Romanian Society of Pharmaceutical Sciences

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THE PROTECTIVE EFFECT OF ULINASTATIN IN SEVERE SEPSIS. A MECHANISTIC APPROACH

SANJUN ZHOU 1, HONG GAO 2, JING CHEN 2, WENBING LIU 2*

1.Department of ICU, The Affiliated Hospital of HangZhou Normal University, HangZhou 310015, Zhejiang, China
2.Department of Rehabilitation, The Third Affiliated Hospital of Zhejiang Chinese Medical University, HangZhou 310015, Zhejiang, China

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The aim of this study was to investigate the effect of ulinastatin on endothelial polysaccharide coating and mortality in patients with severe sepsis and septic shock. Twenty-nine cases of sepsis and septic shock diagnosed from June 2015 to December 2018 were included in the study. According to their time of admission, the patients were randomly divided into ulinastatin group (Y, N = 13), which was subdivided in L15 group (APACHE II (Acute physiology and chronic health evaluation II) ≥ 15) (8 cases) and in S15 group (APACHE II < 15) (5 cases), and control group (N, N = 16), subdivided in L15 group (11 cases) and S15 group (5 cases). All patients were treated in the Intensive Care Unit (ICU). The ulinastatin group (Y) received 100,000 U ulinastatin as an intravenous infusion for a period of 8 h, while the control group received routine treatment. Temperature (T), respiratory rate (RR), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), and pulmonary vascular permeability index (PVPI) at 0 h, 24 h and 72 h after admission were determined for each patient. Moreover, the blood samples were collected in order to evaluate the white blood cell count (WBC), lactate (Lac), C-Reactive Protein (CRP), procalcitonin (PCT), intercellular adhesion molecule (ICAM-1), Syndecan-1 (SDC-1), and systemic central venous oxygen saturation (ScVO2). The results showed that the lactate levels after 72 h of treatment and the 28-day mortality rate of group Y significantly decreased compared to group N (p <0.018). In L15 subgroup, the lactate level and the 28-day mortality rate in group Y significantly decreased compared to group N (p < 0.018). In S15 subgroup, lactate level, PVPI, SDC-1 and The 28-day mortality rate significantly decreased in group Y compared to group N (p < 0.05). In conclusion, for sepsis patients with an APACHE II score ≥ 15, their structure of vascular endothelial polysaccharide coating may be affected by many factors, and the effect of ulinastatin is limited. For sepsis patients with an APACHE II score of < 15, ulinastatin may improve vascular permeability, reduce capillary leakage and improve microcirculation by protecting the structure of endothelial polysaccharide coating. In addition, ulinastatin may reduce the mortality of sepsis patients.