Hörnchen U, Lussi C, Thomas M, Schüttler J
Institut für Anästhesiologie der Rheinischen-Friedrich-Wilhelms-Universität Bonn.
Anasthesiol Intensivmed Notfallmed Schmerzther. 1992 May;27(3):160-5. doi: 10.1055/s-2007-1000272.
In a porcine CPR-model, we investigated the pharmacokinetics and pharmacodynamics of norepinephrine (NE) after intravenous (10 g/kg, n = 10, group A) and endobronchial (e.b., 100 micrograms/kg, n = 10, group B) administration. After 3 min of cardiac arrest induced by electroshock, restitution of spontaneous circulation (ROSC) was achieved in 8 animals in group A after 3.3 +/- 1.6 min, and in group B in 6 animals after 2.5 +/- 0.6 min. Haemodynamics during CPR were not significantly different, but during the first hour after ROSC e.b. NE showed a depot effect. Maximum venous (642 +/- 182 ng/ml after 3.5 +/- 0.3 min) and arterial (147 +/- 21 ng/ml after 4.2 +/- 0.4 min) NE concentrations in group A were significantly higher compared with values in group B (77 +/- 18 ng/ml after 5.5 +/- 0.5 min venous, 46 +/- 11 ng/ml after 6.0 +/- 0.7 min arterial). The area under the curve (AUC) in group A was calculated to be 55 +/- 12 ng/ml min (venous) and 35 +/- 7 ng/ml min (arterial) representing a pulmonary first-pass effect of 40%. In group B, the dose-adjusted AUC (39 +/- 13 ng/ml min venous, 30 +/- 10 ng/ml min arterial) represented a pulmonary first-pass effect of only 25%. Despite this lower pulmonary first pass, however, it is concluded that after e.b. administration of NE absorption is too much delayed and peak concentrations are too low. Therefore, NE should not be given via this route during CPR.
在猪心肺复苏模型中，我们研究了静脉注射（10 μg/kg，n = 10，A组）和支气管内注射（100 μg/kg，n = 10，B组）去甲肾上腺素（NE）后的药代动力学和药效学。在电击诱发心脏骤停3分钟后，A组8只动物在3.3±1.6分钟后实现自主循环恢复（ROSC），B组6只动物在2.5±0.6分钟后实现自主循环恢复。心肺复苏期间的血流动力学无显著差异，但在ROSC后的第一小时内，支气管内注射NE显示出储库效应。A组静脉血NE最高浓度（3.5±0.3分钟后为642±182 ng/ml）和动脉血NE最高浓度（4.2±0.4分钟后为147±21 ng/ml）显著高于B组（静脉血5.5±0.5分钟后为77±18 ng/ml，动脉血6.0±0.7分钟后为46±11 ng/ml）。A组曲线下面积（AUC）经计算为静脉血55±12 ng/ml·min，动脉血35±7 ng/ml·min，代表肺首过效应为40%。B组剂量调整后的AUC（静脉血39±13 ng/ml·min，动脉血30±10 ng/ml·min）代表肺首过效应仅为25%。然而，尽管肺首过效应较低，但得出的结论是，支气管内注射NE后吸收延迟过多且峰值浓度过低。因此，在心肺复苏期间不应通过该途径给予NE。
