Biomedical subjects
G G Lavery
Publications and source records attributed to G G Lavery.
Antagonism of vecuronium-induced neuromuscular blockade with edrophonium or neostigmine.
Antagonism of vecuronium-induced neuromuscular blockade was attempted, at varying degrees of spontaneous recovery, with edrophonium 0.5 mg kg-1 or neostigmine 0.05 mg kg-1 in two groups of 20 patients. Neuromuscular blockade was monitored using a train-of-four (TOF) stimulation. Adequate antagonism of neuromuscular blockade, defined as a sustained TOF ratio of 0.7 or more, was attained in all 20 patients given neostigmine and in 13 out of 20 given edrophonium. Five of the remaining seven patients given edrophonium had shown three or less responses to TOF stimulation before antagonism. While the time to onset of the action of edrophonium (22 s) was not significantly shorter than neostigmine (26 s), the time taken to attain a TOF ratio of 0.7 was significantly shorter with edrophonium (67 s compared with 194 s with neostigmine). It is concluded that edrophonium 0.5 mg kg-1 does not consistently antagonize vecuronium-induced neuromuscular blockade, particularly if there are three or less responses to a TOF stimulation present before antagonism.
The effects of vecuronium on intra-ocular pressure.
The effects of vecuronium on intra-ocular pressure were investigated in doses of 0.1 mg/kg during steady state anaesthesia (n = 5), 0.1 mg/kg as part of a normal sequence induction preceded by thiopentone (n = 10), and 0.15 mg/kg as part of a rapid sequence induction with vecuronium administered prior to thiopentone (n = 10). Administration of vecuronium during steady state anaesthesia was associated with a significant decrease. Vecuronium produced a small reduction in pressure during a normal sequence induction, following a significant reduction after thiopentone. Tracheal intubation during normal sequence and rapid sequence inductions produced increases in pressure above the pre-intubation value (significantly so in the case of normal sequence induction); however, the intra-ocular pressure always remained below the pre-induction value, which suggests that vecuronium 0.15 mg/kg is a suitable relaxant as part of a rapid sequence induction technique where the use of suxamethonium is contraindicated.
Does the choice of the neuromuscular blocking agent affect the cardiovascular response to intubation?
Heart rate and arterial pressure changes induced by tracheal intubation, 3 min after administration of atracurium, vecuronium, tubocurarine, pancuronium or alcuronium, have been studied under thiopentonenitrous oxide-oxygen anaesthesia supplemented by either 0.5% halothane or fentanyl 2 micrograms kg-1. Pancuronium and alcuronium were associated with the greatest increase in heart rate and tubocurarine with the greatest decrease in arterial pressure prior to intubation. Following intubation, all groups, with the exception of tubocurarine showed a similar and significant rise in heart and arterial pressure when compared with control values. The cardiovascular response to intubation, particularly the effect on heart rate, was less marked when fentanyl was given at induction and was short lived with atracurium and vecuronium. Although those patients who received tubocurarine showed no significant rise in arterial pressure following tracheal intubation, this was due to significant hypotension occurring in this group prior to intubation.
The effects of atracurium on intraocular pressure during steady state anaesthesia and rapid sequence induction: a comparison with succinylcholine.
The effects of atracurium 0.5 mg X kg-1 or succinylcholine 1.0 mg X kg-1 on intraocular pressure (IOP) were studied in ten patients during steady state nitrous oxide-oxygen-fentanyl anaesthesia. IOP was unchanged following atracurium but, one minute after succinylcholine, it had increased significantly (p less than 0.025) from 5.6 mmHg to 13.2 mmHg and remained significantly above control for 3 min. Twenty additional patients received either atracurium 0.75 mg X kg-1 or succinylcholine 1.0 mg X kg-1 as part of a rapid sequence induction, atracurium being administered prior to, and succinylcholine after, thiopentone. Intubating conditions were acceptable in all patients in both groups. Administration of thiopentone was associated with a significant (p less than 0.025) decrease in IOP. Although IOP increased in both groups as a result of laryngoscopy and intubation (from 8.0 mmHg to 12.1 mmHg in the atracurium Group and from 7.5 mmHg to 14.5 mmHg in the succinylcholine group) it did not exceed pre-induction IOP in the former. In the succinylcholine group, IOP after intubation exceeded pre-induction values for 2 min, although this increase was significant (p less than 0.05) only at the immediate post-intubation reading. It is concluded that atracurium in a dose of 0.75 mg X kg-1 is a suitable relaxant for use in rapid sequence induction.
Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique).
Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them.
Histaminoid response after intradermal and intravenous administration of atracurium, vecuronium and tubocurarine: a comparative study.
The object of this study was to investigate the histaminoid responses after intradermal administration of atracurium, vecuronium and tubocurarine and to compare these with the cutaneous and cardiovascular responses to intravenous administration of the above relaxants in the same patients. Positive local cutaneous responses to intradermal injection were most common after tubocurarine (92%) and least common after vecuronium (12%). Tubocurarine produced the greatest fall in systolic pressure 3 min after intravenous administration but there was no difference in this respect between atracurium and vecuronium. In any individual patient the response to intradermal injection of a relaxant was not a reliable predictor of the response to subsequent intravenous administration of the same relaxant. Twenty patients had plasma IgE levels below 12 IU ml-1. This abnormally low titre occurred more frequently in female patients and was associated with an increase in the incidence and degree of histaminoid responses to atracurium and tubocurarine. Low plasma IgE may be associated with a deficiency in surface IgE on mast cells which therefore have an increased sensitivity to drugs that cause direct pharmacological histamine liberation.
The effect of atracurium, vecuronium and pancuronium on heart rate and arterial pressure in normal individuals.
Heart rate and rhythm (from ECG) and systolic, diastolic and mean arterial pressures (using an oscillotonometer) were measured for 30 min following administration of atracurium 0.5 mg kg-1 (n = 20), vecuronium 0.1 mg kg-1 (n = 20) or pancuronium 0.1 mg kg-1 (n = 20) during steady-state anaesthesia, with nitrous oxide, oxygen and either 0.75% halothane or fentanyl 4-5 micrograms kg-1, in the absence of any surgical stimulation. Whereas atracurium and vecuronium were associated with only small and clinically unimportant changes in heart rate, pancuronium produced a marked and significant increase associated with a junctional rhythm in four patients. Atracurium produced no significant changes in arterial pressure, vecuronium produced a significant fall (20 mmHg) in diastolic pressure during halothane anaesthesia and pancuronium a significant increase in mean arterial pressure with both anaesthetic techniques. No serious bradycardias were observed with either atracurium or vecuronium. Five patients showed cutaneous signs of histamine liberation after administration of atracurium.
Histaminoid responses to atracurium, vecuronium and tubocurarine.
Sixty patients scheduled for elective surgery underwent intradermal testing with 0.1 ml of the following solutions diluted in 0.9% saline: vecuronium and tubocurarine (1 in 1,000), atracurium (1 in 1,000 and 1 in 10,000), thiopentone (1 in 100) and also a 0.9% saline control. Thirty minutes later, an area of erythema of greater than 1.5 cm, or a wheal exceeding 1.0 cm in diameter, was recorded as a positive reaction. The patients then randomly received equipotent doses of atracurium, vecuronium or tubocurarine during a standardized anaesthetic induction. Any cutaneous reaction and the percentage fall in systolic pressure three minutes after administration of the relaxant were recorded. In 51 patients plasma IgE levels were measured. The incidence of positive cutaneous reactions to intradermal and intravenous relaxants was significantly different with each agent (p less than 0.01). The percentage fall in systolic pressure after tubocurarine was significantly different relative to the other two agents (p less than 0.01). This was regarded as reflecting potency in releasing histamine and placed the relaxants in the same order: tubocurarine, atracurium and vecuronium. The response to intradermal administration was no guide to the subsequent response after intravenous administration of the three relaxants. IgE levels below 15 IU X ml-1 occurred significantly more often in females and were associated with a significantly higher incidence of cutaneous reactions after intradermal atracurium (1 in 1,000 and 1 in 10,000) (p less than 0.05 and 0.001 respectively) and tubocurarine (1 in 1,000). With these two agents, generalized flushing after intravenous administration was also more common in this group, relative to the normal/high IgE group.
Comparison of cumulative and single bolus dose techniques for determining the potency of vecuronium.
The potency of vecuronium was determined using single bolus dose administrations of 10-50 micrograms kg-1 in 28 patients anaesthetized with thiopentone, nitrous oxide, oxygen and fentanyl. The results were compared with those previously obtained using a cumulative dose technique in a comparable group of 10 patients. The 50% and 95% blocking doses (ED50 and ED95) of vecuronium were found to be 23.1 and 39.6 micrograms kg-1, respectively. These were significantly lower than the 30.5 and 56.7 micrograms kg-1 obtained previously using the cumulative dose technique. We recommend the use of single bolus dose method of determining potency for relatively shorter-acting drugs like vecuronium.
