[The pulmonary first pass effect of noradrenaline following intravenous and endobronchial administration for resuscitation].
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.
Hörnchen
U
U
Institut für Anästhesiologie der Rheinischen-Friedrich-Wilhelms-Universität Bonn.
Lussi
C
C
Thomas
M
M
Schüttler
J
J
D000818:Animals; D001980:Bronchi; D016887:Cardiopulmonary Resuscitation; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007275:Injections, Intravenous; D009638:Norepinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D013552:Swine
D009638:Norepinephrine
Untersuchungen zum pulmonalen first-pass-Effekt von Noradrenalin nach intravenöser und endobronchialer Gabe zur Reanimation.