An animal model for the investigation of adverse responses to i.v. anesthetic agents and their solvents

Abstract

In man the number of adverse responses to the Cremophor-containing anaesthetic agents Althesin and propanidid (Epontol) has been reported to be greater than that encountered with thiopentone. The response of the mini-pig to repeated injection of a range of i.v. anaesthetics and their solvents has been investigated in an attempt to ascertain the possible role of Cremophor in the production of these responses. A second injection of Cremophor EL or the Cremophor/Micellophor-containing agents Althesin and propanidid (Epontol), given 7 days after the first, produced a high frequency of adverse responses. On only one occasion, when alphaxalone and alphadolone were given in a mixture of alcohol and propylene glycol, was an abnormal response seen on the first administration of any agent. The second administration of alphaxalone and alphadolone in the same solvent produced abnormal responses in two of four pigs. No such responses were seen when propanidid was administered in alcohol and propylene glycol or when this solvent mixture was given alone. No abnormal responses were seen following the repeated administration of thiopentone. A marked increase in arterial pressure, and an immediate but transient marked decrease in the numbers of circulating polymorphonuclear leucocytes, were consistent findings in animals showing adverse responses. No abnormal responses were found when the interval between two administrations of Althesin was extended to 3 weeks.