Showing papers in "BJA: British Journal of Anaesthesia in 1983"

The laryngeal mask—a new concept in airway management

Abstract: A new type of airway is described, which may be used as an alternative to either the endotracheal tube or the face-mask with either spontaneous or positive pressure ventilation. The results of a pilot study involving 23 patients are presented and the possible merits and disadvantages of the device are discussed, bearing in mind that the study is of a preliminary nature.

Plasma catecholamine responses to tracheal intubation

Abstract: Plasma adrenaline and noradrenaline concentrations were measured in 24 patients during the induction of anaesthesia and the subsequent tracheal intubation. The patients received either suxamethonium 1 mg kg−1 or pancuronium 0.1 mg kg−1 to facilitate tracheal intubation. Mean arterial pressure (MAP) increased in both groups following laryngoscopy and tracheal intubation and there were concomitant increases in the plasma catecholamine concentrations, the changes being more marked in the suxamethonium group. There was a significant correlation between MAP and plasma catecholamine concentrations in the suxamethonium group. Measurement of plasma catecholamine concentrations in samples obtained simultaneously from central venous, peripheral venous and arterial sites were in broad agreement; the greatest changes occurred in central venous samples.

Role of extradural and of general anaesthesia in fibrinolysis and coagulation after total hip replacement

Abstract: Thirty patients undergoing total hip replacement were randomly allocated to one of two groups. One group (n = 14) received extradural anaesthesia with 0.5% bupivacaine with adrenaline continued into the postoperative period (24 h) for pain relief. The other group (n— 16) received general anaesthesia with controlled ventilation, using nitrous oxide in oxygen and fentanyl i.v. Following surgery they received a narcotic analgesic i.m. on demand. Analysis of fibrinolysis inhibition activity and plasminogen activators revealed a significantly better fibrinolytic function in patients given continuous extradural anaesthesia than in those who received general anaesthesia followed by narcotics in the period after operation. Furthermore, the capacity for activation of factor VIII was significantly lower after operation in the former group.

Ketamine disposition in children and adults

Abstract: The pharmacokinetics of ketamine 2 mg kg−1 i.v. and 6 mg kg−1 i.m. were investigated in nine children undergoing minor surgery. After either route of administration plasma ketamine concentrations were similar to those found in adult patients receiving the same dose, except at later times after i.v. injection, when concentrations were smaller in children. Also, absorption after i.m. injection appeared to be more rapid in children. Substantially larger concentrations of the metabolite norketamine were found in children than in adults after the injection of ketamine. Concentrations of ketamine upon awakening in a further group of nine children receiving ketamine as the sole anaesthetic showed large inter-individual variation. The concentrations were greater than those previously reported for adults. The greater dose requirements in children, compared with adults, are probably attributable to pharmacodynamic rather than pharmacokinetic factors.

Difficult laryngoscopy—the “anterior” larynx and the atlanto-occipital gap

Abstract: The atlanto—occipital distance is the major factor which limits extension of the head on the neck. It varies widely in the population at large. When the posterior tubercle of the atlas is already in contact with the occiput in the neutral position, attempts to extend the head result in anterior bowing of the cervical spine, and forward displacement of the larynx. This may be a cause of difficult laryngoscopy.

Differential sensitivity of a and c nerve fibres to long-acting amide local anaesthetics

Abstract: The differential sensitivities of A β, A δ and C fibres of rat vagus nerve to bupivacaine, etidocaine and AL-381 were studied in vitro In A β fibres, at 35—37°C, 50μmole litre−1of the drugs had similar effect on the action potential amplitude, while at greater concentrations (100 and 200 μmole litre−1) the greatest mean depression of amplitude was seen with etidocaine (ns) AL-381 had the most marked effect on the A δ potentials, and it appeared that it was about twice as potent as the others in blocking these fibres Etidocaine 100 μmole litre−1 was more depressant than the same dose of bupivacaine The C fibres were blocked most rapidly by AL-381, while etidocaine had the least effect

GASTRIC CONTENTS AT INDUCTION OF ANAESTHESIA Is a 4-hour fast necessary?

Abstract: The study was undertaken to ascertain whether a light standard breakfast would influence the volume and median pH of gastric contents. Comparisons were obtained between a group of patients (n = 22) fasted overnight and a group (n = 23) allowed a light breakfast. There were no significant differences between the groups in respect of the volume of gastric contents aspirated, the median pH of the gastric contents or the number of patients with a pH of less than 3.0 unit.

