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Biomedical subjects

R S Clarke

Publications and source records attributed to R S Clarke.

At least 19 recordsLinked to original sources
PubMed1992

Synergistic interaction between midazolam and propofol.

We gave either midazolam or propofol for induction of anaesthesia to 140 ASA I or II female patients (18-60 yr). ED50 values were obtained by probit analysis for three clinical end-points: loss of response to command; loss of eyelash reflex; failure to respond to application of an anaesthetic face mask delivering 1% isoflurane. Propofol ED50 values (95% confidence intervals) were 1.25 (0.99-1.48) mg kg-1, 1.61 (1.29-1.94) mg kg-1 and 1.51 (1.20-1.82) mg kg-1, respectively. ED50 values for midazolam were 0.26 (0.20-0.37) mg kg-1, 0.29 (0.23-0.47) mg kg-1 and 0.25 (0.20-0.32) mg kg-1, respectively. An additional 92 similar patients received one of nine dose combinations of midazolam and propofol for induction of anaesthesia, propofol being administered 2 min after midazolam. Success of induction was based on the clinical end-point of loss of response to command. Administration of 25% of the ED50 of midazolam followed by 50% of the ED50 of propofol resulted in loss of response to command in 50% of patients, while 50% of the ED50 of midazolam, followed by 25% of the ED50 of propofol had the same effect. A probit regression model specifying a synergistic interaction between midazolam and propofol fitted the data significantly better than a model specifying no interaction.

Adolescent↗
PubMed1992

Comparison of intubating conditions after administration of Org 9246 (rocuronium) and suxamethonium.

We have assessed intubating conditions after administration of Org 9426 (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1 in similar groups of patients. The influence of prior suxamethonium administration on the potency of Org 9426 was studied also by constructing a dose-response curve. Intubating conditions after Org 9426 were found to be clinically acceptable (good or excellent) in 95% of patients at 60 s and in all patients at 90 s and in all patients at both times after suxamethonium. The average time for the onset of block following Org 9426 at this dose was 89 s (which is shorter than with any of the currently available non-depolarizing neuromuscular blocking drugs); the duration of clinical relaxation (25% recovery of twitch height) 30 min. Prior administration of suxamethonium did not appear to influence the potency of Org 9426.

Adolescent↗
PubMed1992

Clinical evaluation of doxacurium chloride.

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.

Adult↗
PubMed1992

The influence of particle size on the bioavailability of inhaled temazepam.

1. Temazepam was administered by aerosol using a standard protocol to healthy volunteers. Two studies are reported in which different dosage formulations were used: a) 30 mg of the 5 mu diameter particle (n = 6); b) 10 mg of the 2 mu diameter particle (n = 6). 2. An open crossover design was followed in each study. On one occasion in both studies subjects used a gargling procedure to remove drug which had been deposited in the mouth and oropharynx. 3. Serial venous blood samples were drawn for a period of 24 h. The mean total AUC of the 5 mu preparation was significantly reduced by gargling (3153 ng ml-1 h to 1066 ng ml-1 h) (F = 0.32). Gargling also had a significant effect on the mean AUC(0-1 h). 4. In contrast gargling had no significant effect on the mean AUC associated with the smaller diameter particle preparation (630 ng ml-1 h) vs 397 ng ml-1 h (F = 0.74). 5. These findings also indicate that temazepam deposition in the pulmonary tree is enhanced by the use of a 2 mu rather than a 5 mu diameter particle. However, the plasma drug concentrations achieved are unlikely to produce a sufficiently marked sedative effect for endoscopic investigations such as gastroscopy.

Administration, Inhalation↗
PubMed1992

Onset and duration of action of vecuronium in the elderly: comparison with adults.

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.

Adult↗
PubMed1991

Arterial washin of halothane and isoflurane in young and elderly adult patients.

