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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]

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.

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.

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

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.

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 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.

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.

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 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.

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.

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.

Two hundred and ten adult patients undergoing open cholecystectomy, vagotomy or gastrectomy were included in a randomised multicentre study to compare postoperative nausea and vomiting, oxygen saturations for the first three postoperative nights, time to return of gastrointestinal function, mobilisation, and discharge from the hospital following induction and maintenance of anaesthesia with propofol and alfentanil or with thiopentone, nitrous oxide, isoflurane and alfentanil. Recovery from anaesthesia was significantly faster in the propofol group (mean (SD) times to eye opening and giving correct date of birth of 14.0 (SD 13.8) and 25.5 (SD 29.5) minutes, and 18.5 (SD 14.8) and 35.5 (SD 37.2) minutes in the propofol and isoflurane groups respectively). There was significantly less nausea in the propofol group (15.4%) than in the isoflurane group (33.7%) in the first two postoperative hours (p < 0.003) but not thereafter. There were no significant differences between the groups in any other recovery characteristics. The incidence of hypoxaemia (arterial oxygen saturation less than 93%) was close to 70% in both groups for the first three postoperative nights, indicating the need for oxygen therapy after major abdominal surgery.

The forces exerted at laryngoscopy with the McCoy and Macintosh blades have been compared in 40 patients. The variables measured were the duration of laryngoscopy, the three maximally-applied forces and the mean force. The mean (SD) forces recorded were 18.9 (7.82) and 10.1 (5.33) N, respectively, with the Macintosh and the McCoy blades (p < 0.001) with a similar duration of laryngoscopy. There was a significant positive correlation between the mean force and patients' weight, height and body mass index for the Macintosh blade but only for weight and height for the McCoy blade. It is concluded that the use of the McCoy blade results in significantly less force being applied during laryngoscopy. This may be the reason for the reduction in the stress response reported previously with the use of the McCoy blade.

The effect of a bolus and continuous infusion of midazolam on postoperative morphine consumption was assessed in a placebo-controlled, double-blind, randomly allocated trial of 50 patients undergoing elective abdominal hysterectomy. Patients in the trial group received a bolus dose of midazolam 5 mg.70 kg-1 at induction followed by an infusion at a rate of 1 mg.70 kg-1.h-1 over the next 48 h. Morphine consumption in the midazolam group was significantly lower in the first 12 h postoperatively (p < 0.02) but there was no significant difference between the two groups thereafter. Patients in the midazolam treated group had lower pain scores over the first 24 h. Also, a significantly greater number of patients in the midazolam group required no antiemetic medication over the 48 h study period (p < 0.05). Assessment of sedation revealed no significant difference between groups. We conclude that low dose midazolam has a significant, but short-lived, morphine sparing effect.

The effects of 1 MAC of desflurane and isoflurane (in 66% nitrous oxide) on the potency and duration of action of mivacurium were studied in 80 patients. The ED95 of mivacurium was 86 micrograms.kg-1 (74-100) and 88 micrograms.kg-1 (76-103) (mean and 95% confidence intervals) during anaesthesia with desflurane and isoflurane respectively. The onset and duration of recovery to 25, 75 and 90% of T1 (first response in the TOF) of 200 micrograms.kg-1 of mivacurium were 1.4 (0.3) and 1.5 (0.3) min (mean and SD), 22 (4.9) and 19 (4.0), 29 (6.6) and 26 (5.8), and 32 (7.3) and 29 (6.6) min respectively. There was no significant difference in any of the variables between desflurane and isoflurane. It is concluded that the neuromuscular effects of mivacurium are similar during anaesthesia with 1 MAC of desflurane and isoflurane.

