Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review

Sutiman, Natalia; Koh, Janine Cynthia; Watt, Kevin M.; Hornik, Christoph P.; Murphy, Beverly; Chan, Yoke Hwee; Lee, Jan Hau

doi:10.3389/fped.2020.00260

Cited by 18 publications

(12 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the known effect of ECMO on the PK of some drugs ( Sutiman et al, 2020 ), the measurements obtained from three patients (5%) on ECMO were included in the analysis. The decision to include these patients in the analysis was made after ensuring that the PEs obtained for these subjects were not different from the average PE estimated for the respective model.…”

Section: Discussionmentioning

confidence: 99%

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data

et al. 2022

View full text Add to dashboard Cite

Risperidone is approved to treat schizophrenia in adolescents and autistic disorder and bipolar mania in children and adolescents. It is also used off-label in younger children for various psychiatric disorders. Several population pharmacokinetic models of risperidone and 9-OH-risperidone have been published. The objectives of this study were to assess whether opportunistically collected pediatric data can be used to evaluate risperidone population pharmacokinetic models externally and to identify a robust model for precision dosing in children. A total of 103 concentrations of risperidone and 112 concentrations of 9-OH-risperidone, collected from 62 pediatric patients (0.16–16.8 years of age), were used in the present study. The predictive performance of five published population pharmacokinetic models (four joint parent-metabolite models and one parent only) was assessed for accuracy and precision of the predictions using statistical criteria, goodness of fit plots, prediction-corrected visual predictive checks (pcVPCs), and normalized prediction distribution errors (NPDEs). The tested models produced similarly precise predictions (Root Mean Square Error [RMSE]) ranging from 0.021 to 0.027 nmol/ml for risperidone and 0.053–0.065 nmol/ml for 9-OH-risperidone). However, one of the models (a one-compartment mixture model with clearance estimated for three subpopulations) developed with a rich dataset presented fewer biases (Mean Percent Error [MPE, %] of 1.0% vs. 101.4, 146.9, 260.4, and 292.4%) for risperidone. In contrast, a model developed with fewer data and a more similar population to the one used for the external evaluation presented fewer biases for 9-OH-risperidone (MPE: 17% vs. 69.9, 47.8, and 82.9%). None of the models evaluated seemed to be generalizable to the population used in this analysis. All the models had a modest predictive performance, potentially suggesting that sources of inter-individual variability were not entirely captured and that opportunistic data from a highly heterogeneous population are likely not the most appropriate data to evaluate risperidone models externally.

show abstract

Section: Discussionmentioning

confidence: 99%

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Unsurprisingly, antibiotic use is high in ECMO patients [117]. It has been suggested that ECMO may lead to additional PK alterations during antibiotic therapy in critically ill patients [117][118][119].…”

Section: Extracorporeal Organ Support Systems 421 Extracorporeal Membrane Oxygenationmentioning

confidence: 99%

“…The potential impact of ECMO on antibiotic PK can be related to the direct interaction of the antibiotic with the ECMO circuit (e.g., adsorption to the tubing or oxygenator) [117][118][119]. Ex vivo experiments revealed that drugs with a higher degree of lipophilicity and drugs with high plasma protein binding are most at risk of sequestration within the ECMO circuit [118,120].…”

Section: Extracorporeal Organ Support Systems 421 Extracorporeal Membrane Oxygenationmentioning

confidence: 99%

“…Additionally, when used in patients, ECMO can also increase the Vd of the antibiotic with or without altering its CL. Clinical studies reporting antibiotic PK during ECMO have been performed mostly in neonates, although data in older children and adults are increasingly being reported over the last decade [117][118][119]. Nevertheless, data are scarce, and it remains difficult to translate the scarce data to recommendations for clinical practice.…”

Section: Extracorporeal Organ Support Systems 421 Extracorporeal Membrane Oxygenationmentioning

confidence: 99%

“…Due to the smaller amount of circulating blood volume, ECMO-induced hemodilution will have a larger impact in younger children than in older children or adults. Additionally, neonates and infants have a proportionally higher body water composition, which further enhances the impact of ECMO on the Vd of hydrophilic antibiotics [117,119].…”

Section: Extracorporeal Organ Support Systems 421 Extracorporeal Membrane Oxygenationmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine

et al. 2021

View full text Add to dashboard Cite

Children show important developmental and maturational changes, which may contribute greatly to pharmacokinetic (PK) variability observed in pediatric patients. These PK alterations are further enhanced by disease-related, non-maturational factors. Specific to the intensive care setting, such factors include critical illness, inflammatory status, augmented renal clearance (ARC), as well as therapeutic interventions (e.g., extracorporeal organ support systems or whole-body hypothermia [WBH]). This narrative review illustrates the relevance of both maturational and non-maturational changes in absorption, distribution, metabolism, and excretion (ADME) applied to antibiotics. It hereby provides a focused assessment of the available literature on the impact of critical illness—in general, and in specific subpopulations (ARC, extracorporeal organ support systems, WBH)—on PK and potential underexposure in children and neonates. Overall, literature discussing antibiotic PK alterations in pediatric intensive care is scarce. Most studies describe antibiotics commonly monitored in clinical practice such as vancomycin and aminoglycosides. Because of the large PK variability, therapeutic drug monitoring, further extended to other antibiotics, and integration of model-informed precision dosing in clinical practice are suggested to optimise antibiotic dose and exposure in each newborn, infant, or child during intensive care.

show abstract

Pharmacokinetics of Human Plasma‐Derived Antithrombin in Pediatric Patients Supported on Extracorporeal Membrane Oxygenation

Jung,

Procaccini,

Roem

et al. 2024

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated heparin is used commonly for anticoagulation. Given reports of acquired antithrombin (AT) deficiency in this patient population and associated concern for heparin resistance, AT activity measurement and off‐label AT replacement have become common in pediatric ECMO centers despite limited optimal dosing regimens. We conducted a retrospective cohort study of pediatric ECMO patients (0 to <18 years) at a single academic center to characterize the pharmacokinetics (PK) of human plasma‐derived AT. We demonstrated that a two‐compartment turnover model appropriately described the PK of AT, and the parameter estimates for clearance, central volume, intercompartmental clearance, peripheral volume, and basal AT input under non‐ECMO conditions were 0.338 dL/h/70 kg, 38.5 dL/70 kg, 1.16 dL/h/70 kg, 40.0 dL/70 kg, and 30.4 units/h/70 kg, respectively. Also, ECMO could reduce bioavailable AT by 50% resulting in 2‐fold increase of clearance and volume of distribution. To prevent AT activity from falling below predetermined thresholds of 50% activity in neonates and 80% activity in older infants and children, we proposed potential replacement regimens for each age group, accompanied by therapeutic drug monitoring.

show abstract

Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review

Cited by 18 publications

References 74 publications

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data

Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine

Pharmacokinetics of Human Plasma‐Derived Antithrombin in Pediatric Patients Supported on Extracorporeal Membrane Oxygenation

Contact Info

Product

Resources

About