Endotoxin Adsorber Hemoperfusion and Microcirculation
Despite maintaining adequate mean arterial pressure and central venous oxygen saturation, the mortality is still high in severe sepsis and septic shock. Previous studies have demonstrated that derangements in microvascular flow play a role in sepsis-induced multiple organ dysfunction and death. Lipopolysaccharide (LPS) or endotoxin is a specific ligand for Toll-like receptor 4 (TLR4), it can induce the following reactions including excessive immune and inflammatory responses , oxidative stress , capillary leakage, endothelial damage, impaired arteriolar and venular vasoregulation, and activation of the coagulation cascade 8. Subsequently, these reactions can lead to microcirculatory dysfunction. Polymyxin B adsorber hemoperfusion (PMX) have been proved to reduce mortality of severe sepsis and septic shock. Since 1994 to 2007, more than 60,000 patients have received this treatment. In a systematic review, the results show that PMX therapy was associated with significantly lower mortality risk (risk ratio, 0.53; 95% CI, 0.43 to 0.65). In a prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]), the results show that SOFA scores improved in the polymyxin B group, and 28-day mortality was 32% in the polymyxin B group and 53% in the conventional therapy group.
The investigators hypothesize that polymyxin B hemoperfusion can decrease blood endotoxin level and reduce endotoxin-related microcirculatory dysfunction. The purpose of this prospective randomized controlled open study is to investigate the effect of polymyxin B hemoperfusion on the sublingual microcirculation in patient with proven or suspected gram-negative bacteria severe sepsis and septic shock. The serum level of endotoxin, mean arterial pressure, dose of vasopressors and inotropics, SOFA score, PaO2/FiO2 ratio, and 28-day mortality will be investigated.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Effect of Endotoxin Adsorber Hemoperfusion on the Microcirculation in Patients With Severe Sepsis and Septic Shock|
- Total small vessel density of sublingual microcirculation [ Time Frame: 48h ] [ Designated as safety issue: No ]
- Change of SOFA score [ Time Frame: 48h ] [ Designated as safety issue: No ]
- Number of participates die within 28 days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
No Intervention: Control
Treat with NTUH SICU severe sepsis / septic shock practice guideline
Experimental: PMX HP
Treat with NTUH SICU severe sepsis / septic shock practice guideline Treat with PMX-20R Hemoperfusion [Polymyxin B adsorbs and remove endotoxin from the patient's circulating blood].
Device: PMX-20R Hemoperfusion
Polymyxin B adsorbs and remove endotoxin from the patient's circulating blood.
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|Contact: Yu-Chang Yeh, M.D., Ph.D.||email@example.com|
|National Taiwan University Hospital||Recruiting|
|Taipei, Taiwan, 100|
|Contact: Yu-Chang Yeh, M.D., Ph.D. 886-9-10513711 firstname.lastname@example.org|
|Principal Investigator: Yu-Chang Yeh, M.D., Ph.D.|
|Principal Investigator:||Yu-Chang Yeh, M.D., Ph.D.||National Taiwan University Hospital|