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Presenting Characteristics Associated With Outcome in Children With Severe Traumatic Brain Injury: A Secondary Analysis From a Randomized, Controlled Trial of Therapeutic Hypothermia*

Rosario, Bedda L. PhD1; Horvat, Christopher M. MD, MHA2,3; Wisniewski, Stephen R. PhD1; Bell, Michael J. MD2,3,4; Panigrahy, Ashok MD5; Zuccoli, Giulio MD5; Narayanan, Srikala MD5; Balasubramani, Goundappa K. PhD1; Beers, Sue R. PhD6; Adelson, P. David MD7; for the Investigators of the Cool Kids Trial

Pediatric Critical Care Medicine: October 2018 - Volume 19 - Issue 10 - p 957-964
doi: 10.1097/PCC.0000000000001676
Neurocritical Care

Objectives: To identify injury patterns and characteristics associated with severe traumatic brain injury course and outcome, within a well-characterized cohort, which may help guide new research and treatment initiatives.

Design: A secondary analysis of a phase 3, randomized, controlled trial that compared therapeutic hypothermia versus normothermia following severe traumatic brain injury in children.

Setting: Fifteen sites in the United States, Australia, and New Zealand.

Patients: Children (< 18 yr old) with severe traumatic brain injury.

Measurements and Main Results: Baseline, clinical, and CT characteristics of patients (n = 77) were examined for association with mortality and outcome, as measured by the Glasgow Outcome Scale—Extended Pediatric Revision 3 months after traumatic brain injury. Data are presented as odds ratios with 95% CIs. No demographic, clinical, or CT characteristic was associated with mortality in bivariate analysis. Characteristics associated with worse Glasgow Outcome Scale—Extended Pediatric Revision in bivariate analysis were two fixed pupils (14.17 [3.38–59.37]), abdominal Abbreviated Injury Severity score (2.03 [1.19–3.49]), and subarachnoid hemorrhage (3.36 [1.30–8.70]). Forward stepwise regression demonstrated that Abbreviated Injury Severity spine (3.48 [1.14–10.58]) and midline shift on CT (8.35 [1.05–66.59]) were significantly associated with mortality. Number of fixed pupils (one fixed pupil 3.47 [0.79–15.30]; two fixed pupils 13.61 [2.89–64.07]), hypoxia (5.22 [1.02–26.67]), and subarachnoid hemorrhage (3.01 [1.01–9.01]) were independently associated with worse Glasgow Outcome Scale—Extended Pediatric Revision following forward stepwise regression.

Conclusions: Severe traumatic brain injury is a clinically heterogeneous disease that can be accompanied by a range of neurologic impairment and a variety of injury patterns at presentation. This secondary analysis of prospectively collected data identifies several characteristics associated with outcome among children with severe traumatic brain injury. Future, larger trials are needed to better characterize phenotypes within this population.

1Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.

2Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.

3Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA.

4Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA.

5Department of Radiology, University of Pittsburgh, Pittsburgh, PA.

6Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.

7Department of Neurological Surgery, Barrow Neurological Institute of Phoenix Children’s Hospital, Phoenix, AZ.

*See also p. 998.

Drs. Rosario and Horvat contributed equally to this article.

Members of the Investigators of the Cool Kids Trial are listed in the supplemental data (Supplemental Digital Content 4,

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Supported, in part, by the National Institutes of Health grants National Institute of Child Health and Human Development T32 HD40686 (to Dr. Horvat), Clinical and Translational Science Award UL1TR000005 (to Dr. Rosario), National Institute of Neurologic Disorders and Stroke (NINDS) U01NS052478 (to Dr. Adelson), NINDS U01 NS081041 (to Dr. Bell).

Drs. Rosario, Wisniewski, Bell, Beers, and Adelson received support for article research from the National Institutes of Health (NIH). Drs. Rosario’s, Wisniewski’s, and Adelson’s institutions received funding from the NIH. Dr. Adelson’s institution also received funding from Codman Johnson and Johnson and the Integra Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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Copyright © 2018 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies