[Brain death diagnosis and ethics].
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Brain Death↗
Biomedical subjects
B Hallén
Publications and source records attributed to B Hallén.
Single- and multiple-dose pharmacokinetics of terodiline in geriatric patients.
As a target group, geriataric patients were selected for pharmacokinetic studies with terodiline (Mictrol), an anticholinergic and calcium antagonist drug effective in the treatment of urinary incontinence. The single-dose kinetics in the geriatric patients (mean age 82 years) differed significantly from that previously found (Hallén et al. 1987) in healthy volunteers (mean age 35 years). There were higher peak serum concentrations (110 vs 79 micrograms.l-1), increased half-life (189 vs 60 h), lower renal clearance (4.0 vs 10.9 ml.min-1) and lower total clearance (29 vs 75 ml.min-1). Multiple-doses of 12.5 mg b.d. for 6-8 weeks resulted in a mean steady-state concentration of 642 micrograms.l-1, which was in agreement with the single dose parameters. The studied geriatric patients can be characterized not only as old, but also as frail, bedridden, having several diseases and polymedicated. The differences in pharmacokinetics between younger and elderly subjects can be attributed to a variety of complex factors, which may alter the clearance and/or the volume of distribution.
Aged↗
Cardiac arrest during anaesthesia. A computer-aided study in 250,543 anaesthetics.
With the aid of a computer-based anaesthetic record-keeping system, all cardiac arrests during anaesthesia at the Karolinska Hospital between July 1967 and December 1984 were retrieved. There were a total of 170 cardiac arrests and 250,543 anaesthetics in the data file, which gives an incidence of 6.8 cardiac arrests per 10,000 anaesthetics. Sixty patients died, constituting a mortality of 2.4 per 10,000 anaesthetics: 42 were considered as inevitable deaths (rupture of aortic or cerebral aneurysm, multitrauma, etc.); 13 cases of cardiac arrest were considered as non-anaesthetic, i.e. complications due to surgery and other procedures. Nine of these patients died. 115 cases of cardiac arrest were considered as caused by the anaesthetic and nine of these patients died. Thus mortality caused by anaesthesia was 0.3 per 10,000 anaesthetics. The most common cause of cardiac arrest due to anaesthesia was hypoxia because of ventilatory problems (27 patients), postsuccinylcholine asystole (23 patients) and post-induction hypotension (14 patients). The highest mortality was seen when spinal or epidural anaesthetics were given to patients with impaired physical status including hypovolaemia. The incidence of cardiac arrest has declined considerably during the period studied, and this coincides with an increasing number of qualified anaesthetists employed in the department during the same period.
Aged↗
Relationship between gastric emptying and serum concentrations of emepronium in dogs and human volunteers.
Clinical trials with increased dosages, relative to the standard regimen, of the anticholinergic drug emepronium (Cetiprin Novum) resulted in a clear improvement in micturition- and urodynamic parameters in urinary incontinent patients. In the present study possible effects on the gastric emptying were tested in dogs and in human volunteers. In dogs a wide dose range of emepronium (5-100 mg/kg p.o.) was used to establish a relationship between serum concentration and effect on the gastric emptying. Gastric emptying was slightly decreased after 25 mg/kg (peak conc. of emepronium about 100 micrograms/l) and markedly decreased after 50 mg/kg (500 micrograms/l) and 100 mg/kg (5000 micrograms/l). In the volunteers no effect of emepronium on gastric emptying was observed, either after 200 mg q.i.d. or after 400 mg q.i.d. (about 3 and 6 mg/kg q.i.d.), which resulted in peak serum concentrations of 100-300 micrograms/l).
Adult↗
Propofol vs thiopentone as anaesthetic agents for short operative procedures.
In a randomized open study, 120 healthy female patients were included. For short gynaecological procedures they were anaesthetized with either propofol 2.5 mg X kg-1 (n = 60) or thiopentone 5 mg X kg-1 (n = 60) in combination with nitrous oxide/oxygen (67%/33%). Supplementary doses of propofol (10-20 mg) or thiopentone (25-50 mg) were given when necessary during the procedure. Induction characteristics for propofol and thiopentone 1 min after start of induction were similar. Propofol seemed to have a more depressant effect than thiopentone on the circulatory response to anaesthesia. Recovery times from the end of the operative procedure until the patients opened their eyes on command and were orientated were shorter in the propofol patients compared to the thiopentone patients. In the propofol group, patients recalled discomfort on injection more often than patients anaesthetized with thiopentone. Otherwise, the side-effects were similar in both groups. We conclude that propofol is similar to thiopentone in its anaesthetic qualities during induction and maintenance of short anaesthetic procedures. Propofol was associated with a more rapid emergence from anaesthesia than thiopentone.
Anesthesia, Intravenous↗
Gastrointestinal transit rate-related absorption of emepronium: a study in mice.
The gastrointestinal (GI) absorption in mice of the anticholinergic quaternary ammonium compound emepronium, assessed by the urinary excretion of radioactivity and unchanged drug, increased from 1% to 7% and from 0.5% to 5%, respectively, in the dose range 0.1 to 40 mg/kg, whereafter a plateau was reached. Changes in the metabolism were evident at doses exceeding 80 mg/kg when 80% of the radioactivity was excreted as unchanged emepronium, as compared to 50% at lower doses. No dose-dependent urinary excretion of radioactivity was detected following intravenous injection. The increase in the fraction of the dose excreted in the urine after oral administration therefore cannot be easily explained by a dose-dependent metabolism or renal excretion. However, a relationship was seen between the reduced gastrointestinal motility, produced by increasing doses of the drug, and the increased bioavailability. Atropine sulphate given subcutaneously (1-50 mg/kg) more than doubled the urinary recovery of a small pharmacologically inactive oral dose of emepronium (5 mg/kg) and thus confirmed the transit rate-dependent absorption of emepronium. The superimposed effect of the pharmacological action on the GI transit rate, derived from the inherent property of an anticholinergic drug, may be of special significance for a drug with a low degree of absorption and a high variability, such as has been observed in clinical trials with the quaternary drug emepronium (Cetiprin).
Animals↗
Species differences in the intestinal excretion of emepronium.
A substantial proportion of a parenteral dose of emepronium given to dogs is excreted via the gastrointestinal tract by biliary excretion and by excretion through the intestinal mucosa (Hallén et al. 1979). In the present paper the different routes of elimination were further investigated in mouse and man and compared to the dog. The disposition of emepronium-derived radioactivity (14C) in the three species showed that about 45% was excreted via urine and 55% via faeces. The proportion of the faecal excretion of 14C that could be referred to the intestinal route differed between the species and was about 20% in man, 60% in the mouse and most pronounced, 80%, in the dog.
Aged↗
Clinical study of a lignocaine-prilocaine cream to relieve the pain of venepuncture.
The efficacy of a topical anaesthetic formulation, EMLA 5% cream (Eutectic Mixture of Local Anaesthetics) in obtunding the pain produced by venepuncture, was determined in a double-blind randomized, cross-over study in 31 adult volunteers. Pain was registered on a 10-cm visual analogue scale. In each subject the mean pain score after treatment with EMLA was compared with that following placebo. Twenty-eight subjects had lower pain scores with EMLA, and in the remaining three subjects EMLA and placebo were equi-effective. Transient skin reactions (blanching, erythema and oedema) were observed with both formulations. These reactions were not found to be aggravated by repeated applications.
Administration, Topical↗
Plasma fluoride and bromide concentrations during occupational exposure to enflurane or halothane.
The plasma fluoride and bromide concentrations were studied in operating theatre personnel. When enflurane was used, the increase in plasma fluoride concentration could not be distinguished from normal individual variations, but the plasma bromide concentration increased significantly when halothane was used. Seven patients were exposed to enflurane in a concentration of 200 parts per million for 4 h. A significant increase in the plasma concentration of fluoride was observed. The peak concentrations of fluoride occurred during exposure and the increase lasted less than 12 h. The increase in fluoride concentration was larger at this trace concentration than reported after anaesthetic concentrations. Cerebrospinal fluid (CSF) fluoride concentration was also studied; a smaller and delayed increase was found in CSF compared to plasma.
Air Pollutants, Occupational↗
Ion pair formation and gastrointestinal absorption of emepronium.
Ion pair forming agents were evaluated in vitro for their ability to form lipophilic ion pairs with the quaternary ammonium compound emepronium and in vivo to enhance its gastrointestinal absorption. A 5- to 100-fold excess of trichloroacetate (TCA), diethylhexylphosphate (DEHPA), heptafluorobutyrate (HFBA), sodium lauryl sulphate (SLS), bromide or chloride all increased the extractability of the emepronium ion into methylene chloride. The additive with the most marked effect on the apparent partition coefficient of emepronium (Kapp) was SLS. At emepronium 10(-4) M, Kapp increased from a basal value of 0.1 to 368 with a 100-fold molar excess. However, the increased partitioning to methylene chloride was not reflected in an increased gastrointestinal absorption of the emepronium ion when this was given orally to mice. When intestinal juice, instead of distilled water or buffer, was used as the aqueous phase, the partition coefficient was markedly higher (Kapp approximately 2) but it was significantly less influenced by addition of sodium lauryl sulphate (Kapp approximately 6). The preexisting positive influence of the intestinal juice on the lipophilic character of emepronium and the rather limited additive effect of agents that form lipophilic complexes with emepronium, lead to the conclusion that the ion pair concept is not a suitable approach to enhance the gastrointestinal absorption of this drug.
