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Yaroustovsky et al.                                                                                                                                                     Blood purification in intensive care patients

           blood purification in children, it is important to prevent   plasmofiltration  and  adsorption  (CPFA),  convection
           hypothermia. Hypothermia can lead to cardiac output   and  filtration  techniques  using  ultrahigh  permeable
           decrease  by peripheral  vasospasm and an increase   membranes. [53,54]
           in  TPVR  and post-load.  To avoid heat loss during
           MARS-therapy in children,  it is necessary to use a   Many authors have observed that LPS-adsorption
           heat exchanger  and other physical heating means   with PMX cartridges leads to a significant decrease
           and to establish a high temperature (38-39 °C) on the   in  endotoxin  activity  levels  after  two  consecutive
                                                                         [55]
           bicarbonate line. [44]                             procedures.  Positive dynamics of the endotoxin
                                                              concentration (lowering by 38%) in patients with
           EXTRACORPOREAL BLOOD                               abdominal sepsis and septic shock were demonstrated
                                                                                                       [56]
           PURIFICATION IN COMPLEX INTENSIVE                  in the European multicenter study “EUPHAS”.  In the
           THERAPY FOR SEPSIS IN ADULT AND                    MEDIC study conducted in Europe and North America
                                                              on ICU patients, selective LPS-adsorption led to a
           PEDIATRIC PATIENTS AFTER OPEN-                     decrease in the mean endotoxin activity assay (EAA)
           HEART SURGERY                                      level from 0.65 to 0.45 within 12 h after the procedure.
                                                              According to the authors, the average reduction of the
           Sepsis and septic shock are among the most common   endotoxin concentration (26.1%) measured with the
           causes of death in critically ill patients in the ICU. Over   EAA is equivalent to a 50-100-fold decrease in the
           the last decade, clinics worldwide have noted a trend   LPS level. [57]
           towards a decrease in the frequency of Gram-positive
           bacteria and an increase in the frequency of Gram-  In the European multicentre trial, the EUPHAS trial,
           negative bacteria within microbiological studies.  28-day  survival  after  DHP-PMX  was  53%  and  32%
                                                              in  the  study  and  control  groups,  respectively.  The
                                                                                                        [56]
           A  structural  component  of  the  membrane  of    assessment of retrospective data on using selective
           gram-negative    microorganisms    is   bacterial  LPS adsorption in 306 patients with severe sepsis
           lipopolysaccharide (or endotoxin), which is the main   enrolled in the EUPHAS 2 trial indicated that 28-
           trigger of both sepsis and a cascade of inflammatory   day  mortality  was  35%  and  49%  in  the  group  with
           reactions.  When entering the systemic bloodstream   abdominal surgical  pathology  and  in the  group
                    [46]
           from a focus of infection (e.g. pneumonia, mediastinitis)   with  non-abdominal  pathology,  respectively. [58]
           or natural reservoir (for example, the gastrointestinal   Similar results were observed in earlier published
           tract, particularly after CPB), endotoxin interacts   Japanese [59-61]   and  European  studies   and  in  the
                                                                                                 [62]
           with competent cells of the immune system as a     meta-analysis data regarding immobilized Polymyxin
           hormone and activates the synthesis of a wide      B use efficacy during sepsis. [52,63]
           range of mediators. The excess production of which
           determines the clinical manifestations of sepsis, such   Our experience with combined application of various
           as systemic endothelial damage, decreased vascular   techniques in a single circuit (LPS-adsorption +
           tone, hypotension, cardiovascular hyporeactivity,   CPFA  and  LPS-adsorption  +  HD/HDF  using  filters
           fever,  microcirculatory  disorder,  activation  of  with  high cut-off  membranes)  showed  their  safety
           hemostatic system factors, tissue hypoperfusion,   and  pathogenic  efficiency. [53,54]   The application of
           hypoxia and multi-organ failure. [47,48]  The development   convection  and  filtration  techniques  (CPFA,  HDF
           of microcirculatory disorders and tissue hypoxia in the   using  filters  with  high  cut-off  membranes)  allows
           gastrointestinal tract  creates conditions for  bacterial   the correction of water-electrolyte and metabolic
           translocation.  Thus, the vicious circle initiated by   disorders  and  azotemia,  which  often  accompany
           lipopolysaccharide is closed. [49,50]              sepsis-associated MODS. [64-67]

           The pathogenic chain of septic development and     LPS-adsorption     using    Toraymyxin-PMX-20R
           progression determines a need to develop and       Polymyxin  B  immobilized  fiber  cartridges  was  found
           introduce new promising technologies. [47,51,52]   to be effective, simultaneously acting through sorption
                                                              and  apheresis  on  bacterial  endotoxin,  systemic
           Modern  methods  of  blood  purification  allow    inflammatory  mediators  and  activated  immune
           etiopathogenic  therapy application for  sepsis: to   cells. [59-61,68,69]
           eliminate the etiotropic agent (endotoxin) by selective
           lipopolysaccharide  (LPS)-adsorption and to  remove   CPFA performs an immunomodulatory role by acting
           the  effector  substances  of  systemic  inflammation,   on  inflammatory  mediators  (interleukin-1β, -6, -8,
           replacing  the functions  of the affected organs  and   -10,  -18,  tumor  necrosis factor-α  and  others)  via
           recovering  the body’s homeostasis by coupled      various mass transfer mechanisms such as diffusion,
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