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Biomedical subjects

M P Boidin

Publications and source records attributed to M P Boidin.

9 recordsLinked to original sources

Fentanyl in 2% mepivacaine compared with fentanyl in 0.5% bupivacaine: two parallel controlled double blind studies.

The efficacy of epidural mepivacaine and bupivacaine, combined with fentanyl to enhance blockade, was compared in two parallel controlled, double-blind clinical trials. Patients in the studies (n = 91) were scheduled for orthopedic surgery of the legs and a tourniquet was used in all cases. Those patients receiving mepivacaine attended day surgery only, whereas patients receiving bupivacaine were hospitalised. Epidural puncture was performed with a Tuohy needle at the L3-4 level in the lateral decubitus position. Levels of sensory and motor blockade were assessed; adverse reactions and pain during surgery were recorded. There were four groups of patients: 1) 26 received 2% mepivacaine with placebo; 2) 26 received 2% mepivacaine with 0.1 mg fentanyl; 3) 19 received 0.5% bupivacaine with placebo and 4) 20 patients received 0.5% bupivacaine with 0.1 mg fentanyl. The levels of the sensory blockade was comparable in all groups. The degree of motor-blockade was more intense in the mepivacaine groups, but the blockade by mepivacaine lasted shorter. Addition of fentanyl did not change the sensory and motor blockade. Intraoperative pain was reported by: 7 patients in the mepivacaine/placebo group; 4 patients in the mepivacaine/fentanyl group; 4 patients in the bupivacaine/placebo group; and by one patient in the bupivacaine/fentanyl group. These results indicate that fentanyl enhances the quality of epidural blockade when combined with either mepivacaine or bupivacaine.

Adult

Ascorbic acid prevents cimetidine-induced decrease of serum hydrocortisone concentrations.

A blind, parallel, prospective, clinical study was conducted to investigate the effect of ascorbic acid on human serum hydrocortisone concentrations which were decreased by the administration of cimetidine. The study population included 16 male adults scheduled for major abdominal vascular surgery. The study was conducted in surgical patients under anaesthesia, in which steroidogenesis was inhibited by cimetidine. The results showed a reduction in serum hydrocortisone concentrations in patients receiving a placebo. In patients receiving ascorbic acid, there was a significant increase in serum hydrocortisone concentration. This reflects the normal serum hydrocortisone profile for this operation and anaesthetic technique. Cimetidine can bind to cytochrome P-450 covering the active haem group, the cytochrome proves to be of vital importance for hydroxylation reactions, involved in human steroidogenesis. Serum hydrocortisone concentrations will decrease when cytochrome P-450 becomes blocked. Intravenous administration of ascorbic acid was supposed to cause relief for this decrease. The reasons are undetermined yet. This investigation proved that ascorbic acid can prevent cimetidine-induced decrease of human serum hydrocortisone concentrations.

Abdomen

The role of ascorbic acid in etomidate toxicity.

Etomidate, a short-acting hypnotic used in anaesthesia, has been shown to block steroidogenesis in man. The free imidazole radical in etomidate binds to cytochrome P450. Serious side-effects of etomidate have only been observed in guinea-pigs and in man, both species relying for restoration of ascorbic acid pools upon resynthesis and upon the daily dietary intake of vitamin C. It has been shown that ascorbic acid and not ACTH can increase serum cortisol concentration during etomidate infusion. Ascorbic acid even restores the ACTH/cortisol ratio to pre-operative values. It is therefore suggested that etomidate blocks ascorbic acid metabolism. Resynthesis of ascorbic acid cannot occur because of the blockade of cytochrome P450. Depletion of the ascorbic acid pool would then cause inhibition of steroidogenesis. This is the case in man and probably also in the guinea-pig. All other species can synthesize their own ascorbic acid from alpha ketogluconic acid.

Adrenal Glands

Modification of corticosteroid synthesis by etomidate/fentanyl and air anesthesia.

The characteristics of cortisol synthesis blockade by an etomidate/fentanyl combination was explored in a group of seven patients undergoing major abdominal vascular surgery. Cortisol, androstene-dione 11-deoxy cortisol (compound S) and ACTH were measured during surgery for three hours. In the fourth hour an ACTH1-24 stimulation test was performed and the reaction of the corticosteroid synthesis was assessed. ACTH and androstene-dione showed a stable concentration during the study, the reaction of androstene-dione to ACTH1-24 was blunted but normal. Compound S and cortisol concentrations decreased during anesthesia and showed no significant increase after stimulation with ACTH1-24. These results indicate that the infusion of etomidate and fentanyl may cause a blockade of the corticosteroid synthesis. The blockade is situated at the place where the conversion of cholesterol to pregnenolone occurs. Because the study was done in clinical setting the results should be interpreted carefully, and confirmed by experimental laboratory results.

