Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation

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Abstract

Objective: To determine whether, in children, plasma glial fibrillary acidic protein is associated with brain injury during extracorporeal membrane oxygenation and with mortality. Design: Prospective, observational study. Setting: Pediatric intensive care unit in an urban tertiary care academic center. Patients: Neonatal and pediatric patients on extracorporeal membrane oxygenation (n = 22). Interventions: Serial blood sampling for glial fibrillary acidic protein measurements. Measurements and Main Results: Prospective patients age 1 day to 18 yrs who required extracorporeal membrane oxygenation from April 2008 to August 2009 were studied. Glial fibrillary acidic protein was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5-16 yrs) and 59 neonatal intensive care unit infants without neurologic injury. In controls, the median glial fibrillary acidic protein concentration was 0.055 ng/mL (interquartile range, 0-0.092 ng/mL) and the 95th percentile of glial fibrillary acidic protein was 0.436 ng/mL. In patients on extracorporeal membrane oxygenation, plasma glial fibrillary acidic protein was measured at 6, 12, and every 24 hrs after cannulation. We enrolled 22 children who underwent extracorporeal membrane oxygenation. Median age was 7 days (interquartile range, 2 days to 9 yrs), and primary extracorporeal membrane oxygenation indication was: cardiac failure, six of 22 (27.3%); respiratory failure, 12 of 22 (54.5%); extracorporeal cardiopulmonary resuscitation, three of 22 (13.6%); and sepsis, one of 22 (4.6%). Seven of 22 (32%) patients developed acute neurologic injury (intracranial hemorrhage, brain death, or cerebral edema diagnosed by imaging). Fifteen of 22 (68%) survived to hospital discharge. In the extracorporeal membrane oxygenation group, peak glial fibrillary acidic protein levels were higher in children with brain injury than those without (median, 5.9 vs. 0.09 ng/mL, p = .04) and in nonsurvivors compared with survivors to discharge (median, 5.9 vs. 0.09 ng/mL, p = .04). The odds ratio for brain injury for glial fibrillary acidic protein >0.436 ng/mL vs. normal was 11.5 (95% confidence interval, 1.3-98.3) and the odds ratio for mortality was 13.6 (95% confidence interval, 1.7-108.5). Conclusions: High glial fibrillary acidic protein during extracorporeal membrane oxygenation is significantly associated with acute brain injury and death. Brain injury biomarkers may aid in outcome prediction and neurologic monitoring of patients on extracorporeal membrane oxygenation to improve outcomes and benchmark new therapies.

Original languageEnglish (US)
Pages (from-to)572-579
Number of pages8
JournalPediatric Critical Care Medicine
Volume12
Issue number5
DOIs
StatePublished - Sep 2011

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Extracorporeal Membrane Oxygenation
Glial Fibrillary Acidic Protein
Brain Injuries
Biomarkers
Nervous System Trauma
Brain Death
Brain Edema
Blood Proteins
Odds Ratio
Confidence Intervals
Benchmarking
Pediatric Intensive Care Units
Mortality
Intracranial Hemorrhages
Neonatal Intensive Care Units
Cardiopulmonary Resuscitation
Physiologic Monitoring
Immunoassay
Tertiary Care Centers
Catheterization

Keywords

  • Biochemical marker
  • ECMO
  • Extracorporeal membrane oxygenation
  • GFAP
  • Glial fibrillary acidic protein
  • Intracranial hemorrhage

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Critical Care and Intensive Care Medicine