Actions of general anaesthetics on synaptic transmission in the cns

Abstract: This article reviews the actions of general anaesthetics on synapses in the mammalian central nervous system. It is shown that during general anaesthesia, anaesthetics act primarily on the chemical transmission process itself and do not affect the conduction of impulses in nerve axons or change the electrical excitability of neurones. Virtually all general anaesthetics depress excitatory synaptic transmission at concentrations required for surgical anaesthesia but some, notably the barbiturates, also increase the intensity of inhibitory synaptic transmission. Detailed analysis has found that small concentrations of barbiturates increase the amount of inhibitory transmitter released but decrease the amount of excitatory transmitter released. In addition to these effects on the neurosecretory process, anaesthetics directly affect the sensitivity of the postsynaptic receptors to transmitter substances, although the effects vary between anaesthetics and receptors. It is concluded that general anaesthesia results from a summation of a number of effects which together tend to depress the excitability of the CNS as a whole.

Pharmacokinetics of atracurium in acute hepatic failure (with acute renal failure)

Abstract: The pharmacokinetic profile of atracurium was examined in six patients with acute hepatic and renal failure and compared with that in six normal patients after an i.v. bolus (mean dose 0.7 mg kg-1). The plasma concentrations were measured by high pressure liquid chromatography and the data fitted to a two-compartment pharmacokinetic model. The results from the two groups were not significantly different, giving a mean plasma elimination half-life of 22 min in patients with severe hepatic and renal failure and a mean of 21 min in the normal group.

Haemodynamic effects of infusions of diisopropyl phenol (ici 35 868) during nitrous oxide anaesthesia in man

Abstract: The haemodynamic effects of diisopropyl phenol in cremophor EL at infusion rates of 50–55 and 100 μg kg −1 min −1 in combination with inhalation of 67% nitrous oxide have been studied during spontaneous and controlled ventilation in patients premedicated with morphine and atropine. Under all the conditions studied diisopropyl phenol supplementation of nitrous oxide anaesthesia was associated with a decreased arterial pressure (−20% to −31%) compared with the awake patient, related to a decrease in cardiac output (− 27% to 29%) and an increase in systemic vascular resistance (+ 8% to + 30%) during surgery, but to a decrease in cardiac output (− 19%) and a decrease in systemic vascular resistance (− 17%) during anaesthesia without surgery. Doubling the infusion rate of diisopropyl phenol caused no significant haemodynamic changes during either spontaneous or controlled ventilation. The haemodynamic manifestations of sympathetic nerve activity in response to laryngoscopy and intubation were poorly suppressed by diisopropyl phenol

A randomized comparison of midazolam and diazepam for sedation in upper gastrointestinal endoscopy

Abstract: One hundred and eighty-five patients were allocated at random to receive pethidine with diazepam (in an emulsion), or pethidine with midazolam i.v. as sedation for upper gastrointestinal endpscopy. Sedation and conditions for examination were comparable and satisfactory in both groups. Midazolam produced more amnmia (P=

Pharmacokinetics, pharmacodynamics and dose-response relationships of atracurium administered i.v.

Abstract: A complete pharmacokinetic and pharmacodynamic model for the novel non-depolarizing neuromuscular blocking agent atracurium is proposed, which accounts for tetanic and single twitch responses after any i.v. administration of this drug. The means and standard deviations of the kinetic parameters are given from studies in 19 patients, and the pharmacodynamic parameters from eight patients in whom plasma drug concentrations and dynamic responses were recorded concurrently. Similarities in dynamic parameters are noted for atracurium administered to cats, and for other non-depolarizing neuromuscular blocking agents in man. The use of this approach allows clinicians to understand and rationalize all the features associated with the time-course of blockade after varied i.v. regimens, but more importantly, allows them to design any required neuromuscular blocking profile which will also result in minimal drug loading of their patients.

Comparison of midazolam and diazepam in doses of comparable potency during gastroscopy

Abstract: The water soluble bcnzodiazepine midazolam was compared with diazepam, in doses of 0.07 mg kg−1 and 0.l5 mg kg−1 respectively, administered i.v. to 100 patients undergoing gastroscopy. The degree of sedation, ease of endoscopy and recovery were comparable in the two groups. The effects of both drugs on arterial pressure were similar. Compared with diazepam, midazolam had a faster onset of effect, caused virtually no pain on injection, and provided a greater degree of amnesia.

Pharmacokinetic evaluation of ICI 35 868 in man. Single induction doses with different rates of injection.

Abstract: Blood concentrations of ICI 35 868 have been measured in patients following a single bolus dose of 2 mg kg−1. Three different rates of injection of the anaesthetic agent (3–5s, 20s and 40 or 50s) were examined. Pharmacokinetic indices, derived from blood concentrations of ICI 35 868, were independent of the speed of injection. The blood profiles could be described by a two-compartment open model with a mean a-phase half-life of 2.5min and a mean β-phase half-life of 54.5min. The mean total body clearance was 3454 ml min−1. Similar data were obtained from a 4-mgkg−1 dose. The mean recovery time (4.4 min) and concentration of ICI 35 868 at awakening (1.05 ug ml−1) were also independent of the rate of injection. Using the derived pharmacokinetic model, predictions of drug concentrations have been made for repeated bolus doses, or infusions, of ICI 35 868

Atracurium: conception and inception.

Abstract: The rationale underlying the design of atracurium, a bis-quaternary ammonium neuromuscular blocking agent which incorporates the Hofmann elimination as a novel biodegradation pathway, is described. Destruction in vivo, of the bis-quaternary structure essential for neuromuscular blocking activity, by the combination of Hofmann elimination and a parallel ester hydrolysis leads to innocuous breakdown products that are without neuromuscular or cardiovascular effects and to a time-course of action which is unaffected by the level of plasma esterase activity, renal or hepatic function.

Enflurane anaesthesia causes graded changes in the brainstem and early cortical auditory evoked response in man

Abstract: The effect of increasing end-tidal enflurane concentration on the auditory evoked response was studied in six patients. After a standard induction, anaesthesia was maintained with 70‰ nitrous oxide in oxygen and the end-tidal enflurane concentration was increased gradually from 0 to 1 ‰ over a period of 30 min. The averaged auditory evoked response was derived from the electroencephalogram and measurements were made of the latencies and amplitudes of waves I, HI, V, Pa and Nb within the auditory evoked response. The latencies of all waves and the interpeak latencies I to V and HI to V showed significant linear increases and the amplitudes of Pa and Nb showed significant linear decreases with increasing end-tidal enflurane concentration. These results could not be explained by changes in deep body temperature or end-tidal carbon dioxide concentration. The study demonstrated a dose-related direct effect of enflurane on the brainstem and early cortical components of the auditory evoked response.

Ro 15–1788 antagonizes the effects of diazepam in man without affecting its bioavailability

Abstract: In 8 double-blind, placebo-controlled three-way cross over study, the efficacy of Ro 15–1788 200 mg, a new benzodiazepine antagonist, in blocking the amnesic, cognitive, psychomotor and subjective effects of diazepam 20 mg, was investigated in a group of six healthy male volunteers. The amnesic effects of diazepam were markedly attenuated by the combined administration of Ro 15–1788. The psychomotor and subjective effects of diazepam by mouth were most pronounced 2.5 h after administration. Concurrent oral administration of Ro 15–1788 completely prevented these effects at 2.5 h. Plasma diazepam concentrations observed after administration of the combination of diazepam and the antagonist did not differ from those observed following diazepam alone.

In vitro quantitation of benzodiazepine lipophilicity: relation to in vivo distribution

Abstract: In vitro lipophilicity of a series of benzodiazepines was evaluated by octanol: buffer partition ratio at physiological pH, and by retention time on a reverse-phase high-pressure liquid chromatographic (HPLC) system with a neutral-pH mobile phase. Both approaches ranked diazepam as highly lipophilic, but overall the two indices were poorly correlated (r = 0.23). For seven of the benzodiazepines, the in vivo volume of distribution (Vd) was determined in pharmacokinetic studies. After correlation for individual values of protein binding, Vd for unbound drug was significantly correlated with octanol: buffer partition ratio (r = 0.74), and to a greater extent with HPLC retention (r = 0.81). Thus, lipid solubility at least partly determines the extent of benzodiazepine distribution in vivo, which in turn is a major determinant of the duration of clinical action after single doses.

Randomized controlled trial of physiotherapy for postoperative pulmonary complications

Abstract: A prospective randomized controlled trial was conducted in patients undergoing elective cholecystectomy to assess the value of routine chest physiotherapy. One hundred and two patients entered the study: 47 patients developed no pulmonary complications, 29 had pulmonary atelectasis and a further 26 developed chest infection. The pattern of changes in anerial oxygen tension in the period after operation supponed the Hiniral allocation of the patients. Of 51 patients not receiving physiotherapy, 11 developed atelectasis and 19 chest infection. Of 51 treated patients, 18 developed atelectasis and seven chest infection. Routine prophylactic postoperative chest physiotherapy decreased significantly the frequency of chest infection (P

Effects of low intermittent concentrations of nitrous oxide on the developing rat fetus

