Biomedical subjects

R S Clarke

Publications and source records attributed to R S Clarke.

At least 37 records · Page 2Linked to original sources

PubMed1991

Psychomotor and clinical assessment of flumazenil as an antagonist of midazolam.

The benzodiazepine antagonist flumazenil (0.01 mg/kg) has been compared with doxapram (1 mg/kg) and saline for the reversal of anaesthesia with intravenous midazolam, alfentanil, nitrous oxide in oxygen and isoflurane. The completeness of reversal was assessed by means of a four-choice reaction time test, 1 and 3 h following the antagonist. In addition, the level of sedation was graded using a five-point scale. Psychomotor testing showed that 60 min after administration of the antagonist, there were marked increases in reaction times (P less than 0.05) both in the control and doxapram groups, but not in those receiving flumazenil. At 180 min, however, reaction times in all groups had returned to baseline values. In contrast, there was a significant difference in the sedation scores between the saline and flumazenil groups throughout the study period (P less than 0.05). During the 4 h following midazolam, there was no evidence of re-sedation in any of the groups despite the relatively high midazolam dosage.

Adolescent↗

PubMed1991

Neuromuscular effects of pipecuronium bromide.

The neuromuscular effects of pipecuronium bromide have been evaluated in 90 adult patients anaesthetized with thiopentone, nitrous oxide in oxygen and intravenous fentanyl with or without halothane. Eighty patients received pipecuronium 45 micrograms kg-1 and the remaining ten 70 micrograms kg-1. A separate group of 10 patients received pancuronium in a dose of 60 micrograms kg-1 (equipotent to pipecuronium 45 micrograms kg-1). Neuromuscular block was measured using a single-twitch or train-of-four mode of stimulation. The time to onset of maximum block with pipecuronium 45 micrograms kg-1 varied between 3.5 and 5.7 min depending on the mode of stimulation and the anaesthetic technique used. The time to 25% recovery of this dose varied between 41 and 54 min. The recovery index (time from 25 to 75% recovery) averaged 29 min. These values were generally similar in the group receiving pancuronium 60 micrograms kg-1. The time to onset of complete block with 70 micrograms kg-1 of pipecuronium averaged 2.5 min and the duration to 25% recovery 95 min. There were no significant changes in heart rate and arterial pressure with the use of pipecuronium. The results show pipecuronium to be a drug resembling pancuronium in its neuromuscular effects when used in equipotent doses.

Adult↗

PubMed1990

End-tidal concentrations of halothane and isoflurane during induction of anaesthesia in young and elderly patients.

Twenty-two young (18-32 yr) and 22 healthy elderly (60-80 yr) patients received either halothane or isoflurane for maintenance of anaesthesia during controlled ventilation. End-tidal fractional concentrations (FE) of the agents were measured for 20 min after their introduction into inspired gas and the increase in end-tidal concentrations of the two agents was compared during induction of anaesthesia using the ratios of FE to the inspired fraction (FI). FE:FI ratios for isoflurane were higher than those for halothane in both young and elderly patients, confirming that equilibration of end-tidal with inspired concentration occurs more rapidly with isoflurane than with halothane in both age groups. FE:FI ratios for isoflurane became significantly lower in the elderly than in the young after 15 min administration of isoflurane. This suggests slower induction of anaesthesia in the elderly if equipotent concentrations of isoflurane are used; the clinical significance of this difference is probably small. Mean FE:FI ratios for halothane in elderly patients were similar to those in the young throughout induction of anaesthesia.

Adolescent↗

PubMed1990

Effect of flumazenil on midazolam-induced amnesia.

We have studied the effect of i.v. flumazenil 0.01 mg kg-1 on the amnesia and sedation caused by midazolam 2 mg and 5 mg i.v. in volunteers in order to determine the relationship between the actions of the antagonist on these two effects. Midazolam caused dose-dependent central neural depression as assessed by critical flicker fusion frequency, and dose-dependent amnesia for word cards. In subjects given flumazenil 5 min after administration of midazolam, fusion frequency readings and memory were restored to levels comparable to those before midazolam administration. These two effects of flumazenil were similar in time course and extent, suggesting that they share the same mechanism of action. Flumazenil given alone had no effect on memory. The study has demonstrated anterograde amnesia following benzodiazepine administration and antagonism by flumazenil. There was neither retrograde amnesia nor retrograde antagonism of amnesia.

Adult↗

PubMed1989

Analgesia after hip replacement surgery: comparison of nalbuphine with morphine.

Two groups of 40 patients undergoing hip replacement received either nalbuphine 0.3 mg kg-1 or morphine 0.15 mg kg-1 i.m. on up to three occasions: 1 h before operation, as soon as requested after operation, and 3 h subsequently if required. Pain intensity was assessed by the patient as severe, moderate or none, and pain relief by a "blind" nurse observer as slight, moderate or complete. Assessments of pain and sedation were carried out at 30-min intervals for 2 h and at 1-h intervals thereafter for up to 6 h. Six patients who received nalbuphine and eight who received morphine before operation required no postoperative analgesia. Ten patients in the nalbuphine group and two in the morphine group failed to obtain adequate pain relief (P less than 0.05) and were given i.v. morphine.

Analgesia↗

PubMed1989

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 micrograms/kg for atracurium, 43.1 and 39.6 micrograms/kg for vecuronium and 65.9 and 60 micrograms/kg for pancuronium respectively in the elderly and the adults.

Age Factors↗

PubMed1989

Propofol.

