Search

Pancuronium, vecuronium and a combination of these were administered in an incremental fashion to study any potentiation of effect with the combination of the two relaxants. The ED95 (dose producing a 95% block) of the combination was 29 micrograms kg-1 for each component in comparison to 57 micrograms kg-1 for vecuronium and 59 micrograms kg-1 for pancuronium. The dose-response curves for the three groups did not differ from each other and no potentiation was demonstrated. [ABSTRACT FROM AUTHOR]

Neostigmine, the currently used agent for reversal of neuromuscular block, has several drawbacks, such as a slow onset of peak effect, inability to reverse deep block and the occurrence of widespread muscarinic effects. Sugammadex is a new class of reversal agent that acts by encapsulating the molecules of the relaxants rocuronium and vecuronium, for which it is a specific antagonist. Clinical trials in over 2000 subjects have shown it to be effective for reversal of block by these two relaxants even from deep levels, in doses of 2.0-4.0 mg/kg. Sugammadex can also reverse an intense (profound) high-dose rocuronium block, but the dose required in this situation is 16.0 mg/kg. The agent has been found to be safe so far, with few side effects.

The availability of sugammadex allows greater flexibility in the use of rocuronium and vecuronium during anaesthesia and surgery. The neuromuscular block induced by both drugs can be reversed from both superficial and deep levels of block by adjusting the dose of sugammadex. The dose of sugammadex for reversal of shallow block produced by these neuromuscular blocking drugs is approximately 2 mg.kg(-1) and for deep block the dose is 4 mg.kg(-1). A larger dose of sugammadex (16 mg.kg(-1)) administered 3 min after the neuromuscular blocking drug allows rapid reversal of a neuromuscular block induced by 1-1.2 mg.kg(-1) of rocuronium, thereby raising the possibility of using rocuronium as a replacement for suxamethonium. The use of sugammadex has not been reported to be associated with recurrence of block provided a dose that is adequate for reversal has been used. Sugammadex appears to have an acceptable safety profile. There are no requirements for dose adjustment for age or the use of potent volatile anaesthetic agents.

Background: Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated., Methods: Adult surgical patients (ASA class I-III) were randomized to sugammadex 2.0 mg kg(-1) for reversal of block induced by rocuronium 0.6 mg kg(-1), or neostigmine 50 microg kg(-1) for reversal of block induced by cisatracurium 0.15 mg kg(-1). Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch SX). Sugammadex or neostigmine was administered at reappearance of T(2). The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9., Results: Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine (geometric mean=1.9 vs 9.0 min, P<0.0001). Reversal of block was sustained in all patients. There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety, except for similar elevations in urinary N-acetyl glucosaminidase in both groups., Conclusions: Sugammadex 2.0 mg kg(-1) administered at reappearance of T(2) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.

The set of guidelines for good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents, which was developed following an international consensus conference in Copenhagen, has been revised and updated following the second consensus conference in Stockholm in 2005. It is hoped that these guidelines will continue to help researchers in the field and assist the pharmaceutical industry and equipment manufacturers in enhancing the standards of the studies they sponsor.

To demonstrate a direct protective effect of propofol on myocardial contractile performance during an ischemic episode and investigate underlying mechanisms, isolated adult rat ventricular cardiomyocytes were subjected for 2 h to (i) ischemic medium containing 2-deoxyglucose (20 mM), gassed with 100% N(2) at pH 6.4, (ii) normal medium with 95% O(2)/5% CO(2) at pH 7.4 or (iii) normal medium with addition of H(2)O(2) (50 microM). Propofol under normal conditions decreased the peak amplitude of electrically stimulated contraction of cardiomyocytes from a basal value of 6.5+/-0.37 microm to a maximum attenuation ( approximately 37%) at 0.44 to 56 microM. Under ischemic conditions, the contraction amplitude at baseline was 2.8+/-0.34 microm, but propofol, despite having a cardiodepressant effect per se, stimulated contraction, such that at >or=0.44 microM, normal and ischemic values in the presence of propofol were similar. Comparably, pro-oxidant (H(2)O(2))-induced attenuation of cell shortening was reversed by propofol (0.5 microM) to the level of contractile activity produced by the anaesthetic alone. The protective effect against ischemia-induced injury was not reflected in an improved ATP/ADP ratio nor was it mediated through diltiazem-sensitive L-type Ca(2+) channels. Propofol (0.5 microM) did, however, attenuate the ischemia- and H(2)O(2)-induced increases in the membrane lipid hydroperoxides, MDA (by 83% and 30%) and 4-HNE (by 47% and 69%). It is concluded that propofol, at clinically relevant concentrations, can counteract the effects of increased production of free radical compounds by cardiomyocytes subjected to oxidant stress and improve contractile performance.