The cardiovascular changes and catecholamine concentrations were compared in 20 patients before and after laryngoscopy with either the Macintosh or the McCoy laryngoscope blades. Following induction with fentanyl and thiopentone and muscle relaxation with vecuronium the vocal cords were visualised for 10 s with either the Macintosh or McCoy blade, chosen at random. Heart rate, arterial blood pressure and plasma noradrenaline and adrenaline concentrations were measured before, and at, laryngoscopy, and 1, 3 and 5 min later. There was a significant increase in both heart rate (33%) and arterial blood pressure (27%) after laryngoscopy using the Macintosh blade (p < 0.01). Use of the McCoy blade did not result in any significant change in either heart rate or arterial blood pressure. There was a slight increase (p > 0.05) in plasma noradrenaline concentrations using the Macintosh blade which persisted for 5 min after laryngoscopy. This was not observed with the McCoy blade. There was no change in plasma adrenaline concentrations with either blade during the 5 min after laryngoscopy when compared to the values before laryngoscopy. It is concluded that the stress response to laryngoscopy is less marked with the use of the McCoy blade and is probably due to a reduction in the force necessary to obtain a clear view of the larynx.

The TOF-Guard neuromuscular monitor uses an accelerometer to measure the response to nerve stimulation. In this study, we have compared it to a standard mechanomyographic monitor, the Myograph 2000, for neuromuscular monitoring in 28 subjects. A train-of-four mode of stimulation was used in both cases. The times taken for onset of block, and for the recovery of T1 (the first response in the train of four) to 25% of control, the time from recovery of T1 from 25-75% and for the recovery of the train of four ratio to 0.7 were compared with the two monitors. There was a good correlation between the two devices for both onset and recovery times. However, differences were highlighted when the data were analysed by the method of Bland and Altman. The 95% limits of agreement for the T1 recovery to 25%, as measured by the TOF-Guard, ranged from 5 min less to 8 min more than when measured by the Myograph 2000. For recovery of the train of four ratio to 0.7, the limits of agreement were approximately 6 min in either direction. The 95% limits for the TOF-Guard measured train of four ratio were from 0.47 to 0.99, at the Myograph reading of 0.7. We recommend that information from the TOF-Guard and the Myograph 2000 should not be used interchangeably. However, the TOF-Guard is likely to improve considerably on tactile evaluation of the responses to stimulation.

Rapid sequence induction of anaesthesia necessitating the use of suxamethonium may occasionally be needed soon after antagonism of neuromuscular block with anticholinesterase agents. The onset and duration of action of 1 mg kg-1 of suxamethonium was recorded in groups of 10 patients each, 5 or 10 min after the administration of edrophonium 1 mg kg-1 or neostigmine 40 micrograms kg-1 given for the antagonism of atracurium-induced neuromuscular block. Plasma cholinesterase activity was measured before, and 5 and 10 min after the administration of the anticholinesterases. A further 10 patients received suxamethonium 1 mg kg-1 without prior atracurium or anticholinesterase administration to serve as controls. The onset of action of suxamethonium was significantly prolonged when administered 5 min after both anticholinesterases, compared to the control group (P < 0.01). Recovery of suxamethonium block was delayed significantly after neostigmine, compared to both the edrophonium and the control groups (P < 0.05-0.001). Plasma cholinesterase activity was significantly reduced with the use of neostigmine but not with edrophonium (P < 0.001).

The dose-response relationship for edrophonium during antagonism of vecuronium-induced neuromuscular blockade was studied in two groups of adult patients of mean (SD) age 35 (10.0) years (n = 42) and 77 (5.4) years (n = 42) respectively. Neuromuscular block was monitored by recording the force of contraction of the adductor pollicis muscle following train-of-four stimulation. Six patients in each age group received 0.1, 0.3, 0.5, 0.7, 1.0, or 1.5 mg.kg-1 of edrophonium, or normal saline at 10% recovery of T1 (first response in the train-of-four) after a single dose of vecuronium 0.08 mg.kg-1. The train-of-four ratios were recorded continuously over the next 10 min and the values at 1 min intervals from 5 min onwards were used to construct the dose-response curves. The dose-response curves showed no significant difference between the two age groups except at 10 min. The estimated dose of edrophonium required for attaining a train-of-four ratio of 0.7 at 10 min was 0.9 and 1.3 mg.kg-1 in the younger and older groups, respectively (p < 0.05).

