RO 21-3981, a new water soluble benzodiazepine, was studied in 24 patients both as an intravenous premedicant and to induce anesthesia. The premedicant dose of 5 mg produced lack of recall and marked sedation within 1 to 2 minutes after injection and persisted for at least 32 minutes. Subsequent induction of anesthesia required an additional 5 to 25 mg of RO 21-3981. However, anesthesia was not induced in 1 patient with 25 mg and was accomplished only with inhalation anesthesia. Loss of lid reflex was unreliable as a sign of induction for patients in whom tracheal intubation was planned. Although decreases in blood pressure of 10 to 30 mm Hg were noted after administration of RO 21-3981, systolic pressure was not recorded below 90 mm Hg. RO 21-3981, because of its amnesic, sedative, and anxiolytic properties, appears to be an excellent premedicant although the 5 mg dose studied was probably larger than necessary. For induction of anesthesia, RO 21-3981 may be an effective alternative to thiopental.
Fentanyl 0.1 mg and morphine 10 mg alone and in combination with droperidol 2.5 and 5.0 mg were studied for i.v. surgical premedication in 240 patients. Relief of anxiety, sedation, lack of recall, patient acceptance and side-effects were evaluated. The addition of droperidol to fentanyl and morphine produced greater sedation and relief of anxiety before operation, but did not improve patient acceptance or lack of recall.
Although pain and subsequent thrombophlebitis are complications in patients receiving intravenous (IV) diazepam, the mechanism and accompanying histology are unknown. To further elucidate the pathogenesis for this and determine whether it can be minimized, adult female rats received IV diazepam, diazepam vehicle, lidocaine, a combination of lidocaine and diazepam, or N saline solution, and underwent subsequent tissue light microscopy. Vascular tissue from animals receiving IV diazepam alone revealed marked inflammation with inflammatory edema and intramural polymorphonuclear-cell infiltration. Intravascular thrombosis and complete vein-wall destruction were also present in some animals as early as 48 hours after IV diazepam. Diazepam vehicle and diluted diazepam produced similar morphologic alterations. Lidocaine or saline IV resulted in no histologic alterations, while lidocaine added to diazepam did not reduce the inflammatory response. These results represent the first systematic morphologic evaluation of vein response to intravascular diazepam and suggest that it produces rapid and detrimental morphologic alterations. The dilution of diazepam or combination with lidocaine does not appear to alter these findings, and diazepam vehicle appears to assume a role in the production of the vascular injury.
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