Evaluation of a New Benzodiazepine, Flunitrazepam (Ro 5-4200) as an Anesthetic Induction Agent

Chung, Woon Hyok; Suh, Bok Soon; Lee, Sang Choon

Abstract

A new fluorinated benzodiazepine compound Ro 5-4200 was used for induction in 58 surgical patients to evaluate the possibility of an intravenous anesthetic induction agent (Table 2 and 3). The hypnotic properties as well as respiratory, cardiovascular, muscle relaxant and local effects were observed. 1. Ro 5-4200 in doses of 2mg was slowly injected intravenously to adult patients (body weight ; 54.2+/-10.3 kg) and 1 mg to a child (body weight; 22 kg, 5 yr.) (Table 2). The tim between the start of injection and the loss of consciousness was 110.3"+/-68.6", taken from the beginning of the injection until the patient was asleep and eyelash and corneal reflexes abolished. Sleep did not occur in 2 patients (Table 4). 2. But the time to sleep after the injection varied remarkebly according to the dilution of the drug. When the dose of 2 mg of the drug was injected, undiluted directly to the small vein, the time to sleep was 83.2"+/-31.4" and 69.1"+/-31.4"; in the former case the patients complained of pain along the injected vein and the latter did not. 3. The hypnotic time with the diluted solution of the drug was 144.5" +/-4.6" and 117.3"+/-77.8", in which the former complained of pain during injection, and the latter did not. 4. Blood pressure, pulse rate and respiratory rate were measured immediately prior to induction and again 2 and 5 minutes after induction. A slight but insignificant rise in blood pressure with a mean of 3.4% in systolic and 6.7% in diastolic pressure above control value was observed in 2 minutes after injection. And at 5 minutes there was a significant fall in blood pressure, 11.3% and 4.3% respectively (p<0.05) (Table 5). 5. Pulse rate increased significantly by 12.7 beats (14.2%) a minute in 2 minutes after injection and 15.7 beat (17.5%) a minute in 5 minutes after injection from a control level of 89.6 (p<0.01) ,(Table 6). 6 Respiration became shallower and the rate decreased as the patients fell asleep. Apnea occurred in 4 patients (6.9%). In the apnea cases, respiration was controlled by mask and positive pressure ventilation. It needed that the facilities for positive pressure ventilation be available in case apnea develops. 7. During induction, tremors, abnormal muscle movements, and laryngospasm were not observed. Hiccough was observed in 4 cases (6.9%). Hiccugh had the tendency to recur during intra-abdominal procedure. 32 patients (55.0%) had an antegrade amnesia, that is shortly before the injection of the drug. They did not remember being moved to the operating table or the insertion of the injection needle. 8. Ro 5-4200 caused pain on injection when given undiluted directly into a small vein on the dorsum of the hand, and the pain was also complained of even when the drug was diluted to 5 times with normal saline or intravenous drip infusion. A localized thrombophlebitis was not seen. 9. Laryngeal reflexes were retained on induction but endotracheal intubation was tried successfully without muscle relaxant in three cases. In this procedure the patients tended to be awake and showed some resistance. The help of muscle relaxants in intubation is recommended. As to degree of everity and nature of muscle fasciculation after succinylcholine, there was somewhat delayed appearance but degree was not altered by Ro 5-4200 10. Recovery from anesthesia and reversal of muscle relaxation was unaltered. The induction was satisfactory, but slow, and characterized by minimal change in blood pressure, pulse rate and respiration. Because of this delayed induction time and the varied degree of depth of sleep, the agent seemed to be improper as an intravenous induction agent. Acknowledgements: Samples of Ro 5-4200 have been kindly supplied by Hoffmann La Roche, Hong Kong. The authors wish to thank Dr. S.S.Lo and Dr. P.A. Bulhr of Roche Products Ltd., for their assistance and advice.

Evaluation of a New Benzodiazepine, Flunitrazepam (Ro 5-4200) as an Anesthetic Induction Agent

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