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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 muscarinic receptors in rat hearts was investigated in vitro by a tritiated N-methyl hyoscine binding assay. We showed an interaction with cardiac muscarinic receptors with a rank order of potency pancuronium > vecuronium > pipecuronium > rocuronium and demonstrated complex binding characteristics for pancuronium, vecuronium and rocuronium, with "Hill coefficient" of less than unity. We conclude that the haemodynamic differences seen during the use of these neuromuscular blocking drugs may be a result of their interactions with cardiac M2 muscarinic receptors.

Androstanols↗

An alternate method for estimating the dose-response relationships of neuromuscular blocking drugs.

Slopes of the dose-response relationships for all available neuromuscular blocking drugs appear to be essentially parallel and to approximate a log-dose/logit value of 4.75. We tested the possibility of estimating both 50% effective dose (ED(50)) and 95% effective dose (ED(95)) values from a single dose-response data point when that slope is postulated. We compared the ED(50) and ED(95) values of rocuronium and succinylcholine calculated by using traditional log-dose/logit regression analysis with the same values obtained by averaging individual estimates of potency as determined by using the Hill equation. After the induction of anesthesia (propofol/alfentanil), tracheal intubation was accomplished without the administration of neuromuscular blocking drugs. Anesthesia was maintained with nitrous oxide and propofol. The evoked electromyographic response to 0.10-Hz single stimuli was continuously recorded. After baseline stabilization, a single IV bolus of succinylcholine (0.08-0.26 mg/kg, n = 50) or rocuronium (0. 13-0.30 mg/kg, n = 40) was administered and the peak effect noted. By using log-dose/logit regression analysis, we calculated ED(50) and ED(95) values for rocuronium of 0.17 and 0.33 mg/kg and 0.14 and 0.27 mg/kg for succinylcholine. When potency was calculated from the Hill equation, the resultant ED(50) and ED(95) values did not differ by more than +/-4% from those obtained by using regression analysis. Averaging of single-dose estimates of neuromuscular potency provides a useful adjunct and reasonable alternative to conventional regression analysis.

Action Potentials↗

The neuromuscular transmission module versus the relaxometer mechanomyograph for neuromuscular block monitoring.

UNLABELLED: The neuromuscular transmission module (M-NMT) is an integrated piezoelectric motion sensor module incorporated in the AS/3(TM) anesthesia monitor. We compared the neuromuscular block of 0.6 mg/kg rocuronium (twice the 95% effective dose) monitored by the M-NMT with that monitored by the Relaxometer mechanomyograph (MMG). The two monitors were alternately allocated to the left or right hands of 20 patients. T(1)%, the first twitch of the train-of-four (TOF), and the TOF ratio (T(4)/T(1)) were used for evaluating the neuromuscular block. There was no significant difference in the mean (min) plus minus SD onset time or time to 0.8 TOF ratio recovery measured by the M-NMT (1.5 plus/minus 0.3, 49.4 plus/minus 8.1) compared with MMG (1.8 plus/minus 0.6, 50.9 plus/minus 9.9), respectively. However, the time (min) to 25% T(1) recovery was significantly longer when monitored by the M-NMT (25.6 plus/minus 8) than by the MMG (20.2 plus/minus 6.3). During recovery from neuromuscular block, the difference between the TOF ratios measured by the two monitors showed a bias of -0.031, and the limits of agreement (bias plus/minus 1.96 SD) were -0.281 and +0.22. The M-NMT monitor could determine the time to tracheal intubation as well as full recovery from neuromuscular block, but it lagged behind the MMG in determining the time to rocuronium repeat dose administration. IMPLICATIONS: Compared with the Relaxometer mechanomyograph, the neuromuscular transmission module could equally indicate time to tracheal intubation and full recovery from 0.6 mg/kg rocuronium neuromuscular block. Its small quick-fit sensor has the advantage, in an often crowded and busy operating room, of being incorporated in the AS/3(TM) anesthesia workstation.

Androstanols↗

Neuromuscular pharmacology of TAAC3, a new nondepolarizing muscle relaxant with rapid onset and ultrashort duration of action.

UNLABELLED: We selected bis [N-(3,4-diacetoxybenzyl) tropanium-3alpha-yl] glutarate dibromide (TAAC3) from many new tropinyl diester derivatives to evaluate its neuromuscular blocking (NMB) and autonomic side effects on anesthetized rats, rabbits, guinea pigs, cats, pigs, dogs, and monkeys. NMB potency, onset, recovery index, and duration of action were determined. Comparisons of these pharmacologic variables were made between TAAC3 and rocuronium. In the cat, the degrees of train-of-four and tetanic fade, posttetanic potentiation, and pharmacologic antagonism were evaluated. For determination of the NMB maintenance dose, TAAC3 was also given to rabbits and pigs in the initial dose/maintenance infusion mode. Cardiac vagal block was evaluated in the rat, pig, cat, and guinea pig on the basis of the inhibition of the bradycardia to stimulation of the vagus nerve. Sympathetic ganglion block was studied on the superior cervical ganglion-nictitating membrane preparation of the cat. TAAC3 produced nondepolarizing NMB. Its NMB 90% effective doses ranged from 90 to 425 microg/kg, depending on the species. TAAC3 had a faster onset (0.8-1.0 min), shorter recovery index (0.6-1.1 min), and shorter duration of action (1.8-3.5 min) than rocuronium. It produced a slight cumulative effect on infusion, but not on repeated single-dose administration. Cardiac vagal block was present at doses exceeding the NMB 90% effective dose. In the cat and pig at equipotent NMB doses, the degree of cardiac vagal block was similar to that of rocuronium. There was no demonstrable sympathetic ganglion block in the cat. In view of its favorable NMB characteristics, TAAC3 is now undergoing detailed preclinical studies. IMPLICATIONS: We developed a new nondepolarizing muscle relaxant, TAAC3, and investigated it in several animal models. TAAC3 has shown a very rapid onset and an ultrashort duration of neuromuscular blocking action. A minor degree of cardiac vagal block was observed. TAAC3 is promising for further studies.

Androstanols↗

Molar potency is predictive of the speed of onset of neuromuscular block for agents of intermediate, short, and ultrashort duration.

BACKGROUND: The times to peak effect of rocuronium, vecuronium, cisatracurium, mivacurium, and succinylcholine were evaluated to confirm that the correlation between potency and onset time observed for long-acting relaxants also held for drugs of intermediate and short duration. METHODS: The authors recruited 99 patients classified as American Society of Anesthesiologists physical status score 1 or 2 for the study. After anesthesia was induced, tracheal intubation was accomplished without relaxants. Anesthesia was maintained with nitrous oxide and 3% or 4% end-tidal desflurane plus intravenous narcotic supplementation. The evoked electromyographic response to single stimuli administered at 0.10 Hz was recorded continuously. Drug doses were selected to produce approximately 95% twitch depression. If peak twitch depression did not fall in the range of 90% to 98%, the patient was excluded from the study. The time to 50% to 90% of peak effect was plotted as a function of the administered dose. RESULTS: There was no difference in the onset profiles of mivacurium and vecuronium, or in the time to 50% of peak effect between succinylcholine and rocuronium. For all other parameters, onset times ranked as follows: succinylcholine < rocuronium < vecuronium-mivacurium < cisatracurium (P < 0.05). When the log of the ED95 in micromoles per kilogram for all five drugs was plotted against the log of onset time to 50% peak effect, the R2 value for the best fit line was more than 0.98. CONCLUSIONS: The inverse correlation between the molar potency and speed of onset previously described for agents of long duration also applies to nondepolarizing agents of intermediate and short duration. The onset time of succinylcholine also appears to be compatible with this relation.

Adult↗

Lightwand tracheal intubation with and without muscle relaxation.

