„Drug Interaction Stewardship“ (DIS) und therapeutisches Drug-Monitoring (TDM) für die antiinfektive Therapie in der operativen Intensivmedizin, eine monozentrische Beobachtungsstudie

Zusammenfassung

Einleitung Die Medikation des chirurgischen Intensivpatienten ist schwer kalkulierbar durch gestörte Organfunktionen, Organversagen, pathophysiologische Veränderungen bei schwerer Erkrankung und in der Sepsis, laufende Organersatz-, Nierenersatz- und Leberersatzverfahren sowie die unterschiedliche Pharmakokinetik/Pharmakodynamik (PK/PD) von medikamentösen Substanzen und zahlreichen Medikamenteninteraktionen.

Ziel Interdisziplinäres Vorgehen im klinischen Alltag zur Optimierung sowohl der Vielfachmedikation als auch der laufenden medikamentösen Therapie von Patienten vor indizierten Operationen oder Interventionen sowie im Rahmen des peri- und postoperativen intensivmedizinischen Managements.

Methode Etablierung einer „Drug Interaction Stewardship“ (DIS), analog und zeitgleich zur bereits etablierten Antibiotic Stewardship (ABS) in der Routine einer chirurgischen Intensivstation. Erweiterung des etablierten therapeutischen Drug-Monitorings (TDM) auf Standard-Antiinfektiva (Meropenem, Piperacillin-Tazobactam, Ceftazidim, Linezolid, Voriconazol, Fluconazol, Caspofungin), für die bisher kein TDM etabliert ist, an einer konsekutiven Patientenkohorte über einen definierten Zeitraum im Rahmen einer klinisch-systematischen „Single-Center“-Beobachtungsstudie (tertiäres Zentrum).

Ergebnisse Im Zeitraum 01/2012 bis 08/2016 führten 1454 klinisch-pharmakologische Patientenvisiten zu 385 (26,5%) Änderungen einer vorher vom erfahrenen Intensivmediziner eingestellten medikamentösen Therapie, am häufigsten in 156 (10,7%) Fällen infolge einer neu kalkulierten PK/PD. 2333 Proben TDM ergaben in 1130 Fällen (48,4%) einen Talspiegel im gewünschten Bereich. In 427 (18,3%) Fällen war wegen eines zu niedrigen und in 776 (33,3%) Fällen wegen eines zu hohen Substanzspiegels eine Änderung der antiinfektiven Therapie nach Art, Dosis, Dosisintervall oder Applikationsart erforderlich.

Schlussfolgerung DIS und TDM führen bei chirurgischen Intensivpatienten in einer hohen Rate zur Detektion von unerwünschten Medikamenteninteraktionen sowie inadäquaten Substanzspiegeln mit dem Ansatz für gezielte Therapieänderungen.

Abstract

Introduction Appropriate medication of intensive care patients is complicated by disturbed organ functions and organ failure, pathophysiological changes in severely ill patients as well as possible sepsis, ongoing haemodialysis for renal and hepatic insufficiency, varying pharmacokinetics/-dynamics (PK/PD) of drugs as well as numerous drug interactions.

Aim Illustration of an interdisciplinary approach in daily clinical practice to optimise regular “polymedication” as well as the ongoing medication of patients prior to surgical interventions as indicated and as part of the appropriate peri- and postoperative intensive care management.

Method A so-called “drug interaction stewardship” (DIS) is very similar to the already established “antibiotic stewardship” (ABS) during daily clinical routine of an intensive care unit and has been implemented. In addition, therapeutic drug monitoring (TDM) has been extended to antibiotics/antimycotics (such as meropenem, piperacillin-tazobactam, ceftazidime, linezolide, voriconazole, fluconazole, caspofungin), for which TDM had not yet been established. This was in a consecutive cohort of patients with abdominal surgery over a defined time period and was part of a systematic clinical single centre observational study (tertiary centre).

Results From 01 – 2012 to 08 – 2016, 1,454 single drug patient consultations led to 385 (26.5%) changes in medical treatment, which had been previously initiated by an experienced intensive care physician. Most frequently in 156 cases (10.7%) this was due to newly calculated PK/PD. Analysis of 2,333 TDM samples resulted in a minimum serum level within the adequate range in 1,130 cases (48.4%). In 427 cases (18.3%), the drug serum level was too low and in 776 subjects (33.3%), prompting a change in the type, dose, dose interval and application route.

Conclusion DIS and TDM provide a high rate of detection of unwanted drug interactions and inappropriate drug levels in surgical intensive care patients and help to assure targeted therapy changes.

Schlüsselwörter

Antibiotikatherapie - Antibiotikaspiegel - klinisch-pharmakologische Beratung - Medikamenteninteraktionen - Pharmakokinetik

Key words

drug interaction stewardship - drug monitoring - antiinfective treatment - antibiotic stewardship - drug levels - pharmacokinetics

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