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Anesthetics↗

PubMed1988

Comparison of sufentanil-oxygen and fentanyl-oxygen anaesthesia for coronary artery bypass grafting.

Haemodynamic variables were compared in 40 adults undergoing coronary artery bypass grafting during anaesthesia induced with either sufentanil 5 micrograms kg-1 or fentanyl 25 micrograms kg-1 in combination with pancuronium 0.1 mg kg-1. Further doses of sufentanil 2.5 micrograms kg-1 or fentanyl 12.5 micrograms kg-1 were given before skin incision and again before sternotomy. All patients were receiving beta-adrenoceptor blocking therapy. Satisfactory induction of anaesthesia was produced with both drugs and opioid supplementation prevented any marked haemodynamic response to skin incision and to sternotomy. Following induction of anaesthesia, sufentanil produced the greater decrease in mean arterial pressure and left ventricular stroke work index which continued throughout the study. This suggests that, in the doses used in this study, sufentanil is preferable to fentanyl in patients with coronary artery disease.

Anesthesia, General↗

PubMed1988

Factors that influence cutaneous reactions following administration of thiopentone and atracurium.

Atracurium was administered by a variety of techniques to determine whether these influence the onset or duration of muscular relaxation, and the frequency of cutaneous reactions, after a standard induction dose of thiopentone. One-hundred-and-fifty patients were allocated randomly to receive the drug by one of five methods: into a fast-flowing crystalloid infusion in the antecubital fossa; into a winged needle in the antecubital fossa with flushing after the thiopentone; into a winged needle in the antecubital fossa without flushing; into a winged needle in the dorsum of the hand without flushing. The above groups received atracurium freshly removed from the refrigerator whereas the fifth group were given atracurium which had been maintained at room temperature for at least 2 weeks. The frequency of cutaneous reactions was between 60 and 70% overall and there were no significant differences either in this or in the onset or duration of action between the groups. A further 25 patients with a history of drug allergy were also investigated by the first method and showed no significant differences in response, but 25 patients aged over 70 years had a significantly lower frequency of cutaneous reactions with a higher frequency of hypotension than the other groups.

Adult↗

PubMed1988

Administration of vecuronium, atracurium and pancuronium in divided doses: effect on onset and duration of action.

The time to onset of neuromuscular block (as assessed by single twitch stimulation at 0.1 Hz) and the duration to 25% recovery of twitch height were measured after administration of vecuronium 0.1 mg kg-1, atracurium 0.5 mg kg-1 or pancuronium 0.1 mg kg-1, administered either as a single bolus or in divided doses, 10% being administered 4 min prior to the remaining 90%. The patients were anaesthetized with thiopentone, nitrous oxide in oxygen and i.v. fentanyl. There was no significant difference between the single- and divided-dose groups, either in the onset times (2.8 and 2.9 min for vecuronium, 2.7 and 2.4 min for atracurium and 3.3 min each for pancuronium for single- and divided-dose groups, respectively) or the duration to 25% recovery of twitch height (35 and 29 min for vecuronium, 45 and 39 min for atracurium and 87 and 93 min for pancuronium for single- and divided-dose groups, respectively).

Adult↗

PubMed1987

Haemodynamic effects of vecuronium, pancuronium and atracurium in patients with coronary artery disease.

Thirty patients with ischaemic heart disease scheduled for coronary artery bypass grafting were randomly allocated to three equal groups. Following morphine, hyoscine and pentobarbitone premedication, anaesthesia was induced with diazepam 0.3 mg kg-1. Five minutes later neuromuscular blockade was induced with pancuronium 0.1 mg kg-1, vecuronium 0.1 mg-1 or atracurium 0.5 mg kg-1, followed after 6 min by fentanyl 25 micrograms kg-1. Pancuronium and atracurium caused significant increases in heart rate, while vecuronium induced little change. Systemic vascular resistance decreased significantly from 1515 dyn s cm-5 to 1200 dyn s cm-5 following atracurium. Cardiac index was increased transiently in the atracurium group, but a more sustained increase was observed following pancuronium. Nine patients in the atracurium group showed skin flushing and one developed skin weals.

Atracurium↗

PubMed1987

Comparison of nalbuphine, pethidine and placebo as premedication for minor gynaecological surgery.

In a randomized double-blind placebo-controlled trial involving 80 patients nalbuphine 10 mg and 20 mg were compared with pethidine 100 mg and a placebo given i.m. at least 90 min before minor gynaecological surgery. Nalbuphine proved a suitable alternative to pethidine, producing beneficial sedation which was maximum at 60 min after injection. Both nalbuphine and pethidine reduced the excitatory sequelae of methohexitone induction. Increasing the dose of nalbuphine from 10 mg to 20 mg produced no significant additional sedation or intraoperative benefit. Short-lived pain at the injection site was a feature of the use of nalbuphine in either dose. The main disadvantage of nalbuphine was nausea and vomiting of delayed onset, the frequency of which was similar after either dose.

Adult↗

PubMed1987

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.

Adult↗

PubMed1987

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 micrograms/kg), vecuronium (40 or 80 micrograms/kg), pancuronium (60 or 120 micrograms/kg) and tubocurarine (450 micrograms/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.

Adult↗

PubMed1986

Halothane and the liver.

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Chemical and Drug Induced Liver Injury↗

PubMed1986

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.

Adult↗

PubMed1986

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.

Adolescent↗

PubMed1986

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.

Adult↗