The Mechanism Of Ulinastatin's Protection To Endothelium Glycocalyx In Severe Sepsis And Septic Shock

Objective:This study was to explore the mechanism of Ulinastatin's protection to endothelium glycocalyx in severe sepsis and septic shock.Methods: A prospective cohort study was conducted.This study included the patients in February 2016 to December 2016,Diagnosed of severe sepsis and septic shock by various reasons in the fourth hospital affiliated to Hebei medical university Intensive Care Unit(ICU).Inclusion criteria:1)In accordance with SIRS diagnostic criteria:At last two out of four.a.Fever(> 38.3°C)or Hypothermia(core temperature < 36°C);b.Heart rate > 90/min or more than two SD above the normal value for age;c.Respieatory Rate>20/min or PaCO2 <32mmHg.d.Leukocytosis(WBC count > 12,000 ?L–1)Leukopenia(WBC count < 4000 ?L–1),or Normal WBC count with greater than 10% immature forms.2)Have suspect or clear focal infection.3)(1)In accordance with Severe Sepsis diagnostic criteria: a.Sepsisinduced hypotension;b.Lactate above upper limits laboratory normal;c.Urine output<0.5mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation;d.Acute lung injury with Pa O2/FiO2<250mmHg in the absence of pneumonia as infection source;e.Acute lung injury with PaO2/Fi O2<200mmHg in the presence of pneumonia as infection source;f.Creatinine>2.0mg/dL(176.8 ?mol/L);g.Bilirubin>2mg/ dL(34.2 ?mol/L);h.Platelet count<100,000 ?L;i.Coagulo-pathy(international normalized ratio >1.5).(2)In accordance with Septic Shock diagnostic criteria: Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation.Sepsis-induced tissue hypoperfusion is defined as infection-induced hypotension,elevated lactate,or oliguria.Exclusion criteria:diabetes mellitus history,age<18 years old,predict length of stay? 24 h,duration of pregnancy,use chemotherapy drugs in a month.Collect patients' basic information,mainly including: age,gender,APACHE II scores.Clinical and laboratory parameters,mainly including:heart rate,body temperature,MAP,central venous pressure,central venous blood oxygen saturation,lactate,PCT,CRP,ICAM-1,SDC-1,PICCO parameter included:PVPI.collected the dates at 0,24,72 hours.According to the time order,the patients were divided into Y or N group;A according to the APACHE II score,the two groups patients were divided into S/L respectively;Y group use Ulinastatin and based on APACHE II scores,patients divided into less than 15(S15 group),greater than or equal to 15(L15 group);The N group didn't use Ulinastatin and based on APACHE II scores,patients divided into less than 15(S15 group),greater than or equal to 15(L15 group).To assess the function of endothelium glycocalyx,including:ICAM-1,SDC-1,PVPI,at the same time observation and analysis the prognosis of patients,including: 28 days mortality,the fatality rate of ICU in the hospital.Results: 1 29 patients were included in this study,13 patients in Y group: S15 group had 5 patients,L15 group had 8 patients;16 patients in N group: S15 group had 5 patients,L15 group had 11 patients.21 patients(72.4%)had chest infection,6 patients(20.7%)had abdominal infection,1 patient(3.44%)had bloodstream infection,1 patient(3.44%)had urinary system infection.Given ulinastatin applied in patients with 44.8% of the total.2 Application of Ulinastatin on the endothelium glycocalyx and prognosis of patients with severe sepsis and septic shock.2.1 The baseline characteristics between the groups in Y and N groupAPACHE II scores,WBC,Lactate,PVPI,PCT,CRP,ICAM-1 and SDC-1had no statistical difference in Y and N group at 0 hours(P > 0.05),the two groups were comparable.2.2 At 72 hours in the treatment,lactate in Y group was lower than that in N group [1.16±0.23 vs 1.71±0.47mmol/L],the difference is statistically significant(P = 0.001).PVPI,SDC-1,ICAM-1,had no statistical difference in the two groups(P > 0.05).2.3 After the treatment in Y and N group,the 28-day mortality in Y group was 0,the 28-day mortality in N group was 31%,the difference is statistically significant(P = 0.027),ICU length of stay had no statistical difference in the two groups(P > 0.05).3 The comparison of endothelium glycocalyx and prognosis in patients with APACHE II scores?15.3.1 The baseline characteristics between the groups in Y and N group.WBC,Lactate,PVPI,PCT,CRP,ICAM-1 and SDC-1had no statistical difference in Y and N group at 0 hours(P>0.05),the two groups were comparable.3.2 In L15 group,patients in Y and N group at 72 hours in the treatment,lactate in Y group was lower than that in N group [1.09±0.20 vs 1.57± 0.49mmol/L],the difference is statistically significant(P = 0.018).PVPI,SDC-1 and ICAM-1 had no statistical difference in the two groups(P > 0.05).3.3 ICU length of stay and the 28-day mortality had no statistical difference in the two groups(P > 0.05).4 The comparison of endothelium glycocalyx and prognosis in patients with APACHE II scores?15.4.1 The baseline characteristics between the groups in Y and N group.WBC,Lactate,PVPI,PCT,CRP,ICAM-1 and SDC-1 had no statistical difference in Y and N group at 0 hours(P>0.05),the two groups were comparable.4.2 In S15 group,patients in Y and N group at 72 hours in the treatment,lactate in Y group was lower than that in N group [1.30±0.25 vs 2.02± 0.27 mmol/L],the difference is statistically significant(P = 0.003).at 72 hours in the treatment,PVPI in Y group was lower than that in N group [4.28±1.75 vs 12.16±4.95%],the difference is statistically significant(P = 0.008).at 72 hours in the treatment,SDC-1 in Y group was lower than that in N group [984.35(711.58)vs 3588.30(3872.76)pg/ml],the difference is statistically significant(P = 0.049).ICAM-1 had no statistical difference in the two groups(P > 0.05).4.3 ICU length of stay and the 28-day mortality had no statistical difference in the two groups(P>0.05).5 The baseline characteristics between the groups in S15 and L15 group were incomparable.Conclusion:1 APACHE II scores reflect the severity degree of condiction.The patients witch PACHE II scores lager than 15,endothelium glycocalyx was influenced by multi-factors,can't treat by signal medicine.2 For patients witch PACHE II scores less than 15,use Ulinastatin might protection the endothelium glycocalyx,reduce blood capillary leakage and to improvement minicirculation.To the patients who had severe sepsis and septic shock,Ulinastatin might improve mortality...