Premedication with temazepam in minor surgery. The relationship between plasma concentration and clinical effect after a dose of 40 mg.

Fourteen patients received oral premedication of temazepam in soft gelatin capsules before minor surgery. The plasma concentrations of temazepam and its sedative, anxiolytic and amnesic effects were measured for 24 hours. Absorption was rapid and peak concentrations occurred 49 minutes after administration. Clinical effects were evident at 30 minutes and persisted for about 4 hours. The decline in plasma concentration was biexponential with a distribution half-life of 1.24 hours. The end of the distribution phase coincided approximately with the termination of its clinical effects. A relationship between plasma concentration and effect was observed; concentrations above 300 ng/ml produced measurable changes in tests of mental function. Patients had recovered fully from the effects of temazepam after 24 hours. This dose of temazepam is reliable and effective as premedication before surgery.

The relation between lorazepam-induced auditory amnesia and auditory evoked potentials.

We conducted a placebo-controlled double-blind investigation in 15 normal volunteers to study the time course of amnesia to auditory stimulation produced by lorazepam. We also studied the relationship between auditory amnesia and auditory evoked potentials to determine if long-latency auditory evoked potentials (LLAEPs) could be utilized as electrophysiologic predictors of memory. Amnesia was produced by administration of 0.05 mg/kg lorazepam intravenously. To separate the changes in LLAEPs due to generalized sedation from those associated with amnestic properties of a drug, a third group of subjects given 1.5 mg/kg secobarbital was included. Observed frequency and duration of amnesia to auditory stimulation after lorazepam was 58% and 3 hours, respectively (mean values), with marked diminuition of antirecall effect at 120 minutes. Administration of lorazepam increased the latency and decreased the amplitude of N1 and P3 components of LLAEPs. These changes appeared to be a result of generalized sedation rather than the amnestic properties of the drug. We failed to find a definite relationship between amnesia and changes in LLAEPs. We conclude that P3 component of LLAEPs cannot be utilized as an electrophysiologic predictor of amnesia in humans.

Clinical assessment of neuromuscular blockade produced by vecuronium using twitch, train of four, tetanus and post-tetanic twitch responses of the adductor pollicis muscle.

In the present investigation, the phenomenon of post-tetanic twitch potentiation (PTP) has been used to provide a sensitive index for neuromuscular blockade during an intense paralysis of the adductor pollicis muscle in man. We have also used and compared PTP assessment with that of twitch, train of four and tetanus in the same muscle and in the absence and presence of vecuronium (50 micrograms.kg-1). Vecuronium had a rapid onset of blockade (5-10s) and an intermediate duration of action (22-26 min). During the onset of blockade, the PTP response was still remaining (residual) whereas all the other mechanical responses disappeared within 2.5 min (Fig. 1b, c, d). Thus, the PTP values increased (upto 300% of control value of 18%, Fig. 1a) with increasing the intensity of neuromuscular blockade. The PTP value provided a better index for assessing the degree of neuromuscular blockade than did the twitch, train of four or the tetanus. However, during the onset of blockade, the PTP technique can also delay the onset of blockade, i.e. it has a decurarizing effect (Fig. 1b, c, d). During recovery of neuromuscular blockade, the PTP is actively involved in the enhancement of spontaneous recovery process, i.e. enhancement of de-curarization with repetitive stimulation of the ulnar nerve. In this respect, the PTP response recovers first, followed by the tetanus, train of four and the twitch responses. Thus the latter may be considered as a more sensitive index for the recovery process.(ABSTRACT TRUNCATED AT 250 WORDS)

Premedication for day case surgery. A study of oral midazolam.

A double-blind, between-patient trial was used to assess midazolam 7.5 and 15 mg as oral premedication for day case surgery. Midazolam 7.5 mg did not produce significant anxiolysis or sedation in comparison to placebo as measured by patient self-assessment linear analogue scales and observer scores. Midazolam 15 mg caused significant anxiolysis and sedation pre-operatively but also at 2 hours following awakening. Psychomotor performance assessed by digital-symbol substitution tests was significantly impaired by midazolam, in both doses, throughout the period of investigation. Midazolam 15 mg orally provides good premedication but the prolonged effects make it unsuitable for short-stay patients.

Atropine enhances neuromuscular transmission in humans.

