Two different approaches for pharmacokinetic modeling of exhaled drug concentrations.

Online measurement of drug concentrations in patient's breath is a promising approach for individualized dosage. A direct transfer from breath- to blood-concentrations is not possible. Measured exhaled concentrations are following the blood-concentration with a delay in non-steady-state situations. Therefore, it is necessary to integrate the breath-concentration into a pharmacological model. Two different approaches for pharmacokinetic modelling are presented. Usually a 3-compartment model is used for pharmacokinetic calculations of blood concentrations. This 3-compartment model is extended with a 2-compartment model based on the first compartment of the 3-compartment model and a new lung compartment. The second approach is to calculate a time delay of changes in the concentration of the first compartment to describe the lung-concentration. Exemplarily both approaches are used for modelling of exhaled propofol. Based on time series of exhaled propofol measurements using an ion-mobility-spectrometer every minute for 346 min a correlation of calculated plasma and the breath concentration was used for modelling to deliver R(2) = 0.99 interdependencies. Including the time delay modelling approach the new compartment coefficient k(e0lung) was calculated to k(e0lung) = 0.27 min(-1) with R(2) = 0.96. The described models are not limited to propofol. They could be used for any kind of drugs, which are measurable in patient's breath.

[Bleeding after cardiac surgery: the role of recombinant factor VIIa]. / Blutungen nach herzchirurgischen Operationen: Die Rolle des rekombinanten Faktors VIIa.

Cardiac surgery carries a remarkable risk of blood loss requiring transfusion of blood products. Moreover, severe bleeding necessitating reoperation occurs in 3-5% of patients according to international studies. These patients face a significantly higher morbidity and mortality. This underscores the need for a safe and effective haemostatic therapy, which may significantly improve the outcome. Recombinant activated factor VII is approved for haemophiliacs with inhibitors and patients with thrombasthenia Glanzmann and factor VII deficiency. In the proceeding years a series of articles has been published reporting the successful and safe therapy of refractory bleeding after cardiac surgery. This review focuses at presenting the pathophysiological alterations of the haemostatic system related to the cardiopulmonary bypass. These alterations are thought to explain the high risk of bleeding after cardiopulmonary bypass. Furthermore, the use of rFVIIa in paediatric and adult cardiac surgery is reviewed and critically discussed.