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Effectiveness of Pharmacological Therapies for Intracranial Hypertension in Children With Severe Traumatic Brain Injury—Results From an Automated Data Collection System Time-Synched to Drug Administration

Shein, Steven L. MD; Ferguson, Nikki M. MD; Kochanek, Patrick M. MD; Bayir, Hülya MD; Clark, Robert S. B. MD; Fink, Ericka L. MD; Tyler-Kabara, Elizabeth C. MD, PhD; Wisniewski, Stephen R. PhD; Tian, Ye MPH; Balasubramani, G. K. PhD; Bell, Michael J. MD

Pediatric Critical Care Medicine: March 2016 - Volume 17 - Issue 3 - p 236–245
doi: 10.1097/PCC.0000000000000610
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Objectives: To describe acute cerebral hemodynamic effects of medications commonly used to treat intracranial hypertension in children with traumatic brain injury. Currently, data supporting the efficacy of these medications are insufficient.

Design: In this prospective observational study, intracranial hypertension (intracranial pressure ≥ 20 mm Hg for > 5 min) was treated by clinical protocol. Administration times of medications for intracranial hypertension (fentanyl, 3% hypertonic saline, mannitol, and pentobarbital) were prospectively recorded and synchronized with an automated database that collected intracranial pressure and cerebral perfusion pressure every 5 seconds. Intracranial pressure crises confounded by external stimulation or mechanical ventilator adjustments were excluded. Mean intracranial pressure and cerebral perfusion pressure from epochs following drug administration were compared with baseline values using Kruskal-Wallis analysis of variance and Dunn test. Frailty modeling was used to analyze the time to intracranial pressure crisis resolution. Mixed-effect models compared intracranial pressure and cerebral perfusion pressure 5 minutes after the medication versus baseline and rates of treatment failure.

Setting: A tertiary care children’s hospital.

Patients: Children with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8).

Interventions: None.

Measurements and Main Results: We analyzed 196 doses of fentanyl, hypertonic saline, mannitol, and pentobarbital administered to 16 children (median: 12 doses per patient). Overall, intracranial pressure significantly decreased following the administration of fentanyl, hypertonic saline, and pentobarbital. After controlling for administration of multiple medications, intracranial pressure was decreased following hypertonic saline and pentobarbital administration; cerebral perfusion pressure was decreased following fentanyl and was increased following hypertonic saline administration. After adjusting for significant covariates (including age, Glasgow Coma Scale score, and intracranial pressure), hypertonic saline was associated with a two-fold faster resolution of intracranial hypertension than either fentanyl or pentobarbital. Fentanyl was significantly associated with the most frequent treatment failure.

Conclusions: Intracranial pressure decreased after multiple drug administrations, but hypertonic saline may warrant consideration as the first-line drug for treating intracranial hypertension, as it was associated with the most favorable cerebral hemodynamics and fastest resolution of intracranial hypertension.

1Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.

2Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA.

3Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA.

4Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.

Drs. Shein and Ferguson were supported by the National Institutes of Health (NIH) training grant (T32 HD 040686). Dr. Kochanek received salary support by an NIH grant (NS 081041). Dr. Fink was supported by K23 NS065132. Drs. Wisniewski and Bell received salary support by an NIH grant (NS 081041).

Dr. Bell received support for article research from the National Institutes of Health (NIH). His institution received funding: Drs. Shein and Ferguson were supported by NIH training grant (T32 HD 040686). Drs. Bell, Kochanek, and Wisniewski received salary support by an NIH grant (NS 081041). Dr. Fink was supported by K23 NS065132. Dr. Shein received support for article research from the NIH. His institution received funding from the NIH (T32 HD040686). Dr. Ferguson received support for article research from the NIH. Her institution received funding from the NIH/NICHD. Dr. Kochanek has multiple grants from federal agencies including the NIH and the U.S. Army, receives a stipend for serving as editor of Pediatric Critical Care Medicine, served as an expert witness on several cases over the past 36 months, received honoraria for numerous lectures at national meetings and/or as a guest professor at various institutions of higher education, and received support for article research from the NIH. His institution received funding from the NIH. Dr. Bayir received support for article research from the NIH. Dr. Clark received royalties from Elsevier. His institution received funding from NIH grants. Dr. Fink received support for article research from the NIH. Her institution received funding from the NIH, PCORI, and the Laerdal Foundation. Dr. Tyler-Kabara disclosed other support: TK Group LLC, member, consulting group for computer security, occasional medical legal work related to pediatric neurosurgery (none related to severe traumatic head injuries in the last 36 months). Dr. Wisniewski received support for article research from the Department of Defense. His institution received funding from the Department of Defense. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: bellmj4@upmc.edu

©2016The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies