Persistent Multiorgan Failure in Intensive Care Units
Condition: Systemic Inflammatory Response Syndrome; Sepsis; Multiorgan Failure
MeSH terms: Systemic Inflammatory Response Syndrome; Multiple Organ Failure
Study type: Observational [Patient Registry]

Summary: 
      Multiorgan failure (MOF) as a result of any critical condition is a complex set of
      immunological and biochemical interactions leading to death in patients who are effectively
      subjected to primary resuscitation (correction of circulatory hypoxia in trauma and blood
      loss, restoration of blood circulation after operations with artificial circulation. The
      frequency of MOF varies depending on the primary diagnosis of a critical patient and,
      according to a number of authors, is 60% for sepsis, and for severe co-occurring trauma up to
      40% of all critical patients. However, if one remembers that the MOF is verified only by
      clinical scales of assessing the severity of the patient's condition, which presupposes the
      presence of the already existing pathophysiological mechanisms of MOF as multi-organ
      dysfunction, it is possible to declare a 100% presence of MOF in all critical patients. The
      data of Graetz et al (2016) show that none of the available three variants of
      pathophysiological mechanisms (anomaly of microcirculation, persistent inflammation, immune
      suppression and catabolism, cellular hibernation and staning) have been unambiguously
      demonstrated, which also reflected the lack of effectiveness of methods therapy, proposed,
      based on the pathogenesis options for MOF. A so-called danger-model has a special place in
      the genesis of the persistence of the MOF, which justifies an active search for
      distress-associated and pathogen-associated molecular patterns for their objectification and
      probable elimination. The systemic inflammatory response in patients. included in the study,
      is not a primary infection. It is also important to determine the role of danger-associated
      molecular patterns (DAMP) in the genesis of immune suppression as the leading immunological
      phenotype of MOF in later periods and to evaluate the relationship between DAMP expression
      and immunosuppressive cells of monocyte origin. The study has a mixed (retro- and
      prospective) character.
    

Detailed description: 
      1. Based on the patient database analysis, by the method of continuous sampling of the
           cardiac surgery patients to the intensive care unit for the period 2006-2018, to
           determine the clinical risk factors for the development of a persistent MOF (MOF +
           persistent MOF, which lasts more than 7 days and is determined primarily by based on
           indicators of objective assessment of the patient's condition - the SOFA scale is more
           than 8 points on the 7th day of the critical care). To form a prognostic model.

        2. By means of biochemical analysis of blood serum and cells, identify biological markers
           MES specific for distant organs and supplement the prognostic model of persistent MOF.
           It is planned to detect serum concentrations (1) of surfactant protein A (organ-specific
           lung marker for the development of acute respiratory distress syndrome as manifestations
           of MOF), (2) intestinal fatty acid binding protein (organ-specific marker of acute
           intestinal distress (3) S100 protein - a marker of brain damage) with an assessment of
           prognostic and diagnostic significance with respect to the MOF.

        3. To assess the prognostic and diagnostic significance of serum mitochondrial DNA as one
           of the variants of the danger-associated molecular pattern.

        4. To characterize the presence of an immunosuppressive phenotype of a critical patient
           with MOF by examining the expression and serum concentration of: (a) myeloid suppressor
           cells; (b) T-reg cells expressing CD39; (c) CD62 and CD11b expression on neutrophils on
           monocytes; (d) soluble sTREM-1, (e) HLA-DR on monocytes. In addition, it will be planned
           to study the "classic" serum cytokines (tumor necrosis factor alpha, interleukin
           1,6,8,10, HMGB-1).

        5. On the basis of the diagnostic panel obtained, to try to conduct an individualized
           choice of methods of preventive therapy for MOF. It is proposed to use: (1) cytokine
           modulation of the systemic inflammatory response by sorption of cytokines on selective
           sorbents, (2) cytokine modulation by sorption of cytokines on polymethylmethacrylate
           membranes. It is assumed that in order for these methods to be preventative, they should
           be used not only in conditions of treatment in the intensive care unit, but also in the
           operating room at the time of extracorporeal perfusion.
    

Intervention name(s): cytokine adsorbtion during extracorporeal circulation
Intervention type(s): Device
Intervention description(s): preventive use of cytokine adsorption and modulation of the cytokine response in the course of artificial circulation
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients operated on the heart and trunk vessels under conditions of artificial circulation
        (coronary artery bypass grafting, prosthetic / cardiac valve repair, operations on the
        aorta and its branches)
      
Biospecimen description: 
      Blood serum (cytokines, mit DNA)
    
Keywords: Immunology, Suppression, Inflammation, Cardiac, Surgery