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ecmo pharmacokinetics

J N Moore, J R Healy, B N Thoma, M M Peahota, M Ahamadi, L Schmidt, N C Cavarocchi, W K Kraft
The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration-time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log-likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach...
September 2016: CPT: Pharmacometrics & Systems Pharmacology
Nilay Thakkar, Sara Salerno, Christoph P Hornik, Daniel Gonzalez
Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e...
September 1, 2016: Pharmaceutical Research
Jennifer Sherwin, Travis Heath, Kevin Watt
PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device that is used to temporarily support the most critically ill of patients with respiratory and/or cardiac failure. Infection and its sequelae may be an indication for ECMO or infections may be acquired while on ECMO and are associated with a mortality >50%. Effective therapy requires optimal dosing. However, optimal dosing can be different in patients on ECMO because the ECMO circuit can alter drug pharmacokinetics...
September 2016: Clinical Therapeutics
Robin H Steinhorn, Jeffrey Fineman, Andjela Kusic-Pajic, Peter Cornelisse, Martine Gehin, Pegah Nowbakht, Christine M Pierce, Maurice Beghetti
OBJECTIVE: To evaluate the efficacy, safety, and pharmacokinetics of the endothelin receptor antagonist bosentan as adjunctive therapy for neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: This was a phase 3, multicenter, randomized, placebo-controlled exploratory trial (FUTURE-4). Eligible patients were >34 weeks gestation, <7 days old, receiving inhaled nitric oxide (iNO) treatment (≥4 hours), and had persistent respiratory failure (oxygenation index [OI] ≥12)...
October 2016: Journal of Pediatrics
Sixten Selleng, Kathleen Selleng
Thrombocytopenia as well as anti-platelet factor 4/heparin (PF4/H) antibodies are common in cardiac surgery (CS) patients and those treated in the intensive care unit (ICU). In contrast, heparin-induced thrombocytopenia (HIT) is uncommon in these populations (~1 % and ~0.5 %, respectively). A stepwise approach where testing for anti-PF4/H antibodies is performed only in patients with typical clinical symptoms of HIT improves diagnostic specificity of the laboratory assays without losing sensitivity, thereby helping to avoid overdiagnosis and resulting HIT overtreatment...
July 14, 2016: Thrombosis and Haemostasis
Adam S Himebauch, Todd J Kilbaugh, Athena F Zuppa
INTRODUCTION: Pediatric critical illness and associated alterations in organ function can change drug pharmacokinetics (PK). Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for severe cardiac and/or respiratory failure, causes additional PK alterations that affect drug disposition. AREAS COVERED: The purposes of this review are to discuss the PK changes that occur during ECMO, the associated therapeutic implications, and to review PK literature relevant to pediatric ECMO...
October 2016: Expert Opinion on Drug Metabolism & Toxicology
Julie Autmizguine, Christoph P Hornik, Daniel K Benjamin, Kim L R Brouwer, Susan R Hupp, Michael Cohen-Wolkowiez, Kevin M Watt
BACKGROUND: Candida is a leading cause of infection in infants on extracorporeal membrane oxygenation (ECMO). Optimal micafungin dosing is unknown in this population because ECMO can alter drug pharmacokinetics (PK). METHODS: To characterize micafungin PK and safety in infants on ECMO, we conducted an open label PK trial. Infants on ECMO either received IV micafungin 4 mg/kg/day for invasive candidiasis prophylaxis, or 8 mg/kg/day when a fungal infection was suspected or confirmed...
June 16, 2016: Pediatric Infectious Disease Journal
Katharina Karsch, Xi Chen, Oliver Miera, Björn Peters, Patrick Obermeier, Roland C Francis, Válerie Amann, Susanne Duwe, Pieter Fraaij, Alla Heider, Marcel de Zwart, Felix Berger, Albert Osterhaus, Brunhilde Schweiger, Barbara Rath
BACKGROUND AND OBJECTIVES: Patients with severe influenza virus infection, multi-organ failure and organ replacement therapy may absorb and metabolize neuraminidase inhibitors differently. Systematic pharmacokinetic/pharmacodynamic clinical trials are currently lacking in this high-risk group. Inadequate dosing increases the risk of treatment failure and drug resistance, especially in severely ill patients with elevated virus loads. This study aims to explore the impact of organ replacement therapy on oseltamivir drug concentrations...
March 19, 2016: European Journal of Drug Metabolism and Pharmacokinetics
Darryl Abrams, Daniel Brodie
PURPOSE OF REVIEW: Despite advances in extracorporeal membrane oxygenation (ECMO) technology, much is unknown about the optimal management strategies for patients receiving extracorporeal support. There is a growing body of literature investigating patient selection and outcomes, mechanical ventilation approaches, anticoagulation, pharmacokinetics, early mobilization, and the role of ECMO transport among others. RECENT FINDINGS: Nonrandomized data suggest a survival advantage from ECMO compared with conventional management in acute respiratory distress syndrome, with mechanical ventilation practices varying widely across centers...
February 2016: Current Opinion in Critical Care
So Jin Park, Jeong Hoon Yang, Hyo Jung Park, Yong Won In, Young Mi Lee, Yang Hyun Cho, Chi Ryang Chung, Chi-Min Park, Kyeongman Jeon, Gee Young Suh
To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state...
