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Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: Association with severity of injury and excitotoxicity

Robertson, Courtney L. MD; Bell, Michael J. MD; Kochanek, Patrick M. MD; Adelson, P. David MD; Ruppel, Randall A. MD; Carcillo, Joseph A. MD; Wisniewski, Stephen R. PhD; Mi, Zaichuan MB; Janesko, Keri L. BS; Clark, Robert S.B. MD; Marion, Donald W. MD; Graham, Steven H. MD, PhD; Jackson, Edwin K. PhD

CLINICAL INVESTIGATIONS
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Objectives  To measure adenosine concentration in the cerebrospinal fluid of infants and children after severe traumatic brain injury and to evaluate the contribution of patient age, Glasgow Coma Scale score, mechanism of injury, Glasgow Outcome Score, and time after injury to cerebrospinal fluid adenosine concentrations. To evaluate the relationship between cerebrospinal fluid adenosine and glutamate concentrations in this population.

Design  Prospective survey.

Setting  Pediatric intensive care unit in a university-based children’s hospital.

Patients  Twenty-seven critically ill infants and children who had severe traumatic brain injury (Glasgow Coma Scale <8), who required placement of an intraventricular catheter and drainage of cerebrospinal fluid as part of their neurointensive care.

Interventions  None.

Measurements and Main Results  Patients ranged in age from 2 months to 14 yrs. Cerebrospinal fluid samples (n = 304) were collected from 27 patients during the first 7 days after traumatic brain injury. Control cerebrospinal fluid samples were obtained from lumbar puncture on 21 infants and children without traumatic brain injury or meningitis. Adenosine concentration was measured by using high-pressure liquid chromatography. Adenosine concentration was increased markedly in cerebrospinal fluid of children after traumatic brain injury vs. controls (p < .001). The increase in cerebrospinal fluid adenosine was independently associated with Glasgow Coma Scale ≤4 vs. >4 and time after injury (both p < .005). Cerebrospinal fluid adenosine concentration was not independently associated with either age (≤4 vs. >4 yrs), mechanism of injury (abuse vs. other), or Glasgow Outcome Score (good/moderately disabled vs. severely disabled, vegetative, or dead). Of the 27 patients studied, 18 had cerebrospinal fluid glutamate concentration previously quantified by high-pressure liquid chromatography. There was a strong association between increases in cerebrospinal fluid adenosine and glutamate concentrations (p < .005) after injury.

Conclusions  Cerebrospinal fluid adenosine concentration is increased in a time- and severity-dependent manner in infants and children after severe head injury. The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury.

From the Safar Center for Resuscitation Research (CLR, MJB, PMK, PDA, RAR, JAC, KLJ, RSBC), the Departments of Anesthesiology and Critical Care Medicine (PMK, RAR, JAC, RSBC), Pediatrics (PMK, RAR, RSBC), Neurological Surgery (PDA, DWM), the School of Public Health (SRW), and the Center for Clinical Pharmacology (JAC, ZM, EKJ), University of Pittsburgh, Pittsburgh, PA; the Department of Pediatrics (CLR), University of Maryland at Baltimore; the Department of Critical Care Medicine (MJB), Children’s National Medical Center, Washington, DC; the Geriatric Research Educational and Clinical Center (SHG), VA Pittsburgh Health System; the General Clinical Research Center (PMK, PDA), Children’s Hospital of Pittsburgh; and the University of Pittsburgh Center for Injury Control and Research/CIRCL (PMK, KLJ, DWM).

Supported, in part, by grant NS38087 from National Institute of Neurological Disorders and Stroke (to PMK), by the University of Pittsburgh Center for Injury Control and Research (to the CIRCL/Center for Disease Control, PMK, DWM), by the Laerdal Foundation (to CLR), and by the General Clinical Research Center of Children’s Hospital of Pittsburgh (to MJB, PDA, PMK).

Address requests for reprints to: Patrick M. Kochanek, MD, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260. E-mail: kochanekpm@anes.upmc.edu

The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury.

© 2001 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins