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Prostacyclin modulates the systemic inflammatory response in traumatic brain injury: a randomised clinical study
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Anestesi och intensivvård, Sahlgrenska Universitetssjukhuset, Göteborg.
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(English)In: Article in journal (Other academic) Submitted
Abstract [en]


Systemic inflammatory response is common in patients with severe traumatic brain injury (TBI), and may contribute to a less favourable outcome. The aim was to evaluate the effect of prostacyclin on systemic inflammation.


This study is part of a prospective, randomised, clinical trial on the effect of prosta­cyclin (epoprostenol, Flolan®) in patients with severe TBI. Epoprostenol/placebo was given during 72 hours and then de-escalated. Interleukin-6, interleukin-8, soluble intracellular adhesion molecules-1 (sICAM-1) and C-reactive protein (CRP) were sampled daily.


46 patients were included and randomised to 23 of each group (epopros­tenol/placebo). Interleukin-6 was statistically lower within 96 hours (p = 0.04), and CRP within 96 and 120 hours (p = 0.04 and p = 0.008 respectively) after trauma in the epoprostenol group compared to the placebo group. No significant differences were detected between the groups in the levels of interleukin-8 and sICAM-1 or in outcome.


Administration of the prostacyclin analogue epoprostenol, compared to placebo significantly decreased interleukin-6 and CRP levels in patients with severe TBI. The beneficial effect of this decrease is further to investigate.

Keyword [en]
traumatic brain injury, prostacyclin, interleukin-6, C-reactive protein, interleukin-8, intracellular adhesion molecules
National Category
Anesthesiology and Intensive Care
Research subject
URN: urn:nbn:se:umu:diva-21054OAI: diva2:210550
Available from: 2009-04-02 Created: 2009-04-02 Last updated: 2011-04-11
In thesis
1. Severe cerebral emergency: aspects of treatment and outcome in the intensive care patient
Open this publication in new window or tab >>Severe cerebral emergency: aspects of treatment and outcome in the intensive care patient
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Severe Traumatic Brain Injury (TBI) and aneurysmal Subarachnoid Hemorrhage (SAH) are severe cerebral emergencies. They are common reasons for extensive morbidity and mortality in young people and adults in the western world. This thesis, based on five clinical studies in patients with severe TBI (I-IV) and SAH (V), is concentrated on examination of pathophysiological developments and of evaluation of therapeutic approaches in order to improve outcome after cerebral emergency.

The treatment for severe TBI patients at Umeå University Hospital, Sweden is an intracranial pressure (ICP)-targeted therapy according to “the Lund-concept”. This therapy is based on physiological principles for cerebral volume regulation, in order to preserve a normal cerebral microcirculation and a normal ICP. The main goal is to avoid development of secondary brain injuries, thus avoiding brain oedema and worsened microcirculation.

Study I is evaluating retrospectively 41 children with severe TBI, from 1993 to 2002. The boundaries of the ICP-targeted protocol were obtained in 90%. Survival rate was 93%, and favourable outcome (Glasgow Outcome Scale, score 4+5) was 80%.

Study II is retrospectively analysing fluid administration and fluid balance in 93 adult patients with severe TBI, from 1998 to 2001.The ICP-targeted therapy used, have defined fluid strategies. The total fluid balance was positive day one to three, and negative day four to ten. Colloids constituted 40-60% of total fluids given/day. Severe organ failure was evident for respiratory insufficiency and observed in 29%. Mortality within 28 days was 11%.

Study III is a prospective, randomised, double-blind, placebo-controlled clinical trial in 48 patients with severe TBI. In order to improve microcirculation and prevent oedema formation, prostacyclin treatment was added to the ICP-targeted therapy. Prostacyclin is endogenously produced, by the vascular endothelium, and has the ability to decrease capillary permeability and vasodilate cerebral capillaries. Prostacyclin is an inhibitor of leukocyte adhesion and platelet aggregation. There was no significant difference between prostacyclin or placebo groups in clinical outcome or in cerebral microdialysis markers such as lactatepyruvate ratio and brain glucose levels.

Study IV is part of the third trial and focus on the systemic release of pro-inflammatory mediators that are rapidly activated by trauma. The systemically released pro-inflammatory mediators, interleukin-6 and CRP were significantly decreased in the prostacyclin group versus the placebo group.

Study V is a prospective pilot study which analyses asymmetric dimethylarginine (ADMA) concentrations in serum from SAH patients. Acute SAH patients have cerebral vascular, systemic circulatory and inflammatory complications. ADMA is a marker in vascular diseases which is correlated to endothelial dysfunction. ADMA concentrations in serum were significantly elevated seven days after the SAH compared to admission and were still elevated at the three months follow-up.

Our results show overall low mortality and high favourable outcome compared to international reports on outcome in severe TBI patients. Prostacyclin administration does not improve cerebral metabolism or outcome but significantly decreases the levels of pro-inflammatory mediators. SAH seems to induce long-lasting elevations of ADMA in serum, which indicates persistent endothelial dysfunction. Endothelial dysfunction may influence outcome after severe cerebral emergencies.

Place, publisher, year, edition, pages
Umeå: , 2009. 83 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1244
severe traumatic brain injury, intracranial pressure-targeted therapy, albumin, prostacyclin, endothelial dysfunction, pro-inflammatory cytokines, subarachnoid haemorrhage, asymmetric dimethylarginine
National Category
Anesthesiology and Intensive Care
Research subject
urn:nbn:se:umu:diva-21065 (URN)978-91-7264-725-1 (ISBN)
Anestesiologi och intensivvård, 901 87, Umeå
Public defence
2009-04-24, Sal B 9tr, Tandläkarhögskolan, Norrlands Universitetssjukhus, Umeå, 13:00 (Swedish)
Available from: 2009-04-09 Created: 2009-04-02 Last updated: 2010-01-18Bibliographically approved

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Rodling Wahlström, MarieOlivecrona, MagnusAhlm, ClasKoskinen, Lars-OweNaredi, Silvana
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