Klockgether-Radke A, Kersten J, Schröder T, Stafforst D, Kettler D, Hellige G
Zentrum Anaesthesiologie, Rettungs- und Intensivmedizin, Georg-August-Universität Göttingen.
Anaesthesist. 1995 Aug;44(8):573-80. doi: 10.1007/s001010050191.
Propanidid was widely used as a short-acting i.v. anaesthetic until it was withdrawn due to severe haemodynamic side effects.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.
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.
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).
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.
丙泮尼地曾作为短效静脉麻醉剂被广泛使用，后因严重的血流动力学副作用而被停用。据推测，伴有大量组胺释放的类过敏反应是由溶剂聚氧乙烯蓖麻油引起的，而非丙泮尼地本身。在这项动物研究中，对一种新的丙泮尼地脂质体制剂进行了检测，并与聚氧乙烯蓖麻油溶液中的丙泮尼地以及丙泊酚进行了比较。
18只猪被随机分为以下几组：第1组（n = 6）：脂质体制剂中的丙泮尼地（PropaLip；德国布劳恩·梅尔松根公司）。以60mg/kg诱导麻醉，随后以400mg/kg·h持续输注。第2组（n = 6）：聚氧乙烯蓖麻油溶液中的丙泮尼地（PropaCrem；匈牙利布达佩斯吉德昂·里奇特公司的索姆布雷文）15mg/kg，100mg/kg·h。第3组（n = 6）：丙泊酚（德国普朗施塔特阿斯利康公司的得普利麻）5mg/kg，20mg/kg·h。诱导麻醉并气管插管后，动物用含50%氧气的空气进行通气。基本监测包括无创血压测量、心电图监测和二氧化碳描记法。在一个简短的外科手术过程中，分别经右颈动脉和右颈内静脉放置动脉和肺动脉导管。一旦动物对疼痛刺激有反应，就进行第二次麻醉诱导，随后对所研究药物进行60分钟的持续输注，并进行有创血流动力学监测，包括动脉压和肺动脉压以及心输出量。采集血样以测量血清肾上腺素、去甲肾上腺素、皮质醇、醛固酮、促肾上腺皮质激素和组胺水平。
丙泊酚组动物的插管条件和麻醉质量最佳，其次是PropaCrem组动物。尽管PropaLip组动物的剂量高达410mg/kg·h，导致容量负荷高达16.4ml/kg·h，但仍显示出麻醉质量较差的迹象。在第1组中，我们记录到心率（91对115次/分钟）、心输出量（5.4对7.7升/分钟）、血浆儿茶酚胺水平和组胺浓度（124 - 268ng/ml）的升高幅度最大。
在我们的动物研究中，脂质体制剂中的丙泮尼地作为一种新型麻醉剂未能显示出前景。鉴于该药物靶向网状内皮系统的细胞，尤其是肝脏，脂质体在此处从血液中被清除，我们对结果进行了讨论。这可能导致丙泮尼地转运至其主要失活部位之一。
