Interaction of Nondepolarizing Muscle Relaxants with M sub 2 and M sub 3 Muscarinic Receptors in Guinea Pig Lung and Heart

Background: Neuromuscular blocking agents such as gallamine and pancuronium bind to muscarinic cholinergic receptors and alter parasympathetically mediated airway caliber and heart rate. In the lungs, acetylcholine induces bronchoconstriction via M3 muscarinic receptors on airway smooth muscle, whereas in the heart M2 muscarinic receptors mediate bradycardia. Moreover, release of acetylcholine from parasympathetic nerves in the lung is decreased by inhibitory M2 receptors on the nerves, which represent a negative feedback system. Blockade of these receptors potentiates vagally induced bronchoconstriction, which may be clinically important if the M3 receptors on airway muscle are not blocked. These experiments were designed to examine the effects of the newer, nondepolarizing muscle relaxants pipecuronium, doxacurium, and mivacurium on pulmonary and cardiac muscarinic receptors.

Methods: Guinea pigs were anesthetized with urethane, paralyzed with succinylcholine, and their lungs mechanically ventilated. Pulmonary inflation pressure and heart rate were measured before and after electrical stimulation of both vagus nerves to evaluate prejunctional M sub 2 muscarinic receptor function and after intravenous acetylcholine to evaluate post-junctional M3 and M2 receptor function in the presence of increasing concentrations of pancuronium, mivacurium, pipecuronium, and doxacurium.

Results: Pancuronium was an antagonist for M2 and M3 muscarinic receptors. Mivacurium was a more potent antagonist of M3 than M2 receptors. Pipecuronium was an antagonist of M2 but not M3 receptors. Doxacurium was not an antagonist of either M2 or M3 muscarinic receptors. Only pancuronium and pipecuronium potentiated vagally induced bronchoconstriction. With pipecuronium, the potentiation occurred at concentrations greater than those used clinically.     

Neuromuscular blocking agents' differential bronchoconstrictive potential in Guinea pig airways

BACKGROUND: Neuromuscular blocking agents are designed to antagonize nicotinic cholinergic receptors on skeletal muscle but also antagonize muscarinic receptors. Several muscle relaxants have the potential to promote bronchoconstriction due to unintended effects exemplified by histamine release of atracurium or mivacurium and detrimental interactions with muscarinic receptors by rapacuronium. Although interactions of muscle relaxants with muscarinic receptors have been extensively characterized in vitro, limited information is available on their potential interactions with airway tone in vivo. METHODS: Changes in pulmonary inflation pressures and heart rates induced by vagal nerve stimulation and intravenous acetylcholine were measured in the absence and presence of increasing doses of gallamine, pancuronium, mivacurium, vecuronium, cisatracurium, rocuronium, or rapacuronium in guinea pigs. Mivacurium's and rapacuronium's potential of inducing bronchoconstriction by histamine release was also evaluated. RESULTS: Rapacuronium potentiated both vagal nerve-stimulated and intravenous acetylcholine-induced increases in airway pressures, which were totally blocked by atropine but not pyrilamine. Vecuronium, rocuronium, mivacurium, and cisatracurium were devoid of significant airway effects. Mivacurium, at high doses, increased pulmonary inflation pressures, which were attenuated by pyrilamine. CONCLUSION: Rapacuronium was unique among muscle relaxants evaluated in that it potentiated both vagal nerve- and intravenous acetylcholine-induced bronchoconstriction with no evidence of histamine release. The dual detrimental interactions of rapacuronium with muscarinic receptors previously demonstrated in vitro correlate with in vivo muscarinic receptor mechanisms of bronchoconstriction and may account for the profound bronchoconstriction seen with its clinical use. These findings may establish pharmacologic characteristics to avoid with new muscle relaxants intended for clinical use.     

Neuromuscular Blocking Agents' Differential Bronchoconstrictive Potential in Guinea Pig Airways

Background: Neuromuscular blocking agents are designed to antagonize nicotinic cholinergic receptors on skeletal muscle but also antagonize muscarinic receptors. Several muscle relaxants have the potential to promote bronchoconstriction due to unintended effects exemplified by histamine release of atracurium or mivacurium and detrimental interactions with muscarinic receptors by rapacuronium. Although interactions of muscle relaxants with muscarinic receptors have been extensively characterized in vitro, limited information is available on their potential interactions with airway tone in vivo.