2015: PloS One
M O Cotta, J A Roberts, J Lipman
The judicious use of existing antibiotics is essential for preserving their activity against infections. In the era of multi-drug resistance, this is of particular importance in clinical areas characterized by high antibiotic use, such as the ICU. Antibiotic dose optimization in critically ill patients requires sound knowledge not only of the altered physiology in serious infections - including severe sepsis, septic shock and ventilator-associated pneumonia - but also of the pathogen-drug exposure relationship (i...
December 2015: Medicina Intensiva
Danny Tsai, Jeffrey Lipman, Jason A Roberts
PURPOSE OF REVIEW: Antimicrobials are very commonly used drugs in the intensive care setting. Extensive research has been conducted in recent years to describe their pharmacokinetics/pharmacodynamics in order to maximize the pharmacological benefit and patient outcome. Translating these new findings into clinical practice is encouraged. RECENT FINDINGS: This article will discuss mechanistic data on factors causing changes in antimicrobial pharmacokinetics in critically ill patients, such as the phenomena of augmented renal clearance as well as the effects of hypoalbuminemia, renal replacement therapy, and extracorporeal membrane oxygenation...
October 2015: Current Opinion in Critical Care
P Pokorna, E D Wildschut, V Vobruba, John N van den Anker, D Tibboel
Therapeutic hypothermia (HT) is frequently used in neonates with hypoxic-ischemic encephalopathy and young infants during cardiopulmonary bypass (CPB). Hypothermia and CPB result in physiological changes contributing to pharmacokinetic (PK) and pharmacodynamic (PD) changes. Changes in the absorption, the volume of distribution (Vd) and the total body clearance (CL) of drugs used during hypothermia and CPB might lead to the interindividual PK variability resulting in either insufficient or toxic plasma concentrations and have an impact on the biodisposition and action of drugs...
2015: Current Pharmaceutical Design
Scott D Nei, Erica D Wittwer, Kianoush B Kashani, Erin N Frazee
Levetiracetam is a first-line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67-year-old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO...
August 2015: Pharmacotherapy
Chien-Chih Wu, Li-Jiuan Shen, Li-Feng Hsu, Wen-Je Ko, Fe-Lin Lin Wu
BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) alters the pharmacokinetics (PK) of vancomycin in neonates; but data on adults is limited. METHODS: This is a prospective, matched cohort, single center, pharmacokinetic study. For each adult patient who received vancomycin therapy in the ECMO group (with either centrifugal pump or roller pump), a control patient was matched by age (≥ 60 years or < 60 years), gender, and creatinine clearance (CLCr) in intensive care units...
July 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Patrick M Honore, Rita Jacobs, Inne Hendrickx, Elisabeth De Waele, Viola Van Gorp, Herbert D Spapen
No abstract text is available yet for this article.
2015: Critical Care: the Official Journal of the Critical Care Forum
Kiran Shekar, Jason A Roberts, Charles I Mcdonald, Sussan Ghassabian, Chris Anstey, Steven C Wallis, Daniel V Mullany, Yoke L Fung, John F Fraser
INTRODUCTION: Vital drugs may be degraded or sequestered in extracorporeal membrane oxygenation (ECMO) circuits, with lipophilic drugs considered to be particularly vulnerable. However, the circuit effects on protein-bound drugs have not been fully elucidated. The aim of this experimental study was to investigate the influence of plasma protein binding on drug disposition in ex vivo ECMO circuits. METHODS: Four identical ECMO circuits comprising centrifugal pumps and polymethylpentene oxygenators and were used...
2015: Critical Care: the Official Journal of the Critical Care Forum
Kiran Shekar, John F Fraser, Fabio Silvio Taccone, Susan Welch, Steven C Wallis, Daniel V Mullany, Jeffrey Lipman, Jason A Roberts
INTRODUCTION: The scope of extracorporeal membrane oxygenation (ECMO) is expanding; however, optimal drug prescription during ECMO remains a developing science. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This open-label, descriptive, matched-cohort pharmacokinetics (PK) study aimed to compare the PK of meropenem in ECMO patients to critically ill patients with sepsis not receiving ECMO (controls). METHODS: Eleven adult patients on ECMO (venovenous (VV) ECMO, n = 6; venoarterial (VA) ECMO, n = 5) receiving intravenous (IV) meropenem were included...
December 12, 2014: Critical Care: the Official Journal of the Critical Care Forum
C Welsch, P Augustin, J Allyn, L Massias, P Montravers, N Allou
Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support...
February 2015: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Katia Donadello, Elio Antonucci, Stefano Cristallini, Jason A Roberts, Marjorie Beumier, Sabino Scolletta, Frédérique Jacobs, Benoit Rondelet, Daniel de Backer, Jean-Louis Vincent, Fabio Silvio Taccone
Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of β-lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. Therapeutic drug monitoring (TDM) results in ECMO patients were matched with those in non-ECMO patients for (i) drug regimen, (ii) renal function, (iii) total body weight, (iv) severity of organ dysfunction and (v) age...
March 2015: International Journal of Antimicrobial Agents
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