Influence of the pulmonary circulation on adrenaline pharmacokinetics during cardiopulmonary resuscitation

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.