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The hypnotic effect of midazolam on the sleep of pre-surgical patients was studied in 99 patients (53 males, 46 females) due to undergo surgery the following day. One tablet of 15 mg midazolam was administered at 21.00 h and a second was given 45 min later if the subject had not fallen asleep, sleep-onset latency being measured from the time the second tablet was taken. Eighty patients required 1 tablet and 19 required 2 tablets. According to the subjective assessment, patients receiving 1 tablet fell asleep in 22.9 +/- 14.9 min and those taking 2 tablets fell asleep in 38.4 +/- 25.3 min (difference significant P less than 0.05). There was no statistically significant difference between the 1- and 2-tablet groups with regard to sleep duration, number of awakenings, overall assessment of the night's sleep, sleep quality and state on awakening. Factors which had a statistically significant influence on the dosage requirement were (a) sex, 30.4% females requiring a second tablet v. 9.4% males; (b) age, the mean age of the 2-tablet group being 36.5 v. 47 years in the lower dose group; (c) weight, patients with lower body weight requiring the higher dosage, mean 57.5 v. 66 kg; (d) current insomnia or a history of sleeping problems; (e) previous use of hypnotics; (f) degree of insomnia, moderate/severe insomnia needing a higher dosage (42% v. 21%).(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

To test the value of diagnostic and therapeutic data in obstetric DIC, 14 women were selected who presented a severe clotless haemorrhage with fibrin degradation products and/or soluble complexes, decreased fibrinogen (0.87 +/- 0.47 g X 1(-1)), platelet count (75.7 +/- 41 X 10(3) X ml-1) and prothrombin complex (33.7 +/- 12%). The hypovolaemia was treated at the same time as heparin was given in a bolus injection of 0.5 mg X kg-1 followed by a constant flow infusion of 1 mg X kg-1 X day-1 in all patients. Relevant obstetrical treatment was performed in 71.4% of patients. Fibrinogen, fresh frozen plasma, prothrombin complex concentrate and platelet concentrate were given if required. One patient, with severe toxaemia, died. Haemorrhage was stopped in 92.8% of patients after 4.5 +/- 0.8 h. Reversible visceral complications occurred in 28% of cases. The initial data used was easily obtained and seemed to give a reliable diagnosis in acute obstetrical DIC. Substitutive treatment was discussed in correlation with the evolution: PCC seemed pointless; the use of fibrinogen must become exceptional when fresh frozen plasma is available. Heparin remained necessary.

A case of post-partum cardiomyopathy probably due to salbutamol is described. The patient was a young primipara without any cardiovascular disease. She presented a sudden left ventricular failure after Caesarean section for twins: salbutamol had not been given for a week. After 10 days' treatment with diuretics and vasodilators, the patient was cured, no sequellae remaining. It seemed the mechanism was multifactorial: direct myocardial injury, a reduction in the number of receptors, peripheral haemodynamic changes.

This method can assay simultaneously, using 300 microliters of plasma, of the three principle local anesthetic agents used by peridural injection for post-operative anesthesia and analgesia: xylocaïne, etidocaïne, bupivacaïne. The assay method consists of three steps: (a) the addition of an internal calibrating agent (mepivacaïne). (b) defecation using trichlorocetic acid. (c) alcalinization of the supernatent (pH 11), extraction with dichloromethane and concentration at room temperature of the organic phase. (d) chromotography using an SE 30 or OV 17 impregnated column. The method is sensitive between 0.37 mumoles per l-1 (0.1 microgram . ml-1) and the coefficient for the mean deviation is 10.9% for concentration between 0.37 mumoles 1-1 and 75 mumole1-1 (0.1 microgram . ml-1 and 20 micrograms . ml-1). The correspondence of the figures recorded in this large concentration range without any change in the technique means that the kinetics of the plasma concentrations before and after peridural injection can be followed. The results obtained by gas liquid chromatography for the assay of lidocaïne were compared in 115 different plasma samples with concentrations obtained by an immuno enzymatic method ("EMIT") fitted to a centrifuge analyser. The correlation coefficient between the two methods was: (r = 0.95 with y = 0.09 x +0.25 microgram . ml-1 implying the absence of any interference and the specificity of the two methods. The columns also separate in 20 minutes the two main metabolites of lidocaïne: monoethylglycinexylidide (M.E.G.X.) and glycinexylidide (G.X.). These results demonstrate that continuous peridural injection of lidocaïne produces a high plasma concentration without any clinical toxic phenomena.

