Forane (Compound 469): 2. Biochemical effects of repeated administration to animals, response to bleeding, and compatibility with epinephrine

Abstract

Trm EXPERIMENTS ltEPORTED here were designed to reveal some biochemical effects which might be produced by the repeated inhalation of Forane by dogs and monkeys, and to compare its influence on the cardiac irritability of dogs with that of other halogenated anaesthetics. METHODS Biochemical Effects in DogsTwo groups of five mature, pedigreed, female beagles were used, having a mean body weight of 10.6 kg. Each of the dogs in one of these groups had an open liver biopsy taken, under thiopentone anaesthesia, a month before the experiment. These received 3 hours of anaesthesia a day on five consecutive days. The other group of beagles was anaesthetized for 4 hours a day on alternate days, up to a total of 16 hours.After food had been withheld for 12 hours, anaesthesia was induced by mask inhalation of <4 per eent Forane in oxygen, and the dogs were intubated. No premedication or muscle relaxant drugs were used. The animals were then eonneeted to a non-rebreathing system, using Fink valves, and maintained under surgical anaesthesia with spontaneous respiration for the appropriate periods by the administration of between 1.0 and 1.5 per cent Forane in oxygen. Fluotec vapourisers were used which had been recalibrated by gas chromatography. Arterial and venous blood samples were drawn immediately after induction and just before termination of anaesthesia, and these were analysed by standard techniques for the variables listed in Tables I and II. No intravenous fluids were given. The blood chemistry results were studied for evidence of changes occurring during a single day's anaesthesia, those seen between the 'start' samples on the first day and the 'start' samples on the last day, and the effects of serial removal of blood. 1,2After the last anaesthetic, those dogs that received 3 hours of anaesthesia on five successive days were sacrificed by intravenous injection of a barbiturate, and tissue specimens of liver, kidney, pancreas, small bowel, spleen, lungs, and heart were taken for gross and microscopic examination.

Doses of epinephrine causing arrhythmia during enflurane, methoxyflurane and halothane anaesthesia in dogs

“…While enflurane has been reported by some 11' 12 to "sensitize" the myocardium, a comparative evaluation of enflurane and methoxyflurane in beagles by Byles et al 13 found cardiac irritability with both anaesthetics to be similar and significantly less ,as compared with halothane. Similar observations have been made in unpremedicated goats anaesthetized with these anaesthetics.…”

Effects of repeat exposure to inhalation anesthetics on liver and renal function

“…[19] In the prospective human study of repeated sevoflurane anesthesia, the multiple administration of sevoflurane anesthesia was not related to adverse effects of liver and renal damage. [17] Repeated isoflurane anesthesia did not produce liver and renal damage in an animal study,[20] while Brunt et al . reported a case with liver damage by repeated isoflurane anesthesia.…”

Isoflurane as an anesthetic for experimental animal surgery

“…Isoflurane does not need to be stabilized with preservatives and is nonflammable over all ranges of application. Prolonged and/or repetitive isoflurane anesthesia does not cause hepatorenal damage even when administered to animals for up to 35 consecutive days (Byles et al, 1971). No hepatic necrosis is seen with isoflurane administra-tion even under conditions where other anesthetics do cause hepatic necrosis (Harper et al, 1981).…”