ISSN:
1432-055X
Keywords:
Schlüsselwörter Propanidid
;
Liposomen
;
Propofol
;
Hämodynamik
;
Histamin
;
Katecholamine
;
Key words Propanidid
;
Liposomes
;
Propofol
;
Haemodynamics
;
Histamine
;
Catecholamines
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Description / Table of Contents:
Abstract Background. Propanidid was widely used as a short-acting i.v. anaesthetic until it was withdrawn due to severe haemodynamic side effects. It was presumed that anaphylactoid reactions with massive histamine release were caused by the solvent cremophor rather than by propanidid itself. A new liposomal preparation of propanidid was examined in this animal 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 preparation (PropaLip; Braun Melsungen, Germany). Anaesthesia was induced with 60 mg/kg, followed by continuous infusion of 400 mg/kg·h. Group 2 (n=6): Propanidid in cremophor solution (PropaCrem; Sombrevin, Gedeon Richter, 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 short surgical procedure, arterial and pulmonary artery catheters were placed via the right carotid artery and right internal jugular vein, respectively. As soon as the animals responded to a pain stimulus a second anaesthetic induction was performed, followed by a 60-min continuous infusion of the agent studied with invasive haemodynamic monitoring including arterial and pulmonary arterial pressures and cardiac output. Blood samples were taken for the measurement of serum levels of adrenaline, noradrenaline, cortisol, aldosterone, adrenocorticotropic hormone, and histamine. Results. Intubation conditions and quality of anaesthesia were best in propofol animals, followed by PropaCrem animals. In spite of the large dose of 410 mg/kg·h, resulting in a volume load 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 increases in heart rate (91 vs. 115/min), cardiac output (5.4 vs. 7.7 l/min), plasma catecholamine levels, and histamine concentrations (124–268 ng/ml). Conclusions. In our animal study, propanidid in liposomal preparation failed to show promise as a new anaesthetic agent. Our results are discussed in view of a drug targeting the cells of the reticuloendothelial 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.
Notes:
Zusammenfassung In einer tierexperimentellen Studie wurden 18 Läuferschweine untersucht, von denen je 6 Tiere (1) Propanidid in Liposomendispersion (abgekürzt PropaLip), (2) Propanidid in Cremophor (abgekürzt PropaCrem) und (3) Propofol erhielten. Nach Narkoseeinleitung mit 60 mg/kg PropaLip, 15 mg/kg PropaCrem bzw. 5 mg/kg Propofol wurden die Tiere intubiert, für die weiteren Messungen instrumentiert und in einer anschließenden 60minütigen Narkose untersucht. Der Anästhetikaverbrauch betrug 16 mg/kg·h Propofol, 120 mg/kg·h PropaCrem und 410 mg/kg·h PropaLip. Trotz dieser hohen Dosierung und der damit verbundenen Volumenbelastung von 16,4 ml/kg·h war die Anästhesiequalität in der PropaLip-Gruppe unbefriedigend. Bei diesen Tieren traten die ausgeprägtesten Anstiege von Herzfrequenz, HZV, Katecholamin- und Histaminspiegeln auf, weitgehend konstant blieben die genannten Parameter bei der Propofolgruppe, während die PropaCrem-Tiere eine Mittelstellung einnahmen. Offenbar ist die Verfügbarkeit von Propanidid in der Liposomenpräparation schlechter als in der Cremophorlösung. Ein Zusammenhang der geringen Wirksamkeit mit der gezielten Aufnahme von Liposomen in die Zellen des RES, z.B. der Leber, wo Propanidid inaktiviert wird, wird diskutiert.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001010050191
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