SHINE Trauma

SHINE-TRAUMA

Shock-induced Endotheliopathy in Trauma

Aim

The aim is to investigate whether continuos infusion of iloprost for 72-hours is safe and significantly increase the number of ICU free days, within 28 days from admission compared to placebo in trauma patients with haemorrhagic shock and SHINE, across the country.

Background

In 2010 the outcome of critically ill patients needing renal replacement therapy was studied at the University Hospital in Copenhagen. The finding was that those receiving prostacyclin (PGI2) as anticoagulant in the dialysis filter had substantially lower 30-day mortality than patients receiving heparin (21% vs. 39%), despite being more critically ill and we speculated that this may be due to a spillover effect of PGI2 to the systemic circulation. PGI2 is an endogenous prostanoid formed and released by endothelial cells with paracrine function including vasodilation and platelet inhibition.

In the new millennium it was reported that PGI2 also confers potent endothelial cytoprotection by: synthesizing endothelial glycocalyx constituents (hyaluronic acid), acting on prostaglandin I (IP1) receptors on endothelial progenitor cells leading to re endothelium-formation in damaged vessels. 

A clinical trial in healthy volunteers showed that low-dose PGI2 did not affect blood pressure or platelet function but instead appeared to improve endothelial functionality. The effect of low-dose iloprost infusion (1 ng/kg/min) was, therefore investigated in randomized, double-blind pilot studies in coronary stent (n=18), major abdominal surgery (n=56) and septic shock patients (n=18). These trials documented no adverse effect on blood pressure or platelet function. Instead, iloprost infusion significantly improved endothelial function and integrity, measured by validated biomarkers, in all groups. 

Study design and setting

We studied > 500 trauma patients in Copenhagen and Houston and validated that those with hemorrhagic shock had increased levels of circulating syndecan-1 (an EGL component) in plasma, increased injury severity score (ISS) and a doubling of mortality rate (OR 2.2) compared with non-shocked patients. This is pointing towards a denominating factor namely failure of one of the largest “organs” or structures in the body i.e. the endothelium, a disease entity we entitle shock induced endotheliopathy (SHINE)

Population

Trauma patients with haemorrhagic shock and SHINE, across the country.

Intervention

Continuos infusion of iloprost for 72-hours compared to placebo.