Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment

Mehta, Nilesh M.; Halwick, David R.; Dodson, Brenda; Thompson, John E.; Arnold, John H.

doi:10.1007/s00134-007-0606-2

Cited by 159 publications

(160 citation statements)

References 29 publications

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“…However, the data suggest that the ECMO circuit can substantially alter the PK of antimicrobials resulting in changes to elimination and volume of distribution [155][156][157][158][159][160][161][162][163]. In addition, the critical condition of the patients in need of ECMO and the number of days on ECMO may further impact the PK changes observed.…”

Section: Triazoles and Extracoporeal Membrane Oxygenationmentioning

confidence: 99%

“…However, one ex vivo study using blood primed ECMO circuits demonstrated a dramatic decrease in voriconazole levels of 60% over 3 hours [157]. Since the circuit was not connected to a patient and the result was compared to a control specimen, drug loss was attributed to interactions between the drug and circuit [157].…”

Section: Triazoles and Extracoporeal Membrane Oxygenationmentioning

confidence: 99%

See 1 more Smart Citation

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Watt¹,

Manzoni²,

Cohen‐Wolkowiez³

et al. 2013

Current Drug Metabolism

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Invasive fungal infections in infants admitted to the neonatal intensive care unit are common and often fatal. The mainstay of therapy against invasive fungal infections is antifungal agents. Over the last two decades, the development and approval of these drugs evolved tremendously, and the azole class emerged as important agents in the treatment and prevention of invasive fungal infections. Among the azoles, fluconazole has been used extensively due to its favorable pharmacokinetics, excellent activity against Candida spp, and safety profile. This drug has been well studied in children but data for its use in infants are largely limited to Candida prophylaxis studies. Voriconazole, a second generation triazole, has excellent activity against Candida and Aspergillus spp. However, data on its use in neonates are extremely limited. Posaconazole and Ravuconazole are the newest agents of the triazole family. The antimicrobial spectrum of posaconazole is similar to voriconazole, but with additional activity against zygomycetes. Experience with posaconazole in children is very limited, and there are no reports of its use in infants. Ravuconazole is not approved for use by the FDA but studies in animals and humans show that it is often fungicidal and has favorable pharmacokinetics. In conclusion, the management of invasive fungal infections has progressed greatly over the last two decades with the azole antifungals playing a significant role. Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit.

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Section: Triazoles and Extracoporeal Membrane Oxygenationmentioning

confidence: 99%

Section: Triazoles and Extracoporeal Membrane Oxygenationmentioning

confidence: 99%

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Watt¹,

Manzoni²,

Cohen‐Wolkowiez³

et al. 2013

Current Drug Metabolism

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“…7 Newer data have shown no alteration in PB concentrations and a smaller impact (17.6%-31.4%) on phenytoin concentrations. 9 The extent to which the drug was lost in these studies was dependent on the duration of circuit use as well as the agent used to prime the circuit. 7,9 Each study's results vary based on the components used in the ECMO circuit.…”

Section: Introductionmentioning

confidence: 97%

“…9 The extent to which the drug was lost in these studies was dependent on the duration of circuit use as well as the agent used to prime the circuit. 7,9 Each study's results vary based on the components used in the ECMO circuit. There is also evolving technology in which different components of the ECMO circuit are being upgraded.…”

Section: Introductionmentioning

confidence: 97%

Evaluation of the Effects of Extracorporeal Membrane Oxygenation on Antiepileptic Drug Serum Concentrations in Pediatric Patients

Dillman

Messinger

Dinh

et al. 2017

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVESPatients supported on extracorporeal membrane oxygenation (ECMO) have an increased incidence of seizures. Phenobarbital (PB) and fosphenytoin (fos-PHT) are common antiepileptic drugs (AEDs) used to manage seizures in the pediatric population; however, it is unknown what effect ECMO has on the serum concentrations of AEDs. The purpose of this study is to evaluate the effect of ECMO on AED serum concentrations.METHODS A retrospective, matched-cohort study was performed in patients younger than 18 years who received ECMO and were treated with intravenous (IV) PB or fos-PHT at Texas Children's Hospital between 2004 and 2014. Patients receiving IV AED therapy and ECMO were matched, based on age, sex, and weight, with patients receiving IV AED therapy without ECMO. The 24-hour cumulative AED dose, serum concentrations, number of doses per serum concentration drawn ratio, volume of distribution, therapeutic serum concentrations, and time to therapeutic serum concentration were compared between both groups. The fos-PHT and PB groups were analyzed in all patients and in neonates only. CONCLUSION Pediatric patients receiving PB on ECMO and neonatal patients receiving fos-PHT on ECMO required larger doses, and in pediatric patients achieved lower serum concentrations, suggesting the necessity for alternative dosing strategies in these populations.

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“…Generally, ECMO may cause increases in V d for certain drugs as well as the possible binding of drugs in the ECMO circuit [72]. However, the variable characteristics of ECMO technologies and settings (e.g.…”

Section: Extracorporeal Membrane Oxygenationmentioning

confidence: 99%

β-lactam antibiotic pharmacokinetics during continuous venovenous haemofiltration in critically ill patients: continuous infusion versus intermittent bolus administration

Jamal¹

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Sepsis is a pathological syndrome that leads to unique physiological changes in critically ill patients, and can affect antibiotic pharmacokinetics. Acute kidney injury (AKI) is common in critically ill patients. The commencement of renal replacement therapy (RRT) in the management of AKI can further affect antibiotic pharmacokinetics. RRT prescription within intensive care units (ICUs) worldwide is highly variable as it depends on availability, speciality and cost. Thus, antibiotic pharmacokinetic studies in RRT derived from one type of RRT are not readily transferrable to another type of RRT. The major challenge caused by RRT is altered antibiotic clearance by the extracorporeal circuit, which will vary depending on the RRT modality and settings. It follows, that standardisation of antibiotic dosing regimens is not advisable. Clinically, when prescribing antibiotic doses for critically ill patients on RRT, various factors require consideration including; RRT mode and settings, patient characteristics (body size and other organ function), and the likely bacterial pathogen susceptibility. Whilst numerous pharmacokinetic studies have been published on various classes of antibiotics to optimize dosing, continuous infusion (CI) as a method to optimise antibiotic activity, has rarely been studied in these patients. Certainly, there has been much recent interest in this alternative mode of administration for beta-lactam antibiotics (e.g penicillin, cephalosporin, carbapenem antibiotics), as a mechanism to achieve sustained antibiotic concentrations in plasma, as well as optimal pharmacokinetic/pharmacodynamics (PK/PD) indices.This Thesis aims to describe the pharmacokinetics of two commonly used beta-lactam antibiotics in intensive care unit (ICU) setting, namely meropenem and piperacilllin/tazobactam during continuous RRT (CRRT) using ex vivo and clinical pharmacokinetic data. Specifically this work will characterise the pharmacokinetics and the probability of PK/PD attainment of beta-lactam dosing by two methods of antibiotic administration, CI and intermittent bolus (IB) in critically ill patients receiving a common form of CRRT, continuous venovenous haemofiltration (CVVH).This Thesis comprises of nine chapters. Chapter one is an introductory chapter where it provides an overview on the literatures on the Thesis topic. The discussion section in Chapter one outlines a theoretical framework behind the objectives of this Thesis, as well as the specific aims of this Thesis.Chapter two incorporates a published review article that systemically analysed the current literatures on different classes of antibiotic pharmacokinetics in special situations in the ICU iii including patients receiving different types of RRT, burn patients and extracorporeal membrane oxygenation (ECMO). This chapter describes the frequency with which current antibiotic dosing regimens achieve the therapeutic targets or the PK/PD targets and outlines alternative dosing strategies that may optimise antibiotic dosing in these populations....

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Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment

Abstract: Our ex vivo study demonstrates serial losses of several drugs commonly used during ECMO therapy. Therapeutic concentrations of fentanyl, voriconazole, antimicrobials and heparin cannot be guaranteed in patients on ECMO.

Cited by 159 publications

References 29 publications

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Evaluation of the Effects of Extracorporeal Membrane Oxygenation on Antiepileptic Drug Serum Concentrations in Pediatric Patients

β-lactam antibiotic pharmacokinetics during continuous venovenous haemofiltration in critically ill patients: continuous infusion versus intermittent bolus administration

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