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Medikamentendosierung unter extrakorporaler Therapie

  • J.T. Kielstein
Leitthema

Zusammenfassung

Hintergrund

Die Dosierung von Medikamenten bei Intensivpatienten bleibt eine Herausforderung. Während die Dosis von Katecholaminen oder Insulin nach dem biologischen Effekt, also dem mittleren arteriellen Blutdruck oder dem Blutzucker gesteuert werden kann, ist die Anpassung der Dosis von Antibiotika an die Intensität der Nierenersatztherapie deutlich schwieriger. Selbst bei Intensivpatienten mit intakter Nierenfunktion ist die Pharmakokinetik und Pharmakodynamik deutlich verändert.

Problemstellung

Aufgrund eines höheren Verteilungsvolumens („fluid rescucitation“, „capillary leak“) oder einer Hypalbuminämie kann die wirksame Konzentration eines Antibiotikums deutlich vermindert sein. Kommt ein Nierenfunktionsverlust hinzu, wird das Problem noch komplexer und die Dosierung der Antibiotika noch schwieriger, da nur bei wenigen Antibiotika die Möglichkeit des Drug Monitorings besteht. Dosierungsempfehlungen beruhen häufig, auch in der aktuellen Version, auf Verfahren mit heute nicht mehr eingesetzten Filtern und Intensitäten und sind somit häufig nicht mehr zutreffend. Dies ist durch den sog. Vancomycin-Test einfach festzustellen.

Ausblick

Langfristig wird eine Ausweitung des therapeutischen Drug Monitorings in dieser Patientenpopulation notwendig werden. Dies allein reicht aber sicher nicht aus, um patientennahe relevante Endpunkte, wie Beatmungszeit oder Tod, zu beeinflussen, sondern kann nur Ausgangspunkt für eine Qualitätsverbesserung im Bereich Infektiologie/Mikrobiologie/Pharmakotherapie sein. Um das notwendige Wissensfundament hierfür zu legen, sollte diese Problematik auch vermehrt Eingang in die Fort- und Weiterbildungspläne der entsprechenden Facharztdisziplinen aber auch in die CME Programme finden.

Schlüsselwörter

Therapeutisches Drug Monitoring Antibiotika Sepsis Extrakorporale Membranoxygenierung Nierenersatzverfahren 

Drug dosing in extracorporeal therapy

Abstract

Background

The dosing of drugs in critically ill patients remains challenging. While increased volume of distribution after fluid resuscitation and increased cardiac output can increase clearance of antibiotics, liver failure and renal failure can decrease the clearance of drugs. If an extracorporeal device is used, the dosing of drugs becomes even more difficult. Even in intensive care patients with intact renal function, pharmacokinetics and pharmacodynamics are significantly altered.

Current situation

While there are direct readouts such as the mean arterial pressure for catecholamine therapy and measurement of serum glucose to guide insulin dosing, we lack such prompt readouts for dosing of antibiotics. In this manuscript, the principles and basic knowledge needed to improve dosing of anti-infective agents in critically ill patients undergoing extracorporeal treatment are described. Examples are the rapid utility assessment drug dosing reference books and online resources including the vancomycin test. Potential problems of extracorporeal membrane oxygenation and adsober therapy associated with renal replacement therapy are also addressed.

Conclusion

The importance of therapeutic drug monitoring is discussed. Global initiatives to increase quantity and quality of pharmacokinetic studies in this patient population through incentives and guidance of the regulatory agencies, as well as the major unmet educational need to integrate basic knowledge in this field into residency and fellowship programs as well as CME are briefly mentioned.

Keywords

Therapeutic drug monitoring Antibiotics Sepsis Extracorporeal membrane oxygenation Renal replacement therapy 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt. J.T Kielstein erhielt von Fresenius Medical Care und der Novartis GmbH Unterstützung für Investigator Initiated Trials.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Klinik für Nieren- und HochdruckerkrankungenMedizinische Hochschule HannoverHannoverDeutschland

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