Methods: Changes in pulmonary inflation pressures and heart rates induced by vagal nerve stimulation and intravenous acetylcholine were measured in the absence and presence of increasing doses of gallamine, pancuronium, mivacurium, vecuronium, cisatracurium, rocuronium, or rapacuronium in guinea pigs. Mivacurium's and rapacuronium's potential of inducing bronchoconstriction by histamine release was also evaluated.

Results: Rapacuronium potentiated both vagal nerve-stimulated and intravenous acetylcholine-induced increases in airway pressures, which were totally blocked by atropine but not pyrilamine. Vecuronium, rocuronium, mivacurium, and cisatracurium were devoid of significant airway effects. Mivacurium, at high doses, increased pulmonary inflation pressures, which were attenuated by pyrilamine.     

The use of muscle relaxants for routine induction of anesthesia in Germany

The aim of this study was to evaluate the use of muscle relaxants during induction of anesthesia in patients without risk of aspiration of stomach contents.Of the 2,996 questionnaires sent out, 2,054 (68.6%) could be analysed and the results show that succinylcholine is used regularly in 13.6% of anesthesia departments.The next most commonly used muscle relaxants are atracurium, vecuronium and mivacurium, followed by cis-atracrium, rocuronium and pancuronium. Alcuronium is the least frequently used muscle relaxant. During induction of an elective anesthesia procedure, a priming technique is used by 19% of anesthesiologists, 22% utilize precurarization, and a timing technique is performed in 7.1%.The use of muscle relaxants for on-going relaxation follows the same pattern as for induction of neuromuscular blockade and succinylcholine is used in 1.4% if further relaxation is needed.The desire for specific qualities of muscle relaxants is correlated with higher use of the specific substance: short onset time for rocuronium, good controllability with mivacurium, no side-effects with cisatracurium and economical aspects with alcuronium. Of the participants 76.6% voiced the desire for a non-depolarizing replacement for succinylcholine.Private practices use mivacurium more often than hospitals, level one hospitals use rocuronium and cisatracurium more often.This survey could not show a definite standard of use in terms of muscle relaxants for an elective case.Precurarization, priming and timing are used frequently in patients not at risk of aspiration. This should be reduced by on-going teaching.     

Do pipecuronium and rocuronium affect human bronchial smooth muscle?

BACKGROUND: Muscle relaxants affect nicotinic and muscarinic receptors. Interaction of muscle relaxants with muscarinic receptors of human airways has been studied incompletely. METHODS: The effects of pipecuronium bromide (long-acting, nondepolarizing) and rocuronium bromide (intermediate-acting, nondepolarizing) on prejunctional and postjunctional muscarinic receptors were studied in 96 isolated human bronchial rings from 12 patients. Contractile isometric responses to electric field stimulation of pilocarpine-stimulated and nonstimulated M2 muscarinic receptors were compared before and after incubation with the two muscle relaxants. The effect on postjunctional muscarinic receptors was studied by comparing acetylcholine concentration-response curves before and after incubation with the two muscle relaxants. RESULTS: Pipecuronium bromide, but not rocuronium bromide, inhibited pilocarpine-stimulated prejunctional M2 muscarinic receptors. Neither pipecuronium bromide nor rocuronium bromide had significant inhibitory effects on nonstimulated M2 muscarinic receptors and on postjunctional M3 muscarinic receptors. CONCLUSIONS: The inhibitory effect of pipecuronium bromide on pilocarpine-stimulated prejunctional M2 muscarinic receptors occurred at clinical concentrations.     

A mechanism for rapacuronium-induced bronchospasm: M2 muscarinic receptor antagonism

