Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood.

Florian Lemaitre, Nesrine Hasni, Pascal Leprince, Emmanuel Corvol, Ghassen Belhabib, Pierre Fillâtre, Charles-Edouard Luyt, Cyril Leven, Robert Farinotti, Christine Fernandez, Alain Combes

Journal: Critical care (London, England) 2016;19(1):40

PMID: 25886890

Free Full Text on BioMed Central View on PubMed

Abstract

INTRODUCTION

As a result of drug sequestration and increased volume of distribution, the extracorporeal membrane oxygenation (ECMO) procedure might lead to a decrease in drug concentrations during a patient's treatment. The aim of this study was to evaluate sedative, antibiotic and immunosuppressive drug loss in ECMO circuit using ex-vivo and in-vitro experiments.

METHODS

Blood concentrations of propofol, midazolam, cyclosporine and vancomycin were measured in an ex-vivo ECMO circuit primed with whole human blood, and compared to controls stored in polypropylene tubes. In vitro experiments were also conducted to further explore the role of temperature, oxygen exposure and polyvinylchloride surfaces on propofol loss in the ECMO circuit.

RESULTS

Propofol concentration decreased rapidly; 70% of its baseline concentration was lost after only 30 minutes, and only 11% remained after five hours (P <0.001 for the comparison with control polypropylene tube propofol concentration). Further experiments demonstrated that oxygen exposure and contact with polyvinylchloride tubing were respectively responsible for 70% and 85% of propofol loss after 45 minutes. Midazolam concentration also rapidly decreased in the ECMO circuit, with only 54% and 11% of baseline concentration being detected at 30 minutes and 24 hours respectively (P = 0.01 versus control). Alternatively, cyclosporine concentration remained stable for the five first hours, then decreased to 78% and 73% of the baseline value after 24 hours and 48 hours, (P = 0.35 versus control). Lastly, vancomycin concentration remained stable in the ECMO circuit for the 48-hour experimental protocol.

CONCLUSIONS

We observed important losses of propofol and midazolam, while cyclosporine concentration decreased slowly and moderately, and vancomycin concentration remained unchanged in the ex-vivo ECMO circuit primed with whole human blood. These data might help intensive care unit physicians planning clinical trials with a final objective to better adapt doses of these drugs while treating critically ill ECMO patients.

Address: Faculty of Pharmacy, EA4123 Barrières physiologiques et réponses thérapeutiques, Paris Sud University, Châtenay-Malabry, France. [email protected].; Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France. [email protected].; Faculty of Medicine, Laboratory of Experimental and Clinical Pharmacology, Rennes 1 University, Rennes, France. [email protected].; Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France. [email protected].; Faculty of Pharmacy, EA4123 Barrières physiologiques et réponses thérapeutiques, Paris Sud University, Châtenay-Malabry, France. [email protected].; Paris 6 University Pierre et Marie Curie, 91-105 Boulevard de l'Hôpital, 75013, Paris, France. [email protected].; Cardiovascular Surgery department, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, AP-HP, 47-83 Boulevard de l'Hôpital, 75013, Paris, France. [email protected].; Cardiovascular Surgery department, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, AP-HP, 47-83 Boulevard de l'Hôpital, 75013, Paris, France. [email protected].; Faculty of Pharmacy, EA4123 Barrières physiologiques et réponses thérapeutiques, Paris Sud University, Châtenay-Malabry, France. [email protected].; Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France. [email protected].; Faculty of Medicine, Laboratory of Experimental and Clinical Pharmacology, Rennes 1 University, Rennes, France. [email protected].; Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France. [email protected].; Service de Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, iCAN, Institute of Cardiometabolism and Nutrition, 47, Boulevard de l'Hôpital, 75651, Paris, Cedex 13, France. [email protected].; Paris 6 University Pierre et Marie Curie, 91-105 Boulevard de l'Hôpital, 75013, Paris, France. [email protected].; Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France. [email protected].; Faculty of Medicine, Laboratory of Experimental and Clinical Pharmacology, Rennes 1 University, Rennes, France. [email protected].; Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France. [email protected].; Faculty of Pharmacy, EA4123 Barrières physiologiques et réponses thérapeutiques, Paris Sud University, Châtenay-Malabry, France. [email protected].; Faculty of Pharmacy, EA4123 Barrières physiologiques et réponses thérapeutiques, Paris Sud University, Châtenay-Malabry, France. [email protected].; Pharmacy Department, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris, AP-HP, 184 rue du faubourg Saint-Antoine, 75012, Paris, France. [email protected].; Service de Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, iCAN, Institute of Cardiometabolism and Nutrition, 47, Boulevard de l'Hôpital, 75651, Paris, Cedex 13, France. [email protected].; Paris 6 University Pierre et Marie Curie, 91-105 Boulevard de l'Hôpital, 75013, Paris, France. [email protected].

DOI: 10.1186/s13054-015-0772-5

Link outs

Free resources

Full Text Sources:

Other Literature Sources:

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-HLA-B-1

MeSH Terms: Anti-Infective Agents, Blood, Critical Illness, Cyclosporine, Drug Monitoring, Extracorporeal Membrane Oxygenation, Humans, Hypnotics and Sedatives, Midazolam, Models, Biological, Polyvinyl Chloride, Propofol, Vancomycin