The effect of atropine (1-10 micrograms . kg-1) on neuromuscular transmission in humans was studied by analysing its effects on the amplitude of indirectly-elicited twitch (0.2 Hz) and tetanic (50 and 100 Hz for 1 s duration) contractions. Six patients, free from any neuromuscular disorders, undergoing orthopaedic surgery, were included in the present study. The patients received either no premedication or the oral benzodiazepine, temazepam, 30 mg 1-2 h pre-operatively. Anaesthesia was induced with propofol (1-2 mg . kg-1, i.v., over 20 s). The patients breathed no less than 30% oxygen in nitrous oxide, halothane (1%) or enflurane (1-2%). Incremental doses of fentanyl (50-100 micrograms) were given to provide additional analgesia. The ulnar nerve was stimulated, supramaximally, at the wrist, and control mechanical responses of the adductor pollicis muscle, to nerve stimulation at 50 and 100 Hz for 1 s duration, were recorded. Theses responses were repeated at 2, 5 and 10 min intervals, after injection of atropine (1-10 micrograms . kg-1). At the same time, heart rate and blood pressures (systolic and diastolic) were recorded. The results showed that atropine enhanced the tetanic contractions, elicited at 50 and 100 Hz for 1 s duration, by 27 +/- 1.2% (50 Hz and atropine, control 220 +/- 13 g tension), and by 43 +/- 7% (100 Hz and atropine, control 333 +/- 26 g tension) at the 5 min intervals (mean +/- S.E., n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Evoked electromyographic and mechanical responses of the adductor pollicis compared during the onset of neuromuscular blockade by atracurium or alcuronium, and during antagonism by neostigmine.

The effects of atracurium and alcuronium on the evoked mechanical and electromyographic responses of the adductor pollicis were investigated in 30 adult patients. The ulnar nerve was stimulated with trains of four supramaximal pulses of 0.2 ms duration and a frequency of 2 Hz at intervals of 20 s. The mechanical response was measured using a strain gauge force transducer and the evoked compound action potential (ECAP) was recorded simultaneously using a Medelec MS91 electromyography system. Depression of the electromyographic and mechanical responses, caused by atracurium, was similar during onset and antagonism of blockade. During onset of blockade by alcuronium, the mechanical response was depressed to a significantly greater extent compared with the ECAP. This difference was not observed during antagonism with neostigmine. The rates of onset of atracurium and alcuronium were generally similar, but the rate of onset of mechanical fade was greater in the alcuronium group. There was no significant quantitative difference between the rates of antagonism of alcuronium and atracurium when assessed by the mechanical first response ratio. Electromyographic first response and electromyographic and mechanical train-of-four ratios recovered more rapidly in the atracurium group. These findings suggest that the differences between mechanical and electromyographic measurements of neuromuscular blockade are drug-specific and are more pronounced during the onset of blockade than during its antagonism by neostigmine.

Differing potencies of muscle relaxants on rat and guinea-pig phrenic nerve diaphragm preparations.

The sensitivities of two in-vitro preparations to neuromuscular blocking agents have been compared. The guinea-pig phrenic nerve diaphragm preparation proved to be more sensitive to vecuronium, atracurium and pancuronium than the equivalent preparation from the rat. Only tubocurarine had a similar potency on the preparations from both species. This would suggest that the guinea-pig diaphragm would be the most appropriate bioassay preparation if only small quantities of drug were available. Small differences in the cholinesterase content of the preparations was not thought to be a likely reason for the differences between the two preparations.

The 'wake-up test'. A new approach using drug infusions.

A case is presented in which there was a need for a 'wake-up test'. A technique is described, employing alfentanil and vecuronium given by infusion, and the problems of anaesthetic management are discussed.

Antagonism of alcuronium with edrophonium or neostigmine.

The reversal of alcuronium by edrophonium 1 mg kg-1 or neostigmine 35.7 micrograms kg-1 was compared in 23 patients undergoing elective ophthalmic surgery. Neuromuscular transmission was assessed by measuring the force of contraction of the adductor pollicis muscle in response to train-of-four supramaximal stimuli (2 Hz, 0.2 ms duration) delivered via surface electrodes to the ulnar nerve every 10 s. Anaesthesia was induced and maintained with Althesin, and patients were ventilated to normocarbia with 67% nitrous oxide in oxygen. Neuromuscular blockade was induced with alcuronium 0.2-0.3 mg kg-1 and antagonism was attempted when the train-of-four ratio had recovered spontaneously to 0.1. Recovery of the first contraction response of the train-of-four and of fade were more rapid after edrophonium. Although most patients were monitored for at least 30 min no re-curarization was seen. Comparison of the relative rates of recovery of the first contraction, and the response to train-of-four stimuli, suggests that edrophonium has a greater prejunctional effect than neostigmine.

A study of the efficiency of four blood microfilters.

A new blood microfilter, Swank 6000-4, was compared with three established blood microfilters, Pall SQ40S, Fenwal 4C2423 and Intercept HR 18137-00 (1321). The flow rate decreased with increasing volume of filtered blood with all the microfilters (p less than 0.01). When the flow rates through each type of microfilter were compared there was no significant difference between them. Screen filtration pressure was restored to normal by the Swank, Fenwal and Intercept microfilters, but remained higher after filtration through the Pall microfilter (p less than 0.01). There was no evidence of red cell loss or damage with any of the microfilters after filtration.