BACKGROUND: Lightwand tracheal intubation is a suitable technique for patients who are difficult to intubate but who are receiving effective ventilation. The effect of muscle relaxants on the efficacy of lightwand intubation has not yet been evaluated. The authors conducted a prospective, double-blind, placebo-controlled study to assess the effectiveness and incidence of complications of lightwand tracheal intubation performed during general anesthesia with and without the use of a muscle relaxant in patients with apparently normal airway anatomy. METHODS: One hundred seventy-six patients who required orotracheal intubation were prospectively included. Anesthesia was administered using propofol (2 mg/kg, then 3 mg . kg (-1). h(-1)) and remifentanil (1 microg/kg, then 0.3 microg . kg(-1) . min(-1)). Patients were randomly assigned to one of two groups (n = 88 for each) to receive rocuronium 0.6 mg/kg or saline intravenously. Lightwand orotracheal intubation (Trachlight; Laerdal Medical Inc., Armonk, NY) was attempted after 3 min. The authors recorded the number of successful intubations, the number of attempts and their duration, and events during the procedure. RESULTS: The failure rate of lightwand intubation was 12% in the placebo group and 2% in the rocuronium group (P = 0.021). Patients in the placebo group received more multiple intubation attempts (P < 0.001), required a greater intubation time (77 +/- 65 vs. 52 +/- 31 s; P = 0.002) and experienced a greater incidence of events during intubation (61 vs. 0%; P < 0.001) than patients in the rocuronium group. CONCLUSIONS: The use of muscle relaxants in patients with apparently normal airways is associated with a lower failure rate, decreased intubation time, and fewer attempts when performing lightwand orotracheal intubation.

Adult↗

The role of magnesium as an adjuvant during general anaesthesia.

Magnesium sulphate is used extensively in the treatment of eclampsia, and is also used to treat refractory arrhythmias, asthma, myocardial ischaemia and acute respiratory failure. We studied the interaction between magnesium sulphate and the anaesthetic agents propofol, rocuronium bromide and fentanyl citrate. This randomised, double blind study was conducted in 50 patients. The magnesium group A (n = 25) received 30 mg x kg(-1) magnesium sulphate before induction of anaesthesia and 10 mg x kg(-1) continuously intra-operatively until the end of surgery. Group B (n = 25) received the same volume of isotonic saline. Propofol, rocuronium and fentanyl infusions were started and the patients lungs' were ventilated with 33% oxygen in nitrous oxide. Anaesthetic depth was maintained at a bispectral index value of between 40 and 60. Muscle relaxation was maintained at a train-of-four count of 1 throughout surgery using neuromuscular monitoring. The fentanyl infusion was titrated to haemodynamic variables: heart rate and blood pressure. We concluded that magnesium sulphate has anaesthetic, analgesic and muscle relaxation effects and significantly reduces the drug requirements of propofol, rocuronium and fentanyl during anaesthesia.

Adjuvants, Anesthesia↗

Newer neuromuscular blocking agents.

Four neuromuscular blocking drugs, doxacurium, mivacurium, pipecuronium, and rocuronium have been or are about to be introduced into clinical practice. The purpose of this MiniReview is to describe their pharmacology, to consider their place in clinical anaesthetic practice, and to examine whether the needs of the clinician have been met. Two of the agents (doxacurium, mivacurium) are benzylisoquinolines resembling atracurium and two (pipecuronium, rocuronium) are aminosteroids related to pancuronium and vecuronium. Two (doxacurium, pipecuronium) are long-acting compounds, similar in duration of action to pancuronium, although the need for such a profile is questionable. Rocuronium has an intermediate duration of action and produces its maximum effect within two minutes which is much more rapid than any other non-depolarizing relaxant and this is probably a result of its poor potency. However, the onset of paralysis is not as quick as after succinylcholine. Mivacurium is unique because it is metabolized by plasma cholinesterase which produces a rapid recovery although slower than succinylcholine. All of the new drugs are devoid of serious cardiovascular or other side effects. The anaesthetist is now presented with an armamentarium of safe, nondepolarizing muscle relaxants with varying durations of action. However, the rapid onset and recovery associated with succinylcholine are unique and important in the urgent control of a patient's airway and respiration. The indications for succinylcholine will not disappear and the search for a non-polarizing replacement will continue.

