Endotoxin Activity Assay and Microcirculation in Severe Sepsis

Endotoxin Activity Assay and Microcirculation Examination in Patients With Severe Sepsis

Endotoxin is the major mediator of sepsis resulted from systemic inflammatory response syndrome induced by gram-negative bacteria infection. The endotoxin related inflammatory response and hypercoagulation can result in microcirculatory dysfunction. When microcirculatory dysfunction is severe, it can induce multiple organ dysfunction syndrome and death. This is a prospective observational study, and it will not influence the sepsis treatment decision of the medical care team. The critically ill severe sepsis patients will be enrolled only if they meet all inclusion criteria, do not meet any exclusion criteria and sign the consent form after explanation of the aim and process of the trial by the primary investigator or research personnel. After enrollment, the patient will receive serum assay of endotoxin activity (EAA) and endocan level. The patient will also receive examination of sublingual microcirculation by using the incident dark field video microscope. After 24 hours, the patient will receive assay of endocan level and examination of sublingual microcirculation. This study will record the vital signs, laboratory data, dose of vasopressors and inotropic agents, and severity of organ dysfunction. After 28 days, this study will check the survival, stay of intensive care, stay of hospital, ventilator day, and the results of culture of pathogens. The patients will be assign to the following three groups by the EAA level: low EAA group (< 0.40 EAA units); intermediate EAA group (0.40-0.59 EAA units); and high EAA group (≧ 0.60 EAA units). This grouping will be used for statistical analysis and comparison. The primary goal of this study is to investigate the difference of the prevalence of gram-negative bacteria infection, pathogen, infection source, microcirculation, the severity of disease, and the prognosis among these three groups.

Inclusion Criteria:

• patients with the following infections: intraabdominal infection, pneumonia, urinary tract infection, blood stream infection, or wound infection

• patients must also meet any one of the following criteria for severe sepsis

  • SBP < 90 mm Hg, MAP < 65 mm Hg, or requirement of vasopressors or inotropics
  • PaO2/FiO2 < 300
  • Creatinine level > 2 mg/dL or increase > 0.5 mg/dL; or urine output < 0.5 mL/kg/h more than 2 hours
  • Bilirubin level > 4 mg/dL
  • Platelet count < 100 k/uL or decrease more than 50%
  • INR > 1.5 or aPTT > 60 sec
  • GCS < 13 or 9T
  • Lactate > 2 mmol/L (with pH < 7.3 or base excess < -5 mmol/L)

Exclusion Criteria:

• younger than 20 yeras old or greater than 99 years old
• the onset of severe sepsis before enrollment is greater than 24 hours
• pregnant
• have received plymyxin-B hemoperfusion within 24 hours before enrollment
• non-native speaker