Abstract: Five groups of 12 gravid female rats were exposed, during their entire gestation, intermittently for 6 h a day, 5 days per week, to 0.5% (5000 p.p.m.), 0.1% (1000 p.p.m.), 0.05% (500p.p.m.) and 0.025% (250p.p.m.) nitrous oxide-air mixtures (v/v), respectively. After killing the gravid rats on the 19th day of their pregnancies the numbers of corpora lutea of pregnancy were counted. Each uterus was examined for placentation sites and embryonic remnants and a detailed examination of the fetuses was undertaken. A significant reduction in mean litter size occurred only in the group exposed to 0.5% nitrous oxide in air (v/v). The mean litter sizes of the control and other exposed groups were comparable. No signs of fetal resorption or skeletal malformation were found in any group. The threshold of pollution for reduction in litter size has been shown in this study to lie between 0.1% and 0.5% nitrous oxide in air (v/v). A previous study on continuous exposure reported the threshold pollution to lie between 0.05% and 0.1% nitrous oxide in air (v/v). This investigation confirms that intermittent exposure to nitrous oxide-air mixtures increases the threshold for reproductive effects in rats.

Depression of nociceptive sympathetic reflexes by the intrathecal administration of midazolam

Abstract: The effect of the intrathecal administration of midazolam 0.5–1.0 mg in 1–2 ml of physiological saline solution, has been observed on responses evoked in renal sympathetic nerves by supramaximal electrical stimulation of radial and tibial nerves. In artificially ventilated dogs anaesthetized with a-chloralose, the intrathecal administration of midazolam caused a marked depression of reflexes evoked from the tibial nerve but had no effect on either spontaneous sympathetic activity or reflexes evoked by radial nerve stimulation. Neither the small amount (1–2 ulitre) of benzyl alcohol, present as a preservative (administered intrathecally), nor midazolam 1 mg kg−1 i.v. caused any significant depression of the evoked somato-sympathetic reflexes. The effects of intrathecal midazolam were reversed by the benzodiazepine antagonists Ro 15–1788 1 mg kg−1 i.v. and Ro 15–3505 1–2 mg kg−1 i.v. but not by naloxone 2 mg i.v. It is suggested that the antinociceptive effect of locally applied midazolam could be the result of a non-opioid GABA-mediated system which may have implications in the management of pain.

Effects of intrathecal morphine, injectied with bupivacaine, on pain after orthopaedic surgery

Abstract: Morphine hydrochloride 0.4 mg was administered with isobaric 0.5% bupivacaine intrathecally for orthopaedic surgery and produced good analgesia for about 24 h after operation in both elderly (60–80yr) and middle-aged patients (30–50yr). Morphine 0.2 mg (older patients only) was not as effective in preventing pain after operation, but even this dose postponed the requirement for analgesia. Morphine did not change the quality of spinal anaesthesia. In the older groups the capillary PCO2 was increased in two patients receiving morphine 0.2 mg and in one patient receiving 0.4 mg. Severe delayed respiratory depression was not noted. Urinary retention and minor voiding difficulties were the most disturbing side-effects. This complication did not appear to be dose-dependent, and also occurred in patients not receiving morphine.

Clinical comparison of atracurium and vecuronium (org nc 45)

Abstract: The potency, histamine releasing ability, cardiovascular effects, and pharmacodynamics of vecuronium and atracurium were investigated in 64 healthy patients following administration i.v. Cumulative dose-response curves showed vecuronium to be 4.4 times as potent as atracurium. Using the calculated EQ90 of each drug (43 g kg−1 for vecuronium and 188 fig kg−1 for atracurium), vecuronium had a significantly more rapid onset time and shorter duration of action than atracurium. When three times the ED90 doses were used (129 gkg−1 for vecuronium and 564 g kg−1 for atracurium), no statistically significant differences in the pharmacodynamics were seen between the two drugs, although vecuronium tended to be shorter-acting. There was no clinical evidence of histaminr release during the study. No clinically significant changes in arterial pressure or heart rate were seen after the injection of either drug, although vecuronium caused a statistically significant decrease in heart rate (≏5%) at 5 and 10 min after administration. Both drugs would appear to have certain advantages over existing non-depolarizing neuromuscular blocking drugs.

Pharmacokinetics of atracurium besylate in healthy patients (after a single i.v. bolus dose)

Abstract: The plasma decay of atracurium besylate was examined in two groups of six patients. Group I received atracurium 0.6 mg kg−1 and group II 0.3 mg kg−1 as a single bolus dose i.v. The plasma concentrations were measured by high performance liquid chromatography. An individual two-compartment pharmacokinetic model was used for interpretation. The results from the two groups were not significantly different, giving overall mean values of 2 min (±0.2 SEM) for the distribution half-life (Ttα), 19.9 min (±0.6) for the elimination half-hie (Ttβ), 5.5 ml min−1 kg−1 (±0.2) for total clearance (CI) and 157 mlkg−1 (±7) for total distribution volume (V ares).