Androstanols↗

Clinical pharmacokinetics of the newer neuromuscular blocking drugs.

The pharmacokinetics of 6 new neuromuscular blocking drugs are described. These are the aminosteroids pipecuronium bromide, rocuronium bromide and rapacuronium bromide (ORG-9487) and the benzylisoquinolinium diesters doxacurium chloride, mivacurium chloride and cisatracurium besilate. In healthy individuals, these drugs all have similar volumes of distribution. Their pharmacokinetics are influenced little by age or anaesthetic technique, but renal and hepatic disease may significantly alter their distribution and elimination. Pipecuronium resembles pancuronium in its pharmacokinetic and neuromuscular blocking profile, but is devoid of cardiovascular effects. It has a low clearance (0.16 L/h/kg) and long elimination half-life (120 minutes). It is largely eliminated through the kidney. Rocuronium has a similar pharmacokinetic profile to vecuronium but its onset of action is more rapid and duration of action slightly shorter. Its clearance (0.27 L/h/kg) is intermediate between those of pipecuronium and rapacuronium, but its elimination half-life is long (83 minutes). The pharmacokinetics of rocuronium are altered by renal and hepatic disease; the latter probably has the more significant effect. Rapacuronium has a rapid onset, and a bolus dose has a short duration of action. It has a high clearance (0.59 L/h/kg) but a long elimination half-life (112 minutes). Doxacurium has a pharmacokinetic and pharmacodynamic profile similar to pipecuronium. It has a high potency and is devoid of cardiovascular effects. In adults, it has a low clearance (0.15 L/h/kg) and long elimination half-life (87 minutes). Mivacurium is a mixture of 3 stereoisomers. It has a short to intermediate duration of action. It is hydrolysed by plasma cholinesterase. Inherited or acquired alterations in plasma cholinesterase activity are associated with changes in the pharmacokinetics and time course of action of mivacurium. The 2 active isomers (cis-trans and trans-trans) have a high clearance (4.74 L/h/kg) and very short elimination half-lives (approximately 2 minutes). Cisatracurium is the 1R-cis 1'R-cis isomer of atracurium. It has similar pharmacokinetics and pharmacodynamics to atracurium. It is mainly broken down by Hofmann (non-enzymatic) degradation. Cisatracurium has an intermediate clearance (0.3 L/h/kg) and short elimination half-life (26 minutes). Hepatic and renal disease have little effect on its pharmacokinetics.

Aging↗

The train of four ratio decreases to zero in anesthetized children is the guide to achieve a satisfactory intubation condition.

The purpose of this study is to investigate the satisfactory (excellent or good) intubation conditions attained when the TOF ratio was zero in anesthetized children. Sixty children undergoing elective ophthalmic surgery were allocated randomly into three groups. Anesthesia was induced with thiopentone 4 mg/kg and halothane in combination with 66% N2O and O2 (2 L/min). Patients maintained spontaneous breathing with assisted ventilation to limit the values of end tidal CO2 within the range of 36-44 mmHg, maintained the stable end tidal expiratory 1 MAC halothane concentration for three minutes and followed by 0.1 mg/kg vecuronium in group 1, 0.6 mg/kg rocuronium in group 2, and 0.9 mg/kg rocuronium in group 3. Intubation was attempted as the TOF ratio decreased from 1.0 to 0. The intubation condition was scored by assessing the degree of jaw relaxation, vocal cord opening grades, and cough responses. The overall intubation conditions were graded as excellent, good, fair, and poor on the basis of the scores. Excellent or good intubation conditions were considered satisfactory. After neuromuscular blockade administration, TOF ratio required 160.5 +/- 28.9 seconds in group 1, 70.7 +/- 18.5 seconds in group 2, and 55.7 +/- 13.5 seconds in group 3 to decrease to zero. There is a significant difference between group 1 and group 2 and 3 (p < 0.001, group 1 vs group 2 and group 3). All children were intubated, during which procedures satisfactory intubation conditions were observed in all of the group 3 patients, in 17 of the 20 group 2, and in 16 of the 20 group 1 patients. We concluded that zero of TOF from monitoring the adductor pollicis muscle indicated the proper moment for intubation in anesthetized pediatric patients and it was a reliable guide in adequately anesthetized children to achieve satisfactory intubation conditions following 0.9 mg/kg rocuronium administration.