Cite this

@article{857e66bfa5b94864a048c62d64d8b096,
title = "Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation",
abstract = "Objective: To determine whether, in children, plasma glial fibrillary acidic protein is associated with brain injury during extracorporeal membrane oxygenation and with mortality. Design: Prospective, observational study. Setting: Pediatric intensive care unit in an urban tertiary care academic center. Patients: Neonatal and pediatric patients on extracorporeal membrane oxygenation (n = 22). Interventions: Serial blood sampling for glial fibrillary acidic protein measurements. Measurements and Main Results: Prospective patients age 1 day to 18 yrs who required extracorporeal membrane oxygenation from April 2008 to August 2009 were studied. Glial fibrillary acidic protein was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5-16 yrs) and 59 neonatal intensive care unit infants without neurologic injury. In controls, the median glial fibrillary acidic protein concentration was 0.055 ng/mL (interquartile range, 0-0.092 ng/mL) and the 95th percentile of glial fibrillary acidic protein was 0.436 ng/mL. In patients on extracorporeal membrane oxygenation, plasma glial fibrillary acidic protein was measured at 6, 12, and every 24 hrs after cannulation. We enrolled 22 children who underwent extracorporeal membrane oxygenation. Median age was 7 days (interquartile range, 2 days to 9 yrs), and primary extracorporeal membrane oxygenation indication was: cardiac failure, six of 22 (27.3{\%}); respiratory failure, 12 of 22 (54.5{\%}); extracorporeal cardiopulmonary resuscitation, three of 22 (13.6{\%}); and sepsis, one of 22 (4.6{\%}). Seven of 22 (32{\%}) patients developed acute neurologic injury (intracranial hemorrhage, brain death, or cerebral edema diagnosed by imaging). Fifteen of 22 (68{\%}) survived to hospital discharge. In the extracorporeal membrane oxygenation group, peak glial fibrillary acidic protein levels were higher in children with brain injury than those without (median, 5.9 vs. 0.09 ng/mL, p = .04) and in nonsurvivors compared with survivors to discharge (median, 5.9 vs. 0.09 ng/mL, p = .04). The odds ratio for brain injury for glial fibrillary acidic protein >0.436 ng/mL vs. normal was 11.5 (95{\%} confidence interval, 1.3-98.3) and the odds ratio for mortality was 13.6 (95{\%} confidence interval, 1.7-108.5). Conclusions: High glial fibrillary acidic protein during extracorporeal membrane oxygenation is significantly associated with acute brain injury and death. Brain injury biomarkers may aid in outcome prediction and neurologic monitoring of patients on extracorporeal membrane oxygenation to improve outcomes and benchmark new therapies.",
keywords = "Biochemical marker, ECMO, Extracorporeal membrane oxygenation, GFAP, Glial fibrillary acidic protein, Intracranial hemorrhage",
author = "Melania Bembea and William Savage and John Strouse and Jamie Schwartz and Graham, {Ernest M} and Carol Thompson and Everett, {Allen D}",
year = "2011",
month = "9",
doi = "10.1097/PCC.0b013e3181fe3ec7",
language = "English (US)",
volume = "12",
pages = "572--579",
journal = "Pediatric Critical Care Medicine",
issn = "1529-7535",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation

AU - Bembea, Melania

AU - Savage, William

AU - Strouse, John

AU - Schwartz, Jamie

AU - Graham, Ernest M

AU - Thompson, Carol

AU - Everett, Allen D

PY - 2011/9

Y1 - 2011/9

N2 - Objective: To determine whether, in children, plasma glial fibrillary acidic protein is associated with brain injury during extracorporeal membrane oxygenation and with mortality. Design: Prospective, observational study. Setting: Pediatric intensive care unit in an urban tertiary care academic center. Patients: Neonatal and pediatric patients on extracorporeal membrane oxygenation (n = 22). Interventions: Serial blood sampling for glial fibrillary acidic protein measurements. Measurements and Main Results: Prospective patients age 1 day to 18 yrs who required extracorporeal membrane oxygenation from April 2008 to August 2009 were studied. Glial fibrillary acidic protein was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5-16 yrs) and 59 neonatal intensive care unit infants without neurologic injury. In controls, the median glial fibrillary acidic protein concentration was 0.055 ng/mL (interquartile range, 0-0.092 ng/mL) and the 95th percentile of glial fibrillary acidic protein was 0.436 ng/mL. In patients on extracorporeal membrane oxygenation, plasma glial fibrillary acidic protein was measured at 6, 12, and every 24 hrs after cannulation. We enrolled 22 children who underwent extracorporeal membrane oxygenation. Median age was 7 days (interquartile range, 2 days to 9 yrs), and primary extracorporeal membrane oxygenation indication was: cardiac failure, six of 22 (27.3%); respiratory failure, 12 of 22 (54.5%); extracorporeal cardiopulmonary resuscitation, three of 22 (13.6%); and sepsis, one of 22 (4.6%). Seven of 22 (32%) patients developed acute neurologic injury (intracranial hemorrhage, brain death, or cerebral edema diagnosed by imaging). Fifteen of 22 (68%) survived to hospital discharge. In the extracorporeal membrane oxygenation group, peak glial fibrillary acidic protein levels were higher in children with brain injury than those without (median, 5.9 vs. 0.09 ng/mL, p = .04) and in nonsurvivors compared with survivors to discharge (median, 5.9 vs. 0.09 ng/mL, p = .04). The odds ratio for brain injury for glial fibrillary acidic protein >0.436 ng/mL vs. normal was 11.5 (95% confidence interval, 1.3-98.3) and the odds ratio for mortality was 13.6 (95% confidence interval, 1.7-108.5). Conclusions: High glial fibrillary acidic protein during extracorporeal membrane oxygenation is significantly associated with acute brain injury and death. Brain injury biomarkers may aid in outcome prediction and neurologic monitoring of patients on extracorporeal membrane oxygenation to improve outcomes and benchmark new therapies.

AB - Objective: To determine whether, in children, plasma glial fibrillary acidic protein is associated with brain injury during extracorporeal membrane oxygenation and with mortality. Design: Prospective, observational study. Setting: Pediatric intensive care unit in an urban tertiary care academic center. Patients: Neonatal and pediatric patients on extracorporeal membrane oxygenation (n = 22). Interventions: Serial blood sampling for glial fibrillary acidic protein measurements. Measurements and Main Results: Prospective patients age 1 day to 18 yrs who required extracorporeal membrane oxygenation from April 2008 to August 2009 were studied. Glial fibrillary acidic protein was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5-16 yrs) and 59 neonatal intensive care unit infants without neurologic injury. In controls, the median glial fibrillary acidic protein concentration was 0.055 ng/mL (interquartile range, 0-0.092 ng/mL) and the 95th percentile of glial fibrillary acidic protein was 0.436 ng/mL. In patients on extracorporeal membrane oxygenation, plasma glial fibrillary acidic protein was measured at 6, 12, and every 24 hrs after cannulation. We enrolled 22 children who underwent extracorporeal membrane oxygenation. Median age was 7 days (interquartile range, 2 days to 9 yrs), and primary extracorporeal membrane oxygenation indication was: cardiac failure, six of 22 (27.3%); respiratory failure, 12 of 22 (54.5%); extracorporeal cardiopulmonary resuscitation, three of 22 (13.6%); and sepsis, one of 22 (4.6%). Seven of 22 (32%) patients developed acute neurologic injury (intracranial hemorrhage, brain death, or cerebral edema diagnosed by imaging). Fifteen of 22 (68%) survived to hospital discharge. In the extracorporeal membrane oxygenation group, peak glial fibrillary acidic protein levels were higher in children with brain injury than those without (median, 5.9 vs. 0.09 ng/mL, p = .04) and in nonsurvivors compared with survivors to discharge (median, 5.9 vs. 0.09 ng/mL, p = .04). The odds ratio for brain injury for glial fibrillary acidic protein >0.436 ng/mL vs. normal was 11.5 (95% confidence interval, 1.3-98.3) and the odds ratio for mortality was 13.6 (95% confidence interval, 1.7-108.5). Conclusions: High glial fibrillary acidic protein during extracorporeal membrane oxygenation is significantly associated with acute brain injury and death. Brain injury biomarkers may aid in outcome prediction and neurologic monitoring of patients on extracorporeal membrane oxygenation to improve outcomes and benchmark new therapies.

KW - Biochemical marker

KW - ECMO

KW - Extracorporeal membrane oxygenation

KW - GFAP

KW - Glial fibrillary acidic protein

KW - Intracranial hemorrhage

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U2 - 10.1097/PCC.0b013e3181fe3ec7

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JO - Pediatric Critical Care Medicine

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