Animals↗
Pain-free venepuncture. Effect of timing of application of local anaesthetic cream.
This study was designed to assess the effect of time on the analgesic effect of a local anaesthetic cream consisting of a mixture of 5% lignocaine and prilocaine. The cream and placebo were compared in a double-blind, randomized study in 114 children aged 4-17 years, with application times of 20 minutes and longer. A regression analysis revealed no difference in analgesic effect between cream and placebo when application times were less than 60 minutes. A cusum test showed that the effect of the cream became evident at about 60 minutes. Local adverse reactions consisted mainly of transient paleness of the skin, which did not constitute any clinical problem.
Adolescent↗
The effect of local scavenging on occupational exposure to nitrous oxide.
Despite evacuation of excess anaesthetic gases at the expiratory valve of the anaesthetic circuit and a general ventilation system producing 17-20 air changes per hour, mask anaesthesia often causes occupational exposure to anaesthetic gases exceeding the threshold limit values. The effect of a local air exhaust system, a local scavenger, on occupational exposure to nitrous oxide during paediatric mask anaesthesia was studied. The scavenger evacuated 140 m3 of air per hour and was placed at a distance of 20 cm from the face mask. In a very poorly ventilated operating theatre the exposure to nitrous oxide was reduced by 75% during the anaesthetic sessions and exposure to concentrations above 500 ppm was almost eliminated. The experiences from the installation and clinical use are discussed. Local scavenging is an excellent complement to the scavenging of excess gases at the expiratory valve, and it may be considered an alternative to expensive, high-capacity ventilation systems.
Air Conditioning↗
Thermocamera studies of nitrous oxide dispersion in the dental surgery.
Nitrous oxide is used in dentistry for sedation and analgesia. Chronic occupational exposure of dental personnel to trace concentrations of nitrous oxide has been reported as a potential health hazard. A new application of the thermocamera technique was used to study the dispersion of nitrous oxide during dental analgesia. Four breathing systems with different evacuation systems were tested and found to vary in scavenging efficiency. A local exhaust system ensured minimal exposure when nitrous oxide leaks contaminating the air in the dentist's breathing zone occur.
Air Pollutants↗
Oesophageal probe for heart and temperature monitoring during anaesthesia.
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Anesthesia↗
Does lidocaine-prilocaine cream permit painfree insertion of IV catheters in children?
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Adolescent↗
Pharmacological evacuation of the stomach with metoclopramide.
Children admitted for emergency operations because of trauma run a high risk of chemical aspiration pneumonitis syndrome. Fifty-eight children admitted for closed reduction of fractures and suturing of wounds were studied in a double-blind manner in order to see if metoclopramide could be of value in decreasing the risk of aspiration during anaesthesia. Metoclopramide given before anaesthesia proved to enhance gastric evacuation and could thus be of value in these situations. In addition, the study showed that the time from last oral intake until start of anaesthesia is of less importance then the type of trauma in prolonging the gastric emptying time and thus increasing the risk of vomiting and aspiration of vomitus into the lungs during anaesthesia.
Anesthesia↗
Thermocamera, a macroscopic method for the study of pollution with nitrous oxide in operating theatres.
Nitrous oxide (N2O) is used in high concentrations in inhalation anaesthesia and can serve as a tracer of other, more potent anaesthetic agents polluting the air of operating theatres. It has the quality of absorbing infra-red light with a characteristic peak of 4.5 micrometer in the absorption spectrum. N2O in the operating-room atmosphere will absorb infra-red light emitted from a heat screen, and can therefore be registered by an infra-red-camera equipped with a filter eliminating waves outside the 4.5 micrometer waveband. The method was tested during paediatric inhalation anaesthesia. The infra-red-camera measurements are semi-quantitative and sensitive to an extinction of about 1000 ppmcm, comparable to a N2O concentration of 100 ppm measured by an infra-red N2O monitor. It was demonstrated that major pollution occurs during mask anaesthesia and after extubation. The polluting gas is insufficiently evacuated by the operating theatre ventilation. The method makes it possible to visualize the dispersion of spilled or leaking N2O, and is therefore of value when constructing and evaluating new scavenging equipment and in producing educational material.
Absorption↗
Thermocamera studies of enflurane and halothane vapours.
The ability of enflurane and halothane to absorb infra-red (IR) energy was used to visualize their vapours; IR radiation was emitted by a heated screen and the absorption was studied with an IR camera. Even small concentrations of enflurane (0.2 vol %) and halothane (0.5 vol %) could be detected when released into the operating room atmosphere. Enflurane and nitrous oxide were dispersed in a similar way when they leaked from the face mask. Thus when anaesthetic pollution is monitored in the operating room, measurements of the concentration of nitrous oxide are sufficient for routine purposes. The IR method has added a new dimension to the study of occupational exposure to otherwise invisible gases.
Air Pollutants↗