Androstanols↗

Anaesthesia for appendicectomy in childhood: a survey of practice in Northern Ireland.

A postal questionnaire was sent to all members of the Northern Ireland Society of Anaesthetists to determine current practice in anaesthesia for children with acute appendicitis. Respondents were asked to describe their usual practice in such cases. They were also asked about the occurrence of complications due to the use of suxamethonium, and for their views on the use of rocuronium in such cases. Few major differences in anaesthetic technique were demonstrated. 74% of consultants and 84% of trainees always perform a rapid sequence induction for appendicectomy. However 15% of consultants do not feel that this is necessary. Only 6% of consultants and 6% of trainees would normally use rocuronium, with the majority still preferring suxamethonium. Only 28% of consultants and 20% of trainees see rocuronium as a possible alternative to suxamethonium in these cases, although others expressed increasing concern over the use of suxamethonium in children. There was wide variation in the type of intra-operative and post-operative analgesia prescribed, with less than one third of consultants and trainees using combinations of opioids, local anaesthetics and non-steroidal anti-inflammatory drugs.

Adolescent↗

[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.

Anesthesia↗

Recent advances in neuromuscular blocking agents.

Factors driving the development of neuromuscular blocking agents are discussed. The goal of recent development of neuromuscular blocking agents is to develop agents with fewer adverse effects than succinylcholine and greater control. Greater control can be achieved through a short duration of action and a fast onset, similar to that found with succinylcholine. Duration control can be achieved through rapid, reliable metabolism that is organ independent, as with cisatracurium, or that occurs in the liver, because this will fail only in patients with severe hepatic disease. Rapid onset can be achieved by giving higher doses of drugs that have a fast, reliable metabolism or a rapid distribution to tissue. This has been done with succinylcholine, cisatracurium, and mivacurium. It has been shown that a low-potency drug has a faster onset than a higher-potency drug, even at the same relative dose. Rocuronium was the first neuromuscular blocking agent marketed that was developed specifically as a low-potency drug for achieving a rapid onset. In a comparison with two other intermediate-duration neuromuscular blocking agents at equipotent doses, rocuronium's onset was about one minute, which was two minutes faster than that of either vecuronium or atracurium. Rapacuronium is an investigational intermediate-duration agent and is even less potent than rocuronium. Clinical studies have shown it to have a very rapid onset (about 50 seconds) and a short duration of action (15-25 minutes, depending on the dose). Its short duration of action will make it potentially useful for short surgical procedures and procedures in which nerve integrity must be monitored. At the same time, its onset time approaches that of succinylcholine. Recent advances have made the administration of neuromuscular blocking agents much easier because the newer nondepolarizing relaxants offer faster onset and greater control.

Animals↗

Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors.

