[Chronic pain--a field to concentrate on].
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Chronic Disease↗
Biomedical subjects
L Gramstad
Publications and source records attributed to L Gramstad.
Haemodynamic effects of high-dose vecuronium compared with pancuronium in beta-blocked patients with coronary artery disease during fentanyl-diazepam-nitrous oxide anaesthesia.
BACKGROUND: Different combinations of neuromuscular blockers and opioids have been used in patients with angina pectoris to provide cardiovascular stability and reduce risk of myocardial ischaemia during anaesthesia. METHODS: We have compared the haemodynamic effects of high-dose vecuronium (0.3 mg kg-1) with those of a standard dose of pancuronium (0.1 mg kg-1) in patients scheduled for coronary artery bypass grafting during fentanyl-diazepam-nitrous oxide anaesthesia. All patients were receiving beta-adrenergic blocking agents. The given doses of vecuronium and pancuronium are equieffective with respect to duration of neuromuscular blockade. RESULTS: During a 25-min experimental period following the administration of the randomly selected drug, no significant changes in the haemodynamic parameters were observed in the vecuronium group. The administration of pancuronium, however, resulted in a significant mean increase in heart rate (20%), rate-pressure product (23%) and cardiac index (21%). Following endotracheal intubation in the pancuronium group, we observed an additional significant increase in mean arterial pressure and rate-pressure product. CONCLUSION: High-dose administration of vecuronium has minimal haemodynamic effects and may thus offer a better alternative than pancuronium for long-lasting neuromuscular blockade in patients with coronary artery disease during fentanyl-diazepam-nitrous oxide anaesthesia.
Adrenergic beta-Antagonists↗
Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents.
Based on an international consensus conference held in Copenhagen in the autumn of 1994, a set of guidelines for Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents are presented. The guidelines are intended to be a help for people working in this research field, and it is hoped that the guidelines will assist researchers, editors, and drug companies to enhance the quality of their pharmacodynamic studies of neuromuscular blocking agents.
Clinical Trials as Topic↗
A simplified concept for controlling oxygen mixtures in the anaesthetic machine--better, cheaper and more user-friendly?
Modern anaesthetic machines are equipped with several safety components to prevent delivery of hypoxic mixtures. However, such a technical development has increased the complexity of the equipment. We report a reconstructed anaesthetic machine in which a paramagnetic oxygen analyzer has provided the means to simplify the apparatus. The new machine is devoid of several components conventionally included to prevent hypoxic mixtures: oxygen failure protection device, reservoir O2 alarm, N2O/air selector, and proportioning system for oxygen/nitrous oxide delivery. These devices have been replaced by a simple safety system using a paramagnetic oxygen analyzer at the common gas outlet, which in a feed-back system cuts off the supply of nitrous oxide whenever the oxygen concentration falls below 25%. The simplified construction of the anaesthetic machine has important consequences for safety, cost and user-friendliness. Reducing the complexity of the construction also simplifies the pre-use checkout procedure, and an efficient 5-point check list is presented for the new machine.
Anesthesia, Inhalation↗
An evaluation of a time-saving anaesthetic machine checkout procedure.
Although it is generally acknowledged that a pre-use checkout of the anaesthetic machine significantly improves patient safety, an evaluation of such procedures is uncommon. Previous studies have shown that anaesthetic personnel using different check routines are unable to detect the majority of pre-set technical malfunctions. We have shown that it is possible to develop an effective and time-saving check procedure by integrating seven simple steps into one continuous flow procedure, where the settings and results of one step are used in the following step to optimize step interaction. The method is a 'core' procedure adapted to machines sold after 1980 according to the current ISO standard (presently undergoing revision). A user inquiry demonstrated that this pre-use check has been easily adopted in departments of anaesthesia. Moreover, the inquiry showed that most departments would not accept a checkout procedure which required more than 5-6 min. A study on nurse anaesthetists performing this procedure in the operating suite showed an average checking time of approximately 3 min. A performance test was undertaken by activating four different malfunctions in an anaesthetic machine training simulator. Twelve of 17 nurse anaesthetists rapidly identified all faults, whereas five nurses missed one or two faults. Our study suggests that our check procedure (the seven point check) provides a time-saving method for effective pre-use control of the anaesthetic machine.
Anesthesia Department, Hospital↗
Duration of vecuronium-induced neuromuscular blockade predicted by dose and onset time.
We investigated the adequacy of using dose and onset time as variables to predict the duration of action of vecuronium in patients. The onset time until 95% twitch depression and the duration until 25% twitch recovery were measured for doses ranging from 0.1 to 0.3 mg kg-1. Statistical analyses were performed by simple and multiple regressions. The duration of action was better predicted by dose (r2 = 0.61) than by onset time (r2 = 0.51). However, the predictability was significantly improved by a multiple regression model of the variables, and the explanatory power was largest when using the square root of duration as the dependent variable (r2 = 0.69). We conclude that the duration of neuromuscular blockade after vecuronium can be predicted more accurately by the combined use of dose and onset time than by dose alone.