BACKGROUND: A safe and effective ultra-short-acting nondepolarizing neuromuscular blocking agent is required to block nicotinic receptors to facilitate intubation. Rapacuronium, which sought to fulfill these criteria, was withdrawn from clinical use due to a high incidence of bronchospasm resulting in death. Understanding the mechanism by which rapacuronium induces fatal bronchospasm is imperative so that newly synthesized neuromuscular blocking agents that share this mechanism will not be introduced clinically. Selective inhibition of M2 muscarinic receptors by muscle relaxants during periods of parasympathetic nerve stimulation (e.g., intubation) can result in the massive release of acetylcholine to act on unopposed M3 muscarinic receptors in airway smooth muscle, thereby facilitating bronchoconstriction. METHODS: Competitive radioligand binding determined the binding affinities of rapacuronium, vecuronium, cisatracurium, methoctramine (selective M2 antagonist), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; selective M3 antagonist) for M2 and M3 muscarinic receptors. RESULTS: Rapacuronium competitively displaced 3H-QNB from the M2 muscarinic receptors but not from the M3 muscarinic receptors within clinically relevant concentrations. Fifty percent inhibitory concentrations (mean +/- SE) for rapacuronium were as follows: M2 muscarinic receptor, 5.10 +/- 1.5 microm (n = 6); M3 muscarinic receptor, 77.9 +/- 11 microm (n = 8). Cisatracurium and vecuronium competitively displaced 3H-QNB from both M2 and M3 muscarinic receptors but had affinities at greater than clinically achieved concentrations for these relaxants. CONCLUSIONS: Rapacuronium in clinically significant doses has a higher affinity for M2 muscarinic receptors as compared with M3 muscarinic receptors. A potential mechanism by which rapacuronium may potentiate bronchoconstriction is by blockade of M2 muscarinic receptors on prejunctional parasympathetic nerves, leading to increased release of acetylcholine and thereby resulting in M3 muscarinic receptor-mediated airway smooth muscle constriction.     

Do Pipecuronium and Rocuronium Affect Human Bronchial Smooth Muscle?

Background: Muscle relaxants affect nicotinic and muscarinic receptors. Interaction of muscle relaxants with muscarinic receptors of human airways has been studied incompletely.

Methods: The effects of pipecuronium bromide (long-acting, nondepolarizing) and rocuronium bromide (intermediate-acting, nondepolarizing) on prejunctional and postjunctional muscarinic receptors were studied in 96 isolated human bronchial rings from 12 patients. Contractile isometric responses to electric field stimulation of pilocarpine-stimulated and nonstimulated M2 muscarinic receptors were compared before and after incubation with the two muscle relaxants. The effect on postjunctional muscarinic receptors was studied by comparing acetylcholine concentration-response curves before and after incubation with the two muscle relaxants.

Results: Pipecuronium bromide, but not rocuronium bromide, inhibited pilocarpine-stimulated prejunctional M2 muscarinic receptors. Neither pipecuronium bromide nor rocuronium bromide had significant inhibitory effects on nonstimulated M2 muscarinic receptors and on postjunctional M3 muscarinic receptors.     

The non-depolarizing myorelaxants in orotracheal intubation. A clinical comparison

The present study was designed to compare the rapidity of onset of neuromuscular blockade after administration of 5 different neuromuscular relaxants (succinylcholine, d-tubocurarine, pancuronium, atracurium and vecuronium) in 75 patients, randomly allocated in 5 treatment groups. The facilitation for endotracheal intubation was evaluated using a clinical score. The for onset relaxation was shorter when using succinylcholine. Among non-depolarizing relaxants an adequate facilitation for endotracheal intubation was observed, two minutes after administration of atracurium and vecuronium, while endotracheal intubation was difficult when using d-tubocuranine and pancuronium.     

Iontophoretic study of speed of action of various muscle relaxants.

The speed of action of nondepolarizing muscle relaxants is inversely related to potency. The hypothesis that this effect occurs at the end plate was tested in a frog (Rana pipiens) cutaneous pectoris muscle preparation. Brief acetylcholine pulses (10-100 ms) were applied iontophoretically from a central barrel of a triple-barrelled microelectrode located near an end plate. Long pulses (10-200 s) of muscle relaxant (gallamine, rocuronium, d-tubocurarine, atracurium, vecuronium, pancuronium, and doxacurium) were applied from one of two other barrels. The responses were a voltage change at the end plate, measured with an intracellular electrode. To evaluate potency, intracellular voltage changes following iontophoretic acetylcholine pulses were measured after application of various concentrations of muscle relaxants. The following were the equilibrium dissociation constants, which represent concentration of relaxant for 50% inhibition of response (mean plus or minus standard deviation): gallamine, 4.56 +/- 0.44 microM (n = 5); rocuronium, 0.71 +/- 0.09 microM (n = 6); d-tubocurarine, 0.59 +/- 0.07 microM (n = 4); atracurium, 0.31 +/- 0.03 microM (n = 4); vecuronium, 0.23 +/- 0.02 microM (n = 5); pancuronium, 0.18 +/- 0.03 microM (n = 3); doxacurium, 0.11 +/- 0.03 microM (n = 5). Both onset and offset of effect of muscle relaxant proceeded with an exponential time course.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Mechanism for Rapacuronium-induced Bronchospasm: M2 Muscarinic Receptor Antagonism