BACKGROUND: Neuromuscular relaxants such as pancuronium bind to M2 and M3 muscarinic receptors as antagonists. Blockade of muscarinic receptors in atria of the M2 subtype mediates tachycardia. In the lung, blockade of M2 receptors on parasympathetic nerves potentiates vagally induced bronchospasm, whereas blockade of M3 receptors on bronchial smooth muscle inhibits bronchospasm. The current study was designed to quantify the affinity of a series of neuromuscular relaxants for the M2 and M3 muscarinic receptors, which were individually stably transfected in Chinese hamster ovary cell lines. METHODS: Competitive radioligand binding assays determined the relative binding affinities of the neuromuscular relaxants pancuronium, succinylcholine, mivacurium, doxacurium, atracurium, rocuronium, gallamine, and pipecuronium for the muscarinic receptor in the presence of a muscarinic receptor antagonist (3H-QNB) in membranes prepared from cells individually expressing either the M2 or M3 muscarinic receptor. RESULTS: All muscle relaxants evaluated displaced 3H-QNB from muscarinic receptors. The relative order of potency for the M2 muscarinic receptor (highest to lowest) was pancuronium, gallamine, rocuronium, atracurium, pipecuronium, doxacurium, mivacurium, and succinylcholine. The relative order of potency for the M3 muscarinic receptor (highest to lowest) was pancuronium, atracurium, pipecuronium, rocuronium, mivacurium, gallamine, succinylcholine, and doxacurium. CONCLUSIONS: All neuromuscular relaxants studied had affinities for the M2 and M3 muscarinic receptor, but only pancuronium and gallamine had affinities within the range of concentrations achieved with clinical use. The high affinities of gallamine and pancuronium for the M2 muscarinic receptor are consistent with a mechanism of M2 receptor blockade in relaxant-induced tachycardia.

Animals↗

Rapacuronium bromide: a review of its use in anaesthetic practice.

UNLABELLED: Rapacuronium bromide (rapacuronium) is an aminosteroid, nondepolarising neuromuscular blocking agent (NMBA). At the recommended dose for endotracheal intubation (1.5 mg/kg), an intravenous bolus of rapacuronium has a rapid onset (approximately 1.2 to 1.8 minutes) and short duration of action (10.2 to 16.5 minutes) in adults undergoing elective surgery. Rapacuronium 1.5 mg/kg produced clinically acceptable intubating conditions in 68 to 89% of these patients at about 1 minute after administration. The onset, extent and duration of action and clinical efficacy of an intubating dose of rapacuronium appeared to be similar in the general adult population, adult patients with renal or hepatic dysfunction, patients undergoing Caesarean section, and elderly, paediatric or obese adult patients. Onset time with rapacuronium 1.3 to 2.5 mg/kg (0.9 to 1.8 minutes) was similar to or slower than that with a 1 mg/kg dose of the depolarising NMBA suxamethonium chloride (0.8 to 1.2 minutes). Intubating conditions were clinically acceptable about I minute after administration in 86 to 100% of patients with rapacuronium 1.3 to 2.5 mg/kg compared with in 88 to 97% of patients with suxamethonium chloride 1 or 1.5 mg/kg. Spontaneous recovery was slower with rapacuronium than with suxamethonium chloride, but neostigmine 0.04 or 0.05 mg/kg administered 2 or 5 minutes after rapacuronium 1.3 or 1.5 mg/kg accelerated recovery. In the few available comparative clinical trials, rapacuronium 1.5 mg/kg appeared to have a more rapid onset of action than the nondepolarising NMBAs mivacurium chloride 0.25 mg/kg, rocuronium bromide 0.45 or 0.6 mg/kg or vecuronium bromide 0.07 mg/kg, and a shorter duration of action than rocuronium bromide 0.45 or 0.6 mg/kg or vecuronium bromide 0.07 mg/kg. Additional boluses (< or =3) of rapacuronium 0.5 or 0.55 mg/kg after an intubating bolus of 1.5 mg/kg provided continued skeletal muscle relaxation during short surgical procedures in adult patients. However, these patients may recover more slowly than those who receive a single bolus of the drug. Bronchospasm was the most common treatment-related adverse event with rapacuronium 0.3 to 3 mg/kg (3.4% of adult patients). Tachycardia, injection site reaction and hypotension were also reported in small proportions of patients (1.6, 1.1 and 0.9%). The overall incidence of drug-related adverse events was similar with rapacuronium 1.5 or 2.5 mg/kg or suxamethonium chloride 1 mg/kg (8 vs. 6%) but bronchospasm, tachycardia and injection site reaction tended to occur more often with rapacuronium. CONCLUSIONS: At the recommended dose of 1.5 mg/kg, the nondepolarising NMBA rapacuronium has a rapid onset and short duration of action. It may provide a nondepolarising alternative to suxamethonium chloride for endotracheal intubation. Rapacuronium may be preferred over rocuronium bromide, vecuronium bromide or mivacurium chloride in this indication.

