Pharmacokinetics of Imipenem in Critically Ill Patients with Life-threatening Severe Infections During Support with Extracorporeal Membrane Oxygenation

BackgroundExtracorporeal membrane oxygenation (ECMO) has become increasingly used for lifesaving respiratory and/or cardiac failure support in critically ill patients, including those with life-threatening severe infections. This cardiopulmonary bypass device has been shown to enhance the profound pathophysiological changes in this patient population, resulting in an alteration of the pharmacokinetics of antimicrobial agents.ObjectiveThe aim of this study was to determine the effect of ECMO on the pharmacokinetics of imipenem in critically ill patients supported by this cardiopulmonary bypass device.MethodsThe study was conducted in critically ill patients with respiratory and/or cardiac failure and severe infections who were supported by ECMO. All patients received a 1-h infusion of 0.5g of imipenem every 6h and imipenem pharmacokinetics studies were carried out on the fourth dose of drug administration.ResultsTen patients were enrolled in this study. The pharmacokinetics parameters of imipenem were found to be highly variable. The volume of distribution, total clearance, elimination half-life and the area under the concentration-time curve between 0 and 6h were 33.3813.89 L, 9.99 +/- 10.47 L/h, 12.01 +/- 29.63h and 88.93 +/- 54.07mg.h/L, respectively.Conclusions p id=Par5 Pathophysiological changes in critically ill patients with severe infections during support with ECMO had a greater impact on altered pharmacokinetic patterns of imipenem than those that occur in critically ill patients without ECMO support. Therefore, the largest licensed dose, 1g every 6h, of imipenem, may be required to maintain adequate drug concentrations to achieve the pharmacokinetic/pharmacodynamic targets for effective antimicrobial therapy in this patient population.