The Effect of Endotoxin Adsorber Hemoperfusion on the Microcirculation in Patients With Severe Sepsis and Septic Shock
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 6
- 主要终点
- Total small vessel density of sublingual microcirculation
研究概览
简要总结
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, multicenter, 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 mean arterial pressure, dose of vasopressors and inotropics, SOFA score, PaO2/FiO2 ratio, and 28-day mortality will be investigated.
详细描述
Introduction
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. Because of the clinical significance of microcirculatory dysfunction in severe sepsis and septic shock, recent advances in image technology have been used to investigate microcirculation. A sidestream dark-field (SDF) video microscope has been developed to visualize the microcirculation, but its measurement of microvascular blood flow classification is semi-quantitative. Previous studies have shown that a full-field laser perfusion imager can quantitatively measure the change of microcirculatory blood flow intensity. For clinical studies, sublingual microcirculation is most easily investigated using a SDF video microscope.
Because 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. Subsequently, these reactions can lead to microcirculatory dysfunction. Recently, a TLR4 antagonist, eritoran tetrasodium (E5564), has been reported to inhibit LPS response without TLR4 agonistic activity in animals as well as in humans, but it fails to reduce mortality of severe sepsis and septic shock. 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).21 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 but not in the conventional therapy group (change in SOFA, -3.4 vs -0.1; P =0.001), and 28-day mortality was 32% in the polymyxin B group and 53% in the conventional therapy group (unadjusted hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20-0.94; adjusted HR, 0.36; 95% CI, 0.16-0.80). Iba et al. have revealed that polymyxin B hemoperfusion can maintain better microcirculation and survival in a septic rat model.
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 clear or suspected severe sepsis and septic shock by gram-negative bacteria. 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.
Methods
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients will be included in this study if they meet the following criteria (A+B+C):
- •A. Patients with the following conditions:
- •Abdominal cavity infection following emergency surgery.
- •Pneumonia, blood stream infection, urinary tract infection, or other infection, has received adequate treatment and presents with an Endotoxin Activity Assay > 0.6 EAA units.
- •B. SIRS, as defined by the presence of at least 2 of the following conditions (These criteria should have occurred between 12 hours before or 6 hours after the onset of the qualifying first organ dysfunction :
- •Fever or hypothermia (body temperature over 38 ℃ or under 36 ℃)
- •Tachycardia (heart rate > 90 bpm)
- •Tachypnea (respiratory rate over 20 breaths/min or under mechanical ventilation)
- •Leukocyte count more than 12,000 cells/mm3, less than 4,000 cells/mm3, or more than 10 % of immature form (band)
- •C. The presence of at least one of these symptoms of organ dysfunction or shock:
- •Cardiovascular system: an SBP of less than 90 mm Hg, a decrease in SBP of at least 40 mm Hg from baseline, a MAP of less than 65 mm Hg, or that requires treatments with vasoactive medication at any dosage.
- •Acute lung injury: PaO2 / FiO2 ratio less than 300 (ratio in mm Hg)
- •Acute kidney injury: creatinine more than 2 mg/dL, an increase in creatinine of more than 0.5 mg/dL, or diuresis of less than 0.5 mL/kg/h for 2 hours.
- •Acute liver injury: Total bilirubin level more than 4 mg/dL
- •Disseminated intravascular coagulation: platelet count less than 100,000 cells/mm3 or a reduction of more than 50 % of baseline
- •INR > 1.5 or aPTT > 60 sec
- •Altered mental status: GCS under 13 or 9T under endotracheal tube
- •Lactic acidosis: Lactate level more than 2 mmol/L (accompany with pH < 7.3 or Base excess < -5 mmol/L)
排除标准
- •Patients will be excluded if they
- •A. are under 20 years old or older than 99 years old
- •B. have suffered from severe sepsis or septic shock more than 24 hours
- •C. are pregnant
- •D. were treated with another medicine or device in the trial less than 30 days prior to the admission to this trial
- •E. have received organ transplantation less than 1 years prior to this trial
- •F. patients with hemophilia
- •G. have a allergic history of polymyxin B, heparin, or extracorporeal circulation
- •H. are terminally ill, for examples with metastasis, with a life expectancy of less than 30 days (certified by the attending physician)
- •I. have been diagnosed with HIV
- •J. present uncontrolled bleeding in the last 24 hours
- •K. were diagnosed with leukocytopenia (leukocyte count less than 500 cell/mm3) and/or thrombocytopenia (platelet count less than 50,000 cells/mm3)
- •L. have already received other blood cleaning treatments, such as CVVH, HD, HF, and PE upon entry into the trial
- •M. have a prior history of severe chronic organ failure
- •chronic respiratory failure ( COPD at last stage)
- •chronic heart failure (NYHA score = IV)
- •brain death
- •Chronic liver failure (Child Pugh score: C)
- •N. have evidence of infection by gram-positive bacteria, fungal infection, or mixed infection
- •O. have chosen palliative care and signed Do Not Resuscitate sheet
- •P. an APACHE II score over 30 present on entry into the trial
- •Q. non-native speakers
研究组 & 干预措施
Control
Treat with severe sepsis / septic shock practice guideline
PMX HP
Treat with severe sepsis / septic shock practice guideline Treat with PMX-20R Hemoperfusion [Polymyxin B adsorbs and remove endotoxin from the patient's circulating blood].
干预措施: PMX-20R Hemoperfusion (Device)
结局指标
主要结局
Total small vessel density of sublingual microcirculation
时间窗: 48h
次要结局
- Change of SOFA score(48h)