Time Course Of Neuromuscular Blockade Research Articles

Administration of Magnesium Sulphate Prior to Vecuronium: Effects on the Speed of Onset and Duration of Neuromuscular Block

Background: We commonly encounter surgical patients who are on magnesium therapy in the operation theatre. It is important to know the interaction of magnesium on anaesthetic drugs including neuromuscular blocking agents. Our aim is to observe and compare the onset and duration of action of vecuronium following magnesium pre-treatment. Material and Method: 50 patients were randomly divided into 2 groups. Group 1 (n = 25) received placebo (normal saline) and group 2 (n=25) received 40 mg/kg magnesium sulphate added to 100 ml of normal saline infused over a period of 15 minutes prior to induction. Following the induction of anaesthesia muscle relaxation was achieved by 0.1 mg/kg vecuronium and time for onset, duration of neuromuscularblock and vecuronium dose requirement during surgery was assessed by monitoring the tactile response to Train of four stimulation. Results: Onset of time for intubation was significantly reduced to 120.19±6.53 seconds in the magnesium group compared to 259.150±26.131 seconds in thecontrol group(P< 0.001). It was observed that the average duration of neuromuscular blockage of vecuronium was almost doubled and statistically significant (P = 0.001) in the magnesium group(26.89±2.91) as compared to the control group (42.28±1.41).The total dose of vecuronium used or required was significantly less in the magnesium group when compared to the control group (p=0.008). Duration from last dose of vecuronium to reversal of anaesthesia was prolonged in the magnesium group (40.2±3.96) compared to the control group(29.8±6.03) which is statistically significant(p<0.001). Conclusion: Magnesium sulphate administered before vecuronium significantly accelerates the onset of neuromuscular block necessary for intubation of trachea and significantly increase the time course of neuromuscular blockade. Intraoperative consumption of vecuronium was less in the magnesium group.

Time Course of Rocuronium-Induced Neuromuscular Blockade in Pediatric Patients: A Phase III, Randomized, Dose-Response Study

Background: We evaluated the time course of neuromuscular blockade (NMB) of three intubating doses of rocuronium in pediatric patients. Methods: This multicenter, randomized, assessor-blinded study included surgical patients aged 0 to 17 years. Anesthesia was induced with sevoflurane, continued until intubation, and maintained with isoflurane. Neuromuscular function was monitored by acceleromyography. Patients received a rocuronium dose of 0.45, 0.6 or 1.0 mg/kg, and intubation was attempted 60 sec later. Primary outcome variable was time from end of rocuronium administration to reappearance of the third twitch (T3). Time to onset of peak NMB was assessed. Safety assessments included monitoring adverse events. Results: A total of 207 patients were enrolled and randomized. Median times from rocuronium administration to NMB onset were <1.2 minutes in all age groups for each dose in the per-protocol population (n=175). Median time from rocuronium administration to reappearance of T3 ranged from 21 to 114 minutes overall, and was longer in the higher dose groups across age groups, and longer in neonates and infants compared with other age groups. There were no adverse events considered related to rocuronium. Conclusions: Rocuronium at intubating doses of 0.45, 0.6, or 1.0 mg/kg is effective in producing rapid-onset neuromuscular blockade with an intermediate duration of action in pediatric patients during sevoflurane induction/ isoflurane maintenance anesthesia. Longest duration of blockade occurred with the highest dose within all age groups, and in neonates and infants compared with other age groups.

Sevoflurane Induction Shortens the Onset of Vecuronium at the Corrugator Supercilii Muscles: A Randomized Comparison with Propofol Induction

We evaluated if induction with sevoflurane shortened the onset of vecuronium-induced neuromuscular blockade at the corrugator supercilii muscles (which have a similar time course of neuromuscular blockade with laryngeal muscles). Thirty-two patients were randomly allocated to a sevoflurane or propofol group. Anesthesia was induced with 5% sevoflurane in oxygen (sevoflurane group,n=16) or with propofol 2–2.5 mg kg−1(propofol group,n=16), and vecuronium (0.1 mg kg−1) was given in both groups. Evoked responses to train-of-four stimuli were measured by acceleromyography at the corrugator supercilii and adductor pollicis muscles. Sevoflurane induction, as compared with propofol, significantly shortened the onset time at the corrugator supercilii muscles from 138 ± 34 s to 107 ± 28 s (P&lt;0.01). Onset time at the corrugator supercilii was significantly shorter than at the adductor pollicis for both groups (P&lt;0.01). Our results suggest that induction with sevoflurane, as compared with propofol, shortened the onset time of vecuronium at laryngeal muscles.

Influence of Disease Progression on the Neuromuscular Blocking Effect of Mivacurium in Children and Adolescents with Duchenne Muscular Dystrophy

Studies with nondepolarizing neuromuscular blocking agents showed a delayed onset and prolonged recovery in patients with Duchenne muscular dystrophy. The objective of this study was to investigate if these alterations depend on disease progression. The authors studied 11 children (6-9 yr) with moderate Duchenne muscular dystrophy, 11 adolescents (12-16 yr) with advanced Duchenne muscular dystrophy, and 2 age-matched control groups of 8 patients each (5-9 and 10-17 yr). Anesthesia was performed with propofol and remifentanil. Patients received a single intravenous dose of 0.2 mg/kg mivacurium. Neuromuscular transmission was monitored by acceleromyography. The time course of neuromuscular blockade was characterized by the onset time and the times to different levels of recovery. Onset and duration of neuromuscular blockade were significantly prolonged in adolescent Duchenne muscular dystrophy patients (onset time, 4.0 min; recovery index, 12.3 min; median), as compared with Duchenne muscular dystrophy children (onset time, 2.3 min; recovery index, 6.8 min), and also as compared with young controls (onset time, 2.0 min; recovery index, 4.4 min) and adolescent controls (onset time, 2.5 min; recovery index, 4.8 min). Within the Duchenne muscular dystrophy patients, onset time and recovery index increased significantly with age. In the control group, age had no effect. The neuromuscular blocking effects of mivacurium showed a significant age dependency in Duchenne muscular dystrophy patients, which was most probably caused by the progression of the disease.

The pharmacodynamics of mivacurium in the rabbit with carbon tetrachloride-induced liver disease

Neuromuscular blocking effects according to the severity of liver dysfunction have not been evaluated. We assessed the neuromuscular effects of mivacurium in carbon tetrachloride (CCl4)-treated rabbits with toxic hepatitis in vivo. We compared the dose-response relationships and the neuromuscular blocking effects of mivacurium in 66 rabbits randomly treated with 0.3 mL kg(-1) of corn oil, 0.3 mL kg(-1) of CCl4 or 0.6 mL kg(-1) of CCl4 for 11 weeks, respectively. Train-of-four stimuli were applied every 10 s to the common peroneal nerve and the force of contraction of the tibialis anterior muscle was measured. Severe hepatitis was associated with a rightward shift of the mivacurium dose-response curves, but mild hepatitis had no effect. The calculated ED50 values for the control, mild and severe hepatitis were 17.1+/-2.6, 18.2+/-2.7 and 31.8+/-3.2 microg kg(-1), respectively. Rabbits with severe hepatitis had a significantly prolonged recovery time from neuromuscular blockade compared with other rabbits. Cholinesterase activity had a negative correlation with recovery indices of mivacurium even in severe hepatic injury. Severe hepatitis induced a prolongation of action duration of repeated doses, but maintained the constant intervals. The dose-response and the time course of neuromuscular blockade of mivacurium differ in mild hepatitis compared with severe hepatitis, but required no adjustments of different doses for repeated injection after the desired depth of neuromuscular block, and had a negative correlation with the activity of plasma cholinesterase in both hepatic injuries.

Influence of sex and weight on time course of neuromuscular blockade after rocuronium administration

Influence of sex and weight on time course of neuromuscular blockade after rocuronium administration

Neuromuscular blockade at the larynx, the diaphragm and the corrugator supercilii muscle: a review.

To review recent findings concerning neuromuscular blockade and monitoring at the larynx, the diaphragm, and the corrugator supercilii muscle. This narrative review is based on recent publications. Neuromuscular blockade at the larynx and the diaphragm is less intense than at the adductor pollicis muscle; the onset and offset of neuromuscular blockade is more rapid. The corrugator supercilii muscle reflects better the time course of neuromuscular blockade of the larynx than the adductor pollicis muscle, is better suited to monitor the onset of neuromuscular blockade for intubation, and should give a better reflection of the time course and degree of neuromuscular blockade of the larynx or the diaphragm. Recovery of neuromuscular function at the end of any procedure is best reflected at the adductor pollicis muscle where neuromuscular transmission is last restored. Clinical monitoring of the larynx or the diaphragm is still limited by the absence of a simple method. Acceleromyography of the corrugator supercilii muscle is prone to artifacts that do not occur during monitoring of the adductor pollicis muscle. Phonomyography, a new method of monitoring that is currently being tested, is based on the phenomenon that muscle contraction creates low-frequency sound waves, which can be detected using special microphones to quantify neuromuscular blockade. This method seems promising because it can be easily used on all muscles of interest. Research during the last 15 years has greatly enhanced our knowledge about how muscles react differently to muscle relaxants and has enabled us to achieve better surgical conditions with safer use of muscle relaxants. Interesting technologies have been developed to reliably monitor neuromuscular blockade at the larynx and the diaphragm, but are currently restricted to research settings. Our increased understanding should help us in ongoing efforts to develop the "ideal" muscle relaxant and the "ideal" method of neuromuscular monitoring.

Time course of neuromuscular blockade with rocuronium in children with intracardiac shunts

Objective: To evaluate the time course of neuromuscular blockade after rocuronium in children with intracardiac shunts. Design: Prospective study. Setting: University hospital. Participants: Consecutive children (n = 52) with intracardiac shunts scheduled for elective cardiac surgery. Participants were allocated to 2 groups according to the direction of the shunt. Interventions: Rocuronium, 0.6 mg/kg, was administered for muscle relaxation. The ulnar nerve was stimulated at 20-second intervals with a supramaximal 2-Hz train-of-4 stimulation (TOF-Guard nerve stimulator; Biomet International, Odense, Denmark). The onset time to maximal twitch depression and the time to clinical recovery were compared between the 2 groups. Measurements and Main Results: The time to maximal block was significantly faster in children with a right-to-left shunt: 56.8 ± 5.3 seconds versus 77.1 ± 6.6 seconds (p = 0.01). There was a tendency to shorter recovery in children with a right-to-left shunt: 42.3 ± 6.1 minutes versus 55.4 ± 4.9 minutes (p = NS). Conclusion: This study shows a more rapid onset of rocuronium in children with cyanotic congenital heart disease. In these patients, rocuronium is indicated, particularly for rapid airway control. Copyright 2002, Elsevier Science (USA). All rights reserved.

Different effects on different muscles: Clinical implications

N 'EUROMUSCULAR blocking agents must be regarded as having multiple sites of action. The main action of these drugs is competitive blockade at the nicotinic receptor of the neuromuscular junction, but these receptors are found at every muscle in the body. Although all postsynaptic nicotinic receptors are structurally the same throughout the body, muscles vary with respect to blood supply, size of fibers, and architecture of their junctional apparatus. As a result, time course of neuromuscular blockade after a bolus dose of a neuromuscular blocking agent varies from one muscle to the next. It would be tedious to learn and remember the characteristics of all the muscles of the body. In practice, one needs to focus on those having clinical relevance (ie, the muscles of the respiratory system). In addition, it is important to understand the relationship between the muscles used for monitoring and those that are clinically important. The data available on the time course of blockade at the respiratory muscles (diaphragm, intercostals, abdominal muscles), those of the larynx, and upper airway, are remarkably consistent if one considers the confounding effect of dose on onset time, maximum effect, and duration. Because it is impractical to monitor these muscles in clinical practice, surrogate muscle groups have been identified. The most commonly used are those of the hand, foot, and eyebrow. Instead of taking the traditional approach of listing results coming from all muscles using all possible methods of measurement, a discussion of the possible patterns of onset, maximum blockade, and duration will be made, and the influence of dose on these patterns will be presented. Then the

Effects of vecuronium and rocuronium in antagonistic laryngeal muscles and the anterior tibial muscle in the cat.

Adequate vocal cord paralysis and full recovery of laryngeal muscle function are important when muscle relaxants are used perioperatively. This study was designed to compare the effects of vecuronium and rocuronium at the vocal cord abductor and adductor muscles and the anterior tibial muscle in cats. Twelve adult cats were studied under pentobarbitone-N2O/O2-anesthesia. After supramaximal electrical stimulation of the peroneal nerve and the recurrent laryngeal nerve (0.1 Hz and intermittent train-of-four) evoked electromyographic responses were obtained from the anterior tibial muscle, the posterior cricoarytenoid muscle (vocal cord abductor) and two vocal cord adductor muscles, the lateral cricoarytenoid and the vocal muscle. Six cats received bolus doses of increasing size of vecuronium (ED90 22.5 microg x kg(-1)) and six cats rocuronium (ED90 90 microg x kg(-1)). Equipotent doses of vecuronium and rocuronium caused a similar degree of paralysis in all muscles (vecuronium ED90: 70% blockade at the posterior cricoarytenoid, 83% at the lateral cricoarytenoid, 84% at the vocal muscle and 90% at the anterior tibial muscle; rocuronium ED90: 71% at the posterior cricoarytenoid, 67% at the lateral cricoarytenoid, 78% at the vocal muscle and 90% at the anterior tibial muscle; vecuronium 2 x ED90: 93% blockade at the posterior cricoarytenoid, 95% at the lateral cricoarytenoid, 97% at the vocal muscle and 99% at the anterior tibial muscle; rocuronium 2 x ED90: 89% blockade at the posterior and lateral cricoarytenoid, 93% at the vocal muscle and 100% at the anterior tibial muscle). Onset time was significantly shorter at the posterior cricoarytenoid muscle (290 s) compared to the lateral cricoarytenoid muscle (400 s) after vecuronium ED90 and to the vocal muscle (150 s versus 210 s) after rocuronium ED90. Compared to the anterior tibial muscle (interval 25-75%: 6.5 min after vecuronium 2 x ED90 and 3.3 min after rocuronium 2 x ED90 and to the posterior cricoarytenoid muscle (interval 25-75%: 7 min after vecuronium 2 x ED90 and 4.3 min after rocuronium 2 x ED90), recovery of laryngeal adductor muscle function was markedly delayed with both neuromuscular blocking drugs (interval 25-75% at the lateral cricoarytenoid and vocal muscle: 14 min and 15.8 min after vecuronium 2 x ED90 and 10.3 min and 11.6 min after rocuronium 2 x ED90 respectively). In cats, the time course of neuromuscular blockade after vecuronium and rocuronium differs in antagonistic laryngeal muscles. The protective laryngeal function of glottis closure recovers later than vocal cord abduction after both vecuronium and rocuronium.