Background: A safe and effective ultra-short-acting nondepolarizing neuromuscular blocking agent is required to block nicotinic receptors to facilitate intubation. Rapacuronium, which sought to fulfill these criteria, was withdrawn from clinical use due to a high incidence of bronchospasm resulting in death. Understanding the mechanism by which rapacuronium induces fatal bronchospasm is imperative so that newly synthesized neuromuscular blocking agents that share this mechanism will not be introduced clinically. Selective inhibition of M2 muscarinic receptors by muscle relaxants during periods of parasympathetic nerve stimulation (e.g., intubation) can result in the massive release of acetylcholine to act on unopposed M3 muscarinic receptors in airway smooth muscle, thereby facilitating bronchoconstriction.

Methods: Competitive radioligand binding determined the binding affinities of rapacuronium, vecuronium, cisatracurium, methoctramine (selective M2 antagonist), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; selective M3 antagonist) for M2 and M3 muscarinic receptors.

Results: Rapacuronium competitively displaced 3H-QNB from the M2 muscarinic receptors but not from the M3 muscarinic receptors within clinically relevant concentrations. Fifty percent inhibitory concentrations (mean +/- SE) for rapacuronium were as follows: M2 muscarinic receptor, 5.10 +/- 1.5 [mu]m (n = 6); M3 muscarinic receptor, 77.9 +/- 11 [mu]m (n = 8). Cisatracurium and vecuronium competitively displaced 3H-QNB from both M2 and M3 muscarinic receptors but had affinities at greater than clinically achieved concentrations for these relaxants.     

Train-of-Four recovery after pharmacologic antagonism of pancuronium-, pipecuronium-, and doxacurium-induced neuromuscular block in anaesthetized humans

Previous studies have suggested that the increased duration of action of long-acting neuromuscular relaxants may make their pharmacologic antagonism more difficult and, thus, increase the likelihood of residual block. This hypothesis was tested in healthy, adult humans who received a background of isoflurane/N₂O/fentanyl anaesthesia.
Study subjects were paralyzed with either pancuronium (N=8), pipecuronium (N=8), or the longer-acting relaxant, doxacurium (N=8). Neuromuscular function was monitored, and, using a blinded, randomized study design, the relaxants were titrated to identify the ED₉₅ dose in each patient. Thereafter, spontaneous recovery was observed until there was 25% ofbaseline response to the first supramaximal twitch (Tl) in a train-of-four (TOF). At this time, the block was antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 0.014 mg/kg i.v., and recovery of TOF was recorded.
Spontaneous recovery to 25% of the baseline Tl response occurred at 52± 14 min (mean±SD) following administration of either pancuronium and pipecuronium, and 85 ±33 min following doxacurium ( P <0.05 for doxacurium versus pancuronium and pipecuronium). In doxacurium-rreated patients, reversal of block with neostigmine was less predictable and less complete than with the other two relaxants. For example, the ratio of the fourth to first twitch (T4/T1) of the TOF at 10 and 15 min after reversal was significantly less with doxacurium (59 ±14% and 61±16%, respectively) than with either pancuronium (75±6% and 75±10%) or pipecuronium (76±9% for both). At 30 min post-neostigmine, the incidence of residual block (i.e. T4/T1 <0.70) was: pancuronium 2 patients, pipecuronium 1 patient, and doxacurium 5 patients.
These studies support the hypothesis that incomplete reversal of neuromuscular block is more likely with longer-acting neuromuscular relaxants.     

