The Effects of Flunitrazepam upon Respiration and Circulation in Man

Yoo, Myung Chull

Abstract

To 48 surgical patients (23-62 years of age, physical status 1-2), the newest banzodiazepine derivative, flunitrazepam (Ro 5-4200), in the dosage of 0.03 mg/kg was administered intravanously at a rate of 2 mg/min. as an intravenous anesthetic induction agent. All patients inhaled 100%, oxygen during induction except where blood-gas studies were conducted, in which case they breathed room air. Thereafter anesthesia was maintained with nitrous oxicle-oxygen-halothane with or without muscle relaxant following endotracheal intubation. Respiratory rate, pulse rate, tidal volume and blood pressure were measured during the pre- operative visit, immediately prior to and again after induction. All patients were premedicated with 1 mg/kg meperidine and atropine. The lead II ECG and fronto-occipital lead EEG were continuously monitored on an oscilloscope throughout the procedure. In 12 patients femoral artery and central venous catheters were inserted prior to induction and the ECG, EEC, arterial pressure and central venous pressure were recorded continuously on a Beckman Type RM 4-channel recorder. Blood samples were taken before and again 5 minutes after induction and PaO2, PaCO2 and pH were measured with a Beckman Blood Gas Measurement System. Arterial-central vanous O2 coutent difference was calculated from the computer-produced physiological table of Kellmann and Nune. To rule out the possible cardiorespiratory effects of meperidin and atropine, blood pressure, pulse rate, respiratory rate and tidal volume were also measured in 10 young resident volunteers in this department. The results are as follows: 1) Moderate respiratory depression was obvious in most patient.. Tidal volume decreased 12.9 per cent (p<0. 01) with concomitant increase (17.6 per cent, p<0.01) in respiratory rate. There was an insignifincat rise in PaCO2, accompanied by slight fall in pH and a significant fall PaO2 (17. 7 per cent, p<0. 01), which was probably due to hypoventilation and/or ventilation/perfusion irregularities. 2) It is mandatory to assist or control respiration with 100% oxygen in case of hypov ntilation or apaea during induction with flunitrazepam. 3) A slight and insignificant fall in blood pressure and increase in pulse rate were observed. No cardiac arrhythmias were noted. A fall in central venous pressure (13.3 per cent, p<0.05) was uniformly demonstrated in 12 patients in whom CVP was measured. These findings suggest that the fall in blood pressure was not due to negative inotropic effect but rather to peripheral vasodilatation caused by the sedative effect and decreased sympathetic tone produced by flunitrazepam. 4) The arterial-central venous oxygen content difference decreased by 12.1 per cent (p<0.05). It seems reasonable to assume that during induction no rnajor changes in oxygen consumption occurs. It has been shown that the central venous oxygen content or right atrial oxygen content are slightly lower but still an accurate reflection of mixed venous oxygen content. Under these circumstances the arterial-central venous oxygen content difference may be inversely related to the cardiac output. These results seem, to indicate that cardiac output increased during induction with flunitrazepam. 5) It appears that because of its minimal circulatory depressant effects flunitrazepam may be recommended in seriously ill patients, especially those with cardiac disease, in whom it is advisable to avoid hypotension and tachycardia. 6) Subjects not premedicated with meperidine required more flunitrazepam for induction of sleep to result in prolonged drowsiness. To use flunitrazepam as an intravenous anesthetic induction agent, therefore, it is advisable to premedicate the patient with meperidine to keep the dose of flunitrazepam as low as possible.

The Effects of Flunitrazepam upon Respiration and Circulation in Man

Abstract

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