A New Method of Monitoring the Effect of Muscle Relaxants on Laryngeal Muscles Using Surface Laryngeal Electromyography

A New Method of Monitoring the Effect of Muscle Relaxants on Laryngeal Muscles Using Surface Laryngeal Electromyography

Comparison of time course of neuromuscular blockade in young children following rocuronium and atracurium

Comparison of time course of neuromuscular blockade in young children following rocuronium and atracurium

Priming with rocuronium accelerates the onset of neuromuscular blockade

Study Objective: To investigate the effects of priming rocuronium on the time course of neuromuscular blockade. Design: Prospective, controlled, randomized clinical study. Setting: University teaching hospital. Patients: 42 ASA physical status I and II patients undergoing peripheral surgery with general anesthesia. Interventions: Following a standardized propofol-fentanyl induction, patients in Group 1 (n = 21) received a priming dose of rocuronium 0.06 mg/kg followed two minutes later by an intubating dose of rocuronium 0.54 mg/kg. Patients in Group 2 (n = 21) received a saline placebo injection followed two minutes later by rocuronium 0.6 mg/kg. Anesthesia was maintained with isoflurane and nitrous oxide 60% in oxygen. Measurements and Main Results: Neuromuscular function was assessed at the wrist using mechanomyography with a single-twitch mode of stimulation at a frequency of 1 Hz until tracheal intubation and at 0.1 Hz thereafter. The times from injection of the intubating dose of rocuronium until 95% suppression of the twitch tension (onset time), recovery of twitch tension to 25% of control (clinical duration of action), and the time from 25% to 75% spontaneous recovery of twitch tension (recovery index) were recorded. The trachea was intubated at 95% depression of the twitch tension and the intubating conditions were graded using a 3-point scale. The onset times with priming rocuronium (34 ± 6 s) were significantly shorter ( p < 0.01) than those without priming (59 ± 14 s). The intubation conditions were similar in the two groups; however, the intubating times with priming were significantly shorter. The clinical duration of action and the recovery index did not differ significantly between the two groups. Conclusions: Priming rocuronium decreased the onset times and thus, the intubating times without increasing the clinical duration of action or recovery index.

Dose-Response Relation, Neuromuscular Blocking Action, Intubation Conditions, and Cardiovascular Effects of Org 9273, a New Neuromuscular Blocking Agent

The ED50 and the ED90, the time-course of the neuromuscular block, the intubation conditions, and the cardiovascular effects of Org 9273, a new steroidal nondepolarizing neuromuscular blocking agent, have been evaluated in 41 anesthetized patients. From cumulative dose-response curves the ED50 and ED90 were calculated to be 175 and 300 micrograms/kg, respectively. The time-course of neuromuscular blockade after 300- and 500-micrograms/kg doses of Org 9273 appeared to be similar to that of equipotent doses of vecuronium. The neuromuscular block was characterized by a fast initial rate of block development. High-dose Org 9273 (1 mg/kg = 3-4 times the ED90) had a clinical duration comparable to an intubating dose of pancuronium, but a considerably more rapid onset and recovery index. Three hundred micrograms per kilogram and 500 micrograms/kg Org 9273 produced good to excellent intubation conditions 1 min after administration. Org 9273 in a dose of 0.5-2 times the ED90 produced no cardiovascular changes; however, 3-4 times the ED90 increased heart rate 20%-25% (P less than 0.001), probably due to a vagolytic effect.

Frequency-dependent neuromuscular blockade by textilotoxin in vivo

D. R. Lloyd, G. M. Nicholson, I. Spence, M. Connor, M. I. Tyler and M. E. H. Howden. Frequency-dependent neuromuscular blockade by textilotoxin in vivo. Toxicon 29, 1266–1269, 1991.—The effect of stimulation frequency on the timecourse of neuromuscular blockade, following the administration of textilotoxin (20 μg/kg) or β-bungarotoxin (50 μ/kg), was examined in the interdigital muscles of the hindlimb in anaesthetized mice. While the time of death was variable, neuromuscular blockade of the interdigital muscles occurred at the same time as respiratory failure with both textilotoxin and β-bungarotoxin only at stimulation rates of 0.5 Hz and above. Textilotoxin (50 μg/kg) produced an increase in the heart rate prior to death but no change in the shape of the electrocardiogram.

