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      Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation

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          Abstract

          Introduction

          Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, with its success dependent on effective drug therapy that reverses the pathology and/or normalizes physiology. However, the circuit that sustains life can also sequester life-saving drugs, thereby compromising the role of ECMO as a temporary support device. This ex vivo study was designed to determine the degree of sequestration of commonly used antibiotics, sedatives and analgesics in ECMO circuits.

          Methods

          Four identical ECMO circuits were set up as per the standard protocol for adult patients on ECMO. The circuits were primed with crystalloid and albumin, followed by fresh human whole blood, and were maintained at a physiological pH and temperature for 24 hours. After baseline sampling, fentanyl, morphine, midazolam, meropenem and vancomycin were injected into the circuit at therapeutic concentrations. Equivalent doses of these drugs were also injected into four polyvinylchloride jars containing fresh human whole blood for drug stability testing. Serial blood samples were collected from the ECMO circuits and the controls over 24 hours and the concentrations of the study drugs were quantified using validated assays.

          Results

          Four hundred samples were analyzed. All study drugs, except meropenem, were chemically stable. The average drug recoveries from the ECMO circuits and the controls at 24 hours relative to baseline, respectively, were fentanyl 3% and 82%, morphine 103% and 97%, midazolam 13% and 100%, meropenem 20% and 42%, vancomycin 90% and 99%. There was a significant loss of fentanyl (p = 0.0005), midazolam (p = 0.01) and meropenem (p = 0.006) in the ECMO circuit at 24 hours. There was no significant circuit loss of vancomycin at 24 hours (p = 0.26).

          Conclusions

          Sequestration of drugs in the circuit has implications on both the choice and dosing of some drugs prescribed during ECMO. Sequestration of lipophilic drugs such as fentanyl and midazolam appears significant and may in part explain the increased dosing requirements of these drugs during ECMO. Meropenem sequestration is also problematic and these data support a more frequent administration during ECMO.

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          Most cited references 25

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          Pharmacokinetic issues for antibiotics in the critically ill patient.

          To discuss the altered pharmacokinetic properties of selected antibiotics in critically ill patients and to develop basic dose adjustment principles for this patient population. PubMed, EMBASE, and the Cochrane-Controlled Trial Register. Relevant papers that reported pharmacokinetics of selected antibiotic classes in critically ill patients and antibiotic pharmacodynamic properties were reviewed. Antibiotics and/or antibiotic classes reviewed included aminoglycosides, beta-lactams (including carbapenems), glycopeptides, fluoroquinolones, tigecycline, linezolid, lincosamides, and colistin. Antibiotics can be broadly categorized according to their solubility characteristics which can, in turn, help describe possible altered pharmacokinetics that can be caused by the pathophysiological changes common to critical illness. Hydrophilic antibiotics (e.g., aminoglycosides, beta-lactams, glycopeptides, and colistin) are mostly affected with the pathphysiological changes observed in critically ill patients with increased volumes of distribution and altered drug clearance (related to changes in creatinine clearance). Lipophilic antibiotics (e.g., fluoroquinolones, macrolides, tigecycline, and lincosamides) have lesser volume of distribution alterations, but may develop altered drug clearances. Using antibiotic pharmacodynamic bacterial kill characteristics, altered dosing regimens can be devised that also account for such pharmacokinetic changes. Knowledge of antibiotic pharmacodynamic properties and the potential altered antibiotic pharmacokinetics in critically ill patients can allow the intensivist to develop individualized dosing regimens. Specifically, for renally cleared drugs, measured creatinine clearance can be used to drive many dose adjustments. Maximizing clinical outcomes and minimizing antibiotic resistance using individualized doses may be best achieved with therapeutic drug monitoring.
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            Contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era.

            Extracorporeal membrane oxygenation (ECMO) has been used in clinical medicine for 40 years but remains controversial therapy, particularly in adult patients with severe respiratory failure. Over the last few years, there have been considerable advances in extracorporeal technology and clinical practice, ushering in a new era of ECMO. Many institutions adopted ECMO as rescue therapy during the recent H1N1 influenza pandemic, reigniting the controversy. Hollow-fibre oxygenators and Mendler-designed centrifugal pumps have replaced the old silicon oxygenators and roller pumps. The advantages of these novel systems and the principles that underlie their function are outlined. Advances in cannula technology allow greater ease of patient positioning, in some cases facilitating extubation and ambulation on ECMO. Improvements in ECMO circuitry have led to a reduction in heparin and blood product requirements, with consequently fewer complications. Greater understanding of severe acute respiratory distress syndrome has allowed clinicians to successfully support adults on ECMO for months at a time, as a bridge to either recovery or transplantation. ECMO is safer, cheaper, and simpler than in previous eras. Both circuit and patient can be cared for by a single trained nurse. Additional prospective studies of ECMO for adult respiratory failure are underway. Contemporary ECMO in awake, potentially ambulant patients to provide short-term support for those with acute, reversible respiratory failure and as a bridge to transplantation in those with irreversible respiratory failure is now ready for widespread evaluation.
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              Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.

               M Kollef (2000)
              Inadequate antimicrobial treatment, generally defined as microbiological documentation of an infection that is not being effectively treated, is an important factor in the emergence of infections due to antibiotic-resistant bacteria. Factors that contribute to inadequate antimicrobial treatment of hospitalized patients include prior antibiotic exposure, use of broad-spectrum antibiotics, prolonged length of stay, prolonged mechanical ventilation, and presence of invasive devices. Strategies to minimize inadequate treatment include consulting an infectious disease specialist, using antibiotic practice guidelines, and identifying quicker methods of microbiological identification. In addition, clinicians should determine the prevailing pathogens that account for the community-acquired and nosocomial infections identified in their hospitals. Clinicians can improve antimicrobial treatment by using empirical combination antibiotic therapy based on individual patient characteristics and the predominant bacterial flora and their antibiotic susceptibility profiles. This broad-spectrum therapy can then be narrowed when initial culture results are received. Further study evaluating the use of antibiotic practice guidelines and strategies to reduce inadequate treatment is necessary to determine their impact on patient outcomes.
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                Author and article information

                Journal
                Crit Care
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2012
                15 October 2012
                : 16
                : 5
                : R194
                Affiliations
                [1 ]Critical Care Research Group, Adult Intensive Care Services, The Prince Charles Hospital & The University of Queensland, Rode Road, Chermiside, Queensland, Australia, 4032
                [2 ]Burns Trauma and Critical Care Research Centre, The University of Queensland, Cnr Butterfield St and Bowen Bridge Rd, Herston, Queensland, Australia, 4029
                [3 ]Institute of Health and Biomedical Innovation, School of Public Health & Social Work, Queensland University of Technology, Cnr Musk and Victoria Park Rd, Kelvin Grove, Queensland, Australia, 4059
                [4 ]Centre for Integrated Preclinical Drug Development, Cnr Butterfield St and Bowen Bridge Rd Herston, The University of Queensland, Queensland, Australia, 4029
                Article
                cc11679
                10.1186/cc11679
                3682296
                23068416
                Copyright ©2012 Shekar et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research

                Emergency medicine & Trauma

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