Background: Org 25969 is a cyclodextrin compound designed to reverse a rocuronium-induced neuromuscular block. The aim of this study was to explore the efficacy, dose-response relation and safety of Org 25969 for reversal of a prolonged rocuronium-induced neuromuscular block., Methods: Thirty anaesthetized adult patients received rocuronium 0.6 mg kg(-1) as an initial dose followed by increments to maintain a deep block at a level of <10 PTCs (post-tetanic counts) recorded every 6 min. Neuromuscular monitoring was carried out using accelerometry, in a train-of-four (TOF) mode using TOF-WatchSX. At recovery of T2, following at least 2 h of neuromuscular block, patients received their randomly assigned dose of 0.5, 1.0, 2.0, 4.0 or 6.0 mg kg(-1) of Org 25969. Anaesthesia and neuromuscular monitoring were continued for a minimum period of 30 min after Org 25969 administration. The main end-point of the study was the time to achieve a sustained recovery of TOF ratio to 0.9. Patients were followed up for 7 days after anaesthesia., Results: The results showed a dose-related decrease in the average time taken to attain a TOF ratio of 0.9 from 6:49 (min:s) with the 0.5 mg kg(-1) dose to 1:22 with the 4.0 mg kg(-1) dose. Weighted non-linear regression analysis showed the fastest achievable time to TOF ratio of 0.9 to be 1:35. Org 25969 produced no major adverse effects., Conclusion: Org 25969 effectively reversed a deep and prolonged neuromuscular block induced by rocuronium. The effective reversal dose appears to be 2-4 mg kg(-1).

Target-controlled infusion systems have been shown to result in the administration of larger doses of propofol, which may result in delayed emergence and recovery from anaesthesia. The aim of this study was to investigate if this was due to a difference in the depth of hypnosis (using the bispectral index monitoring) between the manual and target controlled systems of administration. Fifty unpremedicated patients undergoing elective surgery were randomly allocated to have their anaesthesia maintained with manual or target-controlled propofol infusion schemes. In both groups, the rate of propofol administration was adjusted according to standard clinical criteria while bispectral index scores were recorded by an observer not involved in the delivery of anaesthesia. The total dose of propofol used was higher in the target controlled group (mean 9.9 [standard deviation 1.6] compared with 8.1 [1.0] mg.kg(-1).h(-1) in the manual group [p < 0.0001]). The times to emergence and recovery end-points were comparable between the two groups. The difference in the total dosage of propofol was mainly due to higher rate of propofol administration in the first 30 min in the target controlled infusion group. The bispectral index scores were lower in the target controlled group during this time, being significantly so over the first 15 min of anaesthesia. We conclude that propofol administration by a target controlled infusion system results in the administration of higher doses of propofol and lower bispectral index values mainly in the initial period of anaesthesia.

A new laryngoscope has been designed, incorporating an adjustable mirror and a levered tip similar to the McCoy blade, in an attempt to bridge the gulf between simple direct laryngoscopy and fiberoptic laryngoscopy. Manual in-line neck stabilisation was used to simulate difficult laryngoscopy in 14 anaesthetised patients after full neuromuscular blockade. The best view at laryngoscopy was assessed using a standard Macintosh laryngsocope, a size 3 McCoy laryngoscope and the mirrored laryngoscope. The best laryngeal view obtained in all cases with the Macintosh blade was a grade 3. The mirrored laryngoscope improved this view in 10 cases (71%) compared with five cases (36%) with the McCoy laryngoscope (p = 0.005); in seven cases (50%), the view improved to a grade 1 compared with no cases when the McCoy was used (p = 0.02). We conclude that the mirrored laryngoscope offers considerable advantages over the Macintosh and the McCoy laryngoscopes in simulated difficult laryngoscopy, is simple to use and requires no special training.

The use of remifentanil has been recommended because of its ability to minimise the hypertensive response to tracheal intubation and surgical stimulation in various types of surgery. We describe the use of remifentanil in the anaesthetic management of three cases of open adrenalectomy, two for removal of a phaeochromocytoma and one for removal of an adrenal cortical tumour. Although the use of remifentanil was associated with no adverse events in the patient undergoing resection of the adrenal cortical tumour, its administration was associated with significant hypotension and bradycardia in the two phaeochromocytoma patients, who had both been given alpha- and beta-adrenergic receptor blocking drugs before surgery. It did not prevent the increases in blood pressure or plasma catecholamine levels associated with tumour manipulation in these patients. Remifentanil should therefore be used with caution in patients receiving alpha- and beta-adrenergic receptor blocking drugs. The use of potent vasodilators may still be necessary during tumour manipulation even if remifentanil is being infused.

Background: The perceived safety of the use of succinylcholine is based on the fact that recovery from its effects will occur before oxygen desaturation occurs in case of failure to intubate or ventilate. The purpose of this study was to examine the incidence of oxygen desaturation after the use of succinylcholine prior to resumption of spontaneous ventilation following four different preoxygenation techniques., Methods: Twenty-five patients each were randomly allocated to preoxygenation with 4 deep breaths of 100% oxygen or by breathing oxygen for 1, 3 or 5 min following which they received a rapid sequence induction of anaesthesia with fentanyl 1 microg kg(-1), a sleep dose of thiopentone and succinylcholine 1 mg kg(-1). Oxygen saturation was monitored continuously using a finger probe. Ventilation was not assisted unless the saturation decreased to

Purpose: To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine., Methods: One hundred and twenty patients, divided into three equal groups, were randomly allocated to maintenance of anesthesia with sevoflurane, isoflurane or propofol. Neuromuscular block was induced with rocuronium and monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. Neostigmine was administered when the first response in TOF had recovered to 25%. At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group (n = 20 in each group). The times to attain TOF ratio of 0.8, and the number of patients attaining this end point within 15 min were recorded., Results: The times (mean +/- SD) to recovery of the TOF ratio to 0.8 were 12.0 +/- 5.5 and 6.8 +/- 2.3 min in the sevoflurane continued and sevoflurane stopped groups, 9.0 +/- 8.3 and 5.5 +/- 3.0 min in the isoflurane continued and isoflurane stopped groups, and 5.2 +/- 2.8 and 4.7 +/- 1.5 min in the propofol continued and propofol stopped groups (P < 0.5-01). Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min (P < 0.001 for sevoflurane)., Conclusions: The continued administration of sevoflurane, and to a smaller extent isoflurane, results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block.

The frequency and duration of postoperative residual neuromuscular block on arrival of 150 patients in the recovery ward following the use of vecuronium (n = 50), atracurium (n = 50) and rocuronium (n = 50) were recorded. Residual block was defined as a train-of-four ratio of <0.8. An additional group of 10 patients received no neuromuscular blocking drugs during anaesthesia. The incidence of postoperative residual neuromuscular block was 64%, 52% and 39% after the use of vecuronium, atracurium and rocuronium, respectively. Similar numbers of patients were not able to maintain a sustained head or leg lift for 5 s on arrival in the recovery ward. The mean [range] times to attaining a train-of-four ratio of > or =0.8 after arrival in the recovery ward were 9.2 [1-61], 6.9 [1-24] and 14.7 [1.5-83] min for vecuronium, atracurium and rocuronium, respectively. None of the 10 patients who did not receive neuromuscular blocking drugs had train-of-four ratios <0.8 on arrival in the recovery ward. It is concluded that a large proportion of patients arrive in the recovery ward with a train-of-four ratio <0.8, even with the use of intermediate-acting neuromuscular blocking drugs. Although the residual block is relatively short lasting, it may occasionally be prolonged, requiring close observation and monitoring of such patients in the recovery ward.

We have examined the effects on recovery end-points of supplementation of a propofol-based anaesthetic with remifentanil. After induction of anaesthesia with propofol and remifentanil 1.0 microg kg(-1), 15 patients each were randomly allocated to target plasma propofol concentrations of 2, 3, 4 or 5 microg ml(-1) for maintenance of anaesthesia. Remifentanil was administered by infusion for supplementation in doses required for maintenance of adequate anaesthesia. All patients received 50% nitrous oxide in oxygen and ventilation was controlled. The total amount of drugs used and times to different recovery end-points were recorded. Cognitive function was also assessed using a Mini-Mental State questionnaire. The median dose of remifentanil for maintenance of adequate anaesthesia (excluding the initial bolus dose) in the four groups was 0.21, 0.15, 0.11 and 0.13 microg kg(-1) min(-1) respectively (P=0.0026). The median times to eye opening and orientation were shortest in the 2 microg ml(-1) group [6.0 and 6.5 min, 8.5 and 10.8 min, 13.4 and 15.8 min, and 14.2 and 19.5 min respectively in the propofol 2, 3, 4, and 5 microg ml(-1) groups respectively (P<0.001)]. The times to discharge from the recovery ward and the Mini-Mental State scores were not significantly different.

The aim of this study was to compare recovery and psychomotor performance after maintenance of anaesthesia with sevoflurane or sevoflurane supplemented with remifentanil. Sixty-six per cent nitrous oxide was used in all patients. Twenty patients each were randomly allocated to maintenance of anaesthesia with sevoflurane only in concentrations necessary to maintain adequate anaesthesia or with 1.5, 1.0 or 0.5 MAC (end-tidal) of sevoflurane supplemented with remifentanil. The median dosage of remifentanil required in the last three groups was 0.21, 0.25 and 0.34 microg x kg(-1) x min(-1), respectively (p < 0.05). The median times to eye opening were 10.3, 12.7, 11.0 and 6.5 min in the four groups (p < 0.05 between the 0.5 MAC and the other groups) and for orientation 12.1, 14.9, 12.3 and 8.3 min, respectively (p < 0.05 between 0.5 and 1.5 MAC groups). There was no significant difference in the mini-mental state assessment scores or the actual discharge times from the recovery ward among the groups. Significantly greater numbers of patients could perform the critical flicker fusion test at 15 min in the group receiving the lowest concentration of sevoflurane and the highest dosage of remifentanil (p < 0.05). Patients in this group also showed the highest incidence of chest wall rigidity (p < 0.003). We conclude that, while the use of remifentanil with lower concentrations of sevoflurane facilitates early recovery, it does not influence discharge time from recovery ward and may be associated with side-effects such as chest wall rigidity.

The need for a rapid-acting non-depolarizing neuromuscular blocking agent with a short duration of action resulted in the synthesis of rapacuronium. The onset of maximum block with rapacuronium occurs in 60-90 s with doses of 1.5-2.5 mg kg-1 with a duration of clinical relaxation of 15-30 min. Rapacuronium provides clinically acceptable intubating conditions in 60 s in a majority of patients with these doses, although the conditions are somewhat inferior to those obtained with succinylcholine in lightly anaesthetized patients, such as those undergoing a rapid-sequence induction. The main drawbacks of rapacuronium are the occurrence of dose-related pulmonary side-effects (increased airway pressure and/or overt bronchospasm) and hypotension and tachycardia. The cause of pulmonary side-effects is not certain but these have been serious enough to make its worldwide introduction doubtful.

The purpose of this nine-centre study in 602 patients was to show that the frequency of acceptable intubating conditions after rapacuronium 2.0 or 2.5 mg kg-1 is not more than 10% lower than the frequency after succinylcholine 1.0 mg kg-1 during rapid-sequence induction of anaesthesia with fentanyl 1-2 micrograms kg-1 and thiopental 2-7 mg kg-1. Laryngoscopy and intubation were carried out 60 s after administration of muscle relaxant by an anaesthetist blinded to its identity. Intubating conditions were clinically acceptable (excellent or good) in 91.8% of patients given succinylcholine and in 84.1 and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg-1 respectively. With respect to the percentage of clinically acceptable intubating conditions, the estimated difference (and the upper limit of the one-sided 97.5% confidence interval) between succinylcholine and rapacuronium 2.0 mg kg-1 was 7.8 (14.4)% and between succinylcholine and rapacuronium 2.5 mg kg-1 it was 4.0 (10.2)%. For both comparisons, the upper limit of the one-sided confidence interval exceeded the predefined 10% difference. Hence, it could not be demonstrated that the intubating conditions with either of the two doses of rapacuronium were not inferior to those with succinylcholine 1.0 mg kg-1. The increase in heart rate was significantly greater during the first 5 min in the rapacuronium groups, but the arterial pressure increased significantly only in the succinylcholine group (P < 0.001). Respiratory side-effects were observed in 4.0, 13.5 and 18.5% of patients after succinylcholine and rapacuronium 2.0 and 2.5 mg kg-1 respectively (P < 0.05). As the non-inferiority of intubating conditions after rapacuronium 2.0 and 2.5 mg kg-1 could not be proven, succinylcholine should be considered the neuromuscular blocking agent that provides better intubating conditions for rapid-sequence induction.

