Phases of systemic inflammation in septic and haemorrhagic shocks
Authors: Solmatina Liliya V. , Zotova Natalia V. , Zhuravleva Yulia A. , Brazhnikov Anatoliy Yu. , Gusev Eugeny Y. 
Published: August 2023

Shocks of different origin (both septic and aseptic) be be considered clinical equivalents of systemic inflammation (SI) with following main manifestations : pronounced hypercytokinemia, other markers of systemic inflammatory response (SIR), coagulopathy, multiple organ failure (MOF), hypothalamic-pituitary-adrenal (HPA) distress, systemic tissue alteration. In general, these phenomena are directly and inversely related to systemic microcirculatory disturbances which determine the pathogenesis of distinct shock states. The aim of our study was to identify the features of SI phases in the development of two variants of septic shock, i.e., acute course (first week of the process) and prolonged/subacute sepsis (2 to 6 weeks from the onset of manifestations), as well as haemorrhagic shock studied 4-12 hours from the onset of massive blood loss. To verify the SI phases, we used the previously proposed SI scale, including the value of six SIR levels (RL-0-5), as well as additional criteria of SI, i.e., evaluation of clinical MOF grade (SOFA scale), plasma D-dimers ( 500 ng/mL), cortisol ( 1380 nmol/mL), tissue alteration markers, e.g., myoglobin ( 800 ng/mL) and/or troponin I ( 0.2 ng/mL). To calculate RL in SIR, plasma CRP and four cytokines (IL-6, IL-8, IL-10, TNF) were determined. The presence of SI was established if the SI scale exceeded 5 points (numerical RL values + presence of additional criteria, each equal to 1 point). The time and severity of the developing critical state, as well as the RL scores, were taken into account when reviewing the phases.

There were three main SI phases: (1) evolving condition, (2) cytokine storm/phlogogenic hit (SD-4-5), and depressive (exhausting) phase. The latter was characterized by relatively low SIR values (RL-2-3). The lethality rate for shock in the presence of acute sepsis (n = 13) was 71.4%, reaching 94.1% in prolonged sepsis (n = 17). For haemorrhagic shock after massive blood loss, if not resolved within 24 hoursm the mortality rates was 53.8% (n = 13). Development of shock in acute sepsis, and haemorrhagic shock (within 4 to 12 hours after the onset of massive blood loss) is accompanied by the severity of critical-phase cytokine storm/PPS with a predominance of RL-5 in cases of lethal outcomes, and by a depression phase (RL-2-3) in prolonged sepsis. Overall mortality (for all groups) was 66.7% in the PS phase, 89.5% in the depressive phase and 15.4% in the evolvingl phase of haemorrhagic shock (with possible transition from this phase to the more critical SI phases until lethal outcome).

Shock states of both septic and aseptic origin are based on a typical pathological process of SI, which should be distinguished from the signs of SIR characteristic of high-intensity canonical inflammation. It is characterized by higher cytokinemia (cytokine storm phase) or by the presence of additional SI phenomena with relatively moderate SIR levels (depressive SI phase). Thus, the depressive phase of SI is more fatal for disease outcome compared to the cytokine storm phase with higher intensity of SIR.