Effects of chronic exposure to nitrous oxide on methionine synthase activity

Abstract: Hepatic methionine synthase activity has been determined in rats continuously exposed (24h day−1 and 7 day week−1) to concentrations of nitrous oxide ranging from 500 to 50000 p.p.m. for periods ranging from 24 h to 28 days. The inactivation of this enzyme was dependent upon both time and concentration of nitrous oxide exposure, but there was no statistical evidence that exposure continuing beyond 48 h increased the effect. However, the dose-response curve for 24 h was significantly different from the curve for pooled data from exposures lasting 2–28 days. These latter data indicated no significant effect with 450 p.p.m. and an ED 50 of 5400 p.p.m. Significant inhibition was detected at 1000 p. p.m. These results suggest that the limit of exposure of 25 p.p.m. recommended by the American National Institute of Occupational Safety & Health may be unduly restrictive.

Fat emulsion as a vechicle for diazepam. a study of 9492 patients

Abstract: Conventional preparations of diazepam for i.v. use contain solvents which cause pain on injection and thrombophlebitis in a high percentage of cases. However, diazepam can be dissolved with advantage in the oleaginous phase of an oil-in-water emulsion (Diazemuls). Diazemuls has been given to 9492 patients without serious side-effects. Following i.v. injection, 2435 patients were studied with respect to pain and clinical effect. Only 0.4 experienced pain. The intended clinical effect was recorded in 99% of the patients. I.m. injection of Diazemuls resulted in a significantly smaller frequency of pain in connection with the injection than did the injection of Valium (7% and 43% respectively). Pharmacokinetic studies have been made after i.v. and i.m. injection of Diazemuls and Valium. The distribution and elimination phases after i.v. injection were the same with both forms. Thus the drug probably quickly separates from the oil particles of the emulsion after injection. After i.m. administration, the plasma concentration shows a wide spread with both preparations. A brief survey of other substances tested in emulsion form is presented.

ANAESTHESIA FOR CAESAREAN SECTION A medical audit of junior anaesthetic staff practice

Abstract: This survey compared the safety of 261 healthy mothers of whom 170 received extradural and 91 general anaesthesia for CaeSarean section. Anaesthetics were conducted in routine hospital practice by six anaesthetic registrars. Failed intubation occurred in one patient, awareness was reported by 12 patients following general anaesthesia and two patients had abnormal reactions to drugs. In contrast, the numerous complications that arose with extradural anaesthesia were less serious and easier to manage. Hypotension occurred in 11 patients, inadequacy of analgesia in 25 patients and a period of unawareness in 16 patients following sedation after delivery. Extradural block for Caesarean section is thus seen as safer than general anaesthesia when performed by the same group of anaesthetic trainees on healthy mothers.

Effect of premedication on drug absorption and gastric emptying

Abstract: The rate of paracetamol absorption after oral administration was used as a model of drug absorption and as an indirect measure of the rate of gastric emptying in 37 patients awaiting elective general surgery after different premedications. After saline (control) and diazepam, paracetamol absorption was normal but after morphine or nefopam, absorption was delayed markedly, presumably as a result of delayed gastric emptying. After naloxone there was a small but insignificant delay.

Influence of high-dose alfentanil anaesthesia on the electroencephalogram: correlation with plasma concentrations.

Abstract: The influence of high-dose alfentanil-oxygen-air anaesthesia on the electroencephalogram was studied in 10 patients undergoing elective coronary artery surgery. Premedication was either lorazepam 5 mg orally (n = 5) or morphine 10 mg and hyoscine 0.4 mg i.m. (n = 5). Anaesthesia was induced with alfentanil 125 micrograms kg-1 h-1 and maintained by a continuous infusion at a rate of 0.25-0.5 mg kg-1. The EEG was recorded on the day before surgery, continuously from before induction of anaesthesia until the end of surgery and at hourly intervals after operation. Blood samples were withdrawn at intervals during and after surgery for measurement of plasma alfentanil concentrations. Anaesthesia was associated with large increases in delta activity and reduction in higher frequency components. There was less synchronization of the EEG than is observed with fentanyl or sufentanil. Spindle activity was prominent in 70% of patients. The changes in the EEG during recovery tended to occur abruptly and there was no obvious correlation between the EEG and plasma concentrations of alfentanil. There was a significant correlation between the total dose of alfentanil and the awake plasma concentration (r = 0.94; P less than 0.01). Plasma concentrations decreased exponentially after operation, with a mean half-life of 304 +/- 54 min.