Annales de l'anesthesiologie francaise最新文献

A protocol of repeated I. V. injections of flunitrazepam was constructed by mathematical simulation on the basis of pharmacokinetic data obtained from single intravenous injections given to healthy subjects. This protocol would given serum blood levels equal to 15 ng . ml-1, rapidly and compatible with long term artificial ventilation, thanks to the pharmacological action of flunitrazepam. Four patients in the ICU benefited from this protocol. The levels desired were not reached but in two cases out of four it was possible to continue artificial ventilation without the addition of any other drug. Furthermore it was possible to show that the three compartment model developed from healthy subjects remains valid in pathological circumstances. A second protocol based on pharmacokinetic data from four patients should allow us to obtain the objective aimed at.

Six samples of ventricular cerebral spinal fluid from an external ventricular drain, and peripheral venous blood were taken during the course of parenteral diazepam administration in man. The diazepam level was measured by gas phase chromatography. The levels of diazepam in the CSF were low compared with the plasms concentrations and around the same level as the free circulating fraction. The drug appears in the CSF relatively late after intravenous administration. It would appear that the passage of the drug from the blood into the CSF is slow and not very marked. Therefore it is not the main cause for the pharmocodynamic effects which are the result of the drug passing the blood barrier in the more restricted sense.

While using a new benzodiazepines flunitrazepam by the intravenous route in ordinary anethesia a competitive action with another benzodiazepine which is being used for the last 15 years, namely diazepam, was demonstrated for the first time in man. This study on 170 patients operated for ear, nose and throat conditions demonstrated this phenomenon, confirmed it and it was possible to reproduce the effect. The interaction is mainly characterized by: - A reduction of the effects of flunitrazepam (less profound sleep, even wakefulness with a waking patient who could talk and could react to pain). This effect was obtained with injection of a normal clinical dose of diazepam. - There was a blocking action or a reduction in the pharmacological action normally expected of flunitrazepam by the previous administration of a clinical dose of diazepam, when given by the intravenous, intramuscular or oral routes. This suggests that there are common receptor sites for these two benzodiazepines at the cerebral level and this would explain this apparently paradoxical action. Even though flunitrazepam has a greater affinity for these receptor sites this molecule seems to be displaced, according to the law of mass action, by diazepam when used at a high dose. This interaction shown for these two benzodiazepines is also seen in other derivatives of the same chemicals series. This is important in therapeutics with the increasing use of these products in general medicine, and anesthetics and neuropsychiatry where they are quite often used in association.

Amikacin serum levels were measured 256 times in 65 patients admitted into the intensive care unit for various reasons over 18 months. These measurements confirmed the dosage of 5 micrograms per kg repeated every 8 hours in patients with normal renal function. Forty eight hours before the first measurement, a control assay is essential to check that there is no residual antibiotic and that the antibacterial activity of the serum is zero. After this a single weekly control is sufficient to check that the residual level is effective and non toxic, i.e. between 2 and 6 micrograms per ml. However, in patients with acute renal insufficiency, there are three dosage schemas which should be used depending on the creatinine level. These three schemas are nevertheless not sufficient to continue effective therapy without a risk of toxic side effects. It is therefore necessary to check both the pack levels and the residual levels regularly from the beginning of treatment. Two to three weekly controls are essential to avoid a risk of toxic side effects.

Daily estimations of urinary 3 methylhistidine, creatinine and total nitrogen were carried out during the first four post-operative days in sixteen patients who had undergone uncomplicated abdominal surgery and receiving parenteral alimentation. Figures obtained for 3 methylhistidine (19.36 +/- 4.48 mumol/kg as a cumulative for the 4 days) could be used to assess the catabolism of muscular protein during this period at approximately 320 g for a 70 kg subject, i.e. approximately twice that found in the healthy adult. There was a good correlation between 3 MEHIS and creatinine. Muscular catabolism is hence proportional to the degree of lean body mass. By contrast, there was no correlation between the excretion of 3 MEHIS and nitrogen excretion. Finally, study of the effect of qualitative and quantitative variations in nitrogen intake on muscular proteolysis did not make possible any conclusion at present. Further studies are hence necessary.