Pharmacokinetics of Imipenem in Critically Ill Patients with Life-threatening Severe Infections During Support with Extracorporeal Membrane Oxygenation
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Extracorporeal 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.
The 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.
The 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 0.5 g of imipenem every 6 h and imipenem pharmacokinetics studies were carried out on the fourth dose of drug administration.
Ten 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 6 h were 33.38 ± 13.89 L, 9.99 ± 10.47 L/h, 12.01 ± 29.63 h and 88.93 ± 54.07 mg∙h/L, respectively.
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, 1 g every 6 h, of imipenem, may be required to maintain adequate drug concentrations to achieve the pharmacokinetic/pharmacodynamic targets for effective antimicrobial therapy in this patient population.
The authors thank Mr David Patterson for English proofreading of the manuscript.
Compliance with Ethical Standards
This work was supported by a grant from the Faculty of Medicine, Prince of Songkla University, Thailand.
Conflicts of interest
Sutep Jaruratanasirikul, Veerapong Vattanavanit, Maseetoh Samaeng, Monchana Nawakitrangsan and Somchai Sriwiriyajan have no conflicts of interest that are relevant to the content of this paper.
All procedures performed in studies involving human participants were in accordance with the study protocol, the Ministerial Ordinance on GCP for Drugs, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol (code EC-56-065-14-1-1) was approved by the IRB at Songklanagarind Hospital on 17 December 2012.
Informed consent was obtained from each subject’s legally acceptable representative before enrollment.
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