Adolescent↗
A training simulator for detecting equipment failure in the anaesthetic machine.
Simulation is often used for training personnel in activities where the consequences of inappropriate actions are serious. We report a realistic training simulator, which can reproduce practically all potential malfunctions in the anaesthetic machine. Using actual standard equipment (Dameca 10750), the interior of the anaesthetic machine has been profoundly modified, whereas the external appearance remains virtually unchanged. The concealed alterations allow 20 different pre-set technical faults to be activated selectively from a mobile control unit. While assisted by an instructor, the trainee performs hands-on interactive experimentation with the simulator, while being exposed to 'unexpected' machine faults, which prompt for interpretation of error symptoms. Alternatively, the trainee can personally activate the simulated symptoms of different component failures, to enhance learning of the functional principles of the apparatus. The latter approach also allows a systematic presentation of defects to be identified by each step in a formal safety checklist for anaesthetic machines.
Anesthesiology↗
Safety testing the Bain circuit--a new test adaptor.
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Anesthesiology↗
Effect of ionized calcium on the neuromuscular blocking actions of atracurium and vecuronium in the cat.
We have determined neuromuscular blocking effects of atracurium and vecuronium at normal, high and low plasma concentrations of ionized calcium ( [Ca2+] ) in the cat. Twitch responses were measured bilaterally in the anterior tibialis muscles, using intact central innervation in one preparation. Plateaus of high and low [Ca2+] were created by infusions of calcium chloride and citrate, respectively. The interactions with changes in [Ca2+] were similar for atracurium and vecuronium, and were unaffected by central muscle innervation. The median increase in [Ca2+] from 1.21 to 1.59 mmol litre-1 shifted the dose-response curves of the drugs to the right, increasing ED50 by 7-13%, whereas the decrease to median 0.78 mmol litre-1 potentiated the drugs by a similar order. This indicates a lesser influence of [Ca2+] on the action of neuromuscular blockers than reported in a previous in vitro study. Even though the interactions were statistically significant, their moderate magnitude suggests minor clinical significance.
Animals↗
[Anaphylaxis during anesthesia--an increasing problem?].
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Anaphylaxis↗
Midazolam does not potentiate the effect of vecuronium in patients.
Reports of midazolam interaction with vecuronium in animals prompted us to compare midazolam (0.25 mg kg-1) with thiopentone (5 mg kg-1) for possible interactions with vecuronium in patients, when used for induction of anaesthesia. After the administration of either of the two induction agents, the patients received vecuronium 0.1 mg kg-1. The onset time, duration of action and 25-75% recovery index of the neuromuscular blockade were recorded by measuring the force of thumb adduction evoked by ulnar nerve stimulation. We found no differences between patients receiving either midazolam or thiopentone in their response to vecuronium. In three of the ten patients receiving midazolam, the injection of this drug produced a 8-29% reduction of the initial twitch height.
Adult↗
Comparison of large dose of vecuronium with pancuronium for prolonged neuromuscular blockade.
Dose-duration relationships for vecuronium were determined and the duration of action produced by vecuronium 0.3 mg kg-1 shown to equal that of pancuronium 0.1 mg kg-1. Using these doses, the neuromuscular blocking properties and cardiovascular effects of the two drugs were compared. With large dose administration of vecuronium (0.3 mg kg-1), both the onset time (mean 81 s) and the 25-75% recovery index (mean 13.9 min) were about one-half those associated with pancuronium (mean 168.5 s and 29.3 min, respectively). The duration of action until 25% recovery was similar with both drugs. There was no evidence of cardiovascular instability with the large dose of vecuronium. Heart rate, however, was significantly slower (range 89.7-94.2% of control) 2-20 min after the injection of vecuronium. Vecuronium 0.3 mg kg-1 may have more favourable neuromuscular blocking effects than pancuronium 0.1 mg kg-1 and may be preferable to pancuronium when prolonged neuromuscular blockade is required.
Adolescent↗
Atracurium, vecuronium and pancuronium in end-stage renal failure. Dose-response properties and interactions with azathioprine.
