British journal of anaesthesia
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The primary objective of this study was to determine in vivo tissue/blood partition coefficients of propofol for use in physiological modelling of its pharmacokinetics. The sheep was used as an animal model. In the main series of experiments, crossbred ewes received a bolus of propofol 1% (Diprivan) followed by an infusion during which blood concentrations were measured at intervals. ⋯ Tissue/blood partition coefficients depend on the amount of triglyceride which accumulates in blood from the propofol vehicle; for blood, free of added triglyceride, the following coefficients were calculated: brain, 3.23; heart, 5.94; kidney, 2.46; spleen, 1.86; semimembranosus muscle, > or = 1.61; triceps muscle, > or = 1.47. Calculated tissue/water coefficients were 35 times greater. There was indirect evidence of extraction of propofol by the lungs.
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If the in vivo effects of anaesthesia are mediated through a specific receptor system, then a relationship could exist between the regional changes in brain metabolism caused by a particular agent and the underlying regional distribution of the specific receptors affected by that agent. Positron emission tomography data from volunteers studied while unconscious during propofol (n=8) or isoflurane (n=5) anaesthesia were used retrospectively to explore for evidence of relationships between regional anaesthetic effects on brain glucose metabolism and known (ex vivo) regional distribution patterns of human receptor binding sites. ⋯ Isoflurane's reductions positively correlated only with muscarinic (acetylcholine) binding density (r=0.85, P<0.05). These findings are consistent with the hypothesis that some of propofol's in vivo anaesthetic effects may be mediated through a GABAergic mechanism and suggest some of isoflurane's in vivo effects might involve antagonism of central acetylcholine functioning.
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Myasthenia gravis is an uncommon autoimmune disease resulting in destruction of the postsynaptic nicotinic receptors at the neuromuscular junction. We describe a 43-yr-old, 95 kg patient who presented for elective laparoscopic cholecystectomy. ⋯ Subsequent investigation led to a diagnosis of myasthenia gravis. We discuss the investigation, diagnosis, and subsequent management of such a patient and emphasize that tactile estimation of the train-of-four ratio is not a reliable indicator of adequate recovery of neuromuscular function.
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The veterinary neurosteroid anaesthetic Saffan has the same formulation as Althesin now withdrawn from human use and is a mixture of two neurosteroids, alphadolone, and alphaxalone. The molecular structures of these two pregnanes and their properties as i.v. anaesthetics were reported to be similar. Preliminary experiments showed that alphadolone caused powerful antinociceptive effects without sedation when given i.p. ⋯ These effects were reversed at the level of the spinal cord by intrathecally-administered bicuculline (10 pmol). We conclude that a metabolite of alphadolone acetate produced in the liver leads to antinociceptive effects after i.p. and intragastric administration of the parent compound. This antinociception involves spinal cord GABA(A) receptors, even though the drug was administered via a non-spinal route.
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Patients suspected of anaphylaxis during anaesthesia have been referred to the senior author's clinic since 1974 for investigation. Since release of rocuronium on to the worldwide market, concern has been expressed about its propensity to cause anaphylaxis. ⋯ The incidence of rocuronium allergy in New South Wales, Australia has risen in parallel with sales, while there has been an associated fall in reactions to other neuromuscular blocking drugs. Data from intradermal testing suggested that rocuronium is intermediate in its propensity to cause allergy in known relaxant reactors compared with low-risk agents (e.g. pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium, succinylcholine).