The fractional clearance K1 of bromsulphthalein was measured in twelve surgical patients at an interval of a least 48 hours. The first measurement was performed pre-operatively and the second postoperatively 24 hours after the operation, whilst the patients were receiving analgesia by the epidural injection of lignocaine at a constant flow rate. Between the two determinations there was a fall in BSP clearance of 25 +/- 11 p. 100 (range: -8 and -40 p. 100) P less than or equal to 0.0001. The clinical implications are discussed on the basis of concrete examples.

Two groups of 27 individuals--12 males and 15 females each--were constituted thanks to the envelopes technique. The first group received 10 mg of midazolam and the second 15 mg of diazepam as an intramuscular premedication, 30 minutes before a surgical operation. Sedation of preoperatoire anxiety was relevant in 26 subjects after midazolam and in 11 after diazepam (p less than 0,001). Amnesia related to the different times of the operative procedure was more frequent in the midazolam group than in the diazepam group: 70 p. 100 versus 4 p. 100 for the arrival into the operating room (p less than 0,001) and 96 p. 100 versus 78 p. 100 for the recovery on operating table (p less than 0,05). The effects on blood pressure, pulse rate and respiratory rate are not significantly different in both groups: neither is the local and general tolerance. Considering its greater efficiency with a similar tolerance, midazolam as compared with diazepam can be regarded as a superior intramuscular premedicant.

The present study aimed to assess the pharmaco-clinical profile of infants premedicated with rectal midazolam. The results were compared with those of a reference drug, flunitrazepam. Infants undergoing minor surgery were divided into three groups: group A (n = 30), with a mean age of 15.8 +/- 13.2 months and a mean weight of 8.6 +/- 3.3 kg, receiving 0.33 mg X kg-1 flunitrazepam; group B (n = 15), with a mean age of 11.2 +/- 10.7 months and a mean weight of 9.3 +/- 3.1 kg, receiving 0.3 mg X kg-1 midazolam; and group C (n = 30), with a mean age of 15.5 +/- 9.1 months and a mean weight of 10.7 +/- 2.5 kg, receiving 0.4 mg X kg-1 midazolam. An aqueous solution of each drug was administered with atropine sulfate (0.02 mg X kg-1) 20 min prior to induction of anaesthesia. The drug was well tolerated in 84% of cases. Statistically significant haemodynamic changes consisted of: a 9 c X min-1 decrease in heart rate (p less than 0.05) and a 12 mmHg decrease in systolic and diastolic blood pressures (p less than 0.05) in group C; a 6 mmHg decrease in systolic blood pressure (p less than 0.05) in group B. The tranquilizer action was either excellent or good in 93% of groups B and C compared with only 40% in group A (p less than 0.001 in both cases). Somnolence was attained in 60% of group A, 26.6% of group B and 30% of group C. A mask was much better accepted in group C (86.6%) than in group B (66.6%; p less than 0.05) or in group A (36.6%; p less than 0.01). Therefore, midazolam given rectally at 0.4 mg X kg-1 was better than flunitrazepam, because of a greater therapeutic effect for an equivalent rate of side effects.

This article first looks at the pharmacokinetics of local anesthetic agents injected intravenously, and then looks at the possible practical applications of this technique: the choice of a local anesthetic agent as a function of its toxic side effects, the use of lidocaïne in local and regional intravenous anesthesia, and the treatment of cardiac rhythm disorders. Finally the article envisages the pharmacokinetics of local anesthetic agents used in local-regional anesthesia. This depends on the following factors: the site of injection, the dosage, the speed of injection, the possible addition of adrenalin and the nature of the local anesthetic itself. On the basis of a personal study the authors underline the difficulty of being precise in the pharmacokinetics of local anesthetic agents injected by the peridural route continuously or discontinuously.

In order to determine the hypnotic effects of midazolam administered per os, the drug was compared with meprobamate and a placebo in patients about to undergo surgery. The study involved 83 patients, 57 female and 26 male: 67 cases of maxillofacial surgery and 16 cases of gynaecological surgery. The study was carried out using the technique of comparison in parallel series of single doses of midazolam (15 mg) with meprobamate (250 mg) and a placebo according to the double placebo technique. The patients were aged between 18 and 60 years, male and female, and were included without any particular attention being paid to sufferers from sleep disturbances or not. The variables selected for the study were 29 in number concerning the assessment of the patient of sleep and awakening, surveillance of the time taken to fall asleep, the duration and quality of sleep and the state after awakening.

Using a standardized anaesthetic protocol, the continuous monitoring of the twitch height after a 0.1 Hz stimulus was used to follow the evolution of curarization following injection of either atracurium (0.6 mg . kg-1) or alcuronium (0.2 mg . kg-1). The maximum twitch height inhibition was always greater than 99% of the control value and occurred after 107 +/- 50 s with atracurium (n = 30) and 172 +/- 120 s for alcuronium (n = 30) (p less than 0.02). Although surgical stage of muscular relaxation (twitch height less than 25% of reference value) was the same for both drugs (55 +/- 15 min for alcuronium versus 52 +/- 10 min for atracurium; n = 30 for both groups), the clinical duration (spontaneous restoration of twitch height to 90% of the reference value) was significantly longer (p less than 0.005) for alcuronium: 89 +/- 20 min (n = 10) versus 62 +/- 9 min for atracurium (n = 10). The spontaneous return to normal of the train of four was also significantly longer (p less than 0.001) for alcuronium: 118 +/- 23 min (n = 10) versus 69 +/- 7 min for atracurium (n = 10). The recovery index (the time required for twitch height to rise from 25% to 75%) was three times quicker (p less than 0.01) for atracurium (10 +/- 3 min; n = 10) than for alcuronium (30 +/- 13 min; n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Two groups of 20 women randomly distributed underwent general anaesthesia based on dextromoramide and droperidol. Midazolam was given 0.2 mg X kg-1 in the first group, 0.4 mg X kg-1 in the second. Induction was considered satisfactory in more than 90 p. cent of patients in both groups (NS). Midazolam produced a decrease of systolic blood pressure of 9 mm Hg in group I (p less than 0,001) and 11 mm Hg in group II (p less than 0,001) as well as a decrease in diastolic blood pressure of 5 mm Hg (p less than 0,025) and 7 mm Hg (p less than 0,005) respectively. Heart rate decreased significantly only in group II (by 4 c X mn-1, p less than 0,01). These alterations were similar in both groups and did not reach physiologic importance. Maintenance of anesthesia as well as recovery were uneventful in all cases. Higher doses of midazolam reduced only slightly the dose of the neuroleptic. Its is concluded that midazolam is a good induction agent neuroleptic-analgesic anaesthesia. The use of more than 0.2 mg X kg-1 is of no particular interest but is well tolerated.

Postoperative plasma cortisol levels were measured in two series of surgical patients who had undergone a gynaecological operation, with respectively 17 and 16 subjects. Samples were drawn on D0 6pm, D1 8am, D2 8am and D3 8 am. A reference sample had been taken before the premedication on D0 at 8 am. The first series had been anaesthetised using a dextromoramidedroperidol type neuroleptanalgesia followed by postoperative analgesia by a noramidopyrine compound. The second series required epidural anaesthesia followed by postoperative analgesia by the injection of lidocaine at constant rate, interrupted between the last two samples. In the neuroleptanalgesia group: from a basal level of 470 nmol.l-1, plasma cortisol rose to 800 nmol.l-1 (p less than 0.01) on D0 at 6 pm to subsequently remain on a plateau between 500 and 550 nmol.l-1 (NS) within the normal physiological limits for the laboratory. In the epidural group, from a basal level of 420 nmol.l-1, plasma cortisol rose to 1000 nmol.l-1 (p less than 0.01) to return to basal levels only on D3: 450 nmol.l-1 (NS) with intermediate values of 700 and 630 nmol.l-1 (respectively: p less than 0.001 and p less than 0.05). Statistical comparison between the two groups showed that the increase in cortisol in the epidural group in relation to the other was significant throughout the period of administration of lidocaine at constant flow rate: p less than 0.05 on D0 at 6pm, D1 and D2. The results are discussed.

One hundred and seventeen caesarean sections performed under epidural anesthesia are reported. Following localization by air myelography, catheterization of the epidural space was performed in all cases. The estimated level of injection was L 1.76 +/- 0.82. The local anesthetic used was: lignocaine 2 p. 100 with adrenalin 1/160,000 (N = 13) in a dose of 388 mg +/- 81.4; bupivacaine 0.5 p. 100 with adrenalin 1/2000,000 (N = 77) in a dose of 106.6 mg +/- 20; or a mixture of bupivacaine 0.5 p. 100 with adrenalin 1/200,000 and lignocaine 2 p. 100 without adrenalin (N = 27) at doses of 91.0 mg +/- 23.9 and 238 mg +/- 53.4 respectively. The failure rate was 5.97 p. 100 and the operative conditions were satisfactory in 91.5 p. 100 of cases. Apgar scores were greater than 7 in 87 p. 100 of cases at one minute and 99 p. 100 of cases at 5 minutes. The proportion of minor incidents was 30 p. 100, and of complications 3.5 p. 100. Their prevention and treatment and the anesthetic protocol are discussed.