The effects of thiopentone and propofol on delayed hypersensitivity reactions and T lymphocyte proliferation were studied in nine healthy volunteers (five women and four men). Thiopentone 5 mg.kg-1 and propofol 2.5 mg kg-1 were given as a 10 min infusion on two separate occasions. The volunteers were exposed to a skin multitest antigen before and after administration of the two agents and their skin reactions assessed. T lymphocyte responses were studied using phytohaemagglutinin (PHA)-induced proliferation. Results showed that both drugs caused a significant depression of skin reactions in vivo but no depression in the T lymphocyte proliferation.

We have compared the efficacy of ondansetron, metoclopramide, droperidol and placebo in the prevention of postoperative nausea and vomiting in 118 day stay patients undergoing laparoscopic gynaecological procedures. All received a standardised general anaesthetic of fentanyl, propofol, nitrous oxide in oxygen and isoflurane. Three to five min before induction of anaesthesia, patients were allocated to receive ondansetron 4 mg, metoclopramide 10 mg, droperidol 1 mg or placebo in a randomised, double-blind manner. Visual analogue scores for nausea, the incidence of emetic episodes, and analgesic and antiemetic consumption were recorded for 48 h postoperatively. The scores for nausea were significantly lower in the ondansetron group (p < 0.01) compared with the other three groups at 1, 2 and 4 h after operation; thereafter there was no difference. The incidence of emesis was lower (p = 0.063) and time to first oral fluids was shorter (p < 0.05) in the ondansetron group. Oral analgesic requirements were significantly greater in the ondansetron group over the 48 h study period. Two patients, one each in the placebo and metoclopramide groups, had to remain in hospital overnight because of persistent emetic symptoms.

In characterising the forces exerted during laryngoscopy it is accepted that the significant force component is that which is parallel to the axis of the laryngoscope handle. This paper describes a new method of evaluating the forces exerted at laryngoscopy. A laryngoscope handle has been redesigned, incorporating a force-displacement transducer on the handle at the end opposite to where the blade is attached. The device is designed specifically to sense the axial component of force. The blade attachment block has been detached from the sleeve and connected to a steel shaft which forms the new battery compartment. This allows the axial force exerted at the blade during laryngoscopy to be transmitted along this shaft to the sensing transducer. Linear ball bearings have been introduced between the new shaft and the handle sleeve (outer casing). The rolling friction has been reduced to less than 0.1% by diamond-lapping the precision ground surface-hardened rod to produce a mirror finish. Thus, the force transmitted to the transducer is essentially constant regardless of where the load is applied along the blade. The output from the system is directly downloaded to a laptop computer and the data analysed almost instantaneously to determine the duration of laryngoscopy, the peak forces applied, the mean force with its standard deviation and graphic display of the data. Provision has been made for data entry checks, recording patient details and study data, and creating a data base for the storage and retrieval of the study details.

Thirty patients received a bolus dose of 0.2 mg.kg-1 of mivacurium followed by an infusion during anaesthesia with thiopentone, fentanyl and halothane. Neuromuscular block was monitored using train-of-four stimulation and mechanomyography and the block maintained to keep the first response in the train-of-four (T1) at 10% of control. At the end of surgery the patients were randomly allocated to reversal with neostigmine or edrophonium or to spontaneous recovery. The mean dosage of mivacurium for maintaining the T1 at 10% was 5.7 micrograms.kg-1.min-1. There was a significant (r = -0.81, p < 0.001) negative correlation between time to recovery of T1 to 10% after the bolus dose and infusion rate. The times taken for T1 to reach 25, 75 and 90% of control and for the train-of-four ratio to reach 0.7 were significantly shorter (p < 0.05 to 0.001) with neostigmine and edrophonium compared to the spontaneously recovering group. The average (SD) times for attaining the train-of-four ratio of 0.7 were 7.0 (1.2), 6.8 (1.4) and 13.5 (2.3) min respectively for neostigmine, edrophonium and spontaneously recovering groups. There were no differences between endrophonium and neostigmine in any of the recovery times.

