Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review

Himebauch, Adam S.; Kilbaugh, Todd J.; Zuppa, Athena F.

doi:10.1080/17425255.2016.1201066

Cited by 18 publications

(18 citation statements)

References 113 publications

(106 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More drugs were isolated in silicone membrane oxygenators than in hollow‐fibre microporous membrane oxygenators; therefore, roller pumps consisting of silicone membrane oxygenators resulted in a larger volume distribution at steady state (Vss) . However, there is disagreement regarding whether the age of a circuit alters sequestration . In addition, priming of the circuit with various fluids may contribute to drug sequestration .…”

Section: Resultsmentioning

confidence: 99%

“…This drug was recommended for severe influenza A (H1N1) infection during the 2009 novel influenza H1N1 pandemic . Previous studies of children have indicated that changes in oseltamivir PK during ECMO were not significant . In a prospective case study of 3 children (6‐15 years old), the oseltamivir dosage was doubled and CVVH was performed following the ECMO protocol.…”

Section: Resultsmentioning

confidence: 99%

“…[16][17][18] The ECMO circuit itself may function as an additional PK compartment by sequestering drugs, increasing Vd and changing drug clearance (CL) and elimination. 19 The binding of drugs into a circuit is called sequestration, which decreases the concentration of drugs in the plasma; however, the circuit may release drugs that have attached to the device after the administration of a drug is stopped.…”

Section: General Pk Changes During Ecmomentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetic changes of antibiotic, antiviral, antituberculosis and antifungal agents during extracorporeal membrane oxygenation in critically ill adult patients

2017

View full text Add to dashboard Cite

SummaryWhat is known and objective: Extracorporeal membrane oxygenation (ECMO) is a life-saving system used for critically ill patients with cardiac and/or respiratory failure.The pharmacokinetics (PK) of drugs can change in patients undergoing ECMO, which can result in therapeutic failure or drug toxicity requiring further management of drug complications. In this review, we discussed changes in the PK of antibiotic, antiviral, antituberculosis and antifungal agents administered to adult patients on ECMO. These drugs are crucial for managing infections, which commonly occur during ECMO. Methods:A literature search was conducted using the PubMed and EMBASE databases with the following keywords: "extracorporeal membrane oxygenation OR extracorporeal membrane oxygenations OR ECMO" and "PK OR pharmacokinetics OR pharmacokinetic*" and "anti infective* OR antibiotic* OR antiviral* OR antituberculosis OR antifungal*."Results and discussion: Generally, the volume of distribution (Vd) increases and drug clearance (CL) and elimination decrease during ECMO. Highly significant changes in drug PK can occur by interactions with the ECMO device itself, drug characteristics, pathological changes and patient characteristics. This may affect the blood concentrations of drugs, which influence the success of therapy. The PK of vancomycin, piperacillin-tazobactam, meropenem, azithromycin, amikacin and caspofungin did not change significantly in adult patients receiving ECMO. However, there were significant changes in the PK of imipenem, oseltamivir, rifampicin and voriconazole. The trough concentrations of imipenem were highly variable; oseltamivir had a decreased CL and increased Vd, and rifampicin concentrations were below therapeutic levels, even when a higher-than-standard dose was used in patients treated with ECMO.Additionally, voriconazole exhibited high mean peak concentrations during ECMO. What is new and conclusion:The impact of ECMO on PK varies among drugs in adult patients, and there is no consistent correlation between the effects observed in adult and infant studies. This review suggested that doses of imipenem, oseltamivir, rifampicin and voriconazole should be adjusted and therapeutic drug monitoring is needed when ECMO is used in adult patients. In the future, large PK trials in adults on ECMO are needed to provide optimal dosing guidelines. A PK/PD modelling approach will be useful for determining the precise impact of ECMO and other factors that *[Correction added on 23 October 2017, after first online publication: Author Contributors section has been added].

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: General Pk Changes During Ecmomentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic changes of antibiotic, antiviral, antituberculosis and antifungal agents during extracorporeal membrane oxygenation in critically ill adult patients

2017

View full text Add to dashboard Cite

show abstract

“…ECMO is an adaptation of cardiopulmonary bypass where blood is drained from the patient’s venous system, pumped into an oxygenator via tubing in the ECMO circuit, and returned back to the arterial or venous system [77–79]. Critically ill children may require ECMO under various conditions, including pneumonia, sepsis, congenital heart disease, and pulmonary abnormalities, and may thus be exposed to numerous drugs [80]. Several studies have shown that ECMO use in critically ill children alters the disposition of drug classes discussed in this review (antibiotics, analgesics, anticonvulsants, and sedatives) [81–91].…”

Section: Effect Of Critical Illness On Pharmacokineticsmentioning

confidence: 99%

“…ECMO may also lead to increased variability of V D and CL. Lastly, renal and hepatic dysfunction are common complications of ECMO support in children, and may impact the CL of drugs used in this patient population (e.g., vancomycin and gentamicin) [64,77–80]. Under the most severe circumstances, patients may be concomitantly supported with ECMO and CRRT, further altering drug disposition [92].…”

Section: Effect Of Critical Illness On Pharmacokineticsmentioning

confidence: 99%

Clinical Pharmacology Studies in Critically Ill Children

et al. 2016

View full text Add to dashboard Cite

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.g., extracorporeal membrane oxygenation and continuous renal replacement therapy). Performing clinical studies in critically ill children is challenging because there is large inter-subject variability in the severity and time course of organ dysfunction; some critical illnesses are rare, which can affect subject enrollment; and critically ill children usually have multiple organ failure, necessitating careful selection of a study design. As a result, drug dosing in critically ill children is often based on extrapolations from adults or non-critically ill children. Dedicated clinical studies in critically ill children are urgently needed to identify optimal dosing of drugs in this population. This review will summarize the effect of critical illness on pediatric PK, the challenges associated with performing studies in this vulnerable subpopulation, and the clinical PK studies performed to date for commonly used drugs.

show abstract

Ketamine and norketamine stability in whole blood at ambient and 4°C conditions

Tran

Moorthy

Zuppa

2017

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

A study was implemented to describe the pharmacokinetics (PK) of ketamine (K) and its metabolite norketamine (NK) in critically ill adults. Conducting studies in these subjects is hindered by the immediate need to process and freeze samples obtained in a busy intensive care setting. The ability to store unprocessed samples at room temperature for an extended time period would overcome this barrier. Stability and blood to plasma partitioning of K and NK were investigated in whole blood for up to 120 h at room temperature and 4°C. Whole blood was spiked with K and NK (1000 ng/mL each). Blood samples were aliquoted at different time points (0-120 h), extracted and analyzed using a validated high-performance liquid chromatography tandem mass spectrometry assay. The study demonstrated the stability of both K and NK in whole blood up to 120 h. These in vitro studies suggest that the concentrations of K and NK measured in the PK samples are reliable. The established stability results were successfully employed to investigate K and NK pharmacology studies in critically ill adults.

show abstract

Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review

Cited by 18 publications

References 113 publications

Pharmacokinetic changes of antibiotic, antiviral, antituberculosis and antifungal agents during extracorporeal membrane oxygenation in critically ill adult patients

Pharmacokinetic changes of antibiotic, antiviral, antituberculosis and antifungal agents during extracorporeal membrane oxygenation in critically ill adult patients

Clinical Pharmacology Studies in Critically Ill Children

Ketamine and norketamine stability in whole blood at ambient and 4°C conditions

Contact Info

Product

Resources

About