Blood Purification in Sepsis: A New Paradigm

Abstract

Sepsis is one of the main causes of death in critically ill patients. The pathophysiology of sepsis is complex and not completely understood. The proinflammatory and anti-inflammatory response leads to cell and organ dysfunction and, in many cases, death. Thus, the goal of the intervention is to restore the homeostasis of circulating mediators rather than to inhibit selectively the proinflammatory or anti-inflammatory mediators. Blood purification has been reported to remove a wide array of inflammatory mediators. The effects are broad-spectrum and auto-regulating. Blood purification has also been demonstrated to restore immune function through improving antigen-presenting capability, adjusting leukocyte recruitment, oxidative burst and phagocytosis, and improving leukocyte responsiveness. A great deal of work has to be done in order to find and optimize the best extracorporeal blood purification therapy for sepsis. New devices specifically target the pathophysiological mechanisms involved in these conditions. High-volume hemofiltration, hemoadsorption, coupled plasma filtration adsorption, and high cutoff membrane are now being tested in septic patients. Preliminary data indicate the feasibility of these modified techniques in sepsis. Their impact on patient prognosis, however, still needs proof by large randomized clinical trials. Finally, the emerging paradigm of sepsis-induced immune suppression provides additional rationale for the development of extracorporeal blood purification therapy for sepsis.

Clinical review: Blood purification for sepsis

“…Finally, Peng and colleagues [12] recently suggested that blood purification therapies act at the inflammatory cell level to restore the immune function through the regulation of monocytes, neutrophils, or even lymphocytes. This theory is supported by recent studies [13,14].…”

“…If this 'cellular level' theory with immune response restoration is confirmed, timing indications for blood purification would need to be reconsidered since optimal timing for initiating a blood purification therapy would not be only in the early phase of septic shock as it is suggested today. Furthermore, a novel component of this hypothesis is that, by removing mediators from the plasma in the setting of systemic inflammation, one can restore the concentration gradient from plasma to infected tissues [12]. This gradient has significant effects on leukocyte tracking and bacterial clearance [14].…”

Cytokine Removal with High Cut-Off Membrane: Review of Literature

“…Furthermore, the reduction in the circulating level of molecules could restore the concentration gradient necessary to guide the reticuloendothelial system to the main production site (i.e., the source of infection) improving the efficiency of the immune system (‘cytokinetic model') [8]. Finally, a direct immune-homeostatic role has been demonstrated for some extracorporeal blood purification therapies that modulate the HLA-DR expression, correlating with cell activation and interaction with some cell reproductive systems [9]. …”

Disease indicators for sepsis and analysis of sepsis treatment in children using the continuous blood purification technique

“…In recent years, several studies on active interventions for sepsis using continuous blood purification (CBP) have been reported in China and internationally. CBP has been shown to prevent and treat severe sepsis (Peng et al, 2010). During treatment of sepsis, CBP lowers the overall in vivo peak concentration of inflammatory mediators, down-regulates the body's inflammatory response.…”