The use of rocuronium (Org 9426) as a single bolus followed by an infusion was assessed in 50 patients under anaesthesia with nitrous oxide-oxygen and halothane. Neuromuscular block was monitored using train-of-four stimulation and recording the force of contraction of the adductor pollicis muscle. Rocuronium was administered in an initial bolus dose of 0.45 mg.kg-1 followed by an infusion adjusted manually to maintain the T1, the first response in the train-of-four, at 10% of control. Following cessation of rocuronium infusion the patients were either allowed to recover spontaneously (n = 10) or were given neostigmine 50 micrograms.kg-1 or edrophonium 1 mg.kg-1 at 10 or 25% recovery of the T1 (n = 10 for each group). Adequate antagonism was defined as attaining a sustained train-of-four ratio of 0.7. Rocuronium requirements showed marked variation among individual patients but were relatively constant in individual patients. The mean (SD) time to attain stable infusion rates was 17.4 (10.9) min. The mean (SD) requirement of rocuronium for steady state 90% block of T1 was 572 (190) micrograms.kg-1.h-1 (range 242-1104 micrograms.kg-1.h-1). The mean (SD) time to attain a train-of-four ratio of 0.7 in the group allowed to recover spontaneously was 36.1 (7.3) min. This interval was 7.5 (1.9), 9.3 (7.0), 4.6 (1.9) and 1.9 (0.9) min respectively in the groups receiving neostigmine at T1 of 10%, edrophonium at T1 of 10%, neostigmine at T1 of 25% and edrophonium at T1 of 25%. The antagonism was significantly faster in those reversed at 25% (p < 0.05). Three patients in the group receiving edrophonium at T1 of 10% and one in the group receiving neostigmine at T1 of 25% failed to attain a train-of-four ratio of 0.7. It is concluded that rocuronium can be administered as a continuous infusion for stable neuromuscular block. Neostigmine may be a more reliable antagonist of deep block, whereas edrophonium is advantageous when there is a greater spontaneous recovery.

Mivacurium chloride has been assessed in respect of intubating conditions and neuromuscular effects. The influence of suxamethonium on the onset and duration of subsequently administered mivacurium was also studied. A dose of 0.15 mg.kg-1 of mivacurium was found to provide unacceptable intubating conditions at 2 min in 9/9 patients and further studies were conducted using 0.2 mg.kg-1. Intubating conditions with this dose were acceptable in 65% and 80% of patients at 2 min and 2.5 min respectively. In comparison, intubating conditions were acceptable in 100% of patients at 1 min following 1 mg.kg-1 of suxamethonium. The onset of block occurred in 96 s and 97 s after 0.15 mg.kg-1 and 0.2 mg.kg-1 respectively, and the durations of block in terms of recovery of the first twitch (T1) to 25% and 90% of control, and to recovery of train-of-four ratio to 0.7, were 16.1 and 17.9; 24.1 and 25.8; and 24.2 and 27.0 min respectively with the two doses. The time for the onset of complete block with suxamethonium 1.0 mg.kg-1 was 50 s and the times to 25% and 90% recovery were 9.8 min and 13.3 min. The differences between suxamethonium and both doses of mivacurium were significant (p < 0.05) but there were no significant differences between the two doses of mivacurium in any of the neuromuscular measurements. Prior administration of suxamethonium had no influence on the effects of mivacurium. Cutaneous flushing was observed in 30 out of 75 patients but this was associated with transient hypotension in only two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The haemodynamic effects of propofol-fentanyl anaesthesia for elective cardiac surgery were compared in 24 patients with good left ventricular function (ejection fraction > 45%, left ventricular end-diastolic pressure < 16 mmHg) and nine patients with impaired function. Anaesthesia was induced with fentanyl 25 micrograms.kg-1 and pancuronium 0.1 mg.kg-1 and was maintained with a variable rate propofol infusion, mean rate 2.61 mg.kg-1 x h-1 in the good ventricular function group and 2.71 mg.kg-1 x h-1 in the impaired function group. Additional fentanyl 7.5 micrograms.kg-1 was given before sternotomy. Ventilation to normocarbia was with air and oxygen (FIO2 0.6). Haemodynamic measurements were made before induction, after tracheal intubation, before and after sternotomy and before aortic cannulation. There were no significant differences between the groups in any haemodynamic variables during the study. Twenty minutes after intubation both groups showed a decrease from pre-induction values in mean arterial pressure (p < 0.05) and left ventricular stroke work index (p < 0.05), the reduction in left ventricular stroke work index remaining significant during the prebypass period in both groups. There were no significant changes in right or left sided filling pressures, systemic vascular resistance or heart rate. The technique decreased cardiac work and effectively controlled the autonomic responses to sternotomy in both groups. This study suggests that propofol may be a suitable adjunct to opioid anaesthesia in patients with impaired ventricular function having cardiac surgery.

The incidence and severity of muscle pains and changes in creatine kinase were assessed following administration of 1 mg.kg-1 suxamethonium either immediately or 2 min after induction of anaesthesia with propofol or thiopentone in patients undergoing elective dental and ophthalmic surgery. The incidence of muscle pains was 35 and 60% respectively in the groups given suxamethonium immediately and 2 min after propofol, and 35 and 55% when given immediately and 2 min after thiopentone, with no statistically significant differences among the groups. Creatine kinase levels increased in all the groups after operation with the least average increase in the group receiving suxamethonium immediately after propofol and the highest increase in the group receiving suxamethonium 2 min after thiopentone. There was no correlation between the incidence and severity of fasciculations, muscle pains and changes in creatine kinase within or between the groups. It is concluded that neither the induction agent nor the time between the induction agent and suxamethonium administration has any significant influence on the incidence of muscle pains or creatine kinase elevation following suxamethonium.

This is a report of a modification of the standard Macintosh laryngoscope blade to facilitate tracheal tube placement in cases of difficult visualisation of the larynx. The modification offers the unique advantage of a hinged blade tip, controlled by a lever on the handle of the laryngoscope which allows elevation of the epiglottis while decreasing the overall laryngoscopic elevation or levering movement required. It is an adaptation which can be applied to most laryngoscope blades, does not require any special training in its use and will prove useful for both routine intubations as well as those which may be difficult and associated with an anterior larynx.

The neuromuscular effects of intravenous rocuronium bromide, 0.6 mg.kg-1 or 0.9 mg.kg-1, were studied in four groups of 10 patients during anaesthesia with or without halothane (0.5-0.75% inspired concentration). Neuromuscular block was monitored using mechanomyography and train-of-four stimulation. The mean times to onset of complete neuromuscular block were 58 and 59 s using the 0.6 mg.kg-1 dose in patients anaesthetised with fentanyl and halothane respectively. The times of 34 min and 33 min for 25% recovery of T1 (first response in the train of four), 54 min and 52 min for 90% recovery of T1, 55 min and 60 min for a train of four ratio of 0.7, and 13 and 13 min respectively for the recovery index (25-75% recovery of T1) were not significantly different in these groups. Complete block with the 0.9 mg.kg-1 dose occurred in 47 s and 44 s respectively in the fentanyl and halothane groups. T1 recovered to 25% in 51 min and 58 min, and to 90% in 77 min and 86 min respectively in the two groups. The recovery indices and the times to spontaneous recovery of the train of four ratio to 0.7 were 17 min and 19 min, and 83 min and 93 min respectively. All the parameters were significantly different between the 0.6 mg.kg-1 and 0.9 mg.kg-1 doses. Halothane in the concentrations used did not influence the neuromuscular effects. It is concluded that rocuronium is a rapidly acting non-depolarising muscle relaxant with a duration of action similar to that of vecuronium and may be a useful alternative to suxamethonium for rapid tracheal intubation.

Peripheral oxygen saturation was recorded on the pre-operative night (between 2400 and 0600 h), the immediate postoperative period (first 60 min) and the first postoperative night (2400 to 0600 h) in 18 elderly patients aged 70 years or over presenting for elective ophthalmic surgery. Nine patients had surgery performed under general anaesthesia employing muscle relaxants and controlled ventilation and nine under local anaesthesia using a peribulbar block. The median (interquartile range) percentage of time during which the patients had an oxygen saturation of less than 90% was 0 (0-0.2) and 0.04 (0-0.4) on the pre-operative night, 0.7 (0-1.4) and 0.3 (0-1.2) in the immediate postoperative period, and 0.05 (0-0.16) and 0 (0-0.3) on the postoperative night in the general and local anaesthesia patients respectively. There were no significant differences between general and local anaesthesia in respect of these data and the overall incidence of significant desaturation was low. The present study could not demonstrate any adverse effect of general anaesthesia on oxygen saturation in patients undergoing minimally invasive surgery.

Doxacurium was administered to 50 adult patients for determination of potency (n = 10), onset and duration of clinical relaxation (n = 40). Cumulative dose-response showed the ED95 to be 33.24 micrograms.kg-1 (95% confidence limits 27.4-39.3). Doxacurium 33 micrograms.kg-1 was then administered to four groups of 10 patients each who had anaesthesia maintained with either fentanyl-droperidol or halothane and nerve stimulation carried out with single-twitch stimulation at 0.1 Hz or train-of-four stimulation at 2 Hz every 12 s. The onset and duration showed wide individual variation. The mean (SD) times to occurrence of maximal block were 8.5 (4.6), 6.1 (1.9), 6.7 (1.8) and 4.7 (1.3) min in the single twitch-fentanyl, train-of-four--fentanyl, single twitch-halothane and train-of-four--halothane groups respectively, although it ranged from 3.4 to 13.1 min in individual patients. The mean (SD) durations of clinical relaxation (recovery of single twitch or first response in train-of-four to 25%) were 65 (22.8), 52 (21.7), 70 (33.4) and 72 (21.0) min respectively with individual values ranging from 31 to 103 min. Although halothane administration increased the duration of clinical relaxation and train-of-four stimulation accelerated the onset of effect, the changes due to these were not significant. There were no adverse effects on heart rate or indirectly measured arterial pressure.

The onset and duration of action of vecuronium were studied in young adult (n = 30; mean age 34 +/- 11.1 (s.d.) yr), middle-aged (n = 20; mean age 60 +/- 5.8 yr) and elderly patients (n = 30; mean age 80 +/- 4.6 yr) anaesthetised with thiopentone, nitrous oxide in oxygen and halothane. Neuromuscular block was monitored by applying the train-of-four (TOF) stimulation at 2 Hz to the ulnar nerve every 12 s. Half the patients in each group received 0.08 and the other half 0.12 mg kg-1 of the relaxant. The time to return of T1 (first response in the TOF sequence) to 25% of control was 28 +/- 5.2 (s.d.), 34 +/- 7.1 and 39 +/- 10.2 min following 0.08 mg kg-1 dose (P less than 0.05 between the elderly and young adults) and 45 +/- 9.2, 48 +/- 6.2 and 69 +/- 19.2 min following 0.12 mg kg-1 dose, respectively, in the three age groups (P less than 0.05 between the elderly and the other two groups). The recovery indices (time for 25-75% recovery of T1) after the 0.08 mg kg-1 was 9.6 +/- 3.4, 13.6 +/- 5.1 and 17.4 +/- 6.1 min, respectively (P less than 0.05 between the elderly and young adults). There was no significant difference in any of the parameters between the young adults and the middle-aged. The onset of block at each dose was not significantly different between the three age groups; however, the time to maximum effect was significantly shorter with the higher dose in the young and the middle-aged, but not in the elderly. Regression analysis of the data between age and the duration of action and recovery index suggested a significant prolongation (P less than 0.05) of these parameters in the elderly.