The excretion of rocuronium and its potential metabolites was studied in 38 anaesthetized patients, ASA I-III and 21-69 yr old. Rocuronium bromide was administered as an i.v. bolus dose of 0.3 or 0.9 mg kg-1. In Part A of the study, the excretion into urine and bile, and the liver content were studied. Plasma kinetics (n = 19) were similar to those reported previously. Urinary recovery within 48 h after administration was 26 (8)% (mean (SD)) (n = 8) of the dose. In bile obtained from T-drains, the recovery within 48 h was 7 (6)% (n = 11). The rocuronium concentration in bile declined bi-exponentially, with half-lives of 2.3 (0.7) and 16 (11) h respectively (n = 6). In three patients from whom stoma fluid was collected, the amount of rocuronium recovered ranged from 0.04 to 12.0% of the dose. In liver tissue obtained from four patients undergoing hemihepatectomy, the estimated amount of rocuronium at 2-5 h after administration ranged between 6.3 and 13.2% (n = 4). In the second part of the study (Part B), urine and faeces were collected over 4-8 days and the recovery was 27 (13)% and 31 (23)% of the dose respectively (n = 10). In most samples, irrespective of the type of biological material, only small amounts of the metabolite 17-desacetyl-rocuronium was found. The results demonstrate that rocuronium is taken up by the liver and excreted into bile in high concentrations. The faecal and urinary excretion of unchanged rocuronium are the major routes of rocuronium elimination.

The neuromuscular blocking effects of a single dose of rapacuronium 1.5 mg x kg(-1) with or without reversal with neostigmine have been examined in the present study and compared with a dose of succinylcholine 1.0 mg x kg(-1). Neuromuscular block was measured mechanomyographically using train-of-four stimulation. Complete block occurred within 1 min with both agents. Twenty-five per cent recovery of the first response of the train-of-four occurred in a median [range] time of 7.6 [5.7-11.3] min in the succinylcholine group and in 14.2 [8.8-23.6] and 15.1 [9.6-23.4] min in the rapacuronium groups with and without neostigmine reversal, respectively. Spontaneous recovery to a train-of-four ratio of 0.8 took 33.4 [20.0-79.0] min with rapacuronium but this was reduced to about 21.2 [13.9-33.7] min when neostigmine was administered at 25% recovery of first twitch of the train-of-four.

Unlabelled: We compared the hemodynamic effects of a bolus administration of 1 microg/kg remifentanil for 1, 3, and 5 min (1, 0.33, and 0.2 microg. kg(-1). min(-1), respectively) in patients scheduled for coronary artery bypass grafting anesthetized with small-dose propofol. The study was terminated after only eight patients had been enrolled (three received remifentanil at a rate of 1.0 microg. kg(-1). min(-1), two at 0.33 microg. kg(-1). min(-1), and three at 0.2 microg. kg(-1). min(-1)) because of severe hemodynamic instability, which was particularly marked in four patients and consisted of severe bradycardia in one patient and severe hypotension with a reduction in systemic vascular resistance in three others. One patient showed evidence of myocardial ischemia. All patients responded to therapeutic interventions. The results show that remifentanil should be given only by slow infusion to such patients., Implications: This study investigates the effect on the heart and blood vessels of various rates of administration of boluses of a relatively new potent opiate, remifentanil, to patients with coronary artery disease. The results show that remifentanil should be given only by slow infusion to such patients.

A patient with a known history of myotubular myopathy presented for surgery for insertion of a tibial nail. Anasthesia was induced and maintained using an intravenous anasthetic technique. Neuromuscular function was assessed using mechanomyography, which showed a profound reduction in muscle contractility. In view of this, the use of muscle relaxants was avoided altogether. Nerve conduction was normal but electromyography showed small motor units, with generalised distribution, suggesting mild to moderately severe myopathy. The patient made a slow but uneventful recovery.

We have assessed the haemodynamic effects of rapacuronium (Org 9487) in adults undergoing cardiac surgery and compared these with vecuronium and placebo. We studied 56 adult patients undergoing coronary artery bypass grafting or valve replacement surgery using a fentanyl-based anaesthetic technique. A pulmonary artery flotation catheter was inserted before induction of anaesthesia. After induction, tracheal intubation and stabilization of haemodynamic measurements, subjects were allocated randomly to receive rapacuronium 1.5 mg kg-1 vecuronium 0.1 mg kg-1 or saline placebo. Haemodynamic measurements were made before drug administration and 1, 3, 5 and 10, and if possible, 15 min after administration. Rapacuronium was associated with statistically significant increases in heart rate (17%) and cardiac index (15%) and decreases in mean arterial pressure (11%) and systemic vascular resistance (18%), whereas vecuronium and placebo were associated with significant decreases in heart rate only (14-15%) (P < 0.05). No cutaneous signs of histamine release were observed. Clinically, the results were within acceptable limits. Our results suggest that administration of rapacuronium may be associated with significant changes in heart rate and arterial pressure in patients undergoing coronary artery bypass grafting.

