Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation.
OBJECTIVE
To determine whether, in children, plasma glial fibrillary acidic protein is associated with brain injury during extracorporeal membrane oxygenation and with mortality.


METHODS
Prospective, observational study.


METHODS
Pediatric intensive care unit in an urban tertiary care academic center.


METHODS
Neonatal and pediatric patients on extracorporeal membrane oxygenation (n = 22).


METHODS
Serial blood sampling for glial fibrillary acidic protein measurements.


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.
Department of Anesthesiology and Critical Care, Johns Hopkins University, Baltimore, MD, USA. mbembea1jhmi.edu
Melania M
MM
Bembea
William
W
Savage
John J
JJ
Strouse
Jamie McElrath
JM
Schwartz
Ernest
E
Graham
Carol B
CB
Thompson
Allen
A
Everett
D000293:Adolescent; D015415:Biomarkers; D001930:Brain Injuries / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein