Propofol, currently available as a lipid emulsion (Intralipid loo/), is widely used for induction and maintenance of general anaesthesia [ 11. We have recently evaluated the effects of total intravenous anaesthesia with propofol on the immune response during minor surgery [2] and found increased percentages of T helper lymphocytes in the blood after propofol anaesthesia but not after conventional balanced anaesthesia with thiopentone and nitrous oxide. T helper cells are a subset of T lymphocytes pivotal in augmenting both cell-mediated [3] and humoral immunity [4]. Major surgery causes changes in the immune response which are related to the extent of surgical trauma [5] and the neuroendocrine stress response [6]. In this study we compared the effects of propofol infusion anaesthesia and combined isoflurane anaesthesia on the immune response to abdominal hysterectomy. Patients and methodsWe studied 30 women (median age 47 years; range 36-65 years), ASA grades 1 or 2 scheduled for elective abdominal hysterectomy. The patients were allocated randomly to two groups. Patients with immunosuppressive treatment, malignant disease or marked obesity (weight exceeding the ideal body weight by 30% or more) were not studied.
In a double-blind randomized study 47 patients received tofizopam 100 mg orally the night before operation, and 100 mg on the morning of operation; 49 patients received nitrazepam 5 mg and 50 patients received placebo. On average the nitrazepam group slept better and were better sedated than the tofizopam or placebo groups. Compared with placebo or nitrazepam, tofizopam decreased the excitement of the patients. The effect tofizopam on apprehension and excitement was significantly better than those of placebo or nitrazepam. Nitrazepam, but not tofizopam, significantly decreased the induction requirements of thiopentone.
The clinical effects of oral flunitrazepam (2 mg on the night before operation followed by 2 mg on the morning of operation) and placebo as premedicants were tested in a double-blind study in 81 gynaecological patients. The separate or total concentrations of flunitrazepam and its demethylated metabolite in plasma (measured by gas chromatography) were correlated with the clinical effects of flunitrapam premedication, assessed both sugjectively and objectively. In most parameters tested (sleep on the night before operation, sedation, apprehension, headache, pulse rate), there was a positive, significant difference between the flunitrazepam group (n = 44) and the placebo group (n = 37). No significant difference was found between the two groups in emetic effect, excitement, systolic blood pressure increase, and vene-puncture, but the patients receiving flunitrazepam felt significantly more dizziness. The temperature of the left forefinger before, during and after the anaesthesia did not vary significantly between the two groups. There was no correlation between the plasma concentration of flunitrazepam and its demethylated metabolite (separate or total concentrations) and any of the parameters tested before induction of anaesthesia. Flunitrazepam is a new oral premedicant with prominent sedative and anxiolytic actions. When the drug is given as a sedative on the night before operation, followed by a second dose on the morning of operation, the beneficial effects last for at least 8 hours after the second dose.
Sixty-one patients received nitrazepam 5 mg by mouth on the night before operation, followed by 2.5 mg given on the morning of operation and were compared with 60 patients who received no premedication. All were undergoing either therapeutic abortion, by dilatation and curettage, or explorative curettage. The plasma concentrations of nitrazepam were determined by gas chromatography and compared with the clinical effects of the drug. The premedicated patients slept better on the night before operation, and were more sedated and less apprehensive. Headache was more frequent following nitrazepam. There was no significant difference between the groups in respect of dizziness and nausea. The unpremedicated patients had a faster average heart rate. There was no obvious relationship between the plasma concentration of nitrazepam and the quality of sleep, degree of sedation, apprehension, excitement or headache.
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