title: Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury-a randomised clinical study.
abstract: OBJECTIVE
  A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI).
  
  
  METHODS
  46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23).
  
  
  METHODS
  Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours.
  
  
  METHODS
  Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI.
  
  
  RESULTS
  A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1.
  
  
  CONCLUSIONS
  Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier, NCT01363583.
authors.affiliation: Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Umeå University, S-901 87 Umeå, Sweden.
authors.forename: Marie Rodling
authors.initials: MR
authors.lastname: Wahlström
authors.affiliation: Department of Pharmacology and Clinical Neurosciences, Neurosurgery, Umeå University, S-901 87 Umeå, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Olivecrona
authors.affiliation: Department of Clinical Microbiology, Infectious Diseases, Umeå University, S-901 87 Umeå, Sweden.
authors.forename: Clas
authors.initials: C
authors.lastname: Ahlm
authors.affiliation: Institute of Clinical Sciences, Department of Anesthesiology and Intensive Care, The Sahlgrenska Academy, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bengtsson
authors.affiliation: Department of Pharmacology and Clinical Neurosciences, Neurosurgery, Umeå University, S-901 87 Umeå, Sweden.
authors.forename: Lars-Owe D
authors.initials: LO
authors.lastname: Koskinen
authors.affiliation: Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Umeå University, S-901 87 Umeå, Sweden.
authors.forename: Silvana
authors.initials: S
authors.lastname: Naredi
authors.affiliation: Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Umeå University, S-901 87 Umeå, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Hultin
keywords: Asymmetric dimethylarginine; Cytokines; Epoprostenol; Systemic inflammatory response; Traumatic brain injury