Studies on the interaction of steroidal neuromuscular blocking drugs with cardiac muscarinic receptors

Interaction of the steroidal neuromuscular blocking drugs pancuronium,pipecuronium, rocuronium and vecuronium with cardiac muscarinicreceptors in rat hearts was investigated in vitro by a tritiatedN-methyl hyoscine binding assay. We showed an interaction withcardiac muscarinic receptors with a rank order of potency pancuronium> vecuronium > pipecuronium > rocuronium and demonstratedcomplex binding characteristics for pancuronium, vecuroniumand rocuronium, with "Hill coefficient" of less than unity.We conclude that the haemodynamic differences seen during theuse of these neuromuscular blocking drugs may be a result oftheir interactions with cardiac M₂ muscarinic receptors. (Br.J. Anaesth. 1994; 72: 86–88)     

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)     

Nitroglycerin and the neuromuscular blockade produced by gallamine, succinylcholine, d-tubocurarine, and pancuronium

The finding in cats of prolonged pancuronium neuromuscular blockade in conjunction with intravenous infusion of nitroglycerin was previously reported by this laboratory. To expand on this finding the present study compared the effects of nitroglycerin on neuromuscular blockade produced by gallamine, d-tubocurarine, succinylcholine, and pancuronium, and further characterized the nitroglycerin-pancuronium interaction. The results indicate that of the relaxants studied only pancuronium neuromuscular blockade is prolonged, and that the prolongation is not due to altered plasma elimination of pancuronium. In vitro pancuronium blockade was not affected by nitroglycerin, suggesting the involvement of a metabolite in the block prolongation response. Reversibility of the prolonged pancuronium block by neostigmine is not influenced by nitroglycerin.     

Doxacurium and mivacurium do not trigger malignant hyperthermia in susceptible swine

The role of succinylcholine in the precipitation of malignant hyperthermia (MH) necessitates the testing of new neuromuscular relaxants for their ability to trigger MH in MH-susceptible swine before general human use. We tested doxacurium and mivacurium, two new nondepolarizing bis-benzylisoquinolinium neuromuscular relaxants, at ED95 and at four times ED95 doses in swine previously documented to be MH-susceptible. In none of the 16 animals was MH triggered after administration of these relaxants, whereas all animals developed fatal MH after administration of halothane or halothane plus succinylcholine. Muscle biopsy specimens taken before administration of the relaxant confirmed that all animals had increased sensitivity to halothane, caffeine, or both. Thus, we conclude that doxacurium and mivacurium are not triggering agents of malignant hyperthermia in MH-susceptible swine.     

Muskelrelaxanzien Neue Substanzen und neuromuskuläres Monitoring

Introduction: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards. Muscle relaxants: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED₉₅ of rocuronium provides good or excellent intubating conditions within 60 to 90?s. Slight vagolytic effects were reported following injection of 0.6?mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED₉₅ did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid breakdown by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.     

The potency of new muscle relaxants on recombinant muscle-type acetylcholine receptors

We studied the inhibition of fetal (gamma-nAChR) and adult (epsilon-nAChR) muscle-type nicotinic acetylcholine receptors by the two new nondepolarizing muscle relaxants (NDMRs) rocuronium and rapacuronium, the metabolite 3-desacetyl rapacuronium (Org 9488), and five other, longer-used NDMRs (pancuronium, vecuronium, mivacurium, d-tubocurarine, and gallamine). Receptors were expressed in Xenopus laevis oocytes by cytoplasmic injection of subunit complementary RNAs. Functional channels were activated with 10 microM acetylcholine, alone or in combination with various concentrations of the NDMRs. Currents were recorded with a whole-cell two-electrode voltage clamp technique. All NDMRs reversibly inhibited acetylcholine-activated currents in a dose-dependent fashion. Potencies of rapacuronium and Org 9488 were not statistically different at either gamma-nAChR (half-maximal response = 58.2 and 36.5 nM, respectively) or epsilon-nAChR (half-maximal response = 80.3 and 97.7 nM, respectively). The rank order of potencies at the epsilon-nAChR (pancuronium > vecuronium similar mivacurium > rocuronium similar d-tubocurarine > rapacuronium similar Org 9488 > gallamine) correlated highly with the clinical doses needed to produce 50% twitch depression at the adductor pollicis muscle in adults. Neuromuscular blockade by rapacuronium may be enhanced by its metabolite Org 9488. Different drug-receptor affinities of the tested NDMRs contribute to the differences in clinical dose requirements of these drugs needed to achieve appropriate muscle relaxation. IMPLICATIONS: Potencies of nondepolarizing muscle relaxants, studied at muscle nicotinic acetylcholine receptors expressed in a recombinant expression system, correlate highly with the clinical doses needed in adults to produce 50% twitch depression at the adductor pollicis muscle.     