Dose-response relations for atracurium, vecuronium and pancuronium were determined in patients in end-stage renal failure for the initial neuromuscular blockade (using three cumulative doses) and for the maintenance of stable 90% response (during continuous infusion). All measurements were during renal transplant surgery, and the interaction of azathioprine on neuromuscular blockade was estimated. Mean ED95 doses were (microgram kg-1): atracurium 375.6, vecuronium 67.2, pancuronium 86.6; the initial blockade required significantly larger doses than in normal patients (37%, 20% and 45%, respectively, using ED50 values). Mean infusion rates for 90% sustained blockade in renal failure were (microgram kg-1 h-1): atracurium 409.4, vecuronium 78.3, pancuronium 14.2. The atracurium dose was not influenced by renal function, whereas vecuronium and pancuronium requirements were significantly reduced by 23.2% and 61.5%, respectively, compared with normal patients (previous study). Azathioprine was injected at the rate of 1 mg kg-1 min-1 for 3 min at stable 90% neuromuscular blockade with constant-rate infusion of the neuromuscular blocking drug. This produced a relatively small and transient antagonism of blockade--probably of negligible clinical significance.
Adolescent↗
Interaction of cyclosporin and its solvent, Cremophor, with atracurium and vecuronium. Studies in the cat.
Interactions between Sandimmun (formulated as cyclosporin (CyA) in Cremophor and ethanol) and atracurium or vecuronium were investigated in anaesthetized cats. During stable 50% blockade and with a constant rate of infusion of the neuromuscular blocking drugs, Sandimmun 0.8 mg kg-1 or an equivalent amount of its solvent moiety was injected over 5 min. Sandimmun potentiated the blockade induced by vecuronium (median infusion rate 110 micrograms kg-1 h-1) from 50.7% before injection to maximum 95.2% 17.3 min after injection (median values), whereas the median blockade in cats receiving atracurium (median 250 micrograms kg-1 h-1) increased from 51.3% to 72.4% after 32.9 min. At 45 min after the injection the median blockades were 93.1% and 69.8%, respectively. In cats receiving vecuronium (median 104 micrograms kg-1 h-1) the solvent produced an increase in effect of from 51.1% to maximum 78.0% blockade after 5.4 min and 61.5% after 45 min (median values). Interaction with solvent was negligible in cats receiving atracurium. We attribute the effect of the solvent to the Cremophor component. The mechanism of the interaction related to the cyclosporin is unknown.
Animals↗
Neuromuscular blocking effects of atracurium, vecuronium and pancuronium during bolus and infusion administration.
The potencies of atracurium, vecuronium and pancuronium were compared using bolus injections and continuous infusions. The sizes of the bolus injections were based on previously determined cumulative dose-response relationships. Dose requirements for 90% and 50% sustained blockade were estimated by use of continuous infusion, and the corresponding plasma concentrations were measured for vecuronium and pancuronium. The effect of single bolus injections correlated well with the cumulative dose-responses, confirming relative potencies for atracurium, vecuronium and pancuronium of approximately 1:5:4. The maintenance doses (microgram kg-1 h-1) for 90% blockade were: atracurium 382.8, vecuronium 101.9, and pancuronium 36.9, making the relative dose requirements 10.4:2.8:1. The same dose ratio was found for atracurium and vecuronium at 50% blockade. This required about 60% of the doses needed for maintenance of 90% response. The relative potency of vecuronium and pancuronium in plasma was 1.1:1. The 25-75% recovery index was significantly shorter for vecuronium than for atracurium.
Adult↗
Comparative study of atracurium, vecuronium (Org NC 45) and pancuronium.
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Adult↗
Dose-response relation for atracurium, ORG NC 45 and pancuronium.
The potencies of atracurium, Org NC 45 and pancuronium were determined using cumulative dose-response curves. The effective doses producing 95% twitch depression were 279 microgram kg-1, 56 microgram kg-1 and 64 microgram kg-1 respectively, the relative potency being 1:5.0:4.3. The calculated log-probit dose-response curves showed the steepest slope for pancuronium, although the slopes did not deviate significantly from the parallel. The three drugs provided equal and generally good intubating conditions at approximately 95% twitch depression. Greater arterial pressure and heart rate were seen with pancuronium than with atracurium and Org NC 45.
Adult↗
Onset time and duration of action for atracurium, Org NC45 and pancuronium.
Speed of onset, maximum block, duration of action and 10-25% recovery time for atracurium, Org NC 45 and pancuronium were determined using equipotent doses: 330 micrograms kg-1, 66 micrograms kg-1 and 75 micrograms kg-1 respectively. Vein-to-muscle and artery-to-muscle onset times were measured by use of simultaneous recordings. Mean speeds of onset to 95% twitch depression were: atracurium 2.7 min, Org NC 45 2.8 min and pancuronium 3.6 min. The median value of maximum neuromuscular block exceeded 98.5% for all drugs and the mean durations of action to 25% recovery of control twitch height were: atracurium 27.6 min, Org NC 45 21.9 min and pancuronium 45.1 min. The differences were statistically significant. The recovery period from 10% to 25% twitch response was considerably longer for pancuronium than for the other drugs, which did not differ significantly from each other. We were unable to validate the artery-to-muscle technique in the determination of onset time.
Adult↗