title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  A tertiary care children's hospital.
  
  
  METHODS
  Children with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8).
  
  
  METHODS
  None.
  
  
  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.
authors.affiliation: 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.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Shein
authors.forename: Nikki M
authors.initials: NM
authors.lastname: Ferguson
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: Ericka L
authors.initials: EL
authors.lastname: Fink
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Tyler-Kabara
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: G K
authors.initials: GK
authors.lastname: Balasubramani
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bell
mesh_terms: D000293:Adolescent; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use; D015600:Glasgow Coma Scale; D006801:Humans; D019586:Intracranial Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007427:Intracranial Pressure / Q000187:drug effects*; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D010424:Pentobarbital / Q000627:therapeutic use; D011446:Prospective Studies; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000959:Antihypertensive Agents; D012462:Saline Solution, Hypertonic; D008353:Mannitol; D010424:Pentobarbital; D005283:Fentanyl