Evidence map›Paper›PMID 30431557›Full record

Observational studyPediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2019

A Population Pharmacokinetic Analysis to Study the Effect of Extracorporeal Membrane Oxygenation on Cefepime Disposition in Children.

Athena F Zuppa, Nicole R Zane, Ganesh Moorthy, Heidi J Dalton, Alan Abraham, Ron W Reeder, Joseph A Carcillo, Andrew R Yates, Kathleen L Meert, Robert A Berg and 6 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Observational
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 8 institutions in 1 country.

Athena F ZuppaCenter for Clinical Pharmacology, The Children's Hospital of Philadelphia, Philadelphia, PA.
Nicole R ZaneCenter for Clinical Pharmacology, The Children's Hospital of Philadelphia, Philadelphia, PA.
Ganesh MoorthyCenter for Clinical Pharmacology, The Children's Hospital of Philadelphia, Philadelphia, PA.
Heidi J DaltonAdult and Pediatric ECLS, INOVA Fairfax Hospital, Falls Church, VA.
Alan Abraham
Ron W ReederDepartment of Pediatrics, University of Utah, Salt Lake City, UT.
Joseph A CarcilloDepartment of Critical Care Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA.
Andrew R YatesDepartment of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH.
Kathleen L MeertDepartment of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, MI.
Robert A BergDepartment of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA.
Anil SapruDivision of Critical Care, UCLA Mattel Children's Hospital, Los Angeles, CA.
Peter MouraniSection of Critical Care, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
Daniel A NottermanDepartment of Molecular Biology, Princeton University, Princeton, NJ.
J Michael DeanDepartment of Pediatrics, University of Utah, Salt Lake City, UT.
Marc R GastonguayMetrum Research Group, Tariffville, CT.
Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN)
Children's Hospital Colorado · USChildren's Hospital of Philadelphia · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USUniversity of Colorado Denver · USChildren's National · USMetrum Research Group (United States) · USResearch Network (United States) · USUniversity of Utah · US

Funding

Data Coordinating Center for the Collaborative Pediatric Critical Care Research NetworkU01HD049934 · NICHD · UNIVERSITY OF UTAH · PI DEAN, JONATHAN MICHAEL · 2005 to 2020
$35.2M
Physiologically Guided Ventilator Strategies in ChildrenU10HD050012 · NICHD · CHILDREN'S HOSPITAL OF LOS ANGELES · PI NEWTH, CHRISTOPHER JOHN · 2005 to 2014
$3.7M
Collaborative Pediatric Critical Care Research NetworkU10HD050096 · NICHD · WAYNE STATE UNIVERSITY · PI MEERT, KATHLEEN L. · 2005 to 2014
$3.2M
Metoclopramide prevents PICU nosocomial infectionU10HD049983 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CARCILLO, JOSEPH A · 2005 to 2014
$3.1M
Pediatric Critical Care Research Network at Children's Hospital of PhiladelphiaUG1HD063108 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BERG, ROBERT ALLEN, ZUPPA, ATHENA F. · 2015 to 2020
$1.7M
Impact of Hypothermia on Midazolam and Morphine PharmacokineticsR01HL112745 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI ZUPPA, ATHENA F. · 2012 to 2015
$1.7M
Collaborative Research to Validate Biomarkers of Pediatric ARDSUG1HD083166 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCQUILLEN, PATRICK SEAN, SAPRU, ANIL · 2015 to 2020
$1.6M
Renewal Application for the Childrens Hospital of Pittsburgh Collaborative Pediatric Critical Care Research Network SiteUG1HD049983 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CARCILLO, JOSEPH A · 2015 to 2020
$1.6M
Collaborative Pediatric Critical Care Research NetworkUG1HD050096 · NICHD · WAYNE STATE UNIVERSITY · PI MEERT, KATHLEEN L. · 2015 to 2020
$1.6M
Collaborative Network Study of Airway Microbiome and Host Responses in Pediatric Respiratory FailureUG1HD083171 · NICHD · UNIVERSITY OF COLORADO DENVER · PI CARPENTER, TODD C · 2015 to 2020
$1.5M
Collaborative Pediatric Critical Care Research Network (UG1)UG1HD083170 · NICHD · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI HALL, MARK W · 2015 to 2020
$1.5M
Pediatric Critical Care Research Network at Children's Hospital of PhiladelphiaU10HD063108 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BERG, ROBERT ALLEN · 2010 to 2014
$1.4M
NHLBI NIH HHS R01 HL112745NICHD NIH HHS K99 HD096123NICHD NIH HHS RL1 HD107773NICHD NIH HHS U01 HD049934NICHD NIH HHS U10 HD049983NICHD NIH HHS U10 HD050012NICHD NIH HHS U10 HD050096NICHD NIH HHS U10 HD063108NICHD NIH HHS U10 HD063114NICHD NIH HHS UG1 HD049983NICHD NIH HHS UG1 HD050096NICHD NIH HHS UG1 HD063108NICHD NIH HHS UG1 HD083166NICHD NIH HHS UG1 HD083170NICHD NIH HHS UG1 HD083171
6 · The paper itself

Abstract

objectivesLimited data exist on the effects of extracorporeal membrane oxygenation on pharmacokinetics of cefepime in critically ill pediatric patients. The objective was to describe cefepime disposition in children treated with extracorporeal membrane oxygenation using population pharmacokinetic modeling.

designMulticenter, prospective observational study.

settingThe pediatric and cardiac ICUs of six sites of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Seventeen critically ill children (30 d to < 2 yr old) on extracorporeal membrane oxygenation who received cefepime as standard of care between January 4, 2014, and August 24, 2015, were enrolled.

interventionsNone. MEASUREMENTS AND MAIN

resultsA pharmacokinetic model was developed to evaluate cefepime disposition differences due to extracorporeal membrane oxygenation. A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data. The typical value of clearance in this study was 7.1 mL/min (1.9 mL/min/kg) for a patient weighing 5.8 kg. This value decreased by approximately 40% with the addition of renal replacement therapy. The typical value for V1 was 1,170 mL. In the setting of blood transfusions, V1 increased by over two-fold but was reduced with increasing age of the extracorporeal membrane oxygenation circuit oxygenator.

conclusionsCefepime clearance was reduced in pediatric patients treated with extracorporeal membrane oxygenation compared with previously reported values in children not receiving extracorporeal membrane oxygenation. The model demonstrated that the age of the extracorporeal membrane oxygenation circuit oxygenator is inversely correlated to V1. For free cefepime, only 14 of the 19 doses (74%) demonstrated a fT_minimum inhibitory concentration of 16 mg/L, an appropriate target for the treatment of pseudomonal infections, for greater than 70% of the dosing interval. Pediatric patients on extracorporeal membrane oxygenation might benefit from the addition of therapeutic drug monitoring of cefepime to assure appropriate dosing.

Indexed as

Anti-Bacterial AgentsBody WeightCefepimeCritical IllnessExtracorporeal Membrane OxygenationFemaleHumansInfantIntensive Care Units, PediatricMaleMetabolic Clearance RateModels, BiologicalProtein BindingAnti-Bacterial AgentsCefepime

Identifiers

PMID30431557
PMCPMC6323642
OpenAlexW2901555047

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.