125 caesarean operations are conducted under peridural anaesthesia with a mixture of local anaesthetics containing per milliliter: 2.5 mg of bupivacaine, 2.5 mg of etidocaine, 12.5 mg of lidocaine, and 5.10(-6) epinephrine. The dose injected is 23.37 +/- 1.98 ml, the volume necessary for blocking a metamer being 1.18 +/- 0.10 ml/segment. Satisfactory analgesia is obtained in 119 cases (95.2 p. cent), with adequate muscle relaxation in all cases. Block anaesthesia occurs after 5.81 +/- 0.67 min, last 197 +/- 62 min, and enable incision after 8.80 +/- 2.55 min with extraction of the infant after 13.72 +/- 2.85 min in 25 "extremely urgent" cases. Apgar is 8.98 +/- 1.62 after one minute and 9.68 +/- 1.31 after five minutes. These results prove that under perfect circumstances it is possible to get out the baby in about ten minutes.

A generator producing painful stimuli every 20 ms by way of 2 ms square wave electrical impulses was used to study pain quantitatively, and the reliability of the measurements carried out on 24 healthy volunteers. The parameters measured were the levels of detection, pain and tolerance. The results showed that these levels were both stable and reproducible. However, there were very important individual differences.

The useful intramuscular premedication dose of midazolam was determined in 100 children divided up in three age groups: one month to three years, 3 to 10 years, 10 to 15 years. All biometric parameters were normal for the age, and comparable between similar age groups. Haemodynamic and respiratory parameters were not altered by the premedication. The reduction in anxiety, as assessed by the child's behaviour, was good or excellent in more than 85% of cases from all age groups; it was proportional to the dose used. The doses that had, for equivalent reductions in anxiety as assessed by the chi-square test, the least hypnotic effect, were: 0.5 mg X kg-1 before three years of age, 0.4 mg X kg-1 for the 3 to 10 yr olds, and 0.25 mg X kg-1 for the 10 to 15 yr olds. This fall in dose with age, quite usual in paediatrics, was not unexpected. The level of consciousness, one hour after surgery, was always normal. No undesirable side-effect was observed. These results, together with its physical, chemical and pharmacodynamic characteristics, make midazolam a choice drug for intramuscular premedication in children, with a foreseeable use in day-care anaesthesia. The unexpected finding of an age-dependent dissociation between the reduction in anxiety and the hypnotic effect is discussed in the light of a study carried out in the adult and recent data from the literature.

Prolactin and somatotrophin were measured during the postoperative period in two series of 15 patients after gynaecological surgery. Samples were collected for four days at the same times during the 24 hours period. The anesthetic given in the first group was a neuroleptanalgesia of dextromoramide-droperidol type followed by postoperative analagesia using a noramidopyrine compound. In the second group, epidural anaesthesia was given, followed postoperatively by the injection of lidocain at constant rate interrupted between the final two samples. In the neuroleptanalgesia group, from a basal levels of 11 micrograms.l-1, prolactin rose to 22 micrograms.l-1 on the evening after surgery (p less than 0.001) to subsequently stay on a plateau between 6 and 8 micrograms.l-1 (p less than 0.025 to p less than 0.005). From a basal level of 2.8 micrograms.l-1, somatotrophin rose to 9 micrograms.l-1 (p less than 0.05) then fell progressively from 7.5 to 2 micrograms.l-1 (NS on D1, D2, D3). In the epidural group, from a basal level of 13.5 micrograms.l-1, prolactin rose to 23 micrograms.l-1 on the evening after surgery (NS) to fall sharply on D1 to 5.6 micrograms.l-1 (p less than 0.01) and then follow a plateau on D2 and D3 of the order of 11 to 12 micrograms.l-1 (NS). From a basal level of 1.9 micrograms.l-1, somatotrophin rose to 10 micrograms.l-1 (p less than 0.001) to fall again to 4.5 micrograms.l-1 on D1 (p less than 0.01) and to 2 micrograms.l-1 on D2 and D3 (NS). Comparison of these two groups showed a difference only on D2 with regard to somatotrophin (p less than 0.05) and on D2 and D3 with regard to prolactin (p less than 0.025 and p less than 0.05). These results are discussed. They do not indicate any fundamental difference in the endocrine response to aggression in relation to the two types of anaesthetic studies.