A clinical double-blind study of flumazenil, antagonist of benzodiazepines, in loco-regional anesthesia.

Flumazenil has been studied for antagonism of the residual sedative effect of midazolam administered as a complement of loco-regional anesthesias. Highly significant differences appeared between the patients receiving placebos and those receiving flumazenil, showing a quick suppression of the lasting sedative effects of midazolam. At the dosage of 1 mg, flumazenil seemed to have a more efficient and complete effect than the 0.5 mg dosage. Tolerance to flumazenil was excellent with the exception of one case of agitation and disorientation, in a patient chronic consumer of benzodiazepines thus this could be considered as a deprivation syndrome. In conclusion, flumazenil should certainly have a place in the pharmacological stores of the anesthesiologist.

Controlled comparison of RO 11-1163 (moclobemide) and placebo in the treatment of depression.

Moclobemide was compared to placebo in two parallel groups of depressed patients, in a multicenter randomized, double-blind study of six weeks treatment duration. Forty seven patients participated in the study: 23 received moclobemide (flexible dose 300-600 mg/day) and 24 placebo. They were evaluated weekly for efficacy and tolerability. Moclobemide was more efficacious than placebo as judged by analysis on the total score on the Hamilton depression scale (p < 0.05) and by the overall assessment of efficacy (p < 0.01). Moclobemide was also more effective than placebo in the subgroup with neurotic depression (p < 0.05). In addition, the number of patients prematurely terminating treatment for inefficacy, was higher in the placebo than in the moclobemide group (12 versus 2, p < 0.01). The number and the severity of side-effects tended to be slightly greater in the moclobemide than in the placebo group, but this did not reach a level of significance. Cardiovascular tolerability was good in both treatment groups. No hypertensive crisis was reported. Hematology, clinical chemistry and urine analysis were not affected by the treatment in any clinically significant fashion.

Clinical evaluation of the short half-life injectable benzodiazepine midazolam, and of the specific antagonist flumazenil in upper digestive tract endoscopy.

In a first step, midazolam 0.1 mg/kg, midazolam 0.05 mg/kg and diazepam 0.15 mg/kg administered intravenously were blindly evaluated as a sedating preparation in 3 groups of each 30 patients undergoing gastroscopy. Although amnesia is better with midazolam 0.1 mg/kg, the induced sedation is protracted, which is not to be wished in ambulatory patients. On the other side, diazepam 0.15 mg/kg was locally less well tolerated. Taking into consideration the efficacy and the general and local tolerance, the dose of midazolam 0.05 mg/kg seems the best compromise. In a second step, the specific benzodiazepine antagonist flumazenil was blindly evaluated at two intravenous doses, 1 mg and 0.5 mg, against placebo for reversal of midazolam (0.1 mg/kg) induced sedation in gastroscopy patients. 1 mg of flumazenil (and to a lesser degree 0.5 mg) suppresses the sedation and amnesia induced by midazolam and normalizes attention and sensori-motor functions. However a certain degree of resedation can reappear 45-60 min. after the administration of flumazenil. Though this phenomenon did not alter the tests measuring attention and sensorimotor functions and the recovery of memory (contrary to placebo), it incites to be cautious when the drug is given to ambulatory patients.

Continuous infusion of midazolam or bolus of diazepam for postoperative sedation in cardiac surgical patients.

Sedation and recovery were studied in 14 patients requiring overnight ventilation in the ICU after aortocoronary bypass surgery performed under high-dose fentanyl anesthesia (120 micrograms/kg). Patients received either IV bolus of diazepam (group D) or a combination of IV bolus with a continuous infusion of midazolam (group M). In the 2 groups, an on-demand mode of administration was used to provide optimal sedation. In the ICU, dosages of plasma catecholamines and serum benzodiazepines were performed. After cessation of benzodiazepine administration at midnight, the rapidity of recovery and time of extubation were recorded. Results showed that in the 2 groups, the association of a high-dose fentanyl anesthesia with a profound postoperative sedation maintained the epinephrine and norepinephrine concentrations at low levels during the whole postoperative period. After benzodiazepine discontinuation, recovery and extubation were faster in group M, which correlated with the significant decrease (p less than 0.05) in blood concentration of midazolam observed the first postoperative day whereas at the same time the blood concentration of diazepam did not fall significantly.

Clinical study of Rocephin, a 3d generation cephalosporin, in various septicaemias.

Rocephin (Ro 13-9904, ceftriaxone) is a new injectable 3d generation cephalosporin characterised by a high intrinsic activity, a high resistance to beta-lactamases and a half-life of 8 h which is 4-10 times as long as the half-lives of the other cephalosporins. We administered Rocephin intravenously at a dosage of 2 x 1 g/day in 23 cases of septicaemia confirmed by positive blood cultures. The results achieved were good in 21 cases (cure of the infection episode), fair in 1 case (need to supplement Rocephin with ampicillin) and poor in 1 case of septicaemia due to resistant enterococci. The clinical and biological tolerance was excellent, and administration was particularly easy.