Spontaneous recovery, and recovery following neostigmine 20, 35 or 50 microgram.kg-1 administered at 10 or 25% of recovery of the first twitch of the train-of-four, was assessed in 80 patients after rocuronium administration under continued isoflurane anaesthesia. In an additional 40 patients, isoflurane administration was discontinued and neostigmine 35 or 50 microgram.kg-1 was given at 10 or 25% recovery. The administration of neostigmine reduced the recovery times significantly. A neostigmine dose of 20 microgram.kg-1 resulted in slower recovery compared with the higher doses, particularly when reversal was attempted at a first twitch height of 10%. Higher doses of neostigmine given at a first twitch height of 25% resulted in rapid reversal of block [mean (SD) times of 7.0 (4.8) and 6.4 (1.9) min with the 35 and 50 microgram.kg-1 doses, respectively, for attaining a train-of-four ratio of 0.8]. Discontinuing isoflurane did not alter recovery times. The incidence of emetic symptoms did not differ between groups, including one group that received atropine instead of glycopyrronium in combination with neostigmine. We conclude that rocuronium block can be antagonised safely using a neostigmine dose of 35 microgram.kg-1, although recovery may be slightly slower if administered at a first twitch of 10% of control.

We have examined spontaneous and neostigmine-induced recovery after an initial dose of Org 9487 1.5 mg kg-1 followed by three repeat doses of Org 9487, a 30-min infusion of Org 9487 or two incremental doses of rocuronium. Mean clinical duration after incremental doses of Org 9487 0.5 mg kg-1 increased from 12.3 (SD 3.4) min to 14.0 (4.0) and 15.9 (5.9) min (P < 0.01), and after rocuronium from 14.4 (5.2) min to 19.2 (5.9) min (P < 0.01). Times for spontaneous recovery from a T1 of 25% to a TOF ratio of 0.8 after the last bolus dose of Org 9487 and after a 30-min infusion were 72.4 (16.5) and 66.1 (26.9) min compared with 36.7 (15.8) min in the group receiving reocuronium. These times were significantly reduced to 9.9 (4.5), 8.6 (6.1) and 5.7 (2.5) min, respectively, after neostigmine administration at a T1 of 25% (P < 0.05). We conclude that administration of Org 9487 by repeat bolus doses or infusion was associated with slow spontaneous recovery but neostigmine administration resulted in adequate recovery in less than 10 min.

We compared the use of sevoflurane and propofol with three different doses of rocuronium for modified rapid-sequence induction of anaesthesia. One hundred and forty adult patients were randomly allocated to have a rapid-sequence intravenous induction with propofol 2-3 mg.kg-1 (group P) or an inhalational induction with sevoflurane 8% in oxygen, using a vital capacity technique (group S). Following loss of the eyelash reflex, cricoid pressure was applied and 20 patients in each group were administered rocuronium 0.3 (groups P/0.3 and S/0.3), 0.45 (groups P/0.45 and S/0.45) or 0.6 (groups P/0.6 and S/0.6) mg.kg-1. An additional 10 patients in each group received only saline placebo in place of the muscle relaxant (groups P/Saline and S/Saline). Laryngoscopy was started 60 s later and intubating conditions evaluated by a blinded anaesthetist according to a standard scoring system. Intubating conditions were acceptable in one patient and no patient, respectively, following induction with sevoflurane and propofol without the muscle relaxant. The conditions were acceptable in 30, 55 and 90% of subjects with sevoflurane induction, and in 45, 80 and 90% of subjects with propofol induction following 0.3, 0.45 and 0.6 mg.kg-1 of rocuronium, respectively (no significant difference for each dose of rocuronium). The present study shows that intubating conditions during a rapid-sequence induction using rocuronium 0.6 mg.kg-1 following induction of anaesthesia with sevoflurane or propofol are similar.