We have studied the effect of age on washin of isoflurane and halothane by comparing end-tidal (PE') and arterial (Pa) partial pressures of the agents in young (18-32 yr) and elderly (63-82 yr) healthy patients for 20 min after introduction of the agents, before surgery. PE' was measured by infra-red analysis and Pa by gas chromatography. Washin of isoflurane occurred at the same rate in the young and elderly, with no significant difference between young and elderly in PE' or Pa as proportions of the inspired partial pressure (PI). After 20 min of isoflurane administration, mean Pa/PI in the young was 0.57 (95% confidence limit (CL) 0.53-0.62) and 0.55 in the elderly (95% CL 0.51-0.59). Washin of halothane was slower in the elderly than in the young, with Pa/PI significantly less in the elderly from 10 min after introduction of halothane. The difference between age groups, however, was small: mean Pa/PI after 20 min of halothane administration 0.45 (95% CL 0.41-0.49) in the young and 0.38 (95% CL 0.35-0.41) in the elderly. Washin of isoflurane was significantly faster than that of halothane in both young and elderly subjects. For isoflurane, the PE'-Pa gradient was small relative to Pa and did not differ significantly between young and elderly. For halothane, PE'-Pa in the young did not differ significantly from that for isoflurane. In the elderly, PE'-Pa for halothane was significantly greater than in the young and than PE'-Pa for isoflurane.

Adolescent↗
PubMed1991

Pathogenesis of suxamethonium-induced muscle damage in the biventer cervicis muscle in the chick.

Muscle damage induced by suxamethonium, and the influence of halothane on it, has been examined by measuring the efflux of creatine kinase (CK) in the biventer cervicis muscle of the chick. Whereas halothane and suxamethonium alone did not increase the enzyme efflux significantly, the combination of the two was associated with significant increase in the concentration of CK in the bathing medium by 59-157%. The increase in CK was prevented by adding chlorpromazine 100 mumol litre-1 to the medium, suggesting the involvement of phospholipases in the pathogenesis of suxamethonium-induced muscle damage.

Animals↗
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

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↗
PubMed1979

Minaxolone: a new water-soluble steroid anaesthetic.

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.

Anesthesia, Intravenous↗
PubMed1979

Effect of preanaesthetic medication on etomidate.

The effects of diazepam and pethidine, when given as preanaesthetic medication, on the induction of anaesthesia and the postanaesthetic sequelae following etomidate were studied in women undergoing minor gynaecological procedures. Pain on injection was present in all the groups. However, the frequency was significantly less with the polyethylene glycol and propylene glycol formulations of the drug compared with the aqueous solution. A fast injection and pethidine premedication decreased the frequency also. The high frequency of excitatory phenomena in unpremedicated patients was decreased significantly by premedication with diazepam and pethidine, especially the latter. Respiratory and cardiovascular effects of the drug were not major problems. The frequency of emetic sequelae was high. Recovery was rapid even in the groups receiving sedative premedication.

Adolescent↗
PubMed1979

Venous sequelae following etomidate.

Five hundred patients receiving one of three different formulations of etomidate were observed on the 2nd and 3rd days after operation for possible venous sequelae. The total frequency of sequelae was 8% or more, the greatest being with the propylene glycol formulation (23%). Formulation of the drug and total dose employed were the most important factors influencing venous sequelae, which were not related to pain on injection.

Adolescent↗
PubMed1979

The influence of dosage and premedication on induction of anesthesia with minaxolone.

Minaxolone, a new steroid induction agent, was administered to unpremedicated patients at three dose levels and at 0.5 mg . kg-1 to patients receiving three different premedicant regimes. The main side effects observed at induction were involuntary muscle movements but hypertonus and tremor were also seen. Respiratory complications consisted mainly of hiccough. Over the range of doses studied only the latter complication appeared to be dose-related. Premedication with diazepam and especially opiate combinations reduced the frequency and severity of excitatory effects and respiratory upset and increased the proportion of acceptable anesthesia. Marked respiratory depression and hypotension of greater than 20 mm Hg were rare even after opiate premedication.

Adult↗
PubMed1978

Frequency of atopy and allergy in an anaesthetic patient population.

Ten thousand patients presenting for anaesthesia in the British Isles were questioned about a possible history of atopic or allergic disorders. The overall percentage frequency of atopy was 8.5, comprising eczema 2.4, hay fever 3.8 and asthma 3.5. The frequency of allergies was 13.5, of which penicillin was the most common (6.2). Females had a significantly greater frequency of atopy or allergy than males. Patients with a history of atopic disorders had a higher frequency of allergies than the non-atopic group (36.2% compared with 11.4%) and vice versa.

Adolescent↗