Hörnchen U, Schüttler J, Stoeckel H
Institute of Anaesthesiology, Rheinische Friedrich-Wilhelms-University of Bonn, Germany.
Eur J Anaesthesiol. 1992 Jan;9(1):85-91.
The influence of the pulmonary circulation on the pharmacokinetics and -dynamics of endogenously released, and intravenously injected (10 micrograms kg-1), and endobronchially (e.b.) administered (100 micrograms kg-1) adrenaline was investigated in an animal cardiopulmonary-resuscitation (CPR) model. During resuscitation 80% of endogenously released and i.v. adrenaline was eliminated before reaching the arterial circulation, whereas arterial availability of adrenaline was higher than mixed-venous availability in the e.b.-medicated animals. Success of resuscitation seemed to depend on maximum adrenaline concentrations and drug availability in arterial blood. Although the average amount of endogenously released adrenaline was calculated to be equivalent to an i.v. bolus of 8 micrograms kg-1, additional i.v. or e.b. adrenaline medication resulted in higher arterial plasma concentrations, improved circulation during CPR, and better resuscitability. It is concluded that, even without a specific pulmonary metabolism, a drastic decrease in blood flow can lead to significant arterio-venous gradients in plasma concentrations and availability of a drug with a very high clearance like adrenaline.
在动物心肺复苏（CPR）模型中，研究了肺循环对内源性释放、静脉注射（10微克/千克）和经支气管内（e.b.）给药（100微克/千克）肾上腺素的药代动力学和药效动力学的影响。在复苏过程中，80%的内源性释放和静脉注射的肾上腺素在到达动脉循环之前就被清除了，而在经e.b.给药的动物中，肾上腺素的动脉可用性高于混合静脉可用性。复苏的成功似乎取决于动脉血中肾上腺素的最大浓度和药物可用性。尽管计算得出内源性释放的肾上腺素平均量相当于8微克/千克的静脉推注量，但额外的静脉注射或e.b.肾上腺素给药导致动脉血浆浓度更高、CPR期间循环改善以及更好的复苏能力。得出的结论是，即使没有特定的肺代谢，血流的急剧减少也会导致血浆浓度和具有非常高清除率的药物（如肾上腺素）可用性出现显著的动静脉梯度。