The effect of three bolus doses of remifentanil on the pressor response to laryngoscopy and tracheal intubation during rapid sequence induction of anaesthesia was assessed in a randomized, double-blind, placebo-controlled study in four groups of 20 patients each. After preoxygenation, anaesthesia was induced with thiopental 5-7 mg kg-1 followed immediately by saline (placebo) or remifentanil 0.5, 1.0 or 1.25 micrograms kg-1 given as a bolus over 30 s. Cricoid pressure was applied just after loss of consciousness. Succinylcholine 1 mg kg-1 was given for neuromuscular block. Laryngoscopy and tracheal intubation were performed 1 min later. Arterial pressure and heart rate were recorded at intervals until 5 min after intubation. Remifentanil 0.5 microgram kg-1 was ineffective in controlling the increase in heart rate and arterial pressure after intubation but the 1.0 and 1.25 micrograms kg-1 doses were effective in controlling the response. The use of the 1.25 micrograms kg-1 dose was however, associated with a decrease in systolic arterial pressure to less than 90 mm Hg in seven of 20 patients.

Purpose: To determine the potency and time course of action of mivacurium neuromuscular block under routine clinical conditions during sevoflurane, isoflurane and intravenous anesthesia., Method: Patients were anesthetized with nitrous oxide 66% in oxygen and 1.5 MAC sevoflurane or isoflurane or a propofol infusion, neuromuscular block being monitored using mechanomyography. Potency was determined using administration of single doses of mivacurium of 40-100 micrograms.kg-1 and construction of dose-response curves (n = 72). The onset and duration of action were determined following a bolus dose of 0.2 mg.kg-1 of mivacurium (n = 30)., Results: The ED50 and ED95 (with 95% confidence limits) were estimated to be 42 (35-51) and 86 (74-98) micrograms.kg-1, 52 (45-60) and 89 (72-110) micrograms.kg-1, and 53 (45-62) and 95 (81-112) micrograms.kg-1 during sevoflurane, isoflurane and propofol anesthesia respectively (P < 0.05 between sevoflurane and propofol). Following administration of the 0.2 mg.kg-1 dose, neither the times (mean +/- SD) to maximum block (1.6 +/- 0.31, 1.7 +/- 0.21 and 1.6 +/- 0.45 min, respectively) nor the times to 25 and 90% recovery of T1 (20 +/- 4.5 and 33 +/- 8.8 min, 21 +/- 3.8 and 33 +/- 6.5 min, and 18 +/- 4.1 and 28 +/- 5.8 min respectively) were different among groups. The times to recovery of TOF ratio to 0.8 were 40 +/- 10.0, 36 +/- 8.5 and 29 +/- 5.5 min in the sevoflurane, isoflurane and propofol groups respectively (P = 0.017 between the sevoflurane and propofol groups)., Conclusions: Under usual conditions of clinical anesthesia the potency of mivacurium was slightly enhanced during sevoflurane compared with intravenous anesthesia but the duration of action was only minimally prolonged during sevoflurane and isoflurane anesthesia.

Neuromuscular blocking drugs exhibit different degrees of fade in response to train-of-four stimulation believed to represent their relative prejunctional effects. The present study was designed to compare the train-of-four fade after cisatracurium and compare this with other commonly used muscle relaxants. Train-of-four fade during onset and recovery of block were recorded after administration of cisatracurium 0.05 or 0.1 mg.kg-1, atracurium 0.5 mg.kg-1, vecuronium 0.08 mg.kg-1, mivacurium 0.15 mg.kg-1 or rocuronium 0.6 mg.kg-1 to patients anaesthetised with fentanyl, nitrous oxide and a propofol infusion. Neuromuscular monitoring was by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The onset and recovery of block were also measured. Train-of-four fade during onset of block was greater with the lower dose of cisatracurium compared with the higher dose of cisatracurium and all other relaxants. Train-of-four fade during recovery was similar. The median times (and ranges) for the onset of maximum block were 3.4 (2.1-5.6), 1.5 (1.2-2.3), 2.1 (1.2-2.6), 2.0 (1.5-2.7) and 1.0 (0.7-1.3) min for cisatracurium 0.1 mg.kg-1 and atracurium, mivacurium, vecuronium and rocuronium, respectively. The median times (and ranges) for the recovery of T1 to 25% of control and to a train-of-four ratio of 0.8 were 41 (21-50) and 65 (40-78); 43 (37-54) and 69 (58-79); 15 (11-20) and 25 (19-30); 31 (23-46) and 60 (45-117); and 33 (18-57) and 50 (28-76) min following cisatracurium, 0.1 mg.kg-1, atracurium, mivacurium, vecuronium and recuronium, respectively.