Diflunisal and blood acid base status in the rabbit.

Both diflunisal and acetylsalicylic acid given orally caused respiratory alkalosis and metabolic acidosis. However the fall in standard bicarbonate was much less in diflunisal-treated rabbits and pH in these animals remained elevated for the duration of the experiment. Whilst the severity of the fall in arterialized venous PCO2 was a good indicator of the degree of acetylsalicylic acid intoxication this was not the case for diflunisal as fatalities occurred with trivial changes in PCO2. Diflunisal toxicity was associated with markedly elevated temperatures. This was not observed in acetylsalicylic acid-treated rabbits.

Extradural analgesia and ichthyosis.

Extradural analgesia is well established for relief of pain but in certain cases unusual difficulties may be encountered. We report our experiences of a patient with congenital ichthyosis who required extradural analgesia for the relief of pain in labour.

Preoperative medication for day-case surgery. A comparison between oxazepam and temazepam.

The effects of temazepam 20 mg, oxazepam 30 mg and placebo were compared when given as preoperative medication to patients undergoing day-case surgery. Temazepam caused a significant decrease in anxiety and produced sedation by 60 min, whereas those patients receiving oxazepam showed only minimal changes. Awakening time was prolonged with oxazepam but not with temazepam. Two hours after surgery, no significant sedation was recorded with either drug, and simple psychomotor testing showed unimpaired performance. Patient acceptability was high with both oxazepam and temazepam.

Plasma concentrations and clinical effects of lorazepam after oral administration.

The relation between plasma concentrations and properties of lorazepam administered orally as premedication was studied in patients undergoing minor surgery. The drug was found to be reliably absorbed in most subjects producing plasma concentrations similar to those reported after injection. Effective concentrations were obtained within 30-60 min, maintained for 4-6 h and were closely related to the action of the drug on memory and its sedative and anxiolytic properties. Its kinetics were described in about half of the subjects by a one-compartment model, but in others two compartments were required. Variable half-lives were found (range 9.3-32.1 h, mean about 20 h). Sufficient drug remains after 24 h to suggest that residual c.n.s. effects may still be present.

Effect of droperidol on dopamine-induced increase in effective renal plasma flow in dogs.

The interaction between small doses of dopamine and droperidol on effective renal plasma flow was studied in dogs. Small doses of dopamine are known to produce renal vasodilatation by a dopaminergic mechanism and droperidol, a selective dopamine antagonist used in neuroleptanaesthesia, may attenuate this response. Effective renal plasma flow was measured non-invasively using 125I-hippuran. A 20-min infusion of dopamine 2 microgram kg-1 min-1 significantly enhanced effective renal plasma flow (mean increase of 16%; P < 0.05) in anaesthetized dogs. This effect was abolished (mean decrease 6.6%) by droperidol 0.2 mg kg-1 administered at the commencement of anaesthesia. It is concluded that droperidol reduces the renal vasodilatation induced by dopamine in anaesthetized dogs.

Effect of Diazepam at the neuromuscular junction. A clinical study.

In patients undergoing surgery under general anaesthesia diazepam 0.16 mg kg-1 had no effect on mechanical twitch height of the adductor pollicis muscle of the thumb when the ulnar nerve was stimulated at the wrist. The muscle responses were evoked by single, repeated supramaximal stimuli at 0.2 Hz and "train-of-four" stimulation at 2 Hz for 2 s. Diazepam 0.16 mg kg-1 had no effect on the depth or recovery of neuromuscular blockade produced by suxamethonium, tubocurarine, pancuronium, fazadinium or alcuronium.

0.125% bupivacaine for obstetric analgesia?

A prospective trial was designed to assess the effectiveness of three different concentrations of bupivacaine (Marcain) for use in obstetric epidural analgesia. The purpose of the study was to see if reduction of the concentration of bupivacaine to 0.125% would reduce the total dose of the drug given without reducing the efficiency of the epidural block. The concentrations studies were 0.125%, 0.25% and 0.375%. The trial was limited to fit primiparous patients at term with singleton pregnancies and vertex presentation. Patients with intercurrent medical disease or with toxaemia were excluded. A total of ninety-three patients were studied, and once admitted to the trial they were randomly allocated to one of the three concentrations. In general the results of the trial show that 0.125% bupivacaine had a significantly higher failure rate than either of the other two concentrations, but in those cases where 0.125% was effective and achieved total pain relief there was a significant reduction in the amount of the drug used.

The value of topical lignocaine for bronchoscopy under general anaesthesia.

Patients for bronchoscopy were randomly allocated to two groups, one receiving 4 ml 4% lignocaine spray and a control group which was not sprayed. There were no significant differences in the incidence of cough and spasm on recovery between the groups. The findings of a double-blind study comparing patients sprayed with 0-9% saline or lignocaine showed a significantly higher incidence of spasm in the saline group.