title: Pharmacologic Treatment Reduces Pressure Times Time Dose and Relative Duration of Intracranial Hypertension.
abstract: BACKGROUND
  Past work has shown the importance of the "pressure times time dose" (PTD) of intracranial hypertension (intracranial pressure [ICP] > 19 mm Hg) in predicting outcome after severe traumatic brain injury. We used automated data collection to measure the effect of common medications on the duration and dose of intracranial hypertension.
  
  
  METHODS
  Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a single, large urban tertiary care facility, were retrospectively enrolled. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. The ICP data were collected automatically at 6-second intervals and averaged over 5 minutes. The percentage of time of intracranial hypertension (PTI) and PTD (mm Hg h) were calculated.
  
  
  RESULTS
  A total of 98 patients with 664 treatment instances were identified. Baseline PTD ranged from 27 (before administration of propofol and fentanyl) to 150 mm Hg h (before mannitol). A "small" dose of hypertonic saline (HTS; ≤250 mL 3%) reduced PTD by 38% in the first hour and 37% in the second hour and reduced the time with ICP >19 by 38% and 39% after 1 and 2 hours, respectively. A "large" dose of HTS reduced PTD by 40% in the first hour and 63% in the second (PTI reduction of 36% and 50%, respectively). An increased dose of propofol or fentanyl infusion failed to decrease PTD but reduced PTI between 14% (propofol alone) and 30% (combined increase in propofol and fentanyl, after 2 hours). Barbiturates failed to decrease PTD but decreased PTI by 30% up to 2 hours after administration. All reductions reported are significantly changed from baseline, P < .05.
  
  
  CONCLUSIONS
  Baseline PTD values before drug administration reflects varied patient criticality, with much higher values seen before the use of mannitol or barbiturates. Treatment with HTS reduced PTD and PTI burden significantly more than escalation of sedation or pain management, and this effect remained significant at 2 hours after administration.
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA Duke University School of Medicine, Durham, NC, USA krcolton@gmail.com.
authors.forename: Katharine
authors.initials: K
authors.lastname: Colton
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Hu
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Bonds
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Stansbury
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Scalea
authors.affiliation: Shock Trauma Anesthesia Research Organized Research Center, University of Maryland School of Medicine and R Adams Cowley Shock Trauma Center, Baltimore, MD, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Stein
mesh_terms: D000328:Adult; D001463:Barbiturates / Q000008:administration & dosage; D001930:Brain Injuries / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D019586:Intracranial Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007427:Intracranial Pressure / Q000187:drug effects*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D008875:Middle Aged; D015742:Propofol / Q000008:administration & dosage; D012189:Retrospective Studies; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001463:Barbiturates; D006993:Hypnotics and Sedatives; D012462:Saline Solution, Hypertonic; D008353:Mannitol; D005283:Fentanyl; D015742:Propofol
keywords: hyperosmolar therapy; hypertonic saline; intracranial pressure; traumatic brain injury