Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury-a randomised clinical study

Abstract

Abstract Objective and design 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). Subjects 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). Treatment 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. Trial registration ClinicalTrials.gov Identifier,NCT01363583