Sutep Jaruratanasirikul1, Veerapong Vattanavanit2, Maseetoh Samaeng2, Monchana Nawakitrangsan2, Somchai Sriwiriyajan3. 1. Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, 90110, Thailand. jasutep@medicine.psu.ac.th. 2. Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, 90110, Thailand. 3. Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla, 90110, Thailand.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become increasingly used for lifesaving respiratory and/or cardiac failure support in critically illpatients, 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. OBJECTIVE: The aim of this study was to determine the effect of ECMO on the pharmacokinetics of imipenem in critically illpatients supported by this cardiopulmonary bypass device. METHODS: The study was conducted in critically illpatients 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. RESULTS: 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. CONCLUSIONS: Pathophysiological changes in critically illpatients with severe infections during support with ECMO had a greater impact on altered pharmacokinetic patterns of imipenem than those that occur in critically illpatients 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.
Authors: Jin Wi; Min Jung Chang; Soyoung Kang; June Young Jang; Jongsung Hahn; Dasohm Kim; Jun Yeong Lee; Kyoung Lok Min; Seungwon Yang Journal: Antimicrob Agents Chemother Date: 2020-04-21 Impact factor: 5.191