R.S.J. Clarke

Neuromuscular effects and intubating conditions following mivacurium: a comparison with suxamethonium

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. Our results show mivacurium to have a duration of action approximately half that of comparable doses of the intermediate acting relaxants atracurium and vecuronium.

Atropine and glycopyrronium premedication. A comparison of the effects on cardiac rate and rhythm during induction of anaesthesia.

The effect of premedication with the cholinergic blocking drugs, atropine and glycopyrronium, was investigated in two groups, each of twenty patients, with regard to their effects on cardiac rate and rhythm during induction of anaesthesia and tracheal intubation. Another similar group of twenty patients was given no anticholinergic premedication. The incidence of dysrhythmias was 35% in the atropine group and 10% in the glycopyrronium group but there were no dysrhythmias in patients given no anticholinergic drug. The average rises in arterial pressure were similar in all three groups. Atropine administration led to a greater initial rise in heart rate before the induction of anaesthesia, although the average heart rates were similar in the three groups at the time of intubation and cuff inflation. The routine use of anticholinergic premedication seems to be unnecessary since the antisialogogue effect does not make any difference to the course of anaesthesia. However, if the antisialogogue action is important, glycopyrronium offers an advantage over atropine.

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 jive different doses of atracurium, which ranged from 0.4 to 1.0 mg/kg were studied in 200 adult patients who were anaesthetised 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 mglkg. 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.

Haemodynamic changes during induction of anaesthesia with midazolam and diazepam (Valium) in patients undergoing coronary artery bypass surgery

Midazolam 0.3 mg/kg and diazepam 0.5 mg/kg were used for induction of anaesthesia in two groups of 10 patients each undergoing coronary artery bypass surgery. Haemodynamic variables were measured during induction of anaesthesia, after pancuronium and following tracheal intubation. Haemodynamic indices were derived, from these measurements using standard formulae. The induction of anaesthesia with midazolam produced a slight but significant increase in heart rate. There was a significant fall in systemic arterial pressure and pulmonary artery pressure following both drugs. Despite the fall in systemic arterial pressure, the cardiac index was maintained in patients who received midazolam. The cardiostimulatory effect of laryngoscopy and tracheal intubation was not prevented by either of the benzodiazepines and morphine in the dosage used. Midazolam is a suitable alternative to diazepam as part of an intravenous induction regimen in patients with ischaemic heart disease.

MINAXOLONE: A NEW WATER-SOLUBLE STEROID ANÆSTHETIC

The induction characteristics of minaxolone, a water-soluble steroid anaesthetic, were studied in fit patients undergoing minor urological or gynaecological operations. Minaxolone acted as rapidly as thiopentone. A dose of 0.25 mg kg-1 did not always produce anaesthesia in patients who had not received premedication but 0.5 mg kg-1 was an adequate dose. Excitatory effects were less common with the higher doses of anaesthetic. These effects were usually slight and rarely interfered with the course of anaesthesia. Unlike propanidid, minaxolone did not prolong the duration of action of suxamethonium. Minaxolone is easy to administer and causes little venous damage.

Dose‐response studies of atracurium, vecuronium and pancuronium in the elderly

Dose‐response curves were constructed for atracurium. vecuronium and pancuronium in elderly subjects in order to assess potency of these relaxants. The results were compared to data previously obtained for adult subjects using the same method. A single‐dose method of potency determination was used in both studies. The results indicate no significant difference in the potency of these relaxants between elderly and adult subjects; the ED95s were 249 and 226 μg/kg for atracurium, 43.1 and 39.6 μg/kg, for vecuronium and 65.9 and 60 μg/kg for pancuronium respectively in the elderly and the adults.

COMPARATIVE TOXICITY OF DIAMORPHINE, MORPHINE, AND METHADONE

Abstract Diamorphine (heroin) has been compared with morphine and methadone during the first 90 minutes of its action after intramuscular injection. In equianalgesic doses it was more sedative than morphine and much more so than methadone but there was little difference in the ability of individual drugs to relieve apprehension or cause euphoria. All produced dizziness but diamorphine was less emetic than morphine. A separate study compared the drugs over a 4-hour period and demonstrated the earlier onset and shorter duration of action of diamorphine and pethidine as compared with morphine and methadone.

Allergy, plasma IgE level and anaphylactoid response: a hypothesis

Any simple test predictive of immediate hypersensitivity‐like (anaphylactoid) response to anaesthetic agents would be clinically useful. Possession of the traits of allergy or atopy, and of raised plasma IgE levels, all easily established, have previously been reported as predisposing factors. The usefulness of such observations has been limited by the fact that many reactions are not immune and do not involve IgE antibodies. This hypothesis suggests how IgE levels may be widely predictive of other reaction mechanisms and partially explains some of the divergent views on the mechanisms of anaphylactoid response which occur in the literature.

The effects of thiopentone and propofol on delayed hypersensitivity reactions

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 2.5mg 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.

Quantification of train‐of‐four responses during recovery of block from non‐depolarising muscle relaxants

Train‐of‐four (TOF) responses were assessed in 70 patients (seven groups of ten patients each) during recovery of neuromuscular block from atracurium (226 or 452 μg/kg), vecuronium (40 or 80 μg/kg), pancuronium (60 or 120 μg/kg) and tubocurarine (450 μg/kg) in order to quantify the height of T1 (first response in the TOF sequence) at which T2, T3 and T4 (2nd, 3rd and 4th response in TOF sequence) reappear. Patients were anaesthetised with thiopentone, nitrous oxide in oxygen and fentanyl. There were small but significant differences between relaxants. The clinically useful parameter, i.e. the 4th response in the TOF sequence, appeared at approximately 30% height of the first response (T1) rather than at 25% as generally believed. It is suggested that the third response in the TOF sequence, which reappeared at an average height of T1 of about 25%, be used for administration of further supplements of muscle relaxants since abdominal muscle relaxation becomes inadequate at this stage.