Unlabelled: The potency and time course of action of rocuronium were studied in patients anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was estimated by using the single-bolus technique. Neuromuscular block was measured by stimulation of the ulnar nerve and by recording the force of contraction of the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95% effective doses were estimated tobe 142 (129-157) and 265 (233-301) microg/ kg, 165 (146-187) and 324 (265-396) microg/kg, and 183 (163-207) and 398 (316-502) microg/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and 1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia, respectively. The respective times to recovery of the first response in the train-of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3 min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62 +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and 14 +/- 6.9 min, respectively. There were no differences among groups in the times for onset of action or to recovery of T1 to 25%. However, the times for recovery of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were all significantly longer compared with the other two groups (P < 0.05, < 0.01, and < 0.01, respectively). We conclude that the effects of rocuronium, especially duration of action, are significantly enhanced during sevoflurane compared with isoflurane and propofol anesthesia., Implications: In routine clinical use, the effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane and propofol anesthesia, and the recovery is slower. Particular attention should be paid to monitoring of neuromuscular block during sevoflurane anesthesia.

This study was designed to compare the tracheal intubating conditions during a rapid sequence induction of anaesthesia using rocuronium 0.6 (n = 61) or 1.0 mg.kg-1 (n = 130) or suxamethonium 1.0 mg.kg-1 (n = 127) as the neuromuscular blocking drugs. Anaesthesia was induced with fentanyl 1-2 micrograms.kg-1 and thiopentone 5 mg.kg-1 (median dose) and intubating conditions were assessed 60s after the administration of the neuromuscular blocking drug by an observer unaware of which drug had been given. Intubating conditions were graded on a three-point scale as excellent, good or poor, the first two being considered clinically acceptable. The study was carried out in two parts. At the end of the first part a comparison between the two doses of rocuronium was carried out when at least 50 patients had been enrolled in each group. The results showed the intubating conditions to be significantly superior with the 1.0 mg.kg-1 dose of rocuronium (p < 0.01). Final comparison between the 1.0 mg.kg-1 doses of rocuronium and suxamethonium showed no significant difference in the incidence of acceptable intubations (96 and 97%, respectively). The incidence of excellent grade of intubations was, however, significantly higher with suxamethonium (80% vs. 65%; p = 0.02). It is concluded that rocuronium 1.0 mg.kg-1 can be used as an alternative to suxamethonium 1.0 mg.kg-1 as part of a rapid sequence induction provided there is no anticipated difficulty in intubation. The clinical duration of this dose of rocuronium is, however, 50-60 min.

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mg.kg-1 were compared with those of atracurium 0.5 mg.kg-1 during anaesthesia with propofol, nitrous oxide and isoflurane. Neuromuscular block was monitored using train-of-four stimulation while recording the mechanomyographic response of the adductor pollicis muscle. The block was either allowed to recover spontaneously or was antagonised with neostigmine 50 micrograms.kg-1 at 10% or 25% recovery of the first twitch of the train-of-four. The median times to maximum block were 2.7, 2.2 and 1.5 min following cisatracurium 0.1 and 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1, respectively. After cisatracurium 0.1 mg.kg-1 had been given, the median time to recovery of the train-of-four ratio to 0.8 ('adequate recovery') was 74 min during spontaneous recovery, 48 min after reversal with neostigmine when the first twitch of the train-of-four had returned to 10% of control and 50 min after reversal when the first twitch of the train-of-four had returned to 25% of control. These times for cisatracurium 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1 were 90, 66 and 57 min and 75, 56 and 54 min, respectively. Administration of neostigmine significantly shortened the time to adequate recovery for both drugs but there were no significant differences in the case of either neuromuscular blocking drug between the groups of patients given neostigmine at 10 or 25% recovery of the first twitch of the train-of-four.

Eighty women undergoing elective Caesarean section under spinal anaesthesia using hyperbaric bupivacaine 0.5% were randomly allocated to receive, in addition, intrathecal diamorphine 0.125, 0.25 or 0.375 mg or saline. Postoperative morphine requirements, measured using a patient-controlled analgesia system, were reduced in a dose-dependent manner by diamorphine. Pain scores were significantly lower at 2 and 6 h following the two larger doses of diamorphine. Less supplemental analgesia was required intra-operatively if intrathecal diamorphine had been given. The incidences of vomiting and pruritus were also dose-related. No respiratory rates of less than 14 breath.min-1 were recorded and the incidence of oxygen saturation readings less than 95% and 90% did not differ between groups. There were no adverse neonatal effects. Intrathecal diamorphine in the present study was found to be safe in doses of up to 0.375 mg following Caesarean section. However, minor side-effects were frequently observed.