The incidence of muscle pains and changes in serum concentrations of potassium, calcium and creatine kinase following suxamethonium were investigated after no pretreatment or pretreatment with intravenous tubocurarine 0.05 mg.kg-1, intravenous chlorpromazine 0.1 mg.kg-1, alphatocopherol (vitamin E) 600 mg in three divided doses orally, aspirin 600 mg orally or intravenous calcium chloride 5 mg.kg-1 in groups of 20 patients each. The incidence of myalgia was reduced significantly by tubocurarine, chlorpromazine and alphatocopherol. However, the increase in creatine kinase was attenuated only in the groups of patients who received tubocurarine and chlorpromazine. The changes in serum potassium and calcium concentrations were within acceptable limits. The intubating conditions were not as good in the patients who received tubocurarine as in the other groups. Effectiveness of chlorpromazine in preventing both the myalgia and the biochemical changes suggests the involvement of phospholipases in the pathogenesis of suxamethonium-induced muscle damage.

The efficacy of five different techniques of pre-oxygenation before a modified rapid intubation sequence was assessed, using oxygen saturation measurement, in patients aged over 65 years. Twenty patients in each group were pre-oxygenated using four deep breaths or normal tidal breathing for 1, 2, 3, or 4 minutes. The acceptable period of apnoea was defined as the time taken to desaturate to 93%. The mean times (SD) taken to reach this end-point were 3.7 (1.6), 4.1 (1.2), 5.4 (1.7), 5.4 (1.4) and 5.2 (1.7) minutes respectively. The apnoea times with 2, 3 and 4 minutes pre-oxygenation were not significantly different from each other but were significantly longer than after four deep breaths and 1 minute. It is concluded that a pre-oxygenation period of at least 2 minutes should be employed in the elderly before a rapid sequence induction.

Haemodynamic variables were measured following administration of pipecuronium 70 micrograms.kg-1 and pancuronium 90 micrograms.kg-1 (approximately equivalent to 1.5 x ED95) in patients anaesthetised with fentanyl 50 micrograms.kg-1 and scheduled to undergo coronary artery bypass grafting. There were significant increases in heart rate (22%), mean arterial pressure (10%), cardiac index (16%), and the rate pressure product (35%) following administration of pancuronium. The absolute values of these parameters were, however, within acceptable clinical limits. Administration of pipecuronium produced minimal and insignificant changes in these parameters. Other measured or derived indices showed only small changes with both agents and these were generally insignificant. There were no incidences of significant bradycardia following pipecuronium administration. The results from the present study suggest that pipecuronium would have advantages for use in patients with significant cardiovascular disease.

Intraocular pressure (IOP) was measured in four groups of patients receiving isoflurane or halothane in consecutively increasing or decreasing concentrations (1.0, 2.0 and 3.0 MAC in 70% nitrous oxide). IOP decreased significantly in all groups irrespective of whether the higher or the lower concentration of the volatile agent was used first. There were no further significant changes in IOP whether the concentrations were increased or decreased, suggesting no dose-relation. Maximum reductions in IOP were slightly greater in those receiving the higher concentrations of the volatile agents first (64 and 66% with isoflurane and halothane, respectively) in comparison to those receiving the lower concentrations first (54 and 46%, respectively).