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

Marie Rodling Wahlström,Anders Bengtsson,Magnus Olivecrona,Clas Ahlm,Lars-Owe D Koskinen,Silvana Naredi,Magnus Hultin

doi:10.1186/2193-1801-3-98

Marie Rodling Wahlström, Anders Bengtsson + Show 5 more

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https://doi.org/10.1186/2193-1801-3-98

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Journal: SpringerPlus	Publication Date: Feb 18, 2014
Citations: 13	License type: cc-by

Affiliation: Umeå University, University of Gothenburg

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Objective and designA 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).Subjects46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23).TreatmentEpoprostenol, 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.MethodsInterleukin-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.ResultsA 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.ConclusionsAdministration 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 registrationClinicalTrials.gov Identifier, NCT01363583

Highlights

Following traumatic injuries with or without severe traumatic brain injury (TBI), an inflammatory response is induced both in the brain and in the systemic circulation (Holmin et al 1998; Lu et al 2009)
Administration of the prostacyclin analogue epoprostenol significantly decreased C-reactive protein (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

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Following traumatic injuries with or without severe traumatic brain injury (TBI), an inflammatory response is induced both in the brain and in the systemic circulation (Holmin et al 1998; Lu et al 2009). Severe injury is associated with a systemic host-defence reaction – known as systemic inflammatory response syndrome (SIRS) – that can progress into multiple organ failure (Lenz et al 2007). Experimental studies and clinical studies in trauma patients have shown that increased production of inflammatory mediators is associated with SIRS and subsequent organ failure (Lenz et al 2007; Stahel et al 2007), and several different inflammatory mediators have been used to measure the inflammatory response (Lu et al 2009; Lenz et al 2007). Modulating the systemic pro-inflammatory response and reducing cytokine overproduction might be an effective therapeutic strategy for preventing organ failure due to SIRS after traumatic injuries, including severe TBI (Neunaber et al 2011). Reduced production and/or effects of endogenous prostacyclin due to an imbalance in the prostaglandin-thromboxane pathways have been found experimentally to be associated with TBI (Orfeo et al 1994)

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