Probable histamine liberation with atracurium. A case report.
An histaminoid reaction after the administration of thiopentone and atracurium is described. Serial blood sampling showed no evidence of complement activation. Intradermal testing 6 weeks later yielded a positive result with atracurium (1 in 1000), but not with thiopentone. The clinical course of the reaction and the subsequent investigations suggest a direct pharmacological liberation of histamine.
Possible histamine release after vecuronium.
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Atracurium in clinical anaesthesia: effect of dosage on onset, duration and conditions for tracheal intubation.
Conditions for tracheal intubation at 90 seconds, time to onset of maximum block and duration of clinical relaxation after five different doses of atracurium, which ranged from 0.4 to 1.0 mg/kg were studied in 200 adult patients who were anaesthetized with nitrous oxide, oxygen and halothane or fentanyl. The conditions for intubation improved significantly with increasing doses, and were acceptable in 55% patients with a 0.4 mg/kg dose and in about 90% of those who received the two higher doses. The time to onset of complete block was 257 seconds with 0.4 mg/kg and decreased progressively to 124 seconds with 1.0 mg/kg. The duration of clinical relaxation under fentanyl anaesthesia averaged 29 minutes with 0.4 mg/kg and increased in a dose-related manner to 57 minutes with 1.0 mg/kg: halothane anaesthesia produced only a marginal increase. There was no evidence of cumulation with up to six repeat doses of 0.125 mg/kg. The only side effect noticed was cutaneous flushing observed in 42% of patients. This was again dose dependent, being 18% with 0.4 mg/kg and increasing to 73% after 1.0 mg/kg. There was associated hypotension and bronchospasm in one patient.
Vecuronium and atracurium in the elderly: a clinical comparison with pancuronium.
The intubating conditions, time to complete block and duration of clinical relaxation were observed in a group of 101 elderly patients (aged over 65 years) following pancuronium 0.1 mg kg-1, vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1. The intubating conditions in the three groups were similar when assessed at 2 min following relaxant administration. The time to complete block was shortest with vecuronium (4.3 min) in comparison to atracurium (5.0 min) and pancuronium (6.0 min), but the differences were not statistically significant. The duration of clinical relaxation, however, was significantly shorter with vecuronium (37 min) and atracurium (35 min) in comparison to pancuronium (99 min).
A comparison of edrophonium and neostigmine for the antagonism of atracurium-induced neuromuscular block.
Edrophonium, 0.5 mg/kg, or neostigmine, 0.05 mg/kg, was administered to groups of 20 patients each, for antagonism of atracurium-induced block at varying degrees of spontaneous recovery. Neuromuscular block was studied using train-of-four (TOF) stimulation. Adequate reversal of neuromuscular block (TOF ratio of 0.7) was achieved in all patients given neostigmine but only in 13 of the 20 given edrophonium. The onset of action of edrophonium (23 sec) was significantly more rapid than that of neostigmine (40 sec), as was the time taken to attain a TOF ratio of 0.7 in those in whom adequate antagonism was achieved (68 sec for edrophonium and 246 sec for neostigmine). Five of the seven patients in the edrophonium group who failed to be reversed adequately had shown three or fewer twitches to a TOF stimulation. It is concluded that edrophonium in a dose of 0.5 mg/kg does not consistently antagonize neuromuscular blockade induced by atracurium, particularly if all four responses to a TOF stimulation are not elicited prior to antagonism of the block.
Potency of atracurium: a comparison of single dose and cumulative dose techniques.
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Atracurium besylate in paediatric anaesthesia.
Atracurium was evaluated in clinical anaesthesia in 50 children undergoing elective surgery. The time to onset of maximum block (182 seconds) was similar to that of vecuronium but shorter than that of pancuronium as previously reported. The duration of clinical relaxation (33 minutes) is between those of vecuronium and pancuronium. The antagonism of block at 25% recovery was easy. There was no untoward cardiovascular effects but skin reactions were observed in over 30% of patients.
Intensive care patients in district hospitals. A case for transfer?
Patients, admitted and primarily treated in a rural hospital, who required varying periods of intensive care management have been reviewed. The criteria for transfer of such patients to more specialised units and the hazards associated with ambulance travel are discussed. We describe measures to reduce these hazards and also a scheme for more uniform documentation and follow-up of such cases by the anaesthetist involved in primary care.