Animals↗

[Use of average-acting nondepolarizing myorelaxants in abdominal surgery].

The efficiency and safety of use of average-acting nondepolarizing myorelaxants, such as atracurium, vecuronuim, rocuronium, and cisatracurum, during abdominal surgical interventions under general anesthesia (combined or total intravenous anesthesia) were investigated in 162 patients. There is evidence that the use of the above agents ensures a qualitative myorelaxation during different types of operations (laparoscopic and laparotomic) and no impact on hemodynamics (according to the data of continuous non-invasive monitoring) allows these myorelaxants to be used in patients with concomitant cardiovascular diseases. Rocuronium is the myorelaxant of choice for rapid tracheal intubation. The high degree of predictability of the duration of an effect produced by atracurium and cisatracurium enables these myorelaxants to be used without monitoring neuromuscular conduction. With the equally good quality of myoplegia and with virtually comparable consumed diseases, the infusion procedure of relaxation maintenance is preferable for early activation of patients. Insignificant effects on histamine release make it possible to use vecuronium, rocuronium, and cisatracurium in patients with the compromised immune system.

Abdomen↗

Nondepolarizing neuromuscular blocking drugs and train-of-four fade.

The aim of this study was to examine differences in prejunctional effects of different relaxants by measuring the train-of-four (TOF) fade during the onset and recovery of neuromuscular block. The relaxants studied were atracurium (225 micrograms.kg-1), mivacurium (65 micrograms.kg-1) rocuronium (300 micrograms.kg-1) and vecuronium (40 micrograms.kg-1). The TOF ratios were measured at approximate heights of T1 (first response in the TOF) of 90, 75, 50, and 25%. The TOF fade (as shown by lower TOF ratios) increased with a decrease in the T1 during onset of neuromuscular block. Although there was a slightly greater fade with atracurium and rocuronium during the onset of block, the differences among the relaxants were insignificant. It is concluded that the relative prejunctional effects of these relaxants are similar.

Adult↗

[Application of muscle relaxants for rapid-sequence induction of anaesthesia].

The present study evaluates the use of muscle relaxants for rapid-sequence induction (RSI) and different application techniques (pre-curarisation, priming, timing) as a part of a nationwide survey in Germany. In 86.8% of anaesthesia departments succinylcholine is used for RSI and an average of 56.5% of respondents used only succinylcholine for RSI. Of all non-depolarising muscle relaxants rocuronium is the most frequently used alternative. Of the anaesthesia departments 2.6% use rocuronium regularly in patients with increased risk for aspiration of stomach contents; level one centres significantly more than others, 12.9% answered that pre-curarisation techniques were never used, whereas 45.6% use non-depolarising neuromuscular blocking drugs before giving succinylcholine in 80-100% of cases. Priming is not used by 64.4% of respondents, as opposed to 9.8% who utilise this technique regularly. The statements regarding timing are 71.1% and 5.4%, respectively. Alcuronium is used for RSI in departments in which the financial aspect is the primary decision criteria. Despite ist known side-effects and the on-going discussion over the past years, succinylcholine is still the most frequently used muscle relaxants for RSI. Priming is often declined by anaesthetists in Germany, most probably due to the absence of clear advantages and the possibility of severe complications. It is the opinion of the authors that timing but also drugs with a slow onset (e.g., alcuronium and Pancuronium) are obsolete in the context of RSI.

Alcuronium↗