PROPANIDID IN LIPOSOMAL PREPARATION - AN EXPERIMENTAL-STUDY IN PIGS

Background. Propanidid was widely used as a short-acting i.v. anaesthe tic until it was withdrawn due to severe haemodynamic side effects. It was presumed that anaphylactoid reactions with massive histamine rele ase were caused by the solvent cremophor rather than by propanidid its elf. A new liposomal preparation of propanidid was examined in this an imal study and compared with propanidid in cremophor solution and with propofol. Methods. Eighteen pigs were randomly assigned to one of the following groups: Group 1 (n = 6): Propanidid in liposomal preparatio n (PropaLip; Braun Melsungen, Germany). Anaesthesia was induced with 6 0 mg/kg, followed by continuous infusion of 400 mg/kg . h. Group 2 (n = 6): Propanidid in cremophor solution (PropaCrem; Sombrevin, Gedeon R ichter, Budapest) 15 mg/kg, 100 mg/kg . h. Group 3 (n = 6): Propofol ( Disoprivan, Zeneca, Plankstadt, Germany) 5 mg/kg, 20 mg/kg . h. After induction and tracheal intubation, the animals were ventilated with 50 % oxygen in air. Basic monitoring included noninvasive blood pressure measurements, electrocardiographic monitoring, and capnography. In a s hort surgical procedure, arterial and pulmonary artery catheters were placed via the right carotid artery and right internal jugular vein, r espectively. As soon as the animals responded to a pain stimulus a sec ond anaesthetic induction was performed, followed by a 60-min continuo us infusion of the agent studied with invasive haemodynamic monitoring including arterial and pulmonary arterial pressures and cardiac outpu t. Blood samples were taken for the measurement of serum levels of adr enaline, noradrenaline, cortisol, aldosterone, adrenocorticotropic hor mone, and histamine. Results. Intubation conditions and quality of ana esthesia were best in propofol animals, followed by PropaCrem animals. In spite of the large dose of 410 mg/kg . h, resulting in a volume lo ad of as much as 16.4 ml/kg . h, the PropaLip animals showed evidence of poor anaesthetic quality. In group 1 we recorded the highest increa ses in heart rate (91 vs, 115/min), cardiac output (5.4 vs. 7.7 1/min) , plasma catecholamine levels, and histamine concentrations (124-268 n g/ml). Conclusions. In our animal study, propanidid in liposomal prepa ration failed to show promise as a new anaesthetic agent. Our results are discussed in view of a drug targeting the cells of the reticuloend othelial system, especially the liver, where liposomes are eliminated from the blood. This may result in the transport of propanidid to one of its major places of inactivation.