurium patients and 47% of the vecuronium patients; these symptoms were well tolerated by the patients. At the time of intubation the adductor pollicis muscle was relaxed to approximately the same degree in all groups (mean +/- SD for the TOF ratios in the bolus groups was 0.46 +/- 0.37 for atracurium, 0.45 +/- 0.4 for vecuronium; in the priming groups 0.52 +/- 0.39 for atracurium, 0.53 +/- 0.36 for vecuronium). The administration of the relaxants in divided doses significantly shortened the intubating time after atracurium (100 vs 124 s) and improved the intubating conditions of vecuronium (good vs tolerable), but had no effect on the time course of the neuromuscular blockade (onset times in the bolus groups 224 +/- 84 s for atracurium and 209 +/- 64 s for vecuronium; in the priming groups 249 +/- 112 s for atracurium and 205 +/- 52 s for vecuronium). CONCLUSIONS. The priming technique presented here is clinically superior to the bolus method and therefore should be preferred in all elective cases and in those patients in whom succinylcholine is contraindicated.

Adult↗
PubMed1987

Glycopyrrolate intensifies neuromuscular blockade produced by atracurium in the rat diaphragm preparation.

The effect of glycopyrrolate (Glycopyrronium, a muscarinic antagonist) (10 mumol.litre-1) and neostigmine (1 mumol.litre-1) on atracurium (0.1-100 mumol.litre-1) - induced neuromuscular blockade was studied in the rat isolated phrenic nerve-diaphragm preparation, to see if glycopyrrolate intensified the neuromuscular blockade produced by atracurium in this preparation. Atracurium had a rapid onset of blockade, reaching a complete block in 30-40 s. Glycopyrrolate had no significant effect on indirectly-elicited twitch (0.2 Hz) tension, whereas it significantly increased atracurium-induced depression of twitch tension and shortened the time needed to a complete block by 10 s. Combinations of glycopyrrolate+ neostigmine, only slightly reversed atracurium-induced blockade, if compared to the reversal by neostigmine alone. The mean concentrations to produce 50% depression of twitch tension were: 1.6 +/- 0.1 (atracurium), 0.3 +/- 0.1 (atracurium +glycopyrrolate), 4.8 +/- 0.2 (atracurium +neostigmine) and 2.7 +/- 0.1 mumol.litre-1 (atracurium +glycopyrrolate +neostigmine) (means +/- SEM, n = 6, P less than 0.001, with respect to control value of atracurium alone). It was concluded that glycopyrrolate enhanced atracurium-induced neuromuscular blockade in the rat diaphragm preparation, and that this effect should be noted when dosing glycopyrrolate in man.

Animals↗
PubMed1995

Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium-induced neuromuscular block.

STUDY OBJECTIVE: (1) To determine the time to peak effect of neostigmine (time to peak antagonism) during atracurium- or vecuronium-induced neuromuscular block; and (2) to determine the effect on time to peak effect of neostigmine during atracurium-induced neuromuscular block, when the dose of neostigmine is increased from 35 micrograms/kg to 70 micrograms/kg. DESIGN: Prospective, randomized clinical study. SETTING: Gynecologic operating room suite at a university hospital. PATIENTS: 45 ASA I and II women admitted for gynecologic laparotomy. INTERVENTIONS: Anesthesia was performed with thiopental sodium, fentanyl, halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF) stimulation and mechanomyography were used to monitor neuromuscular transmission. Neostigmine was administered while a constant degree of neuromuscular block was maintained at a twitch height at a point between 4% and 11% of the control twitch height, using a continuous infusion of atracurium or vecuronium. The patients were randomized to three groups, with 15 patients in each group. Group 1 received atracurium block antagonized with neostigmine 35 micrograms/kg; group 2 received vecuronium block antagonized with neostigmine 35 micrograms/kg; and group 3 received atracurium block antagonized with neostigmine 70 micrograms/kg. MEASUREMENTS AND MAIN RESULTS: The degree of neuromuscular block at antagonism was similar in the three groups. Time to peak effect (mean +/- SD) on TOF ratio was significantly longer in Group 1 (9.7 +/- 3.0 minutes) versus Group 2 (6.6 +/- 1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium-induced block was reduced from 9.7 +/- 3.0 minutes to 6.3 +/- 2.0 minutes when the dose of neostigmine was increased from 35 micrograms/kg to 70 micrograms/kg (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3 compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2. CONCLUSION: The time to peak effect of neostigmine 35 micrograms/kg is about 6 to 10 minutes when antagonizing a constant degree of atracurium- or vecuronium-induced neuromuscular block at a twitch height at a point between 4% and 11%. Even though the time to peak effect was longer with atracurium than with vecuronium, clinically significant differences between the antagonizing effect of atracurium versus vecuronium block were not demonstrated. The time to peak effect during atracurium-induced block decreased when the dose of neostigmine was increased from 35 micrograms/kg to 70 micrograms/kg.

Adult↗