Visual estimation of onset time at the orbicularis oculi after five muscle relaxants: application to clinical monitoring of tracheal intubation.

The onset time of neuromuscular blockade at the adductor pollicis (AP) is different among neuromuscular blocking drugs, but these discrepancies had never been studied at the orbicularis oculi (OO). The purpose of this study was to verify if the differences in onset time observed at the AP still existed at the OO and to score the intubating conditions using monitoring at the OO after five muscle relaxants. The study included 172 adults aged 18-75 yr. Anesthesia was induced with fentanyl and propofol. Atracurium (0.5 mg/kg), mivacurium (0.20 mg/kg), rocuronium (0.6 mg/kg), succinylcholine (1.0 mg/kg), or vecuronium (0.08 mg/kg) was injected by random allocation. Time to complete disappearance of the response at the OO was assessed visually after train-of-four stimulation of the facial nerve. Laryngoscopy was then performed, and intubating conditions were determined on a scale of 1-4. Results were based on 150 patients. Onset time at the OO was (mean +/- SD): succinylcholine (57 +/- 17 s) < mivacurium (99 +/-19 s) = rocuronium (99 +/- 47 s) < atracurium (129 +/-33 s) = vecuronium (135 +/- 38 s) (P < 0.05). Overall intubating conditions were excellent (84%), good (14%), poor (1.3%), impossible (0.7%), and were similar among the five groups. We conclude that differences in onset time of muscle relaxants observed at the AP were also found at the OO. Visual estimation of the response at the OO correctly predicted good-to-excellent intubating conditions in more than 90% of cases for all the currently available muscle relaxants. IMPLICATIONS: Onset time of neuromuscular blockade, as estimated visually at the orbicularis oculi, depends on the muscle relaxants given. Regardless of the relaxant used, intubating conditions at loss of orbicularis oculi are acceptable.     

Rocuronium-induced Neuromuscular Block Is Affected by Chronic Carbamazepine Therapy

Background: Patients on chronic anticonvulsant drugs are relatively resistant to certain nondepolarizing neuromuscular blockers such as pancuronium, vecuronium, pipecuronium, doxacurium, or metocurine, but not resistant to mivacurium and atracurium. This study investigated the influence of chronic carbamazepine therapy on the neuromuscular block induced by the new muscle relaxant rocuronium.

Methods: Twenty-two otherwise healthy individuals scheduled for neurosurgical operations were studied: 11 of them were on chronic treatment with carbamazepine; the others served as control subjects. The median duration of carbamazepine therapy was 9 weeks (range, 4-312 weeks). After premedication with oral diazepam, anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide/oxygen and 0.5% inspired isoflurane. Rocuronium, 0.6 mg/kg (2 x ED95), was given for intubation. The ulnar nerve was stimulated, and the evoked electromyogram recorded using a Datex NMT monitor.

Results: Based on the response to the first of four stimuli, neither the lag time nor the onset-time differed between the two groups. However, the intervals of recovery to 10%, 25%, 50%, and 75% of the baseline response and the recovery index (RI, 25%-75%) were significantly shorter in patients on chronic carbamazepine therapy.     

Investigation of fading responses induced by non-depolarising muscle relaxants in the evoked EMG of the gastrocnemius muscle of the cat

BACKGROUND: During partial neuromuscular blockade indirect repetitive nerve stimulation causes fade in the response of the muscle. We studied the intensity of the fade induced by intravenous administration of three steroidal muscle relaxants, and investigated the mechanism of fade by comparing with results obtained during partial blockade with animal toxins and vesamicol. METHODS: In 60 cats, we measured the fade in the compound action potentials of the gastrocnemius muscle evoked by repetitive sciatic nerve stimulation at 100 Hz during partial neuromuscular blockade with rocuronium, vecuronium, pancuronium, alpha-bungarotoxin, mu-conotoxin and vesamicol, respectively. RESULTS: Profound fade was induced by all three non-depolarising muscle relaxants (rocuronium=vecuronium相似文献