A Pharmacokinetic Explanation for Increasing Recovery Time Following Larger or Repeated Doses of Nondepolarizing Muscle Relaxants

The authors used pharmacokinetic and pharmacodynamic modeling to explain the time course of neuromuscular blockade following single or multiple doses of three nondepolarizing muscle relaxants. Published and unpublished pharmacokinetic and pharmacodynamic data for 13 normal subjects were used to simulate the duration of neuromuscular blockade (time from administration of the muscle relaxant to 25% recovery of control twitch tension) following six successive doses of atracurium (150-400 micrograms/kg initially, followed by 100 micrograms/kg), vecuronium, or pancuronium (30-80 micrograms/kg initially, followed by 20 micrograms/kg). With atracurium, duration of action was similar for the second and sixth doses, regardless of the initial dose. With vecuronium (initial doses of 30-80 micrograms/kg) and pancuronium (initial doses of 30-60 micrograms/kg), duration of action was longer after the sixth dose than after the second; with larger initial doses of pancuronium (70 and 80 micrograms/kg), duration of action was similar following the second and sixth doses. The authors also determined two recovery times (time for twitch tension to recover from 5-25% and from 25-75% of control value) for varying single doses of atracurium, vecuronium, or pancuronium. When the dose of atracurium was increased from 200 to 400 micrograms/kg, neither recovery time increased. When the dose of vecuronium was increased from 40 to 80 micrograms/kg, 5-25% recovery time increased from 6.0 +/- 2.5 min to 8.8 +/- 4.0 min (mean +/- SD) and 25-75% recovery time increased from 8.7 +/- 4.3 min to 12.6 +/- 4.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular Effects of Vecuronium (ORG NC45) in Infants and Children during N2O, Halothane Anesthesia

The authors determined the neuromuscular effects of vecuronium (ORG NC45, Norcuron) during anesthesia with nitrous oxide and 0.9 MAC halothane. To determine potency, they administered vecuronium (15, 20, or 25 micrograms/kg) to 18 infants (less than 1 year old) and 18 children (1-8 years old). They then compared these dose-response relationships with values obtained for adults (greater than 18 years old) under comparable anesthetic conditions. The ED50S (dose producing 50% depression of adductor pollicis twitch tension) of 16.5, 19.0, and 15.0 micrograms/kg for infants, children, and adults, respectively, did not differ significantly. To determine the time course of neuromuscular blockade, the authors administered vecuronium, 70 micrograms/kg, to six infants, six children, and six adults. Onset time (time to maximal effect) was shortest for infants (1.5 +/- 0.6 min, mean +/- SD) compared with that for children (2.4 +/- 1.4 min) and adults (2.9 +/- 0.2 min). Duration (time from injection to 90% recovery) was longest for infants (73 +/- 27 min) compared with that for children (35 +/- 6 min) and adults (53 +/- 21 min). The authors conclude that vecuronium can be used in infants and children in doses similar to those recommended for adults. The time interval for supplemental doses will be longest in infants and shortest in children.

INHIBITION OF SUXAMETHONIUM RELAXATION BY TUBOCURARINE AND GALLAMINE PRETREATMENT DURING INDUCTION OF ANAESTHESIA IN MAN

The effect of tubocurarine and gallamine pretreatments on suxamethonium relaxation was measured in 81 patients. The blocking effect of a constant infusion of suxamethonium (0.58 mg/sec) on the recorded thumb adduction in response to supramaximal ulnar nerve stimulation was reproducible in 18 control subjects: infusion time for 50% block was 37.7 (+/- SEM 1.02) sec. Tubocurarine 3 mg and 6 mg increased the infusion time required to produce 50% block by 33.4 and 54.8% respectively. Gallamine had a similar effect. Clinical conditions for endotracheal intubation were evaluated on a blind basis. Both drugs produced impairment of clinical conditions for intubation after suxamethonium 60 mg infusion. However, when pretreatment by tubocurarine 3 mg was followed by suxamethonium infusion at 1 mg/sec the time course of neuromuscular blockade was identical to that of the controls. There were no fasciculations with this dosage and conditions for endotracheal intubation were excellent.