Abdomen

Can etomidate cause an Addisonian crisis?

The purpose of this study was to assess if it could have been possible to discover the side effects of etomidate by infusion in an earlier phase of its introduction on the market, using the routine parameters of everyday anesthesiological practice. The study was undertaken in twelve patients scheduled for major abdominal vascular surgery. The effect of etomidate-fentanyl and air anesthesia was compared with the effects of neurolept anesthesia. Arterial blood-pressure, central venous blood pressure, pulse rate, peripheral and central body temperature were recorded continuously. Blood samples were taken every two hours during anesthesia for the estimation of arterial blood gases, cortisol, sodium, potassium and chloride. Significant differences were found mainly for the peripheral-, core temperature difference, the cumulative sodium and cumulative fluid balance from which the diagnosis addisonian crisis could have been made. There were also differences in the incidence of early and late complications and in the recovery rate of the patients after etomidate infusions.

Addison Disease

Airway patency in the unconscious patient.

Airway patency was explored in patients breathing spontaneously under deep halothane anaesthesia. Opening and closing of the airway was observed with a flexible bronchoscope looking proximally from the nasopharynx at the epiglottis and the tongue. With the occiput elevated at various angles the smallest angle of retroflexion of the neck necessary to open the airway was measured. The influence of artificial airways on this angle of retroflexion was measured. Cadaveric preparations of the upper airway were studied to assess the mechanisms involved in airway patency. The results indicate that the epiglottis and not the tongue is the main cause of obstruction of the upper airway. When methods are applied to displace the hyoid anteriorly, the airway will be cleared on most occasions.

Adolescent

Steroid response to ACTH and to ascorbinic acid during infusion of etomidate for general surgery.

The characteristics of the steroid response during an etomidate-fentanyl combination was explored in two groups of five patients undergoing major abdominal vascular surgery. Cortisol, androstene-dion, compound-S and ACTH were measured during surgery for three hours. In the fourth hour, an ACTH1-24 stimulation test was performed in one group and the steroid response was assessed. The other group received ascorbinic acid intravenously and the reaction of the adrenals was measured in the same way. The result indicates that etomidate causes a blockade of the adrenal corticosteroid synthesis at the site of the hydroxylation of cholesterol. This blockade is due to the interaction of the imidazole structure with the cytochrome p-450. Ascorbinic acid is able to overcome this blockade, indicating that cytochrome p-450 is involved in the ascorbinic acid metabolism which is obligatory for the hydroxylation of cholesterol.

Adrenal Cortex Hormones

Serum levels of cortisol in man during etomidate, fentanyl and air anesthesia, compared with neurolept anesthesia.

The effects of etomidate and fentanyl given as a mixture in continuous infusion and of a classical neuroleptanalgesia, with droperidol and fentanyl, on the serum cortisol levels were compared during and after anesthesia in sixteen patients who were to undergo major abdominal surgery. The results showed that the postoperative increase of serum cortisol levels which occurred in the neurolept group was absent in the group receiving etomidate and fentanyl infusion. During etomidate-fentanyl anesthesia there was a more significant decrease of serum cortisol and no rise in serum cortisol levels in response to synthetic ACTH injection. Etomidate and fentanyl, given as a continuous infusion during major abdominal surgery, block the adrenal mechanism to secrete endogenous cortisol in response to stress or after the administration of adreno-corticotrope hormone.

Adrenocorticotropic Hormone

Inhibition of corticosteroidogenesis by etomidate.

The effects of the intravenous anesthetic etomidate have been investigated on ACTH-induced steroidogenesis in vitro, using purified isolated rat adrenal cells. It was found that etomidate almost completely blocked corticosterone production induced by physiological concentrations of ACTH at doses of 200 ng or greater. The mean inhibitory etomidate concentration resulting in 50% inhibition approximated 1.5 X 10(-7)M which is in the range of concentrations measured after clinical doses of etomidate.

Adrenal Cortex