Blood Purification for Sepsis

Removal of Inflammatory Mediators

The pathophysiology of sepsis is complex and not yet completely understood. Sepsis includes the concomitant presence of an invasive infection and the host systemic inflammatory response syndrome (SIRS), which is characterized by an overinflammatory state resulting from a massive and deregulated activation of innate and adaptive immunity, usually followed by an equally massive and deleterious counterregulatory response leading to the so-called “immune paralysis.” Therefore in septic patients there is a first early phase resulting from SIRS and a second late phase caused by immunosuppression and lymphocyte exhaustion.

Septic AKI currently is considered to be the consequence of several concomitant factors: a dysfunction of the renal microvascular system, direct interaction of pathogen fragments with renal resident cells, the cytotoxic effect of the so-called “cytokine storm,” and the deleterious cross-talk between failing organs. However, it generally is accepted that circulating inflammatory mediators directly may affect the renal parenchyma and are associated with an increased risk of mortality in AKI patients. These soluble mediators include eicosanoids, leukotrienes, complement components, cytokines, chemokines, coagulation factors, and other potentially important small peptides and vasogenic substances.

Multiple attempts have been made to block the inflammatory response. Early efforts to block specifically the proinflammatory mediators failed. Thus the goal of EBP is to restore homeostasis rather than to selectively inhibit pro- or antiinflammatory mediators.

Most immune mediators are water soluble and fall into the middle-molecular-weight category (roughly 5–50 kD) and therefore can be removed theoretically by EBP using standard techniques. EBP technologies can remove these inflammatory mediators via convection, diffusion, or adsorption. The effects are broad spectrum, autoregulating, and limited to the circulating pool of inflammatory mediators rather than influencing local tissue concentrations. These advantages provide a powerful rationale for blood purification used in sepsis.

Organ Support

The use of renal replacement therapy (RRT) in septic patients has been evaluated for renal support and immunomodulation. Although the modulation of inflammatory mediators appears to be the major objective of blood purification in sepsis, this therapy also may offer additional physiologic benefits, including temperature control, acid-base control, fluid balance control, cardiac support, protective lung support, brain protection, bone marrow protection, and blood detoxification and liver support. The extracorporeal circulation can be a potent modulator of body temperature and overall thermal balance. Negative thermal balance can be obtained depending on the length of blood lines, room temperature, and the replacement fluid temperature. Cardiac support can be achieved by optimizing fluid balance, reducing organ edema, and restoring preload and afterload to desirable levels. Optimizing the patient's volume state and removing interstitial fluid through the use of extracorporeal therapy may provide additional support to the failing lung. Blood purification may improve the encephalopathy of sepsis by removing uremic toxins and amino acid derivatives and correcting acidemia. Through the removal of uremic toxins, blood purification also offers bone marrow support. Through the combination of membrane separation processes and adsorption mechanisms, the blood purification system is available for detoxification and potentially has some role in liver support.