[Anesthesia with propanidid in a liposomal preparation. An experimental study in swine].
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Propanidid was widely used as a short-acting i.v. anaesthetic until it was withdrawn due to severe haemodynamic side effects.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.
Klockgether-Radke
A
A
Zentrum Anaesthesiologie, Rettungs- und Intensivmedizin, Georg-August-Universität Göttingen.
Kersten
J
J
Schröder
T
T
Stafforst
D
D
Kettler
D
D
Hellige
G
G
D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D002395:Catecholamines / Q000097:blood; D004337:Drug Carriers / Q000009:adverse effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000097:blood; D008081:Liposomes / Q000009:adverse effects; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000009:adverse effects; D011229:Preanesthetic Medication; D011410:Propanidid / Q000008:administration & dosage / Q000009:adverse effects; D013552:Swine
D018686:Anesthetics, Intravenous; D002395:Catecholamines; D004337:Drug Carriers; D008081:Liposomes; D014677:Pharmaceutical Vehicles; C022131:cremophor; D011092:Polyethylene Glycols; D006632:Histamine; D011410:Propanidid
Anästhesie mit Propanidid in liposomaler Zubereitung. Eine experimentelle Studie am Schwein.